Vazalore

Drug overview for VAZALORE (aspirin):

Generic name: aspirin (AS-pir-in)
Drug class: Non-Steroidal Anti-Inflammatory (NSAID) and Salicylates
Therapeutic class: Analgesic, Anti-inflammatory or Antipyretic

Aspirin (the prototype of the salicylates) is a nonsteroidal anti-inflammatory agent (NSAIA) and also exhibits antithrombotic, analgesic, and antipyretic activity.

Aspirin is used extensively in the treatment of mild to moderate pain, fever, and inflammatory diseases. Aspirin is also used in the prevention of arterial and venous thrombosis. Aspirin, however, should be used with extreme caution, if at all, in patients in whom urticaria, angioedema, bronchospasm, severe rhinitis, or shock is precipitated by other salicylates or other NSAIAs.

(See Cautions: Sensitivity Reactions in the Salicylates General Statement 28:08.04.24.)

DRUG IMAGES

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The following indications for VAZALORE (aspirin) have been approved by the FDA:

Indications:
Acute coronary syndrome
Acute myocardial infarction
Acute thromboembolic stroke
Cerebral thromboembolism prevention
Dysmenorrhea
Fever
Headache disorder
Juvenile idiopathic arthritis
Myocardial infarction prevention
Myocardial reinfarction prevention
Osteoarthritis
Pain
Prevention of cerebrovascular accident
Prevention of transient ischemic attack
Rheumatoid arthritis
Thrombosis prevention after percutaneous coronary intervention
Transient cerebral ischemia
Unstable angina pectoris

Professional Synonyms:
Acute cerebral infarction due to thromboembolism
Acute MI prophylaxis
Acute MI
Acute myocardial infarction prophylaxis
AMI prophylaxis
Arthritis deformans
Arthrosis deformans
Cardiac infarct prophylaxis
Cardiac infarction prophylaxis
Cardiac infarction
Cephalgia
Cephalodynia
Crescendo angina
CVA prophylaxis
Degenerative arthritis
Degenerative joint disease
Degenerative polyarthritis
Difficult menses
Difficult menstruation
Febrile reaction
Febrile
Hypertrophic arthritis
Juvenile RA
Juvenile rheumatoid arthritis
Maintenance therapy of thrombosis prevention after PCI
MI prophylaxis
Myocardial infarct prophylaxis
Myocardial infarct
Myocardial infarction prophylaxis
Myocardial reinfarction prophylaxis
Nodose rheumatism
Osteoarthrosis
Painful menses
Painful menstrual cramps
Preinfarction syndrome
Pyrexia
Rheumatic arthritis
Rheumatic gout
Stroke prophylaxis
Stroke thromboembolism prophylaxis
Thrombosis prophylaxis after percutaneous coronary intervention
TIA prophylaxis
TIAs prophylaxis
Transient ischemic attack prophylaxis
Transient ischemic attacks
Unstable angina
Vascular thrombosis prevention after percutaneous coronary intervention

The following dosing information is available for VAZALORE (aspirin):

Dosing
Administration
VAZALORE
Generic

Dosage of aspirin must be carefully adjusted according to individual requirements and response, using the lowest possible effective dosage. When used at high (e.g., anti-inflammatory) dosages, the development of tinnitus can be used as a sign of elevated serum salicylate concentrations, except in patients with high-frequency hearing impairment.

When preparations containing aspirin in fixed combination with other drugs are used, the cautions, precautions, and contraindications applicable to each ingredient must be considered.

Following oral administration of single doses of rapidly absorbed aspirin dosage forms, salicylate is detected in serum within 5-30 minutes, and peak serum salicylate concentrations are attained within 0.25-2 hours, depending on dosage form and specific formulation. Clinically important differences in the onset or intensity of analgesia produced by rapidly absorbed dosage forms or specific preparations have not been established.

Following oral administration of a single 650-mg dose of aspirin as an effervescent or noneffervescent aqueous solution in healthy adults, average peak plasma aspirin concentrations of about 13 mcg/mL are attained within 15-40 minutes and average peak plasma salicylate concentrations of about 40-55 mcg/mL are attained within 30-60 minutes. After a single 650-mg oral dose of aspirin (as two 325-mg uncoated plain tablets) in fasting healthy adults, average peak plasma aspirin concentrations of about 7-9 mcg/mL occur within 25-40 minutes and average peak plasma salicylate concentrations of about 35-50 mcg/mL occur within 1.5-2 hours.

Following oral administration of a single 650-mg dose of buffered aspirin (as 2 tablets, each containing 325 mg of aspirin), average peak plasma salicylate concentrations of about 40-60 mcg/mL are attained within 45-60 minutes.

In one study in healthy fasting adults given a single 975-mg oral dose of aspirin (as three 325-mg uncoated plain tablets), peak serum salicylate concentrations averaged 60-75 mcg/mL and occurred within 2 hours. In another study in fasting rheumatoid arthritis patients given a single 1.95-g oral dose of aspirin (as six325-mg uncoated plain tablets), peak plasma aspirin concentrations of about 12-16 mcg/mL occurred within 1 hour and peak plasma salicylate concentrations of about 110-160 mcg/mL occurred within 4 hours. When these patients were given the same dose of buffered aspirin (as 6 tablets, each containing 325 mg of aspirin), peak plasma aspirin concentrations of about 14-18 mcg/mL occurred within 1-2 hours and peak plasma salicylate concentrations of about 140-160 mcg/mL occurred within 1-2 hours.

Aspirin is usually administered orally, preferably with food or a large quantity (240 mL) of water (unless the patient is fluid restricted) or milk to minimize gastric irritation. In patients unable to take or retain oral medication, aspirin suppositories may be administered rectally; however, rectal absorption may be slow and incomplete. (See Pharmacokinetics: Absorption.)Aspirin tablets should not be administered rectally, since they are likely to cause irritation and erosion of the rectal mucosa.

Aspirin preparations should not be used if a strong vinegar-like odor is present. (See Chemistry and Stability: Stability.) If an unpleasant taste or aftertaste, burning in the throat, or difficulty in swallowing occurs with uncoated aspirin-containing tablets, these effects may be reduced with film-coated tablets. Although specific data are not available, these effects are also likely to be reduced with enteric-coated tablets.

If gastric irritation and/or symptomatic GI disturbances occur with uncoated aspirin-containing tablets, these effects may be reduced with enteric-coated tablets or extended-release tablets. If a liquid dosage form of aspirin is desired for short-term treatment of pain, an oral solution may be prepared from commercially available effervescent tablets (e.g., Alka-Seltzer(R)) by dissolving tablets in 120 mL of water; ingest the entire solution to ensure adequate dosing. In addition to potentially reducing adverse GI effects, some clinicians suggest that enteric-coated tablets may be swallowed more easily by children receiving chronic therapy with the drug and may therefore result in increased compliance.

Aspirin or buffered aspirin preparations should not be chewed before swallowing for at least 7 days following tonsillectomy or oral surgery because of possible injury to oral tissues from prolonged contact with aspirin particles. In addition, aspirin or buffered aspirin tablets should not be placed directly on a tooth or gum surface because of possible injury to tissues. Capsules containing the fixed combination of aspirin and extended-release dipyridamole should be swallowed whole and should not be chewed.

Chewable aspirin tablets may be chewed, crushed, and/or dissolved in a liquid, or swallowed whole, followed by approximately 120 mL of water, milk, or fruit juice immediately after administration of the drug. For information on the concomitant administration of aspirin with nonsteroidal anti-inflammatory agents (NSAIAs), see Drug Interactions: Nonsteroidal Anti-inflammatory Agents, in the Salicylates General Statement 28:08.04.24.

Dosing information for VAZALORE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
VAZALORE 81 MG CAPSULE	Maintenance	Adults take 1 capsule (81 mg) by oral route once daily

No generic dosing information available.

The following drug interaction information is available for VAZALORE (aspirin):

Contraindicated
Severe
Moderate

There are 3 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Ketorolac (Non-Injection)/NSAID; Aspirin (Greater Than 300 mg); Salicylates SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Possible additive or synergistic side effects.(1,2) CLINICAL EFFECTS: Concurrent use of multiple doses of ketorolac with other non-steroidal anti-inflammatory agents (NSAIDs), salicylates or aspirin may result in an increase in NSAID-related side effects such as bleeding or renal impairment.(1-3) PREDISPOSING FACTORS: Patients with pre-existing renal impairment may be at an increased risk of adverse effects from this interaction. The risk for bleeding episodes may be greater in patients with multiple disease-associated factors (e.g. thrombocytopenia, advanced liver disease). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g., anticoagulants, antiplatelets, corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Risk of GI bleed may be increased in patients who are of older age, in poor health status, or who use alcohol or smoke. Risk may also be increased with longer duration of NSAID use and prior history of peptic ulcer disease and/or GI bleeding. PATIENT MANAGEMENT: Manufacturers of ketorolac state that concurrent use of ketorolac with either other NSAIDs or aspirin is contraindicated.(1,2) If concurrent therapy is deemed medically necessary, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Conduct periodic monitoring of renal function, especially in patients with renal impairment. Instruct patients to report any signs and symptoms of bleeding, such as unusual bruising; red or black, tarry stools; acute abdominal or joint pain and/or swelling. DISCUSSION: Based upon similar pharmacodynamic effects and potentially cumulative risks of serious NSAID-related adverse events, manufacturers of ketorolac state the concurrent administration of ketorolac with other NSAIDs or aspirin is contraindicated.(1,2)	KETOROLAC TROMETHAMINE, SPRIX
Mifepristone/Anticoagulants; Antiplatelets SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Anticoagulants may result in excessive bleeding following the abortion. CLINICAL EFFECTS: The concurrent use of mifepristone with anticoagulants may result in excessive bleeding following the abortion. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The manufacturer of mifepristone states that mifepristone is contraindicated in patients receiving concurrent anticoagulant therapy.(1) If concurrent therapy is deemed medically necessary, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: The manufacturer of mifepristone states that mifepristone is contraindicated in patients receiving concurrent anticoagulant therapy.(1)	MIFEPREX, MIFEPRISTONE
Ketorolac (Injectable)/NSAIDs; Aspirin (Greater Than 300 mg); Salicylates SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Possible additive or synergistic side effects.(1) CLINICAL EFFECTS: Concurrent use of multiple doses of ketorolac with other non-steroidal anti-inflammatory agents (NSAIDs), salicylates or aspirin may result in an increase in NSAID-related side effects such as bleeding or renal impairment.(1-3) PREDISPOSING FACTORS: Patients with pre-existing renal impairment may be at an increased risk of adverse effects from this interaction. The risk for bleeding episodes may be greater in patients with multiple disease-associated factors (e.g. thrombocytopenia, advanced liver disease). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g., anticoagulants, antiplatelets, corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Risk of GI bleed may be increased in patients who are of older age, in poor health status, or who use alcohol or smoke. Risk may also be increased with longer duration of NSAID use and prior history of peptic ulcer disease and/or GI bleeding. PATIENT MANAGEMENT: The manufacturer of ketorolac states that concurrent use of ketorolac with either other NSAIDs, salicylates or aspirin is contraindicated.(1) If concurrent therapy is deemed medically necessary, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: Manufacturers of ketorolac state that concurrent use of ketorolac with either other NSAIDs, salicylates or aspirin is contraindicated.(1,2) If concurrent therapy is deemed medically necessary, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Conduct periodic monitoring of renal function, especially in patients with renal impairment.	BUPIVACAINE-KETOROLAC-KETAMINE, KETOROLAC TROMETHAMINE, R.E.C.K.(ROPIV-EPI-CLON-KETOR), ROPIVACAINE-CLONIDINE-KETOROLC, ROPIVACAINE-KETOROLAC-KETAMINE, TORONOVA II SUIK, TORONOVA SUIK

There are 15 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Selected Anticoagulants (Vitamin K antagonists)/Aspirin (Greater Than 100 mg); Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Multiple processes are involved: 1) Salicylate doses greater than 3 gm daily decrease plasma prothrombin levels. 2) Salicylates may also displace anticoagulants from plasma protein binding sites. 3) Aspirin is an irreversible platelet inhibitor. Salicylates impair platelet function, resulting in prolonged bleeding time. 4) Salicylates may cause gastrointestinal(GI) bleeding due to irritation. CLINICAL EFFECTS: The concurrent use of anticoagulants and salicylates leads to blockade of two distinct coagulation pathways and may increase the risk for bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Avoid concomitant administration of these drugs. When aspirin is required for cardioprotection, a low dose (less than 100 mg daily) is recommended to decrease the risk for aspirin-induced GI bleeding. If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: This interaction has been reported between aspirin and warfarin and between aspirin and dicumarol. Diflunisal, sodium salicylate, and topical methyl salicylate have been shown to interact with anticoagulants as well. Based on the proposed mechanisms, other salicylates would be expected to interact with anticoagulants as well. A self-controlled case study of 1,622 oral anticoagulant-precipitant drug pairs were reviewed and found 14% of drug pairs were associated with a statistically significant elevated risk of thromboembolism. Concurrent use of warfarin and diflunisal resulted in a ratio of rate ratios (RR) (95% CI) of 3.85 (1.34-11.03); warfarin and aspirin ratio of RR 2.13 (1.72-2.64); warfarin and dipyridamole ratio of RR 2.07 (1.65-2.6); and warfarin and clopidogrel ratio of RR 1.69 (1.56-1.84). A large systematic review was performed on 72 warfarin drug-drug interactions studies that reported on bleeding, thromboembolic events, or death. Most studies were retrospective cohorts. A meta-analysis of 38 of those studies found a higher rate of clinically significant bleeding in patients on warfarin and antiplatelets (OR=1.74; 95% CI 1.56-1.94). Increased bleeding risk was also seen in subgroup analyses with aspirin (OR=1.50; 95% CI 1.29-1.74), clopidogrel (OR=3.55; 95% CI 2.78-4.54), and aspirin plus clopidogrel or ticlopidine (OR=2.07, 95% CI 1.33-3.21).(17)	ANISINDIONE, DICUMAROL, JANTOVEN, PHENINDIONE, WARFARIN SODIUM
Influenza Virus Vaccine Live/Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Use of salicylates during influenza infection has been associated with Reye's Syndrome.(1,2) CLINICAL EFFECTS: Use of the live influenza virus vaccine in children and adolescents (patients age 2-17 years) receiving salicylate therapy may increase the risk of Reye's Syndrome.(1,2) Symptoms of Reye's syndrome include drowsiness, confusion, seizures, coma. In severe cases, Reye's syndrome can result in death. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The use of live influenza virus vaccine in children and adolescents (patients age 2-17 years) receiving salicylate therapy is contraindicated.(1,2) Use of salicylates should be avoided for 4 weeks after administration of live influenza vaccine.(1) DISCUSSION: Because the use of salicylates during influenza infection has been associated with Reye's Syndrome, the use of live influenza virus vaccine in children and adolescents (patients age 2-17 years) receiving salicylate therapy is contraindicated.(1,2)	FLUMIST TRIVALENT 2024-2025
Dabigatran/Antiplatelets; Aspirin (Greater Than 100 mg) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Dabigatran is a direct thrombin inhibitor and when taken with agents that effect platelet aggregation increased bleeding episodes can occur.(1,2) CLINICAL EFFECTS: Concurrent use of dabigatran with antiplatelet agents may result in additive or synergistic effects resulting in unwanted bleeding episodes.(1,2) PREDISPOSING FACTORS: Factors associated with an increase risk for bleeding include renal impairment, concomitant use of P-glycoprotein inhibitors, patient age >74 years, coexisting conditions (e.g. recent trauma) or use of drugs (e.g. NSAIDs) associated with bleeding risk, and patient weight <50 kg.(1-3) The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Patients requiring concurrent therapy with dabigatran and an antiplatelet agent should be closely monitored for signs of bleeding. If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. Discontinue dabigatran in patients with active bleeding. DISCUSSION: Dabigatran is a direct thrombin inhibitor and when taken with agents that effect platelet aggregation and/or other clotting factors increased bleeding episodes can occur.(1,2) In the RE-LY trial, 40% of patients were on aspirin at baseline.(1) In the RE-MEDY trial, 7.7% of patients were on aspirin at baseline.(1) In the RE-DUAL PCI trial, patients were randomly assigned to one of three treatments: (A) dual therapy with dabigatran 110 mg twice daily plus either clopidogrel or ticagrelor, (B) dual therapy with dabigatran 150 mg twice daily plus either clopidogrel or ticagrelor, or (C) triple therapy with warfarin (goal INR 2-3) plus aspirin (< or = 100 mg daily) plus either clopidogrel or ticagrelor. The incidence of the first major or clinically relevant non-major (CRNM) bleeding event was 15.4% in group A compared with 26.9% in group C (hazard ratio, 0.52; 95% CI 0.42 to 0.63; p<0.001 for noninferiority; p<0.001 for superiority) and 20.2% in group B compared to 25.7% in corresponding group C (hazard ratio, 0.72; 95% CI 0.58 to 0.88; p<0.001 for noninferiority). For major bleeding as defined by Thrombolysis in Myocardial Infarction (TIMI) criteria, the rate was lower in both dual-therapy groups than in the triple-therapy group: 1.4% in group A compared to 3.8% in group C (hazard ratio, 0.37; 95% CI 0.2 to 0.68; p=0.002) and 2.1% in group B compared to 3.9% in corresponding group C (hazard ratio, 0.51; 95% CI 0.28 to 0.93; p=0.03). Incidence of composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization was 13.7% in groups A and B compared to 13.4% in group C (hazard ratio, 1.04; 95% CI 0.84 to 1.29; p=0.005 for noninferiority).(4) A meta-analysis of 9 studies identified 13,459 patients taking direct oral anticoagulants (DOACs), 1,692 of whom also took an antiplatelet agent. Of the patients on antiplatelet agents, 1,254 took aspirin while the rest was unspecified. Most of the trials restricted patients to use of low-dose aspirin, with the highest allowable dose being 165 mg/day. Compared with DOACs alone, the use of DOACs with antiplatelet agents was associated with an increased risk of major bleeding (OR 1.89; 95% CI, 1.04-3.44) and CRNM bleeding (OR 1.82; 95% CI, 1.50-2.22). There was no difference between groups in the efficacy outcome of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death.(5)	DABIGATRAN ETEXILATE, PRADAXA
Varicella Virus Vaccine Live/Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Use of salicylates during natural varicella infection has been associated with Reye's Syndrome.(1-4) CLINICAL EFFECTS: Use of the live varicella virus vaccine in patients receiving salicylate therapy or use of salicylates within 6 weeks after vaccination with the live varicella virus vaccine may increase the risk of Reye's Syndrome.(1-4) Symptoms of Reye's syndrome include drowsiness, confusion, seizures, coma. In severe cases, Reye's syndrome can result in death. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The Canadian, UK, and US manufacturers of live varicella virus vaccine indicated for the prevention of chicken pox state that vaccine recipients should avoid the use of salicylates for 6 weeks after vaccination.(1-4) There is no such restriction in the labeling for live varicella virus vaccine indicated for the prevention of shingles, which is only indicated for patients age 60 and older.(5) DISCUSSION: Because the use of salicylates during natural varicella infection has been associated with Reye's Syndrome, the use of salicylates for 6 weeks following vaccination with live varicella virus vaccine should be avoided.(1-4)	PROQUAD, VARIVAX VACCINE
Sodium Phosphate Bowel Cleanser/NSAIDs; Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Bowel cleansing with sodium phosphate causes dehydration, decreased intravascular volume and hyperphosphatemia, which increases phosphate levels in the renal tubules. Abnormally high levels of calcium and phosphate in the renal tubules may precipitate out, resulting in renal injury.(1) CLINICAL EFFECTS: Use of sodium phosphate for bowel cleansing in patients maintained on nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of acute phosphate nephropathy, which is an acute kidney injury associated with deposits of calcium phosphate crystal in the renal tubules that may result in permanent renal function impairment. Acute phosphate nephropathy presents as acute kidney injury with minimal proteinuria and a bland urine sediment.(2) Use of oral sodium phosphate products at laxative doses has not been associated with acute kidney injury.(3) PREDISPOSING FACTORS: Patients who may be at an increased risk of acute phosphate nephropathy include those who are over age 55; are hypovolemic or have decreased intravascular volume; have baseline kidney disease, bowel obstruction, or active colitis; and who are using medications that affect renal perfusion or function (such as diuretics, ACE inhibitors, angiotension receptor blockers [ARBs]), and NSAIDs.(2) PATIENT MANAGEMENT: If possible, use an alternative agent for bowel cleansing.(1) Use sodium phosphate products with caution in patients taking medications that affect kidney function or perfusion, such as ACE inhibitors or ARBs. Obtain baseline and post-procedure labs (electrolytes, calcium, phosphate, BUN, creatinine, and [in smaller, frail individuals] glomerular filtration rate). Instruct patients to drink sufficient quantities of clear fluids before, during, and after bowel cleansing and to avoid other laxatives that contain sodium phosphate. Consider hospitalization and intravenous hydration during bowel cleansing to support frail patients who may be unable to drink an appropriate volume of fluid or who may be without assistance at home.(2) Use of an electrolyte solution for rehydration may decrease the risk of acute phosphate nephropathy.(4,5) DISCUSSION: Since May 2006, the FDA has received 20 reports of acute phosphate nephropathy associated with the use of Osmo Prep. Concomitant medications included ACE inhibitors or ARBs (11), diuretics (6), and NSAIDs (4).(2) In a retrospective review of colonoscopy patients, simultaneous use of ACE inhibitors or ARBs significantly increased the risk of acute kidney injury from oral sodium phosphate. Diuretic use was also a risk factor.(6) In a case series study of 21 cases of acute phosphate nephropathy in patients who had used oral sodium phosphate, 14 patients received an ACE inhibitor or ARB, 4 used a diuretic, and 3 used an NSAID.(7) Cases have also been reported with rectal products.(8)	MB CAPS, SODIUM PHOSPHATE DIBASIC, URIMAR-T, URNEVA
Ticagrelor/High-Dose Aspirin SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. CLINICAL EFFECTS: Chronic use of high-dose aspirin may decrease the efficacy of ticagrelor.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: After an initial loading dose, low dose aspirin is indicated with concurrent ticagrelor for the prevention of thrombotic events. Specific dosage recommendations vary between countries, however all agree that the maintenance aspirin dose should be < or = 150 mg per day. US prescribing information recommends the following based on indication: -For Acute Coronary Syndrome or Myocardial Infarction - Initiate ticagrelor with a maintenance dose of aspirin 75 mg to 100 mg. -For Coronary Artery Disease but No Prior Stroke or Myocardial Infarction - Use ticagrelor with a daily maintenance dose of aspirin of 75 mg to 100 mg. -For Acute Ischemic Stroke or Transient Ischemic Attack - Use ticagrelor with a loading dose of aspirin (300 mg to 325 mg) and a daily maintenance dose of 75 mg to 100 mg.(1) Canada and UK prescribing information recommends a maintenance aspirin dose of 75 mg to 150 mg daily.(2,3) For use other than platelet aggregation, it would be prudent to recommend an alternative product that does not contain aspirin for patients maintained on ticagrelor. DISCUSSION: Ticagrelor is indicated with concurrent aspirin for the prevention of thrombotic events. In the PLATO trial, there was a relationship between the maintenance dose of aspirin and efficacy of ticagrelor. At increased aspirin dosages, ticagrelor was less effective.(1-3)	BRILINTA, TICAGRELOR
Rivaroxaban/Selected Antiplatelets; Aspirin (Greater Than 100 mg) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Additive effects on hemostasis.(1) CLINICAL EFFECTS: Concurrent use of rivaroxaban with anticoagulants, antiplatelets, or thrombolytics may increase the risk of bleeding.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Avoid concurrent use of rivaroxaban and higher doses of aspirin unless the benefit is expected to outweigh the increased risk of bleeding. In the ROCKET AF trial, concomitant use of low dose aspirin (almost exclusively at less than or equal to 100 mg daily) was identified as an independent risk factor for bleeding.(1) If the benefit of concurrent use of rivaroxaban with other antiplatelets is expected to outweigh the increased risk of bleeding, closely monitor patients for signs or symptoms of bleeding.(1) The UK manufacturer of rivaroxaban states that rivaroxaban 2.5 mg twice daily is indicated with aspirin 75 - 100 mg with or without clopidogrel 75 mg or standard dose ticlopidine for post-acute coronary syndrome and in patients with CAD and PAD, weighing the risk for ischemic events against the bleeding risks. Long-term dual antiplatelet therapy should be avoided. Clinical monitoring is recommended throughout treatment.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: In two clinical trials in healthy subjects, concurrent clopidogrel (300 mg loading dose, then 75 mg daily) and rivaroxaban (15 mg single dose) increased bleeding time to 45 minutes in 45% and 30% of subjects. This was twice the maximum increase in bleeding time seen with either agent alone.(1) In the ROCKET AF trial, concomitant aspirin use (almost exclusively at < or = to 100 mg daily) was identified as an independent risk factor for bleeding.(1) In a study, concurrent enoxaparin (40 mg) and rivaroxaban (10 mg) resulted in additive effects on anti-factor Xa activity with no effects on the pharmacokinetics of rivaroxaban.(1) In a study, concurrent warfarin (15 mg) and rivaroxaban (5 mg) resulted in additive effects on factor Xa inhibition and PT with no effects on the pharmacokinetics of rivaroxaban.(1) In a single dose study, there were no pharmacokinetic or pharmacodynamic interactions between rivaroxaban and aspirin.(1) A self-controlled case study of 1,622 oral anticoagulant-precipitant drug pairs were reviewed and found 14% of drug pairs were associated with a statistically significant elevated risk of thromboembolism. Concurrent use of rivaroxaban and dipyridamole resulted in a ratio of rate ratios (95% CI) of 3.49 (1.08-6.64); and rivaroxaban and aspirin ratio of rate ratios 2.19 (1.21-2.95).(3) A meta-analysis of 9 studies identified 13,459 patients taking direct oral anticoagulants (DOACs), 1,692 of whom also took an antiplatelet agent. Of the patients on antiplatelet agents, 1,254 took aspirin while the rest was unspecified. Most of the trials restricted patients to use of low-dose aspirin, with the highest allowable dose being 165 mg/day. The use of DOACs with antiplatelet agents was associated with an increased risk of major bleeding (OR 1.89; 95% CI, 1.04-3.44) and clinically relevant non-major bleeding (OR 1.82; 95% CI, 1.50-2.22). There was no difference between groups in the efficacy outcome of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death.(4)	RIVAROXABAN, XARELTO
Apixaban/Antiplatelets; Aspirin (Greater Than 100 mg) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Additive effects on hemostasis.(1-4) CLINICAL EFFECTS: Concurrent use of apixaban with antiplatelets may increase the risk of bleeding.(1-4) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Patients requiring concurrent therapy with apixaban and an antiplatelet agent should be closely monitored for signs of bleeding. Monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. Discontinue apixaban in patients with active bleeding. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Concurrent administration of enoxaparin (40 mg single dose) and apixaban (5 mg single dose) resulted in additive effects on anti-Factor Xa activity.(1) Concurrent apixaban and aspirin (325 mg daily) resulted in no pharmacokinetic or pharmacodynamic interactions.(1) Concurrent apixaban with clopidogrel (75 mg daily) or with combination clopidogrel (75 mg daily) and aspirin (162 mg daily) produced no relevant increases in bleeding time, platelet aggregation, or clotting tests (PI, INR, and aPTT) compared either clopidogrel alone or clopidogrel with aspirin without apixaban.(1) Significant bleeding risk was reported with the combination of apixaban, aspirin, and clopidogrel in patients with acute coronary syndrome.(1) A self-controlled case study of 1,622 oral anticoagulant-precipitant drug pairs were reviewed and found 14% of drug pairs were associated with a statistically significant elevated risk of thromboembolism. Concurrent use of apixaban and clopidogrel resulted in a ratio of rate ratios (95% CI) of 1.96 (1.53-2.51).(5) A meta-analysis of 9 studies identified 13,459 patients taking direct oral anticoagulants (DOACs), 1,692 of whom also took an antiplatelet agent. Of the patients on antiplatelet agents, 1,254 took aspirin while the rest was unspecified. Most of the trials restricted patients to use of low-dose aspirin, with the highest allowable dose being 165 mg/day. The use of DOACs with antiplatelet agents was associated with an increased risk of major bleeding (OR 1.89; 95% CI, 1.04-3.44) and clinically relevant non-major bleeding (OR 1.82; 95% CI, 1.50-2.22). There was no difference between groups in the efficacy outcome of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death.(3)	ELIQUIS
Anagrelide/Aspirin SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Anagrelide may affect platelet function in a way that synergizes with low-dose aspirin.(1) CLINICAL EFFECTS: Concurrent use of anagrelide and aspirin may increase the risk of hemorrhage.(1,2) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The concurrent use of anagrelide and aspirin should be approached with caution, especially in patients with a high risk profile for hemorrhage.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: In healthy subjects, the administration of of single dose anagrelide (1 mg) and aspirin (900 mg) or multiple dose anagrelide (1 mg daily) and aspirin (75 mg daily) resulted in greater anti-platelet aggregation effects than aspirin alone. Concurrent single doses of both anagrelide and aspirin had no effects on bleeding time, prothrombin time, or activated partial thromboplastin time.(2) A study in 809 patients with essential thrombocythemia compared the combination of low-dose aspirin with hydroxyurea to the combination of low-dose aspirin with anagrelide. While patients receiving low-dose aspirin with anagrelide had lower rates of venous thromboembolism, the combination was associated with increased rates of arterial myelofibrosis, serious hemorrhage, and transformation to myelofibrosis.(1)	AGRYLIN, ANAGRELIDE HCL
Edoxaban/Antiplatelets; Aspirin (Greater Than 100 mg) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Anticoagulants and antiplatelet agents have additive effects on hemostasis.(1) In addition, aspirin doses greater than or equal to 325 mg daily increase edoxaban exposure.(1) CLINICAL EFFECTS: Concurrent use of edoxaban with antiplatelets may increase the risk of bleeding.(1) PREDISPOSING FACTORS: Bleeding risk may be increased in patients with renal impairment and in patients > 75 years of age.(1) Use of multiple agents which affect hemostasis increases the risk for bleeding. The risk for bleeding episodes may be greater in patient with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Patients requiring concurrent therapy with edoxaban and an antiplatelet agent should be closely monitored for signs of bleeding. Edoxaban and aspirin at dosages of 100 mg or less may be coadministered.(2,3) Monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. Discontinue edoxaban in patients with active bleeding. DISCUSSION: Concomitant use of edoxaban and antiplatelet agents may increase the risk of bleeding. In edoxaban clinical trials concomitant use of low dose aspirin (< or = 100 mg daily), thienopyridines, and NSAIDs was permitted and resulted in increased rates of clinically relevant bleeding. The rates of major bleeding on edoxaban and warfarin were generally consistent among subgroups. Bleeding rates appeared higher in both treatment arms (edoxaban and warfarin) in patients taking aspirin. Co-administration of aspirin (100 mg or 325 mg) and edoxaban increased bleeding time relative to that seen with either drug alone.(1) About 30% of the population in ENGAGE-AF received concomitant therapy with aspirin because of co-morbid conditions. While aspirin is known to increase risk for bleeds and the annualized event rate for major bleeds was higher than that in patients not receiving aspirin (3.87% vs. 2.13%), the risk for bleeds in patients receiving edoxaban 60 mg on a background of aspirin was lower than that for warfarin on a background of aspirin (HR 0.78 (95%CI 0.65,0.94). Based on these data no dose adjustments/contraindications are required.(4) Edoxaban and aspirin at dosages of 100 mg or less may be coadministered.(2,3) A meta-analysis of 9 studies identified 13,459 patients taking direct oral anticoagulants (DOACs), 1,692 of whom also took an antiplatelet agent. Of the patients on antiplatelet agents, 1,254 took aspirin while the rest was unspecified. Most of the trials restricted patients to use of low-dose aspirin, with the highest allowable dose being 165 mg/day. The use of DOACs with antiplatelet agents was associated with an increased risk of major bleeding (OR 1.89; 95% CI, 1.04-3.44) and clinically relevant non-major bleeding (OR 1.82; 95% CI, 1.50-2.22). There was no difference between groups in the efficacy outcome of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death.(5)	SAVAYSA
Ketorolac (Non-Injectable)/Aspirin (Less Than or Equal To 300 mg) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: There are two potential mechanisms: 1) Possible additive or synergistic pharmacodynamic side effects from concurrent NSAID use.(1,2) 2) Ketorolac is a reversible platelet inhibitor, while aspirin is an irreversible platelet inhibitor. CLINICAL EFFECTS: Concurrent use of multiple doses of ketorolac with aspirin may result in increased risk for NSAID-related side effects such as bleeding.(1,2) Nonselective NSAIDs such as ketorolac may interfere with the antiplatelet effects of aspirin.(3) PREDISPOSING FACTORS: Bleeding risk may increase due to disease (e.g. recent GI ulcer or bleed) or other concurrent drugs (e.g.anticoagulants, heparinoids). Elderly patients are at increased risk for severe GI events from ketorolac.(1,2) The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (NSAIDs). PATIENT MANAGEMENT: The manufacturer of prescription extended-release aspirin used for cardiovascular protection notes that concurrent treatment with NSAIDs may interfere with the antiplatelet effect of aspirin and increase the risk for NSAID associated bleeding or renal impairment, but does not contraindicate concurrent use.(3) However, manufacturers of ketorolac state that concurrent use of ketorolac with aspirin is contraindicated.(1,2) If concurrent therapy or ketorolac with low dose aspirin is needed, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Conduct periodic monitoring of renal function, especially in patients with preexisting renal impairment. Instruct patients to report any signs and symptoms of bleeding, such as unusual bruising; red or black, tarry stools; acute abdominal or joint pain and/or swelling. DISCUSSION: Based upon similar pharmacodynamic effects and potentially cumulative risks for serious NSAID-related adverse events, manufacturers of ketorolac state the concurrent administration of ketorolac with other NSAIDs or aspirin is contraindicated.(1,2) Prescribing information for an FDA approved lower strength prescription aspirin product used for cardiovascular risk reduction describes potential interactions, but does not contraindicate concomitant NSAID use.(3)	KETOROLAC TROMETHAMINE, SPRIX
Ketorolac (Injectable)/Aspirin (Less Than or Equal To 300 mg) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: There are two potential mechanisms: 1) Possible additive or synergistic pharmacodynamic side effects from concurrent NSAID use.(1,2) 2) Ketorolac is a reversible platelet inhibitor, while aspirin is an irreversible platelet inhibitor. CLINICAL EFFECTS: Concurrent use of multiple doses of ketorolac with aspirin may result in increased risk for NSAID-related side effects such as bleeding.(1,2) Nonselective NSAIDs such as ketorolac may interfere with the antiplatelet effects of aspirin.(3) PREDISPOSING FACTORS: Bleeding risk may increase due to disease (e.g. recent GI ulcer or bleed) or other concurrent drugs (e.g.anticoagulants, heparinoids). Elderly patients are at increased risk for severe GI events from ketorolac.(1,2) The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (NSAIDs). PATIENT MANAGEMENT: The manufacturer of prescription extended-release aspirin used for cardiovascular protection notes that concurrent treatment with NSAIDs may interfere with the antiplatelet effect of aspirin and increase the risk for NSAID associated bleeding or renal impairment, but does not contraindicate concurrent use.(3) However, manufacturers of ketorolac state that concurrent use of ketorolac with aspirin is contraindicated.(1,2) If concurrent therapy or ketorolac with low dose aspirin is needed, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Conduct periodic monitoring of renal function, especially in patients with preexisting renal impairment. Instruct patients to report any signs and symptoms of bleeding, such as unusual bruising; red or black, tarry stools; acute abdominal or joint pain and/or swelling. DISCUSSION: Based upon similar pharmacodynamic effects and potentially cumulative risks for serious NSAID-related adverse events, manufacturers of ketorolac state the concurrent administration of ketorolac with other NSAIDs or aspirin is contraindicated.(1,2) Prescribing information for an FDA approved lower strength prescription aspirin product used for cardiovascular risk reduction describes potential interactions, but does not contraindicate concomitant NSAID use.(3)	BUPIVACAINE-KETOROLAC-KETAMINE, KETOROLAC TROMETHAMINE, R.E.C.K.(ROPIV-EPI-CLON-KETOR), ROPIVACAINE-CLONIDINE-KETOROLC, ROPIVACAINE-KETOROLAC-KETAMINE, TORONOVA II SUIK, TORONOVA SUIK
Vorapaxar/Aspirin (> 100 mg) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Additive effects on hemostasis.(1-3) CLINICAL EFFECTS: Concurrent use of vorapaxar with high-dose aspirin may increase the risk of bleeding while decreasing the efficacy of vorapaxar.(1-3) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Vorapaxar is indicated for concurrent use with antiplatelet dosages of aspirin. Use of high-dose aspirin should be avoided with vorapaxar. Patients requiring concurrent therapy with vorapaxar and high-dose aspirin should be closely monitored for signs of bleeding.(1-3) Monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. Discontinue vorapaxar in patients with active bleeding. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: In the TRA2P and TRACER clinical trials, GUSTO moderate/severe bleeding was increased with higher dosages of aspirin (>= 300 mg), while efficacy of vorapaxar was decreased.(2,3)	ZONTIVITY
Abrocitinib/Antiplatelets; Aspirin (Greater Than 100 mg) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Abrocitinib has been associated with transient, dose-dependent thrombocytopenia. The nadir platelet count occurs at a median of 24 days after receiving abrocitinib 200 mg once daily and a 40% recovery occurs by 12 weeks. Concurrent use with agents that affect platelet aggregation may result in an additive risk of bleeding.(1) CLINICAL EFFECTS: Concurrent use of abrocitinib with antiplatelet agents may increase the risk of bleeding.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. pre-existing thrombocytopenia). Abrocitinib is not recommended for patients with a platelet count less than 150,000/mm3.(1) Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding. PATIENT MANAGEMENT: The concurrent use of abrocitinib with antiplatelet agents (except aspirin < or = 81 mg daily) is contraindicated during the first 3 months of abrocitinib therapy. Prior to starting abrocitinib therapy, obtain a complete blood count and recheck at 4 weeks after initiation and 4 weeks after a dose increase. Discontinuation of abrocitinib is required if platelets drop below 50,000/mm3.(1) If concurrent therapy is warranted after the first 3 months of abrocitinib therapy, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: Abrocitinib has been associated with transient, dose-dependent thrombocytopenia and is more severe with lower baseline platelet counts. At baseline platelet counts of 170,000/mm3, 220,000/m3 and 270,000/mm3, the nadirs were -41.2%, -33.4%, and -26.5%, respectively. Recovery of platelet count (about 40% recovery by 12 weeks) occurred without discontinuation of the treatment.(1)	CIBINQO
Caplacizumab/Anticoagulants; Antiplatelets SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Bleeding has been reported with the use of caplacizumab.(1) CLINICAL EFFECTS: Concurrent use of caplacizumab with either anticoagulants or antiplatelets may increase the risk of hemorrhage.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. hemophilia, coagulation factor deficiencies). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Avoid the use of caplacizumab with anticoagulants and antiplatelets. Interrupt caplacizumab therapy if clinically significant bleeding occurs. Patients may require von Willebrand factor concentrate to rapidly correct hemostasis. If caplacizumab is restarted, closely monitor for signs of bleeding.(1) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Bleeding has been reported with caplacizumab. In clinical studies, severe bleeding adverse reactions of epistaxis, gingival bleeding, upper gastrointestinal hemorrhage, and metrorrhagia were each reported in 1% of patients. Overall, bleeding events occurred in approximately 58% of patients on caplacizumab versus 43% of patients on placebo.(1) In post-marketing reports, cases of life-threatening and fatal bleeding were reported with caplacizumab.(1)	CABLIVI

There are 33 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Uricosurics/Aspirin (Greater Than 100 mg); Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Not clearly established. Protein binding displacement is a possibility. CLINICAL EFFECTS: May observe hyperuricemia and gout resulting from reduced uricosuric response. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid chronic, moderate to high doses of salicylates. DISCUSSION: This interaction is well documented. Occasional small doses of salicylates do not appear to inhibit the action of uricosurics.	DUZALLO, PROBENECID, PROBENECID-COLCHICINE
NSAIDs; Salicylates/Loop Diuretics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: During concurrent administration of a loop diuretic and a nonsteroidal anti-inflammatory drug (NSAID), patients may retain sodium as a result of NSAID-induced prostaglandin inhibition. CLINICAL EFFECTS: The pharmacological effects of loop diuretics may be decreased due to reduced antihypertensive and diuretic actions. Concurrent use of NSAIDs with loop diuretics and renin-angiotensin system (RAS) inhibitors may result in increased risk of acute kidney injury (AKI). PREDISPOSING FACTORS: Low water intake/dehydration, drug sensitivity, greater than 75 years of age, and renal impairment may increase an individuals susceptibility to AKI. PATIENT MANAGEMENT: Monitor patients for a decrease in the effects of the loop diuretic. It may be necessary to administer a higher dose of the diuretic or an alternative anti-inflammatory agent. Concurrent use of NSAIDs with loop diuretics and RAS inhibitors should be used with caution and monitored closely for signs of AKI. DISCUSSION: In a computational study, the risk of AKI using triple therapy with a diuretic, RAS inhibitor, and NSAID was assessed. The study found the following factors may increase an individual's susceptibility to AKI: low water intake, drug sensitivity, greater than 75 years of age, and renal impairment.(19,20) In an observational study, current use of a triple therapy with a diuretic, RAS inhibitor, and NSAID, was associated with an increased rate of acute kidney injury (rate ratio (RR) 1.31, 95% confidence interval (CI) 1.12-1.53). The highest risk of AKI associated with triple therapy were observed in the first 30 days of use (RR 1.82, CI 1.35-2.46). (21) Administration of indomethacin alone has been reported to decrease sodium excretion and increase blood pressure. In patients receiving a loop diuretic (e.g., bumetanide, furosemide), these effects interfere with clinical management. Several NSAIDs have been shown to interact with loop diuretics interfering with the pharmacological effects of the diuretic. In volunteers on sodium restricted diets, ibuprofen and indomethacin inhibited furosemide diuresis.	BUMETANIDE, EDECRIN, ETHACRYNATE SODIUM, ETHACRYNIC ACID, FUROSCIX, FUROSEMIDE, FUROSEMIDE-0.9% NACL, LASIX, SOAANZ, TORSEMIDE
Antidiabetics, Oral/Aspirin (Greater Than 100 mg); Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Complex. Salicylates appear to have intrinsic glucose lowering properties via several proposed mechanisms. Also, salicylates may cause protein binding displacement of antidiabetics. Decreased renal clearance may also occur. CLINICAL EFFECTS: Potentiation of hypoglycemic effects may be observed. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Hypoglycemic signs and blood glucose levels should be monitored. Adjust the antidiabetic dose as needed. Particular caution should be taken when salicylates are started or stopped in patients previously stabilized on antidiabetics. DISCUSSION: Additional documentation is necessary to confirm this potential interaction.	DUETACT, GLIMEPIRIDE, GLIPIZIDE, GLIPIZIDE ER, GLIPIZIDE XL, GLIPIZIDE-METFORMIN, GLUCOTROL XL, GLYBURIDE, GLYBURIDE MICRONIZED, GLYBURIDE-METFORMIN HCL, NATEGLINIDE, PIOGLITAZONE-GLIMEPIRIDE
NSAIDs; Salicylates/Lithium SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Decreased renal excretion of lithium, possibly resulting from NSAID-induced prostaglandin inhibition. CLINICAL EFFECTS: May observe increased lithium toxicity. PREDISPOSING FACTORS: Risk factors for lithium toxicity include: renal impairment or worsening of existing renal disease, dehydration, low sodium diet, and concomitant use of multiple medications which may impair renal elimination of lithium (e.g. ARBs, ACE Inhibitors, NSAIDs, diuretics). Patients who require higher therapeutic lithium levels to maintain symptom control are particularly susceptible to these factors. PATIENT MANAGEMENT: The magnitude of this interaction is highly variable. Patients with predisposing factors, e.g. dehydration, renal impairment, or concurrent use of other agents which may impair lithium elimination, are expected to have a higher risk for lithium toxicity. If both drugs are administered, monitor plasma lithium levels and observe the patient for signs and symptoms of lithium toxicity or changes in renal function. Full effects of the addition or an increase in NSAID dose may not be seen for one to two weeks. Adjust the dose of lithium accordingly. If lithium is to be started in a patient stabilized on chronic NSAID therapy, consider starting with a lower lithium dose and titrate slowly as half-life may be prolonged. Monitor lithium concentrations until stabilized on the combination. Counsel the patient to contact their prescriber before starting an OTC NSAID. Assure that patients are familiar with signs and symptoms of lithium toxicity (e.g. new or worsening tremor, nausea/vomiting, diarrhea, ataxia, or altered mental status) and to report signs and symptoms of toxicity. DISCUSSION: Numerous studies and case reports have been documented that administration of a NSAID to a patient stabilized on lithium therapy may result in increased serum lithium levels and possible toxicity. Full effects may take 1 to 2 weeks to develop and may persist for a week after the NSAID is discontinued.	LITHIUM CARBONATE, LITHIUM CARBONATE ER, LITHIUM CITRATE, LITHIUM CITRATE TETRAHYDRATE, LITHOBID
Angiotensin II Receptor Blocker (ARB)/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Angiotensin II receptor blockers (ARBs) can cause vasodilation of the efferent renal arteriole which may result in decreased glomerular filtration rate. NSAIDs inhibit prostaglandin synthesis which can lead to afferent arteriolar vasoconstriction and may negate any decrease in blood pressure. CLINICAL EFFECTS: Concurrent use of ARBs with NSAIDs may result in decreased antihypertensive effects. In patients with existing renal impairment, the use of these agents together may also result in further deterioration of renal clearance caused by renal hypoperfusion. Concurrent use of ARBs with NSAIDs and diuretics may result in increased risk of acute kidney injury (AKI). PREDISPOSING FACTORS: Low water intake/dehydration, drug sensitivity, greater than 75 years of age, and use of diuretics can lead to hypovolemia and increased risk of AKI. PATIENT MANAGEMENT: Patients maintained on ARBs should be monitored for a loss of blood pressure control and a change in renal function if an NSAID is added to their regimen. Patients receiving concurrent therapy may require higher doses of ARBs. If blood pressure control cannot be achieved or if the patient's renal function deteriorates, the NSAID may need to be discontinued. Patients should be monitored for hypotension if NSAIDs are withdrawn from concurrent ARB therapy. Concurrent use of ARBs with NSAIDs and diuretics should be used with caution and monitored for signs of AKI. DISCUSSION: In a computational study, the risk of AKI using triple therapy with a diuretic, renin-angiotensin system (RAS) inhibitor, and NSAID was assessed. The study found the following factors may increase an individual's susceptibility to AKI: low water intake, drug sensitivity, greater than 75 years of age, and renal impairment.(22,23) In an observational study, current use of a triple therapy combination was associated with an increased rate of acute kidney injury (rate ratio (RR) 1.31, 95% confidence interval (CI) 1.12-1.53). The highest risk of AKI associated with triple therapy were observed in the first 30 days of use (RR 1.82, CI 1.35-2.46).(24) In a population based cohort study, the concurrent use of NSAIDs with renin-angiotensin system (RAS) inhibitors in 5,710 hypertensive patients stabilized on antihypertensive therapy required hypertension treatment intensification. Adjusted hazard ratios (HR) for hypertension treatment intensification were 1.34 [95% CI 1.05-1.71] for NSAIDs in general, 1.79 (95% CI 1.15-2.78) for diclofenac and 2.02 (95% CI 1.09-3.77) for piroxicam. There were significant interactions between NSAIDs and angiotensin converting enzyme inhibitors (ACE inhibitors; HR 4.09, 95% CI 2.02-8.27) or angiotensin receptor blockers (ARBs; HR 3.62, 95% CI 1.80-7.31), but not with other antihypertensive drugs.	AMLODIPINE-OLMESARTAN, AMLODIPINE-VALSARTAN, AMLODIPINE-VALSARTAN-HCTZ, ARBLI, ATACAND, ATACAND HCT, AVALIDE, AVAPRO, AZOR, BENICAR, BENICAR HCT, CANDESARTAN CILEXETIL, CANDESARTAN-HYDROCHLOROTHIAZID, COZAAR, DIOVAN, DIOVAN HCT, EDARBI, EDARBYCLOR, ENTRESTO, ENTRESTO SPRINKLE, EPROSARTAN MESYLATE, EXFORGE, EXFORGE HCT, HYZAAR, IRBESARTAN, IRBESARTAN-HYDROCHLOROTHIAZIDE, LOSARTAN POTASSIUM, LOSARTAN-HYDROCHLOROTHIAZIDE, MICARDIS, MICARDIS HCT, OLMESARTAN MEDOXOMIL, OLMESARTAN-AMLODIPINE-HCTZ, OLMESARTAN-HYDROCHLOROTHIAZIDE, TELMISARTAN, TELMISARTAN-AMLODIPINE, TELMISARTAN-HYDROCHLOROTHIAZID, TRIBENZOR, VALSARTAN, VALSARTAN-HYDROCHLOROTHIAZIDE
Acetazolamide; Methazolamide/Aspirin (Greater Than 100 mg); Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Acetazolamide and methazolamide may reduce blood pH, causing a shift of salicylates from plasma into tissues (eg, central nervous system). Alternatively, toxicity may be due to salicylate-induced displacement of the carbonic anhydrase inhibitor from its protein binding sites and inhibition of renal tubular secretion. CLINICAL EFFECTS: An increase in the pharmacologic effects of salicylates with possible toxicity may occur. PREDISPOSING FACTORS: High doses of salicylates, low body weight. PATIENT MANAGEMENT: Avoid the combination if possible. If it is necessary to administer these drugs concurrently, monitor salicylate levels and monitor the patient for symptoms of toxicity. Adjust the dose as needed. DISCUSSION: Two young patients with unimpaired renal and hepatic function were found to have developed metabolic acidosis after treatment for glaucoma and joint pain with a combination of salicylates and carbonic anhydrase inhibitors in normal doses.(1) A 67-year old woman and a 75-year old woman taking carbonic anhydrase inhibitors for therapy of glaucoma and high doses of aspirin for arthritis developed severe acid-base imbalance and salicylate intoxication.(2) Neither patient exhibited ill effects when taking high aspirin doses without a carbonic anhydrase inhibitor. Carbonic anhydrase inhibitor-induced acidemia increases the risk of developing salicylate intoxication in patients receiving high aspirin doses. Two elderly patients, who were chronically receiving aspirin developed lethargy, incontinence, and confusion after dosing with acetazolamide.(3) These effects could have been due to either drug (see mechanism).	ACETAZOLAMIDE, ACETAZOLAMIDE ER, ACETAZOLAMIDE SODIUM, METHAZOLAMIDE
Triamterene; Amiloride/Selected NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown; however, nonsteroidal anti-inflammatory (NSAID) inhibition of prostaglandins may allow triamterene or amiloride- induced nephrotoxicity or hyperkalemia to occur in some patients. CLINICAL EFFECTS: Possible renal failure or hyperkalemia. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: When possible, avoid concurrent therapy with triamterene or amiloride with NSAIDs. If these agents are used concurrently, monitor renal function and serum electrolytes. If decreased renal function or hyperkalemia develops, discontinue both agents. DISCUSSION: Although acute renal failure and hyperkalemia have only been reported in studies and case reports involving indomethacin, diclofenac, flurbiprofen, and ibuprofen with either triamterene or amiloride, the proposed mechanism suggests that all nonsteroidal anti-inflammatory agents may be capable of this interaction. Patients receiving diuretics are at an increased risk of NSAID-induced renal failure.	AMILORIDE HCL, AMILORIDE-HYDROCHLOROTHIAZIDE, DYRENIUM, TRIAMTERENE, TRIAMTERENE-HYDROCHLOROTHIAZID
Valproic Acid/Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Multiple mechanisms appear to be involved. Salicylates may displace valproic acid from plasma protein binding sites. Salicylates may also affect the metabolism of valproate by increasing conjugation and decreasing oxidation of valproic acid. CLINICAL EFFECTS: Concurrent use of salicylates may increase the unbound fraction of serum valproic acid concentration, resulting in toxicity. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving concurrent salicylate therapy should be observed for signs of valproic acid toxicity (e.g., ataxia, drowsiness, nystagmus, tremor). The dosage of valproic acid may need to be adjusted. DISCUSSION: In two studies involving 6 epileptic children taking valproic acid, concurrent aspirin led to an increase in serum valproic acid free fraction and an increased half-life. Renal clearance of free valproic acid was found to decrease.(1,2) In another study involving 5 children, concurrent valproic acid and aspirin resulted in a decrease in free valproic acid clearance although total valproic acid levels did not change significantly.(3) However, one study reported that the concurrent use of valproic acid and aspirin leads to an increased excretion of valproic acid and a decreased total salicylate excretion.(4) In 3 case reports, aspirin given to children taking valproic acid resulted in valproic acid toxicity (tremor, nystagmus, truncal ataxia). There was an increase in free valproic acid levels in two cases, however, a reduction in the free fraction and the total valproic acid levels occurred in the third patient.(5) In another case report, a patient was maintained on divalproex sodium (2500 mg/day) and aspirin (325 mg/day) with a trough valproate level of 24.7 ng/ml and a total valproate level of 64.0 ng/ml. Five days after aspirin was discontinued for a procedure, trough valproate levels fell to 3.9 ng/ml and a total valproate level fell to 36.0 ng/ml with no change in divalproex dosing.(6) In a study in 7 healthy males, concurrent diflunisal (250 mg twice daily) increased the unbound fraction of valproic acid (200 mg twice daily) by 20%. The area-under-curve (AUC) of 3-oxo-valproic acid increased by 35%. There were no effects on diflunisal levels.(7)	DEPAKOTE, DEPAKOTE ER, DEPAKOTE SPRINKLE, DIVALPROEX SODIUM, DIVALPROEX SODIUM ER, SODIUM VALPROATE, VALPROATE SODIUM, VALPROIC ACID
SSRIs; SNRIs/Selected NSAIDs; Aspirin SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Serotonin release by platelets plays a role in hemostasis.(1,2) The increased risk of bleeding may be a result of a decrease in serotonin reuptake by platelets. CLINICAL EFFECTS: Concurrent use of a selective serotonin reuptake inhibitor(1-7,13) or a serotonin-norepinephrine reuptake inhibitor(8-10) and a NSAID may result in bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with multiple disease-associated factors (e.g. thrombocytopenia, advanced liver disease). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g., anticoagulants, antiplatelets, or corticosteroids. Risk of GI bleed may be increased in patients who are of older age, in poor health status, or who use alcohol or smoke. Risk may also be increased with longer duration of NSAID use and prior history of peptic ulcer disease and/or GI bleeding. Renal impairment has been associated with an elevated risk of GI bleed in patients on SSRIs.(15) PATIENT MANAGEMENT: Selective serotonin reuptake inhibitors(1-7,13) or serotonin-norepinephrine reuptake inhibitors(8-10) and NSAIDs should be used concurrently with caution. Patients should be warned about the increased risk of bleeding and be educated about signs and symptoms of bleeding.(1-11,13) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Discontinue anti-platelet agents in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: In a retrospective review of 5 years of data from the Pharmaco-Epidemiologic Prescription Database, hospitalizations for upper gastro-intestinal bleeding in antidepressant users were compared to those in non-antidepressant users. The risk of a bleed in a patient using an NSAID only based on an observed-expected ratio was 4.5 and in a patient using low-dose aspirin only was 2.5. Concurrent use of a selective serotonin reuptake inhibitor with NSAIDs or low-dose aspirin increased the risk of bleeding to 12.2 and 5.2, respectively.(11) In another study, there were 16 cases of upper gastrointestinal bleeding in patients receiving concurrent therapy with selective serotonin reuptake inhibitors and NSAIDs. Adjusted relative risk of bleeding with NSAIDs, selective serotonin reuptake inhibitors, or both were 3.7, 2.6, or 15.6, respectively.(12)	CELEXA, CITALOPRAM HBR, CYMBALTA, DESVENLAFAXINE ER, DESVENLAFAXINE SUCCINATE ER, DRIZALMA SPRINKLE, DULOXETINE HCL, DULOXICAINE, EFFEXOR XR, ESCITALOPRAM OXALATE, FETZIMA, FLUOXETINE DR, FLUOXETINE HCL, FLUVOXAMINE MALEATE, FLUVOXAMINE MALEATE ER, LEXAPRO, OLANZAPINE-FLUOXETINE HCL, PAROXETINE CR, PAROXETINE ER, PAROXETINE HCL, PAROXETINE MESYLATE, PAXIL, PAXIL CR, PRISTIQ, PROZAC, SAVELLA, SERTRALINE HCL, TRINTELLIX, VENLAFAXINE BESYLATE ER, VENLAFAXINE HCL, VENLAFAXINE HCL ER, VIIBRYD, VILAZODONE HCL, ZOLOFT
ACE Inhibitors/High-Dose Aspirin SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aspirin's inhibition of prostaglandin synthesis may inhibit the release of vasodilating prostaglandins by ACE inhibitors. CLINICAL EFFECTS: Concurrent use of aspirin may result in decreased antihypertensive effects of the ACE inhibitor. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor patients receiving doses of aspirin higher than 150 mg daily for decreased antihypertensive effects of their ACE inhibitor. The use of alternative agents may need to be considered. DISCUSSION: Several studies have documented decreased effectiveness of various ACE inhibitors, including captopril, enalapril, and lisinopril following the addition of aspirin therapy. Conflicting evidence exists on the use of small (less than 150 mg) daily doses of aspirin with ACE inhibitors, although some guidelines still suggest they may be beneficial. One or more of the drug pairs linked to this monograph have been included in a list of interactions that could be considered for classification as "non-interruptive" in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology.	ACCUPRIL, ACCURETIC, ALTACE, AMLODIPINE BESYLATE-BENAZEPRIL, BENAZEPRIL HCL, BENAZEPRIL-HYDROCHLOROTHIAZIDE, CAPTOPRIL, CAPTOPRIL-HYDROCHLOROTHIAZIDE, ENALAPRIL MALEATE, ENALAPRIL-HYDROCHLOROTHIAZIDE, ENALAPRILAT, EPANED, FOSINOPRIL SODIUM, FOSINOPRIL-HYDROCHLOROTHIAZIDE, LISINOPRIL, LISINOPRIL-HYDROCHLOROTHIAZIDE, LOTENSIN, LOTENSIN HCT, LOTREL, MOEXIPRIL HCL, PERINDOPRIL ERBUMINE, PRESTALIA, QBRELIS, QUINAPRIL HCL, QUINAPRIL-HYDROCHLOROTHIAZIDE, RAMIPRIL, TRANDOLAPRIL, TRANDOLAPRIL-VERAPAMIL ER, VASERETIC, VASOTEC, ZESTORETIC, ZESTRIL
Drospirenone/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Drospirenone has antimineralocorticoid activity and may cause hyperkalemia. NSAIDs may also increase potassium levels.(1) CLINICAL EFFECTS: Concurrent use of drospirenone and NSAIDs may result in hyperkalemia.(1) PREDISPOSING FACTORS: Renal insufficiency, hepatic dysfunction, adrenal insufficiency, and use of potassium supplements, ACE inhibitors, angiotensin II receptor antagonists, heparin, and potassium-sparing diuretics may increase potassium levels.(1) PATIENT MANAGEMENT: Patients receiving drospirenone with a NSAID should have their serum potassium level checked during the first treatment cycle.(1) DISCUSSION: Drospirenone has antimineralocorticoid activity comparable to 25 mg of spironolactone and may result in hyperkalemia. Concurrent use of NSAIDs may also increase potassium levels.(1) Occasional or chronic use of NSAIDs was not restricted in clinical trials of drospirenone.(1)	ANGELIQ, BEYAZ, DROSPIRENONE-ETH ESTRA-LEVOMEF, DROSPIRENONE-ETHINYL ESTRADIOL, JASMIEL, LO-ZUMANDIMINE, LORYNA, NEXTSTELLIS, NIKKI, OCELLA, SAFYRAL, SLYND, SYEDA, VESTURA, YASMIN 28, YAZ, ZARAH, ZUMANDIMINE
Aspirin (for Cardioprotection)/Selected NSAIDs SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Some non-steroidal anti-inflammatory agents (NSAIDs) are reversible inhibitors of cyclooxygenase and aspirin is an irreversible inhibitor. If these NSAIDs are given before aspirin, the aspirin will not be able to bind to the cyclooxygenase site, which will result in a lack of effect. CLINICAL EFFECTS: The antiplatelet and cardioprotective effect of aspirin may be decreased with the concurrent use of some NSAIDs, particularly during the washout period of the NSAID. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Consideration should be given to use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic if appropriate. If an NSAID must be used, cardioprotective doses of aspirin should be administered before taking any NSAIDs. Single doses of ibuprofen should be given at least 8 hours before or at least 2 hours after immediate release aspirin. The administration of other NSAIDs should be separated from aspirin by at least 2 hours. DISCUSSION: The cardioprotective effect from aspirin is based on the antiplatelet effects. The irreversible inhibition of cyclooxygenase mediates the antiplatelet effects. Administration of a reversible inhibitor or cyclooxygenase blocks the irreversible effect of aspirin on the platelets. This effect has been seen with celecoxib, flufenamic acid, ibuprofen, indomethacin, naproxen, nimesulide, oxaprozin, piroxicam, and tiaprofenic acid but not with diclofenac, etoricoxib, ketorolac, meloxicam, or sulindac. In a study of 80 healthy volunteers, aspirin antiplatelet activity, measured by % thromboxane B2 inhibition (TxB2), was decreased when naproxen 220 mg daily was given simultaneously with or 30 minutes before aspirin 81 mg daily for 10 days (98.7% aspirin alone vs 93.1% and 87.7% naproxen and aspirin). The interaction persisted at least 1 day following discontinuation of naproxen but was normalized by the 3rd day. In a nationwide cohort study, patients were evaluated for thromboembolic cardiovascular and clinically relevant bleeding events with concurrent antithrombotic and ongoing NSAID treatment. A total of 108,232 patients were followed for a mean of 2.3 +/- 1.8 years after diagnosis of myocardial infarction. Concomitant NSAID treatment significantly increased the risk for cardiovascular events (hazard ratio (HR) 6.96; 95% CI 6.24 - 6.77; p<0.001) and bleeding events (HR 4.08; 95% CI 3.51 - 4.73; p<0.001) compared to no NSAID treatment. NSAIDs were further evaluated and revealed the use of celecoxib (HR: 4.65; 95% CI: 3.17 to 6.82; p < 0.001, and 3.44; 95% CI: 2.20 to 5.39; p < 0.001, respectively) and meloxicam (HR: 3.03; 95% CI: 1.68 to 5.47; p < 0.001, and 2.80; 95% CI: 1.40 to 5.60; p < 0.001, respectively) had the lowest risk for cardiovascular and bleeding events, receptively.	ANAPROX DS, CALDOLOR, CELEBREX, CELECOXIB, COMBOGESIC, COMBOGESIC IV, CONSENSI, COXANTO, DAYPRO, EC-NAPROSYN, ELYXYB, FELDENE, HYDROCODONE-IBUPROFEN, IBU, IBUPAK, IBUPROFEN, IBUPROFEN LYSINE, IBUPROFEN-FAMOTIDINE, INDOCIN, INDOMETHACIN, INDOMETHACIN ER, NAPRELAN, NAPROSYN, NAPROTIN, NAPROXEN, NAPROXEN SODIUM, NAPROXEN SODIUM CR, NAPROXEN SODIUM ER, NAPROXEN-ESOMEPRAZOLE MAG, NEOPROFEN, OXAPROZIN, PIROXICAM, SUMATRIPTAN SUCC-NAPROXEN SOD, TOXICOLOGY SALIVA COLLECTION, TREXIMET, VIMOVO
Apixaban/Aspirin (Less Than or Equal To 100 mg) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Additive effects on hemostasis.(1-4) CLINICAL EFFECTS: Concurrent use of apixaban with aspirin may increase the risk of bleeding.(1-4) PREDISPOSING FACTORS: Factors associated with an increase risk for bleeding may include renal impairment, concomitant use of P-glycoprotein inhibitors, patient age greater than 74 years, coexisting conditions (e.g. recent trauma) or use of drugs (e.g. NSAIDs) associated with bleeding risk, and patient weight less than 50 kg.(5-7) The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: Concurrent apixaban and aspirin (325 mg daily) resulted in no pharmacokinetic or pharmacodynamic interactions.(1) In a clinical trial examining the use of apixaban in atrial fibrillation, concurrent use of aspirin increased risk of major bleeding with apixaban from 1.8% per year to 3.4% per year and increased the bleeding risk with warfarin from 2.7% per year to 4.6% per year. Concomitant dual antiplatelet therapy was used in 2.1% of patients.(3,4) In a clinical trial examining the use of apixaban in high-risk post acute coronary syndrome patients with multiple cardiac and non-cardiac comorbidities, who received ASA or the combination of ASA and clopidogrel, the risk of major bleeding (defined by ISTH -International Society on Thrombosis and Haemostasis criteria) was increased for apixaban (5.13% per year) compared to placebo (2.04% per year).(3,4) A meta-analysis of 9 studies identified 13,459 patients taking direct oral anticoagulants (DOACs), 1,692 of whom also took an antiplatelet agent. Of the patients on antiplatelet agents, 1,254 took aspirin while the rest was unspecified. Most of the trials restricted patients to use of low-dose aspirin, with the highest allowable dose being 165 mg/day. The use of DOACs with antiplatelet agents was associated with an increased risk of major bleeding (OR 1.89; 95% CI, 1.04-3.44) and clinically relevant non-major bleeding (OR 1.82; 95% CI, 1.50-2.22). There was no difference between groups in the efficacy outcome of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death.(8)	ELIQUIS
Dabigatran/Aspirin (Less Than or Equal To 100 mg) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Additive effects on hemostasis.(1-3) CLINICAL EFFECTS: Concurrent use of dabigatran with aspirin may increase the risk of bleeding.(1-3) PREDISPOSING FACTORS: Factors associated with an increase risk for bleeding may include renal impairment, concomitant use of P-glycoprotein inhibitors, patient age greater than 74 years, coexisting conditions (e.g. recent trauma) or use of drugs (e.g. NSAIDs) associated with bleeding risk, and patient weight less than 50 kg.(1-3) The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulants/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: A Phase II study in patients with atrial fibrillation examined the effects of dabigatran and concurrent aspirin on the risk of major bleeds. Concurrent use of aspirin and dabigatran etexilate (150 mg twice daily) increased the risk for any bleeding from 12 % to 18 % and 24 % with 81 mg and 325 mg ASA, respectively, when compared to dabigatran alone.(3) In the RE-DUAL PCI trial, patients were randomly assigned to one of three treatments: (A) dual therapy with dabigatran 110 mg twice daily plus either clopidogrel or ticagrelor, (B) dual therapy with dabigatran 150 mg twice daily plus either clopidogrel or ticagrelor, or (C) triple therapy with warfarin (goal INR 2-3) plus aspirin (less than or equal to 100 mg daily) plus either clopidogrel or ticagrelor. The incidence of the first major or clinically relevant non-major (CRNM) bleeding event was 15.4% in group A compared with 26.9% in group C (hazard ratio, 0.52; 95% CI 0.42 to 0.63; p<0.001 for noninferiority; p<0.001 for superiority) and 20.2% in group B compared to 25.7% in corresponding group C (hazard ratio, 0.72; 95% CI 0.58 to 0.88; p<0.001 for noninferiority). Major bleeding as defined by Thrombolysis in Myocardial Infarction (TIMI) criteria, the rate was lower in both dual-therapy groups than in the triple-therapy group: 1.4% in group A compared to 3.8% in group C (hazard ratio, 0.37; 95% CI 0.2 to 0.68; p=0.002) and 2.1% in group B compared to 3.9% in corresponding group C (hazard ratio, 0.51; 95% CI 0.28 to 0.93; p=0.03). Incidence of composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization was 13.7% in groups A and B compared to 13.4% in group C (hazard ratio, 1.04; 95% CI 0.84 to 1.29; p=0.005 for noninferiority).(4) A meta-analysis of 9 studies identified 13,459 patients taking direct oral anticoagulants (DOACs), 1,692 of whom also took an antiplatelet agent. Of the patients on antiplatelet agents, 1,254 took aspirin while the rest was unspecified. Most of the trials restricted patients to use of low-dose aspirin, with the highest allowable dose being 165 mg/day. Compared with DOACs alone, the use of DOACs with antiplatelet agents was associated with an increased risk of major bleeding (OR 1.89; 95% CI, 1.04-3.44) and CRNM bleeding (OR 1.82; 95% CI, 1.50-2.22). There was no difference between groups in the efficacy outcome of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death.(5)	DABIGATRAN ETEXILATE, PRADAXA
Methotrexate (Oncology-Injection)/Aspirin (<=330 mg) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Salicylates may inhibit the renal tubular excretion of methotrexate. CLINICAL EFFECTS: The concurrent use of methotrexate and salicylates may result in an increase in the therapeutic and toxic effects of methotrexate, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression, including neutropenia. PREDISPOSING FACTORS: Risk factors for methotrexate toxicity include: - High-dose oncology regimens - Anti-inflammatory doses of aspirin/salicylates - Impaired renal function, ascites, or pleural effusions PATIENT MANAGEMENT: US manufacturer prescribing information for methotrexate states nonsteroidal anti-inflammatory drugs including aspirin should not be administered prior to or concomitantly with high doses of methotrexate. If concurrent therapy is warranted, methotrexate plasma levels should be monitored and patients should be observed for methotrexate toxicity. The dosage of methotrexate may need to be adjusted. Use caution when administering higher doses of salicylates with lower doses of methotrexate. Salicylate doses > or = 2 grams per day have been associated with hepatic impairment or impaired renal elimination of methotrexate. It would be prudent to avoid high-dose aspirin, especially near the time of methotrexate dosage in patients receiving intermittent methotrexate therapy, and in patients with renal impairment. DISCUSSION: Several studies and case reports have reported increased and prolonged methotrexate levels in patients receiving concurrent aspirin. One study noted an effect with average weekly doses of methotrexate of 16.6 mg, but not weekly doses of 7.5 mg. Decreased renal function has also been reported with the combination. Single ingredient aspirin or buffered aspirin products with strengths < or = to 325 mg or formulations which are associated with once daily use for cardiovascular protection are included in this interaction. Other aspirin and salicylate products are linked to higher severity level interactions.	METHOTREXATE, METHOTREXATE SODIUM
Ibrutinib/Selected Anticoagulants; Antiplatelets SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ibrutinib administration lowers platelet count in the majority of patients.(1,2) In addition, ibrutinib has been shown to inhibit collagen-mediated platelet aggregation.(3-4) Bleeding has been reported with the use of ibrutinib,(1-4) anticoagulants, or antiplatelets alone. CLINICAL EFFECTS: Concurrent use of ibrutinib with either anticoagulants or antiplatelets may increase the risk of hemorrhage. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The Canadian product monograph for ibrutinib recommends concurrent use with anticoagulants or antiplatelets should be approached with caution. If therapeutic anticoagulation is required, consider temporarily withholding ibrutinib therapy until stable anticoagulation in achieved.(2) The US prescribing information for ibrutinib states patients receiving concurrent therapy with ibrutinib and anticoagulants and/or antiplatelets should be closely monitored for changes in platelet count or in International Normalized Ratio (INR). Carefully weigh the risks vs. benefits of concurrent therapy in patients with significant thrombocytopenia. If a bleeding event occurs, follow manufacturer instructions for ibrutinib dose adjustment.(1) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Bleeding has been reported with ibrutinib alone.(1-3) Across 27 clinical trials, grade 3 or higher bleeding events, e.g. subdural hematoma, gastrointestinal bleeding or hematuria, have occurred in up to 4% of patients, with 0.4% fatality. Grade 3 or 4 thrombocytopenia occurred in 5-19% of patients. Bleeding events of any grade occurred in 39% of patients treated with ibrutinib.(1) Concurrent use of anticoagulants or antiplatelets has been reported to increase the risk for major bleeding. In clinical trials, major bleeding occurred in 3.1% of patients taking ibrutinib without concurrent anticoagulants or antiplatelets, 4.4% of patients on concurrent antiplatelets with or without anticoagulants, and 6.1% of patients on concurrent anticoagulants with or without antiplatelets.(1) In an open-label, phase 2 trial of patients with relapsed/refractory mantle cell lymphoma on ibrutinib, 61 patients (55%) on concurrent anticoagulants or antiplatelets had a higher rate of bleeding (69% any grade, 8% grade 3-4) than patients not on anticoagulants or antiplatelets (28% any grade, 4% grade 3-4).(5) A retrospective trial found a hazard ratio of 20 (95% CI, 2.1-200) for patients on ibrutinib with concurrent anticoagulants and antiplatelets. There was a trend towards an increased bleeding risk in patients on either anticoagulants or antiplatelets, but this was not statistically significant on multivariate analysis.(6) A case report of 2 patients with chronic lymphocytic leukemia (CLL) on ibrutinib and dabigatran demonstrated no stroke nor bleeding events during the mean 11.5 month follow-up.(7) A case report of 4 patients with lymphoproliferative disease on concurrent dabigatran and ibrutinib demonstrated no stroke nor major bleeding events. 1 patient experienced grade 2 conjunctival hemorrhage whilst on both ibrutinib and dabigatran. The anticoagulant was withheld and successfully re-initiated at a lower dose with no further bleeding events.(8)	IMBRUVICA
Selected Anticoagulants (Vitamin K antagonists)/Aspirin (Less Than or Equal To 100 mg) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Multiple processes are involved: 1)Aspirin is an irreversible platelet inhibitor. It impairs platelet function, resulting in prolonged bleeding time. 2) Aspirin may cause gastrointestinal (GI) bleeding due to irritation. CLINICAL EFFECTS: The concurrent use of anticoagulants and aspirin leads to blockade of two distinct coagulation pathways and may increase the risk for bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Weigh the patient specific benefits versus risk for concomitant use. If concurrent therapy of low dose aspirin and an anticoagulant is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; severe headache, acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: This interaction has been reported between aspirin and warfarin and between aspirin and dicumarol. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated, altered, or discontinued. A self-controlled case study of 1,622 oral anticoagulant-precipitant drug pairs were reviewed and found 14% of drug pairs were associated with a statistically significant elevated risk of thromboembolism. Concurrent use of warfarin and aspirin resulted in a ratio of rate ratios (95% CI) of 2.13 (1.72-2.64). A large systematic review was performed on 72 warfarin drug-drug interactions studies that reported on bleeding, thromboembolic events, or death. Most studies were retrospective cohorts. A meta-analysis of 38 of those studies found a higher rate of clinically significant bleeding in patients on warfarin and antiplatelets (OR=1.74; 95% CI 1.56-1.94). Increased bleeding risk was also seen in subgroup analyses with aspirin (OR=1.50; 95% CI 1.29-1.74), clopidogrel (OR=3.55; 95% CI 2.78-4.54), and aspirin plus clopidogrel or ticlopidine (OR=2.07, 95% CI 1.33-3.21).(16)	ANISINDIONE, DICUMAROL, JANTOVEN, PHENINDIONE, WARFARIN SODIUM
Rivaroxaban/Aspirin (Less Than or Equal To 100 mg) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Additive effects on hemostasis.(1) CLINICAL EFFECTS: Concurrent use of rivaroxaban with antiplatelets may increase the risk of bleeding.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (NSAIDs). PATIENT MANAGEMENT: Monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or blood pressure and promptly evaluate patients with any symptoms. Discontinue rivaroxaban in patients with active pathological bleeding.(2) The US manufacturer states concurrent use of rivaroxaban 2.5 mg and aspirin 81 mg is an approved indication for the reduction of cardiovascular events in patients with coronary artery disease (CAD) or peripheral artery disease (PAD). Discontinue rivaroxaban in patients with active pathological bleeding. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: In the ROCKET AF trial, concomitant aspirin use (almost exclusively at less than or equal to to 100 mg daily) was identified as an independent risk factor for bleeding.(1-2) In a single dose study, there were no pharmacokinetic or pharmacodynamic interactions between rivaroxaban and aspirin.(1) A self-controlled case study of 1,622 oral anticoagulant-precipitant drug pairs were reviewed and found 14% of drug pairs were associated with a statistically significant elevated risk of thromboembolism. Concurrent use of rivaroxaban and aspirin resulted in a ratio of rate ratios (95% CI) of 2.19 (1.21-2.95).(3) A meta-analysis of 9 studies identified 13,459 patients taking direct oral anticoagulants (DOACs), 1,692 of whom also took an antiplatelet agent. Of the patients on antiplatelet agents, 1,254 took aspirin while the rest was unspecified. Most of the trials restricted patients to use of low-dose aspirin, with the highest allowable dose being 165 mg/day. The use of DOACs with antiplatelet agents was associated with an increased risk of major bleeding (OR 1.89; 95% CI, 1.04-3.44) and clinically relevant non-major bleeding (OR 1.82; 95% CI, 1.50-2.22). There was no difference between groups in the efficacy outcome of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death.(4) In the VOYAGER PAD trial, 6564 patiens were enrolled with peripheral artery disease (PAD). Rivaroxaban 2.5 mg twice daily in combination with aspirin 81 mg was found to reduce the total number of arterial and venous events by 23% compared to aspirin 81 mg alone. The combination increased the risk of bleeding. If 10,000 patients were treated, 181 cardiovascular events would be prevented at a cost of 29 bleeding events, a 6:1 benefit to risk ratio.(5) The COMPASS trial enrolled 27,395 patients with PAD or coronary artery disease (CAD) to determine whether combined rivaroxaban and aspirin reduced the risk of cardiovascular events more than aspirin alone. The combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg daily reduced mortality by 18% compared to aspirin alone.(6) A secondary analysis of incidence and predictors of major gastrointestinal (GI) bleeding in patients enrolled in the COMPASS trial demonstrated that compared to the use of aspirin (100 mg daily) alone, use of rivaroxaban (5 mg twice daily) significantly increased the odds of overall GI bleeding (OR 1.44; 95% CI 1.05-1.99), and the use of the combination of rivaroxaban (2.5 mg twice daily) and aspirin (100 mg daily) further increased the odds (OR 2.17; 95% CI 1.61-2.93).(7)	RIVAROXABAN, XARELTO
Pemetrexed/Aspirin (Greater Than 81 mg and Less Than or Equal To 325 mg) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Higher doses of aspirin may decrease the clearance of pemetrexed.(1) This decreased clearance may be the result of chronic renal toxicity or competition with pemetrexed for renal tubular secretion.(2) CLINICAL EFFECTS: Concurrent use of pemetrexed and higher aspirin doses may result in elevated levels of and toxicity from pemetrexed, including myelosuppression, neutropenia, renal toxicity, and gastrointestinal toxicity.(1) PREDISPOSING FACTORS: This interaction is expected to be more severe in patients with mild to moderate renal insufficiency (creatine clearance (CrCl) of 45 ml/min to 79 ml/min).(1) PATIENT MANAGEMENT: Aspirin in low to moderate doses (325 mg every 6 hours) does not affect the pharmacokinetics of pemetrexed.(1) If higher dose aspirin (or an NSAID) is required, patients should be monitored for pemetrexed toxicity, especially myelosuppression, renal toxicity, and gastrointestinal toxicity.(1) The manufacturer of pemetrexed recommends in patients with mild to moderate renal insufficiency (CrCl from 45 ml/min to 79 ml/min), NSAIDs with short half-lives should be avoided for 2 days before, the day of, and 2 days after pemetrexed administration. (1) NSAIDs and salicylates with long half-lives should be avoided for at least 5 days before, the day of, and 2 days following pemetrexed administration in all patients.(1,2) DISCUSSION: In patients with normal renal function, ibuprofen (400 mg 4 times daily) decreased the clearance of pemetrexed by 20% and increased its area-under-curve (AUC) by 20%.(1) In a Phase I clinical trial, two patients receiving high dose pemetrexed therapy experienced severe toxicity, both were receiving a NSAID. Following these reports, all patients were required to stop aspirin or other NSAIDs 2 days before and not resume these agents until 2 days after pemetrexed.(2) In two randomized, controlled cross-over trials, 27 cancer patients with a creatinine clearance (CrCl) less than or equal to 60 ml/min received pemetrexed (500 mg/m2) infusion on Day 1 of a 21-day cycle and either aspirin 325 mg or ibuprofen 400 mg orally every 6 hours starting 2 days before pemetrexed administration. Coadministration of aspirin did not affect pemetrexed pharmacokinetics. Ibuprofen decreased the clearance of pemetrexed by 16%, increased its maximum concentration (Cmax) by 15%, and increased the AUC by 20%.(3) Aspirin products linked to this monograph are single ingredient aspirin or buffered aspirin products with strengths greater than 81 mg and less than or equal to 325 mg strength. Combination aspirin products (e.g. aspirin combined with a statin) where aspirin greater than 81 mg or less than or equal to 325 mg is used for cardiovascular protection are excluded from this monograph.	ALIMTA, AXTLE, PEMETREXED, PEMETREXED DISODIUM, PEMFEXY, PEMRYDI RTU
Aldosterone Receptor Antagonists/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown; however, nonsteroidal anti-inflammatory (NSAID) inhibition of prostaglandins may allow eplerenone, finerenone, or spironolactone-induced nephrotoxicity or hyperkalemia to occur in some patients.(1-3) In some patients, NSAIDs may reduce the diuretic, natriuretic and antihypertensive effects of eplerenone, finerenone, or spironolactone.(1-3) CLINICAL EFFECTS: Concurrent use of eplerenone, finerenone, or spironolactone with NSAIDs may result in renal failure or hyperkalemia. The effects of the diuretic, natriuretic, or antihypertensive effects of eplerenone, finerenone, or spironolactone may be decreased.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: When possible, avoid concurrent therapy with eplerenone, finerenone, or spironolactone with NSAIDs. If these agents are used concurrently, monitor renal function and serum electrolytes. If decreased renal function or hyperkalemia develops, discontinue both agents. The manufacturer of eplerenone recommends checking serum potassium and serum creatinine within 3-7 days of concurrent therapy with NSAIDs.(1) The manufacturer of spironolactone states concurrent use with NSAIDs may lead to severe hyperkalemia and extreme caution should be used during concurrent therapy.(2) DISCUSSION: Although acute renal failure and hyperkalemia have only been reported in studies and case reports involving indomethacin, diclofenac, flurbiprofen, and ibuprofen with either triamterene or amiloride, the proposed mechanism suggests that all nonsteroidal anti-inflammatory agents may be capable of this interaction with all potassium-sparing diuretics. Patients receiving diuretics are at an increased risk of NSAID-induced renal failure.	ALDACTONE, CAROSPIR, EPLERENONE, INSPRA, KERENDIA, SPIRONOLACTONE, SPIRONOLACTONE-HCTZ
Edoxaban/Aspirin (Less Than or Equal To 100 mg) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Edoxaban and aspirin have additive effects on hemostasis.(1) In addition, aspirin doses greater than or equal to 325 mg daily increase edoxaban exposure.(1) CLINICAL EFFECTS: Concurrent use of edoxaban with aspirin may increase the risk of bleeding compared to either agent alone.(1) PREDISPOSING FACTORS: Bleeding risk may be increased in patients with renal impairment and in patients greater than 75 years of age.(1) Use of multiple agents which affect hemostasis increases the risk for bleeding. The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Patients requiring concurrent therapy with edoxaban and aspirin should be closely monitored for signs of bleeding. Edoxaban and aspirin at dosages of 100 mg or less may be coadministered.(2,3) Monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. Discontinue edoxaban in patients with active bleeding. DISCUSSION: Concomitant use of edoxaban and antiplatelet agents may increase the risk of bleeding. In edoxaban clinical trials concomitant use of low dose aspirin (less than or equal to 100 mg daily), thienopyridines, and NSAIDs was permitted and resulted in increased rates of clinically relevant bleeding. The rates of major bleeding on edoxaban and warfarin were generally consistent among subgroups. Bleeding rates appeared higher in both treatment arms (edoxaban and warfarin) in patients taking aspirin. Co-administration of aspirin (100 mg or 325 mg) and edoxaban increased bleeding time relative to that seen with either drug alone.(1) About 30% of the population in ENGAGE-AF received concomitant therapy with aspirin because of co-morbid conditions. While aspirin is known to increase risk for bleeds and the annualized event rate for major bleeds was higher than that in patients not receiving aspirin (3.87% vs. 2.13%), the risk for bleeds in patients receiving edoxaban 60 mg on a background of aspirin was lower than that for warfarin on a background of aspirin (HR 0.78 (95%CI 0.65,0.94). Based on these data no dose adjustments/contraindications are required.(4) Edoxaban and aspirin at dosages of 100 mg or less may be coadministered.(2,3) A meta-analysis of 9 studies identified 13,459 patients taking direct oral anticoagulants (DOACs), 1,692 of whom also took an antiplatelet agent. Of the patients on antiplatelet agents, 1,254 took aspirin while the rest was unspecified. Most of the trials restricted patients to use of low-dose aspirin, with the highest allowable dose being 165 mg/day. The use of DOACs with antiplatelet agents was associated with an increased risk of major bleeding (OR 1.89; 95% CI, 1.04-3.44) and clinically relevant non-major bleeding (OR 1.82; 95% CI, 1.50-2.22). There was no difference between groups in the efficacy outcome of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death.(5)	SAVAYSA
Mifepristone (Cushing)/Anticoagulants; Antiplatelets SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Mifepristone is an antagonist at the progesterone receptor which can result in endometrium thickening, cystic dilatation of endometrial glands, or excessive vaginal bleeding. Concurrent use with anticoagulants or antiplatelets may further increase risk. CLINICAL EFFECTS: The concurrent use of mifepristone with anticoagulants or antiplatelets may result in endometrium thickening, cystic dilatation of endometrial glands, or excessive vaginal bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The manufacturer of mifepristone states that mifepristone should be used with caution in patients receiving concurrent anticoagulant or antiplatelet therapy.(1) If concurrent therapy is deemed medically necessary, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. Women experiencing vaginal bleeding during concurrent use should be referred to a gynecologist for further evaluation. DISCUSSION: The manufacturer of mifepristone states that mifepristone should be used with caution in patients receiving concurrent anticoagulant or antiplatelet therapy.(1)	KORLYM, MIFEPRISTONE
Aliskiren/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown. It is believed to be related to inhibition of prostaglandin synthesis by the NSAIDs. Use of an NSAID in combination with aliskiren, whose hypotensive effects may be related to the increase in hypotensive prostaglandins, may negate any decrease in blood pressure. CLINICAL EFFECTS: Concurrent use of aliskiren with NSAIDs may result in decreased antihypertensive effects. In patients with existing renal impairment, the use of these agents together may also result in further deterioration of renal clearance caused by renal hypoperfusion. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients maintained on aliskiren should be monitored for a loss of blood pressure control and a change in renal function if an NSAID is added to their regimen. Patients receiving concurrent therapy may require higher doses of aliskiren. If blood pressure control cannot be achieved or if the patient's renal function deteriorates, the NSAID may need to be discontinued. Patients should be monitored for hypotension if NSAIDs are withdrawn from concurrent aliskiren therapy. DISCUSSION: Indomethacin has been shown to inhibit the antihypertensive effect of captopril, cilazapril, enalapril, losartan, perindopril, and valsartan. Ibuprofen has been shown to decrease the antihypertensive effects of captopril. Two separate case reports describe individuals suspected of ACEI-associated angioedema precipitated by NSAIDs. Both cases reported symptom resolution after cessation of the NSAID. Studies have shown that sulindac does not affect the antihypertensive effects of captopril and enalapril.	ALISKIREN, TEKTURNA
Dichlorphenamide/Aspirin (Less Than or Equal To 325 mg) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Carbonic anhydrase inhibitors (eg, acetazolamide) may reduce blood pH, causing a shift of salicylates from plasma into tissues (eg, central nervous system).(1) Alternatively, toxicity may be due to salicylate-induced displacement of the carbonic anhydrase inhibitor from its protein binding sites and inhibition of renal tubular secretion. CLINICAL EFFECTS: An increase in the pharmacologic effects of salicylates with possible toxicity may occur. Anorexia, tachypnea, lethargy, and coma have been reported.(1) PREDISPOSING FACTORS: High doses of salicylates, low body weight. PATIENT MANAGEMENT: The concurrent use of high-dose aspirin or other salicylates with dichlorphenamide is contraindicated. If it is necessary to administer a low-dose salicylate concurrently, use the lowest dose possible or replace it with a non-salicylate anti-inflammatory agent. Monitor salicylate levels and serum bicarbonate concentrations, and monitor the patient for symptoms of toxicity. Adjust the dose as needed.(1) DISCUSSION: An 8-year-old boy with unimpaired renal and hepatic function was found to have developed metabolic acidosis after treatment for glaucoma and joint pain with a combination of aloxiprin 3.6 gram daily and dichlorphenamide 25 mg three times daily. His symptoms resolved after discontinuation of both aloxiprin and dichlorphenamide and did not recur on subsequent therapy with naproxen and dichlorphenamide.(2) A 75-year old woman taking dichlorphenamide 100 mg to 150 mg daily for therapy of glaucoma and high doses of aspirin (975 mg 4 to 5 times daily) for arthritis developed severe acid-base imbalance and salicylate intoxication. The patient did not exhibit ill effects when taking high aspirin doses without dichlorphenamide.(3)	DICHLORPHENAMIDE, KEVEYIS, ORMALVI
Icosapent Ethyl/Anticoagulant;Antiplatelet;Thrombolytic SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: In vitro data suggests that fish oils can competitively inhibit cyclooxygenase which decreases synthesis of thromboxane A1 leading to a decrease in platelet aggregation.(1) CLINICAL EFFECTS: Concurrent use of anticoagulant, antiplatelet, or thrombolytic agents increase bleeding risks. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: If concurrent therapy is deemed medically necessary, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Specific studies with icosapent ethyl and affects on bleeding risk have not been conducted. Concurrent use of anticoagulant, antiplatelet, or thrombolytic agents may increase bleeding risks by impairing platelet function and prolonging bleeding time.(1) Several case reports have shown increased bleeding time and an increased risk of adverse effects from concurrent therapy.(2,3,4) A randomized placebo controlled study of 40 people taking omega-3 fatty acids and oral anticoagulants showed a significant prolongation in bleeding time.(5)	ICOSAPENT ETHYL, VASCEPA
Fruquintinib; Surufatinib/Anticoagulants; Antiplatelets SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Bleeding has been reported with the use of fruquintinib and surufatinib.(1,2) CLINICAL EFFECTS: Concurrent use of fruquintinib or surufatinib with either anticoagulants or antiplatelets may increase the risk of hemorrhage.(1,2) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Patients receiving concurrent therapy with fruquintinib and anticoagulants and/or antiplatelets should be closely monitored for changes in platelet count or in International Normalized Ratio (INR). If a serious bleeding event occurs, the manufacturer recommends permanent discontinuation of fruquintinib.(1) Patients receiving concurrent therapy with surufatinib and anticoagulants and/or antiplatelets should be closely monitored for changes in platelet count or in INR.If a serious bleeding event occurs, the manufacturer recommends permanent discontinuation of surufatinib.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Bleeding has been reported with fruquintinib in three randomized, double-blinded, placebo-controlled clinical trials. The incidence of grade 1 and grade 2 bleeding events was 28.2%, including gastrointestinal bleeding (10.9%), hematuria (10.6%), and epistaxis (7.5%). The incidence of grade 3 or higher bleeding events was 2.1% and included gastrointestinal bleeding (1.6%) and hemoptysis (0.5%).(1) Bleeding has been reported with surufatinib in clinical trials. Grade 1 and 2 bleeding events included gastrointestinal bleeding, blood in the urine, and gum bleeding. The incidence of grade 3 or greater bleeding events was 4.5%, including gastrointestinal hemorrhage (1.9%), and cerebral hemorrhage (1.1%). Fatalities due to bleeding were reported in 0.3% of patients. The incidence of permanent discontinuation due to bleeding was 2.6% and the incidence of suspension of surufatinib due to bleeding was 3.8%.(2)	FRUZAQLA
Plasminogen/Anticoagulants; Antiplatelets SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Bleeding has been reported with the use of plasminogen.(1) CLINICAL EFFECTS: Concurrent use of plasminogen with either anticoagulants or antiplatelets may increase the risk of active bleeding during plasminogen therapy, including bleeding from mucosal disease-related lesions that may manifest as gastrointestinal (GI) bleeding, hemoptysis, epistaxis, vaginal bleeding, or hematuria.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Patients receiving concurrent therapy with plasminogen and anticoagulants and/or antiplatelets should be closely monitored during plasminogen therapy for active bleeding from mucosal disease-related lesions, including GI bleeding, hemoptysis, epistaxis, vaginal bleeding, or hematuria.(1) Prior to initiation of treatment with plasminogen, confirm healing of lesions or wounds suspected as a source of a recent bleeding event. Monitor patients during and for 4 hours after infusion when administering plasminogen with concurrent anticoagulants, antiplatelet drugs, or other agents which may interfere with normal coagulation.(1) If patient experiences uncontrolled bleeding (defined as any gastrointestinal bleeding or bleeding from any other site that persists longer than 30 minutes), seek emergency care and discontinue plasminogen immediately.(1) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Plasminogen has not been studied in patients at an increased risk of bleeding. Bleeding has been reported with plasminogen in a two single-arm, open-label clinical trials as well as in compassionate use programs. The incidence of hemorrhage in patients with Plasminogen Deficiency Type 1 was 16% (3/19 patients).(1) One of the bleeding events occurred two days after receiving the second dose of plasminogen in a patient with a recent history of GI bleeding due to gastric ulcers. The patient received plasminogen through a compassionate use program and the dose was 6.6 mg/kg body weight every 2 days. Endoscopy showed multiple ulcers with one actively bleeding ulcer near the pylorus.(1)	RYPLAZIM
Tisotumab/Anticoagulants; Antiplatelets SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Bleeding, including hemorrhage, has been reported with the use of tisotumab.(1) CLINICAL EFFECTS: Concurrent use of tisotumab with either anticoagulants, antiplatelets, or NSAIDs may increase the risk of hemorrhage.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Patients receiving concurrent therapy with tisotumab and anticoagulants, antiplatelets, and/or NSAIDs should be closely monitored for signs and symptoms of bleeding and changes in platelet count or International Normalized Ratio (INR). For patients experiencing pulmonary or central nervous system (CNS) hemorrhage, permanently discontinue tisotumab. For grade 2 or greater hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage. After resolution, either resume treatment or permanently discontinue tisotumab.(1) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Hemorrhage occurred in 62% of patients with cervical cancer treated with tisotumab across clinical trials. The most common all grade hemorrhage adverse reactions were epistaxis (44%), hematuria (10%), and vaginal hemorrhage (10%). Grade 3 hemorrhage occurred in 5% of patients.(1)	TIVDAK
Sparsentan/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Sparsentan is an endothelin and angiotensin II receptor antagonist.(1) Angiotensin II receptor blockers can cause vasodilation of the efferent renal arteriole which may result in decreased glomerular filtration rate. NSAIDs inhibit prostaglandin synthesis which can lead to afferent arteriolar vasoconstriction. CLINICAL EFFECTS: Concurrent use of sparsentan with NSAIDs (including selective COX-2 inhibitors) may result in renal hypoperfusion and deterioration of renal clearance, including possible acute kidney injury (AKI). These effects are usually reversible.(1) PREDISPOSING FACTORS: Patients older than 75 years old, with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion (including from diuretic use and dehydration) may be at greater risk for AKI.(1-3) PATIENT MANAGEMENT: Monitor for signs of worsening renal function if an NSAID (including selective COX-2 inhibitors) is used concurrently with sparsentan. If renal function deteriorates, the NSAID may need to be discontinued.(1) DISCUSSION: In a computational study, the risk of AKI using triple therapy with a diuretic, renin-angiotensin system (RAS) inhibitor, and NSAID was assessed. The study found the following factors may increase an individual's susceptibility to AKI: low water intake, drug sensitivity, greater than 75 years of age, and renal impairment.(2,3) In an observational study, current use of a triple therapy combination was associated with an increased rate of acute kidney injury (rate ratio (RR) 1.31, 95% confidence interval (CI) 1.12-1.53). The highest risk of AKI associated with triple therapy were observed in the first 30 days of use (RR 1.82, CI 1.35-2.46).(4)	FILSPARI
Lecanemab/Antiplatelets SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Microhemorrhage has been reported with the use of lecanemab. Radiographic changes on brain MRI have been noted as amyloid related imaging abnormalities-hemosiderin deposition (ARIA-H) which included microhemorrhage. In addition, intracerebral hemorrhages (ICH) greater than 1 cm in diameter have occurred in patients treated with lecanemab.(1) CLINICAL EFFECTS: Concurrent use of lecanemab with antiplatelets may increase the risk of hemorrhage.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Lecanemab should be used with extreme caution in patients treated with antiplatelets. Evaluate the risks and benefits of concurrent use of lecanemab with antiplatelets.(1) Appropriate use recommendations for lecanemab state antiplatelets may be used at standard doses if patients meet other criteria for lecanemab therapy. Use of antiplatelet agents in patients who are homozygous for the APOE4 gene may have an increased risk of ARIA with lecanemab therapy.(2) Patients receiving concurrent therapy with lecanemab and antiplatelets should be closely monitored for signs and symptoms of bleeding and changes in platelet count or International Normalized Ratio (INR).(1) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of microhemorrhage, including headache, nausea/vomiting, confusion, dizziness, visual disturbance, gait difficulties, and loss of coordination. General signs of blood loss include decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Instruct patients to report any signs and symptoms of bleeding, such as confusion, headache, dizziness, nausea, visual changes, unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: In clinical studies, lecanemab was observed to increase ARIA-H, including microhemorrhage and intracerebral hemorrhage. Radiographic changes were classified as mild (<=4 new incidences), moderate (5 to 9 new incidences), or severe (10 or more new incidences. Patients were excluded from clinical trials if taking concurrent anticoagulants or anti-platelets.(1) In Studies 1 and 2, the maximum severity of ARIA-H microhemorrhage was mild in 9% (79/898), moderate in 2% (19/898), and severe in 3% (28/898) of patients. Intracerebral hemorrhage greater than 1 cm in diameter was reported in 0.7% (6/898) of patients in Study 2 after treatment with lecanemab compared to 0.1% (1/897) on placebo. Fatal events of intracerebral hemorrhage in patients taking lecanemab have been observed.(1) In Study 2, baseline use of antithrombotic medications (aspirin, other antiplatelets, or anticoagulants) were allowed if patient was on a stable dose. Aspirin was the most common antithrombotic agent. The incidence of ICH was 0.9% (3/328 patients) in patients taking lecanemab with a concomitant antithrombotic medication at the time of the event compared to 0.6% (3/545 patients) in those who did not receive an antithrombotic. Patients taking lecanemab with an anticoagulant alone or combined with an antiplatelet medication or aspirin had an incidence of intracerebral hemorrhage of 2.5% (2/79 patients) compared to none in patients who received placebo.	LEQEMBI
NSAIDs; Salicylates/Minoxidil SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Oral minoxidil functions as a direct-acting peripheral vasodilator, lowering elevated systolic and diastolic blood pressure by reducing resistance in peripheral blood vessels. This triggers a compensatory increase in cardiac output and renin secretion and results in sodium and water retention. NSAIDs inhibit prostaglandin synthesis and also result in sodium and water retention.(1,2) CLINICAL EFFECTS: The risk of heart failure may increase with oral minoxidil and NSAIDs due to their combined effects on blood vessel dilation, fluid retention, and altered sodium balance. Minoxidil efficacy may be compromised.(1,2) PREDISPOSING FACTORS: Higher doses of oral minoxidil have been associated with serious adverse events, including hypotensive syncope, pericarditis, pericardial effusion, and myocardial infarction.(1-5) PATIENT MANAGEMENT: Closely monitor body weight, fluid and electrolyte balance, and blood pressure when using oral minoxidil and NSAIDs concurrently. Minoxidil tablets should be co-administered with an appropriate diuretic to prevent fluid retention and potential congestive heart failure. A high-ceiling (loop) diuretic is often necessary alongside vigilant monitoring of body weight. Without concurrent diuretic use, minoxidil may lead to the retention of salt and water within a few days.(1,2) DISCUSSION: While the manufacturer of minoxidil does not provide specific recommendations regarding NSAID co-administration, it emphasizes the necessity of combining minoxidil with a beta-blocker to prevent tachycardia and increased myocardial workload. Additionally, concurrent use with a diuretic is recommended to avert serious fluid accumulation and potential congestive heart failure. NSAID labeling warns about fluid retention, edema, an elevated risk of heart failure, and potential drug interactions with beta-blockers and diuretics which can result in a blunting of the antihypertensive and cardiovascular effects of these agents.(1-5)	MINOXIDIL
T Cell Immunotherapies/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: NSAIDs augment the immune system. Concurrent use with NSAIDs may interfere with the activity of CAR-T cell immunotherapies.(1) CLINICAL EFFECTS: NSAIDs may decrease the efficacy of CAR-T cell immunotherapies.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: NSAIDs should be used with caution with or after CAR-T cell immunotherapy.(1) DISCUSSION: An in vitro study showed aspirin and celecoxib negatively affected CD19.CAR-T cells through their effects on the induction of apoptosis, reduction of activation, and impairment of proliferation.(1)	ABECMA, AMTAGVI, AUCATZYL, BREYANZI, BREYANZI CD4 COMPONENT, BREYANZI CD8 COMPONENT, CARVYKTI, KYMRIAH, TECARTUS, TECELRA, YESCARTA
Donanemab/Antiplatelets SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Microhemorrhage has been reported with the use of donanemab. Radiographic changes on brain MRI have been noted as amyloid related imaging abnormalities-hemosiderin deposition (ARIA-H) which included microhemorrhage. In addition, intracerebral hemorrhages (ICH) greater than 1 cm in diameter have occurred in patients treated with donanemab.(1) CLINICAL EFFECTS: Concurrent use of donanemab with antiplatelets may increase the risk of hemorrhage.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Donanemab should be used with extreme caution in patients treated with antiplatelets. Evaluate the risks and benefits of concurrent use of donanemab with antiplatelets.(1) The manufacturer of donanemab recommends testing for AP0E4 status prior to initiation of treatment.(1) Use of antiplatelet agents in patients who are homozygous for the APOE4 gene, may have an increased risk of ARIA with donanemab therapy.(1-3) Patients receiving concurrent therapy with donanemab and antiplatelets should be closely monitored for signs and symptoms of bleeding and changes in platelet count.(1) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of microhemorrhage, including headache, nausea/vomiting, confusion, dizziness, visual disturbance, gait difficulties, and loss of coordination. General signs of blood loss include decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Instruct patients to report any signs and symptoms of bleeding, such as confusion, headache, dizziness, nausea, visual changes, unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: In a double-blind, placebo-controlled clinical study of 1736 participants randomized to receive donanemab (n = 860) or placebo (n = 876), donanemab was observed to increase amyloid related imaging abnormalities-hemosiderin deposition (ARIA-H), including microhemorrhage and intracerebral hemorrhage (ICH). Radiographic changes were classified as mild (<=4 new incidences), moderate (5 to 9 new incidences), or severe (10 or more new incidences). The maximum severity of ARIA-H microhemorrhage was observed as mild in 17% (143/853), moderate in 4% (34/853), and severe in 5% (40/853) of patients taking donanemab.(1) Baseline use of antithrombotic medications (aspirin, other antiplatelets, or anticoagulants) was allowed. The majority of exposures to antithrombotic medications were to aspirin. The incidence of ARIA-H was 30% (106/349) in patients taking donanemab with a concomitant antithrombotic medication within 30 days compared to 29% (148/504) who did not receive an antithrombotic within 30 days of an ARIA-H event.(1) The incidence of ICH greater than 1 cm in diameter was 0.6% (2/349 patients) in patients taking donanemab with a concomitant antithrombotic medication compared to 0.4% (2/504) in those who did not receive an antithrombotic. One fatal ICH occurred in a patient taking donanemab in the setting of focal neurologic symptoms of ARIA and the use of a thrombolytic agent.(1)	KISUNLA

The following contraindication information is available for VAZALORE (aspirin):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

No enhanced Contraindications information available for this drug.

There are 8 contraindications. Absolute contraindication.

Contraindication List
Aspirin exacerbated respiratory disease
Gastrointestinal hemorrhage
Hemolytic anemia from pyruvate kinase and g6PD deficiencies
Hemorrhage
Increased risk of bleeding due to coagulation disorder
Lactation
Pregnancy
Reye's syndrome

There are 8 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Alcohol use disorder
Gastrointestinal ulcer
Hypoprothrombinemia
Increased risk of bleeding due to coagulation disorder
Salicylate intoxication
Systemic mastocytosis
Thrombocytopenic disorder
Thrombotic thrombocytopenic purpura

There are 6 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Anemia
Disease of liver
Gout
Kidney disease with reduction in glomerular filtration rate (GFr)
Nasal polyp
Vitamin K deficiency

The following adverse reaction information is available for VAZALORE (aspirin):

Overview
Severe
Less Severe

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

There are 30 severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare
Acute eruptions of skin Allergic dermatitis Anaphylaxis Anemia Angioedema Blistering skin Bronchospastic pulmonary disease Bullous dermatitis DRESS syndrome Drug-induced hepatitis Dyspnea Exfoliative dermatitis Gastrointestinal hemorrhage Gastrointestinal perforation Gastrointestinal ulcer Hemolytic anemia Hemorrhage Interstitial nephritis Intracranial bleeding Leukopenia Platelet aggregation inhibition Purpura Rectal bleeding Renal papillary necrosis Seizure disorder Stevens-johnson syndrome Thrombocytopenic disorder Toxic epidermal necrolysis Urticaria Wheezing

Rare/Very Rare

Acute eruptions of skin
Allergic dermatitis
Anaphylaxis
Anemia
Angioedema
Blistering skin
Bronchospastic pulmonary disease
Bullous dermatitis
DRESS syndrome
Drug-induced hepatitis
Dyspnea
Exfoliative dermatitis
Gastrointestinal hemorrhage
Gastrointestinal perforation
Gastrointestinal ulcer
Hemolytic anemia
Hemorrhage
Interstitial nephritis
Intracranial bleeding
Leukopenia
Platelet aggregation inhibition
Purpura
Rectal bleeding
Renal papillary necrosis
Seizure disorder
Stevens-johnson syndrome
Thrombocytopenic disorder
Toxic epidermal necrolysis
Urticaria
Wheezing

There are 20 less severe adverse reactions.

More Frequent	Less Frequent
Abdominal pain with cramps Gastric acid hypersecretory conditions Gastrointestinal irritation Heartburn Nausea Vomiting	None.

Rare/Very Rare
Abnormal hepatic function tests Anorexia Black tarry stools Drowsy Dyspepsia Ecchymosis Epistaxis Erythema Gastritis Gingival bleeding Hematoma Pruritus of skin Skin rash Tinnitus

The following precautions are available for VAZALORE (aspirin):

Pediatric
Pregnant
Lactation
Geriatric

No enhanced Pediatric Use information available for this drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

No enhanced Pregnancy information available for this drug.

No enhanced Lactation information available for this drug.

No enhanced Geriatric Use information available for this drug.

The following icd codes are available for VAZALORE (aspirin)'s list of indications:

Acute coronary syndrome
I20.0	Unstable angina
I20.2	Refractory angina pectoris
I20.81	Angina pectoris with coronary microvascular dysfunction
I20.89	Other forms of angina pectoris
I21	Acute myocardial infarction
I21.0	ST elevation (STEMi) myocardial infarction of anterior wall
I21.01	ST elevation (STEMi) myocardial infarction involving left main coronary artery
I21.02	ST elevation (STEMi) myocardial infarction involving left anterior descending coronary artery
I21.09	ST elevation (STEMi) myocardial infarction involving other coronary artery of anterior wall
I21.1	ST elevation (STEMi) myocardial infarction of inferior wall
I21.11	ST elevation (STEMi) myocardial infarction involving right coronary artery
I21.19	ST elevation (STEMi) myocardial infarction involving other coronary artery of inferior wall
I21.2	ST elevation (STEMi) myocardial infarction of other sites
I21.21	ST elevation (STEMi) myocardial infarction involving left circumflex coronary artery
I21.29	ST elevation (STEMi) myocardial infarction involving other sites
I21.3	ST elevation (STEMi) myocardial infarction of unspecified site
I21.4	Non-ST elevation (NSTEMi) myocardial infarction
I21.9	Acute myocardial infarction, unspecified
I21.A	Other type of myocardial infarction
I21.A1	Myocardial infarction type 2
I21.A9	Other myocardial infarction type
I21.B	Myocardial infarction with coronary microvascular dysfunction
I22	Subsequent ST elevation (STEMi) and non-ST elevation (NSTEMi) myocardial infarction
I22.0	Subsequent ST elevation (STEMi) myocardial infarction of anterior wall
I22.1	Subsequent ST elevation (STEMi) myocardial infarction of inferior wall
I22.2	Subsequent non-ST elevation (NSTEMi) myocardial infarction
I22.8	Subsequent ST elevation (STEMi) myocardial infarction of other sites
I22.9	Subsequent ST elevation (STEMi) myocardial infarction of unspecified site
I24	Other acute ischemic heart diseases
I24.0	Acute coronary thrombosis not resulting in myocardial infarction
I24.81	Acute coronary microvascular dysfunction
I24.89	Other forms of acute ischemic heart disease
I24.9	Acute ischemic heart disease, unspecified
I25.110	Atherosclerotic heart disease of native coronary artery with unstable angina pectoris
I25.112	Atherosclerotic heart disease of native coronary artery with refractory angina pectoris
I25.700	Atherosclerosis of coronary artery bypass graft(s), unspecified, with unstable angina pectoris
I25.702	Atherosclerosis of coronary artery bypass graft(s), unspecified, with refractory angina pectoris
I25.710	Atherosclerosis of autologous vein coronary artery bypass graft(s) with unstable angina pectoris
I25.712	Atherosclerosis of autologous vein coronary artery bypass graft(s) with refractory angina pectoris
I25.720	Atherosclerosis of autologous artery coronary artery bypass graft(s) with unstable angina pectoris
I25.722	Atherosclerosis of autologous artery coronary artery bypass graft(s) with refractory angina pectoris
I25.730	Atherosclerosis of nonautologous biological coronary artery bypass graft(s) with unstable angina pectoris
I25.732	Atherosclerosis of nonautologous biological coronary artery bypass graft(s) with refractory angina pectoris
I25.750	Atherosclerosis of native coronary artery of transplanted heart with unstable angina
I25.752	Atherosclerosis of native coronary artery of transplanted heart with refractory angina pectoris
I25.760	Atherosclerosis of bypass graft of coronary artery of transplanted heart with unstable angina
I25.762	Atherosclerosis of bypass graft of coronary artery of transplanted heart with refractory angina pectoris
I25.790	Atherosclerosis of other coronary artery bypass graft(s) with unstable angina pectoris
I25.792	Atherosclerosis of other coronary artery bypass graft(s) with refractory angina pectoris
I25.85	Chronic coronary microvascular dysfunction
Acute myocardial infarction
I21	Acute myocardial infarction
I21.0	ST elevation (STEMi) myocardial infarction of anterior wall
I21.01	ST elevation (STEMi) myocardial infarction involving left main coronary artery
I21.02	ST elevation (STEMi) myocardial infarction involving left anterior descending coronary artery
I21.09	ST elevation (STEMi) myocardial infarction involving other coronary artery of anterior wall
I21.1	ST elevation (STEMi) myocardial infarction of inferior wall
I21.11	ST elevation (STEMi) myocardial infarction involving right coronary artery
I21.19	ST elevation (STEMi) myocardial infarction involving other coronary artery of inferior wall
I21.2	ST elevation (STEMi) myocardial infarction of other sites
I21.21	ST elevation (STEMi) myocardial infarction involving left circumflex coronary artery
I21.29	ST elevation (STEMi) myocardial infarction involving other sites
I21.3	ST elevation (STEMi) myocardial infarction of unspecified site
I21.4	Non-ST elevation (NSTEMi) myocardial infarction
I21.9	Acute myocardial infarction, unspecified
I21.A	Other type of myocardial infarction
I21.A1	Myocardial infarction type 2
I21.A9	Other myocardial infarction type
I21.B	Myocardial infarction with coronary microvascular dysfunction
I22	Subsequent ST elevation (STEMi) and non-ST elevation (NSTEMi) myocardial infarction
I22.0	Subsequent ST elevation (STEMi) myocardial infarction of anterior wall
I22.1	Subsequent ST elevation (STEMi) myocardial infarction of inferior wall
I22.2	Subsequent non-ST elevation (NSTEMi) myocardial infarction
I22.8	Subsequent ST elevation (STEMi) myocardial infarction of other sites
I22.9	Subsequent ST elevation (STEMi) myocardial infarction of unspecified site
Acute thromboembolic stroke
I63	Cerebral infarction
I63.0	Cerebral infarction due to thrombosis of precerebral arteries
I63.00	Cerebral infarction due to thrombosis of unspecified precerebral artery
I63.01	Cerebral infarction due to thrombosis of vertebral artery
I63.011	Cerebral infarction due to thrombosis of right vertebral artery
I63.012	Cerebral infarction due to thrombosis of left vertebral artery
I63.013	Cerebral infarction due to thrombosis of bilateral vertebral arteries
I63.019	Cerebral infarction due to thrombosis of unspecified vertebral artery
I63.02	Cerebral infarction due to thrombosis of basilar artery
I63.03	Cerebral infarction due to thrombosis of carotid artery
I63.031	Cerebral infarction due to thrombosis of right carotid artery
I63.032	Cerebral infarction due to thrombosis of left carotid artery
I63.033	Cerebral infarction due to thrombosis of bilateral carotid arteries
I63.039	Cerebral infarction due to thrombosis of unspecified carotid artery
I63.09	Cerebral infarction due to thrombosis of other precerebral artery
I63.1	Cerebral infarction due to embolism of precerebral arteries
I63.10	Cerebral infarction due to embolism of unspecified precerebral artery
I63.11	Cerebral infarction due to embolism of vertebral artery
I63.111	Cerebral infarction due to embolism of right vertebral artery
I63.112	Cerebral infarction due to embolism of left vertebral artery
I63.113	Cerebral infarction due to embolism of bilateral vertebral arteries
I63.119	Cerebral infarction due to embolism of unspecified vertebral artery
I63.12	Cerebral infarction due to embolism of basilar artery
I63.13	Cerebral infarction due to embolism of carotid artery
I63.131	Cerebral infarction due to embolism of right carotid artery
I63.132	Cerebral infarction due to embolism of left carotid artery
I63.133	Cerebral infarction due to embolism of bilateral carotid arteries
I63.139	Cerebral infarction due to embolism of unspecified carotid artery
I63.19	Cerebral infarction due to embolism of other precerebral artery
I63.2	Cerebral infarction due to unspecified occlusion or stenosis of precerebral arteries
I63.20	Cerebral infarction due to unspecified occlusion or stenosis of unspecified precerebral arteries
I63.21	Cerebral infarction due to unspecified occlusion or stenosis of vertebral arteries
I63.211	Cerebral infarction due to unspecified occlusion or stenosis of right vertebral artery
I63.212	Cerebral infarction due to unspecified occlusion or stenosis of left vertebral artery
I63.213	Cerebral infarction due to unspecified occlusion or stenosis of bilateral vertebral arteries
I63.219	Cerebral infarction due to unspecified occlusion or stenosis of unspecified vertebral artery
I63.22	Cerebral infarction due to unspecified occlusion or stenosis of basilar artery
I63.23	Cerebral infarction due to unspecified occlusion or stenosis of carotid arteries
I63.231	Cerebral infarction due to unspecified occlusion or stenosis of right carotid arteries
I63.232	Cerebral infarction due to unspecified occlusion or stenosis of left carotid arteries
I63.233	Cerebral infarction due to unspecified occlusion or stenosis of bilateral carotid arteries
I63.239	Cerebral infarction due to unspecified occlusion or stenosis of unspecified carotid artery
I63.29	Cerebral infarction due to unspecified occlusion or stenosis of other precerebral arteries
I63.3	Cerebral infarction due to thrombosis of cerebral arteries
I63.30	Cerebral infarction due to thrombosis of unspecified cerebral artery
I63.31	Cerebral infarction due to thrombosis of middle cerebral artery
I63.311	Cerebral infarction due to thrombosis of right middle cerebral artery
I63.312	Cerebral infarction due to thrombosis of left middle cerebral artery
I63.313	Cerebral infarction due to thrombosis of bilateral middle cerebral arteries
I63.319	Cerebral infarction due to thrombosis of unspecified middle cerebral artery
I63.32	Cerebral infarction due to thrombosis of anterior cerebral artery
I63.321	Cerebral infarction due to thrombosis of right anterior cerebral artery
I63.322	Cerebral infarction due to thrombosis of left anterior cerebral artery
I63.323	Cerebral infarction due to thrombosis of bilateral anterior cerebral arteries
I63.329	Cerebral infarction due to thrombosis of unspecified anterior cerebral artery
I63.33	Cerebral infarction due to thrombosis of posterior cerebral artery
I63.331	Cerebral infarction due to thrombosis of right posterior cerebral artery
I63.332	Cerebral infarction due to thrombosis of left posterior cerebral artery
I63.333	Cerebral infarction due to thrombosis of bilateral posterior cerebral arteries
I63.339	Cerebral infarction due to thrombosis of unspecified posterior cerebral artery
I63.34	Cerebral infarction due to thrombosis of cerebellar artery
I63.341	Cerebral infarction due to thrombosis of right cerebellar artery
I63.342	Cerebral infarction due to thrombosis of left cerebellar artery
I63.343	Cerebral infarction due to thrombosis of bilateral cerebellar arteries
I63.349	Cerebral infarction due to thrombosis of unspecified cerebellar artery
I63.39	Cerebral infarction due to thrombosis of other cerebral artery
I63.4	Cerebral infarction due to embolism of cerebral arteries
I63.40	Cerebral infarction due to embolism of unspecified cerebral artery
I63.41	Cerebral infarction due to embolism of middle cerebral artery
I63.411	Cerebral infarction due to embolism of right middle cerebral artery
I63.412	Cerebral infarction due to embolism of left middle cerebral artery
I63.413	Cerebral infarction due to embolism of bilateral middle cerebral arteries
I63.419	Cerebral infarction due to embolism of unspecified middle cerebral artery
I63.42	Cerebral infarction due to embolism of anterior cerebral artery
I63.421	Cerebral infarction due to embolism of right anterior cerebral artery
I63.422	Cerebral infarction due to embolism of left anterior cerebral artery
I63.423	Cerebral infarction due to embolism of bilateral anterior cerebral arteries
I63.429	Cerebral infarction due to embolism of unspecified anterior cerebral artery
I63.43	Cerebral infarction due to embolism of posterior cerebral artery
I63.431	Cerebral infarction due to embolism of right posterior cerebral artery
I63.432	Cerebral infarction due to embolism of left posterior cerebral artery
I63.433	Cerebral infarction due to embolism of bilateral posterior cerebral arteries
I63.439	Cerebral infarction due to embolism of unspecified posterior cerebral artery
I63.44	Cerebral infarction due to embolism of cerebellar artery
I63.441	Cerebral infarction due to embolism of right cerebellar artery
I63.442	Cerebral infarction due to embolism of left cerebellar artery
I63.443	Cerebral infarction due to embolism of bilateral cerebellar arteries
I63.449	Cerebral infarction due to embolism of unspecified cerebellar artery
I63.49	Cerebral infarction due to embolism of other cerebral artery
I63.5	Cerebral infarction due to unspecified occlusion or stenosis of cerebral arteries
I63.50	Cerebral infarction due to unspecified occlusion or stenosis of unspecified cerebral artery
I63.51	Cerebral infarction due to unspecified occlusion or stenosis of middle cerebral artery
I63.511	Cerebral infarction due to unspecified occlusion or stenosis of right middle cerebral artery
I63.512	Cerebral infarction due to unspecified occlusion or stenosis of left middle cerebral artery
I63.513	Cerebral infarction due to unspecified occlusion or stenosis of bilateral middle cerebral arteries
I63.519	Cerebral infarction due to unspecified occlusion or stenosis of unspecified middle cerebral artery
I63.52	Cerebral infarction due to unspecified occlusion or stenosis of anterior cerebral artery
I63.521	Cerebral infarction due to unspecified occlusion or stenosis of right anterior cerebral artery
I63.522	Cerebral infarction due to unspecified occlusion or stenosis of left anterior cerebral artery
I63.523	Cerebral infarction due to unspecified occlusion or stenosis of bilateral anterior cerebral arteries
I63.529	Cerebral infarction due to unspecified occlusion or stenosis of unspecified anterior cerebral artery
I63.53	Cerebral infarction due to unspecified occlusion or stenosis of posterior cerebral artery
I63.531	Cerebral infarction due to unspecified occlusion or stenosis of right posterior cerebral artery
I63.532	Cerebral infarction due to unspecified occlusion or stenosis of left posterior cerebral artery
I63.533	Cerebral infarction due to unspecified occlusion or stenosis of bilateral posterior cerebral arteries
I63.539	Cerebral infarction due to unspecified occlusion or stenosis of unspecified posterior cerebral artery
I63.54	Cerebral infarction due to unspecified occlusion or stenosis of cerebellar artery
I63.541	Cerebral infarction due to unspecified occlusion or stenosis of right cerebellar artery
I63.542	Cerebral infarction due to unspecified occlusion or stenosis of left cerebellar artery
I63.543	Cerebral infarction due to unspecified occlusion or stenosis of bilateral cerebellar arteries
I63.549	Cerebral infarction due to unspecified occlusion or stenosis of unspecified cerebellar artery
I63.59	Cerebral infarction due to unspecified occlusion or stenosis of other cerebral artery
I63.8	Other cerebral infarction
I63.9	Cerebral infarction, unspecified
Cerebral thromboembolism prevention
Z86.73	Personal history of transient ischemic attack (TIa), and cerebral infarction without residual deficits
Dysmenorrhea
N94.4	Primary dysmenorrhea
N94.5	Secondary dysmenorrhea
N94.6	Dysmenorrhea, unspecified
Fever
R50	Fever of other and unknown origin
R50.2	Drug induced fever
R50.8	Other specified fever
R50.81	Fever presenting with conditions classified elsewhere
R50.82	Postprocedural fever
R50.83	Postvaccination fever
R50.84	Febrile nonhemolytic transfusion reaction
R50.9	Fever, unspecified
Headache disorder
G43	Migraine
G43.0	Migraine without aura
G43.00	Migraine without aura, not intractable
G43.009	Migraine without aura, not intractable, without status migrainosus
G43.01	Migraine without aura, intractable
G43.019	Migraine without aura, intractable, without status migrainosus
G43.1	Migraine with aura
G43.10	Migraine with aura, not intractable
G43.109	Migraine with aura, not intractable, without status migrainosus
G43.11	Migraine with aura, intractable
G43.119	Migraine with aura, intractable, without status migrainosus
G43.4	Hemiplegic migraine
G43.40	Hemiplegic migraine, not intractable
G43.409	Hemiplegic migraine, not intractable, without status migrainosus
G43.41	Hemiplegic migraine, intractable
G43.419	Hemiplegic migraine, intractable, without status migrainosus
G43.5	Persistent migraine aura without cerebral infarction
G43.50	Persistent migraine aura without cerebral infarction, not intractable
G43.509	Persistent migraine aura without cerebral infarction, not intractable, without status migrainosus
G43.51	Persistent migraine aura without cerebral infarction, intractable
G43.519	Persistent migraine aura without cerebral infarction, intractable, without status migrainosus
G43.6	Persistent migraine aura with cerebral infarction
G43.60	Persistent migraine aura with cerebral infarction, not intractable
G43.609	Persistent migraine aura with cerebral infarction, not intractable, without status migrainosus
G43.61	Persistent migraine aura with cerebral infarction, intractable
G43.619	Persistent migraine aura with cerebral infarction, intractable, without status migrainosus
G43.7	Chronic migraine without aura
G43.70	Chronic migraine without aura, not intractable
G43.709	Chronic migraine without aura, not intractable, without status migrainosus
G43.71	Chronic migraine without aura, intractable
G43.719	Chronic migraine without aura, intractable, without status migrainosus
G43.8	Other migraine
G43.80	Other migraine, not intractable
G43.809	Other migraine, not intractable, without status migrainosus
G43.81	Other migraine, intractable
G43.819	Other migraine, intractable, without status migrainosus
G43.82	Menstrual migraine, not intractable
G43.829	Menstrual migraine, not intractable, without status migrainosus
G43.83	Menstrual migraine, intractable
G43.839	Menstrual migraine, intractable, without status migrainosus
G43.9	Migraine, unspecified
G43.90	Migraine, unspecified, not intractable
G43.909	Migraine, unspecified, not intractable, without status migrainosus
G43.91	Migraine, unspecified, intractable
G43.919	Migraine, unspecified, intractable, without status migrainosus
G43.B	Ophthalmoplegic migraine
G43.B0	Ophthalmoplegic migraine, not intractable
G43.B1	Ophthalmoplegic migraine, intractable
G43.C	Periodic headache syndromes in child or adult
G43.C0	Periodic headache syndromes in child or adult, not intractable
G43.C1	Periodic headache syndromes in child or adult, intractable
G43.D	Abdominal migraine
G43.D0	Abdominal migraine, not intractable
G43.D1	Abdominal migraine, intractable
G43.E	Chronic migraine with aura
G43.E0	Chronic migraine with aura, not intractable
G43.E09	Chronic migraine with aura, not intractable, without status migrainosus
G43.E1	Chronic migraine with aura, intractable
G43.E19	Chronic migraine with aura, intractable, without status migrainosus
G44	Other headache syndromes
G44.0	Cluster headaches and other trigeminal autonomic cephalgias (TAc)
G44.00	Cluster headache syndrome, unspecified
G44.001	Cluster headache syndrome, unspecified, intractable
G44.009	Cluster headache syndrome, unspecified, not intractable
G44.01	Episodic cluster headache
G44.011	Episodic cluster headache, intractable
G44.019	Episodic cluster headache, not intractable
G44.02	Chronic cluster headache
G44.021	Chronic cluster headache, intractable
G44.029	Chronic cluster headache, not intractable
G44.03	Episodic paroxysmal hemicrania
G44.031	Episodic paroxysmal hemicrania, intractable
G44.039	Episodic paroxysmal hemicrania, not intractable
G44.04	Chronic paroxysmal hemicrania
G44.041	Chronic paroxysmal hemicrania, intractable
G44.049	Chronic paroxysmal hemicrania, not intractable
G44.05	Short lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCt)
G44.051	Short lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCt), intractable
G44.059	Short lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCt), not intractable
G44.09	Other trigeminal autonomic cephalgias (TAc)
G44.091	Other trigeminal autonomic cephalgias (TAc), intractable
G44.099	Other trigeminal autonomic cephalgias (TAc), not intractable
G44.1	Vascular headache, not elsewhere classified
G44.2	Tension-type headache
G44.20	Tension-type headache, unspecified
G44.201	Tension-type headache, unspecified, intractable
G44.209	Tension-type headache, unspecified, not intractable
G44.21	Episodic tension-type headache
G44.211	Episodic tension-type headache, intractable
G44.219	Episodic tension-type headache, not intractable
G44.22	Chronic tension-type headache
G44.221	Chronic tension-type headache, intractable
G44.229	Chronic tension-type headache, not intractable
G44.3	Post-traumatic headache
G44.30	Post-traumatic headache, unspecified
G44.301	Post-traumatic headache, unspecified, intractable
G44.309	Post-traumatic headache, unspecified, not intractable
G44.31	Acute post-traumatic headache
G44.311	Acute post-traumatic headache, intractable
G44.319	Acute post-traumatic headache, not intractable
G44.32	Chronic post-traumatic headache
G44.321	Chronic post-traumatic headache, intractable
G44.329	Chronic post-traumatic headache, not intractable
G44.4	Drug-induced headache, not elsewhere classified
G44.40	Drug-induced headache, not elsewhere classified, not intractable
G44.41	Drug-induced headache, not elsewhere classified, intractable
G44.5	Complicated headache syndromes
G44.51	Hemicrania continua
G44.52	New daily persistent headache (NDPh)
G44.53	Primary thunderclap headache
G44.59	Other complicated headache syndrome
G44.8	Other specified headache syndromes
G44.81	Hypnic headache
G44.82	Headache associated with sexual activity
G44.83	Primary cough headache
G44.84	Primary exertional headache
G44.85	Primary stabbing headache
G44.89	Other headache syndrome
R51	Headache
R51.9	Headache, unspecified
Juvenile idiopathic arthritis
M08.0	Unspecified juvenile rheumatoid arthritis
M08.00	Unspecified juvenile rheumatoid arthritis of unspecified site
M08.01	Unspecified juvenile rheumatoid arthritis, shoulder
M08.011	Unspecified juvenile rheumatoid arthritis, right shoulder
M08.012	Unspecified juvenile rheumatoid arthritis, left shoulder
M08.019	Unspecified juvenile rheumatoid arthritis, unspecified shoulder
M08.02	Unspecified juvenile rheumatoid arthritis of elbow
M08.021	Unspecified juvenile rheumatoid arthritis, right elbow
M08.022	Unspecified juvenile rheumatoid arthritis, left elbow
M08.029	Unspecified juvenile rheumatoid arthritis, unspecified elbow
M08.03	Unspecified juvenile rheumatoid arthritis, wrist
M08.031	Unspecified juvenile rheumatoid arthritis, right wrist
M08.032	Unspecified juvenile rheumatoid arthritis, left wrist
M08.039	Unspecified juvenile rheumatoid arthritis, unspecified wrist
M08.04	Unspecified juvenile rheumatoid arthritis, hand
M08.041	Unspecified juvenile rheumatoid arthritis, right hand
M08.042	Unspecified juvenile rheumatoid arthritis, left hand
M08.049	Unspecified juvenile rheumatoid arthritis, unspecified hand
M08.05	Unspecified juvenile rheumatoid arthritis, hip
M08.051	Unspecified juvenile rheumatoid arthritis, right hip
M08.052	Unspecified juvenile rheumatoid arthritis, left hip
M08.059	Unspecified juvenile rheumatoid arthritis, unspecified hip
M08.06	Unspecified juvenile rheumatoid arthritis, knee
M08.061	Unspecified juvenile rheumatoid arthritis, right knee
M08.062	Unspecified juvenile rheumatoid arthritis, left knee
M08.069	Unspecified juvenile rheumatoid arthritis, unspecified knee
M08.07	Unspecified juvenile rheumatoid arthritis, ankle and foot
M08.071	Unspecified juvenile rheumatoid arthritis, right ankle and foot
M08.072	Unspecified juvenile rheumatoid arthritis, left ankle and foot
M08.079	Unspecified juvenile rheumatoid arthritis, unspecified ankle and foot
M08.08	Unspecified juvenile rheumatoid arthritis, vertebrae
M08.09	Unspecified juvenile rheumatoid arthritis, multiple sites
M08.0A	Unspecified juvenile rheumatoid arthritis, other specified site
M08.2	Juvenile rheumatoid arthritis with systemic onset
M08.20	Juvenile rheumatoid arthritis with systemic onset, unspecified site
M08.21	Juvenile rheumatoid arthritis with systemic onset, shoulder
M08.211	Juvenile rheumatoid arthritis with systemic onset, right shoulder
M08.212	Juvenile rheumatoid arthritis with systemic onset, left shoulder
M08.219	Juvenile rheumatoid arthritis with systemic onset, unspecified shoulder
M08.22	Juvenile rheumatoid arthritis with systemic onset, elbow
M08.221	Juvenile rheumatoid arthritis with systemic onset, right elbow
M08.222	Juvenile rheumatoid arthritis with systemic onset, left elbow
M08.229	Juvenile rheumatoid arthritis with systemic onset, unspecified elbow
M08.23	Juvenile rheumatoid arthritis with systemic onset, wrist
M08.231	Juvenile rheumatoid arthritis with systemic onset, right wrist
M08.232	Juvenile rheumatoid arthritis with systemic onset, left wrist
M08.239	Juvenile rheumatoid arthritis with systemic onset, unspecified wrist
M08.24	Juvenile rheumatoid arthritis with systemic onset, hand
M08.241	Juvenile rheumatoid arthritis with systemic onset, right hand
M08.242	Juvenile rheumatoid arthritis with systemic onset, left hand
M08.249	Juvenile rheumatoid arthritis with systemic onset, unspecified hand
M08.25	Juvenile rheumatoid arthritis with systemic onset, hip
M08.251	Juvenile rheumatoid arthritis with systemic onset, right hip
M08.252	Juvenile rheumatoid arthritis with systemic onset, left hip
M08.259	Juvenile rheumatoid arthritis with systemic onset, unspecified hip
M08.26	Juvenile rheumatoid arthritis with systemic onset, knee
M08.261	Juvenile rheumatoid arthritis with systemic onset, right knee
M08.262	Juvenile rheumatoid arthritis with systemic onset, left knee
M08.269	Juvenile rheumatoid arthritis with systemic onset, unspecified knee
M08.27	Juvenile rheumatoid arthritis with systemic onset, ankle and foot
M08.271	Juvenile rheumatoid arthritis with systemic onset, right ankle and foot
M08.272	Juvenile rheumatoid arthritis with systemic onset, left ankle and foot
M08.279	Juvenile rheumatoid arthritis with systemic onset, unspecified ankle and foot
M08.28	Juvenile rheumatoid arthritis with systemic onset, vertebrae
M08.29	Juvenile rheumatoid arthritis with systemic onset, multiple sites
M08.2A	Juvenile rheumatoid arthritis with systemic onset, other specified site
M08.3	Juvenile rheumatoid polyarthritis (seronegative)
M08.4	Pauciarticular juvenile rheumatoid arthritis
M08.40	Pauciarticular juvenile rheumatoid arthritis, unspecified site
M08.41	Pauciarticular juvenile rheumatoid arthritis, shoulder
M08.411	Pauciarticular juvenile rheumatoid arthritis, right shoulder
M08.412	Pauciarticular juvenile rheumatoid arthritis, left shoulder
M08.419	Pauciarticular juvenile rheumatoid arthritis, unspecified shoulder
M08.42	Pauciarticular juvenile rheumatoid arthritis, elbow
M08.421	Pauciarticular juvenile rheumatoid arthritis, right elbow
M08.422	Pauciarticular juvenile rheumatoid arthritis, left elbow
M08.429	Pauciarticular juvenile rheumatoid arthritis, unspecified elbow
M08.43	Pauciarticular juvenile rheumatoid arthritis, wrist
M08.431	Pauciarticular juvenile rheumatoid arthritis, right wrist
M08.432	Pauciarticular juvenile rheumatoid arthritis, left wrist
M08.439	Pauciarticular juvenile rheumatoid arthritis, unspecified wrist
M08.44	Pauciarticular juvenile rheumatoid arthritis, hand
M08.441	Pauciarticular juvenile rheumatoid arthritis, right hand
M08.442	Pauciarticular juvenile rheumatoid arthritis, left hand
M08.449	Pauciarticular juvenile rheumatoid arthritis, unspecified hand
M08.45	Pauciarticular juvenile rheumatoid arthritis, hip
M08.451	Pauciarticular juvenile rheumatoid arthritis, right hip
M08.452	Pauciarticular juvenile rheumatoid arthritis, left hip
M08.459	Pauciarticular juvenile rheumatoid arthritis, unspecified hip
M08.46	Pauciarticular juvenile rheumatoid arthritis, knee
M08.461	Pauciarticular juvenile rheumatoid arthritis, right knee
M08.462	Pauciarticular juvenile rheumatoid arthritis, left knee
M08.469	Pauciarticular juvenile rheumatoid arthritis, unspecified knee
M08.47	Pauciarticular juvenile rheumatoid arthritis, ankle and foot
M08.471	Pauciarticular juvenile rheumatoid arthritis, right ankle and foot
M08.472	Pauciarticular juvenile rheumatoid arthritis, left ankle and foot
M08.479	Pauciarticular juvenile rheumatoid arthritis, unspecified ankle and foot
M08.48	Pauciarticular juvenile rheumatoid arthritis, vertebrae
M08.4A	Pauciarticular juvenile rheumatoid arthritis, other specified site
Myocardial reinfarction prevention
I21	Acute myocardial infarction
I21.0	ST elevation (STEMi) myocardial infarction of anterior wall
I21.01	ST elevation (STEMi) myocardial infarction involving left main coronary artery
I21.02	ST elevation (STEMi) myocardial infarction involving left anterior descending coronary artery
I21.09	ST elevation (STEMi) myocardial infarction involving other coronary artery of anterior wall
I21.1	ST elevation (STEMi) myocardial infarction of inferior wall
I21.11	ST elevation (STEMi) myocardial infarction involving right coronary artery
I21.19	ST elevation (STEMi) myocardial infarction involving other coronary artery of inferior wall
I21.2	ST elevation (STEMi) myocardial infarction of other sites
I21.21	ST elevation (STEMi) myocardial infarction involving left circumflex coronary artery
I21.29	ST elevation (STEMi) myocardial infarction involving other sites
I21.3	ST elevation (STEMi) myocardial infarction of unspecified site
I21.4	Non-ST elevation (NSTEMi) myocardial infarction
I21.9	Acute myocardial infarction, unspecified
I21.A	Other type of myocardial infarction
I21.A1	Myocardial infarction type 2
I21.A9	Other myocardial infarction type
I21.B	Myocardial infarction with coronary microvascular dysfunction
I22	Subsequent ST elevation (STEMi) and non-ST elevation (NSTEMi) myocardial infarction
I22.0	Subsequent ST elevation (STEMi) myocardial infarction of anterior wall
I22.1	Subsequent ST elevation (STEMi) myocardial infarction of inferior wall
I22.2	Subsequent non-ST elevation (NSTEMi) myocardial infarction
I22.8	Subsequent ST elevation (STEMi) myocardial infarction of other sites
I22.9	Subsequent ST elevation (STEMi) myocardial infarction of unspecified site
I25.2	Old myocardial infarction
I25.85	Chronic coronary microvascular dysfunction
Osteoarthritis
M15	Polyosteoarthritis
M15.0	Primary generalized (osteo)arthritis
M15.1	Heberden's nodes (with arthropathy)
M15.2	Bouchard's nodes (with arthropathy)
M15.3	Secondary multiple arthritis
M15.4	Erosive (osteo)arthritis
M15.8	Other polyosteoarthritis
M15.9	Polyosteoarthritis, unspecified
M16	Osteoarthritis of hip
M16.0	Bilateral primary osteoarthritis of hip
M16.1	Unilateral primary osteoarthritis of hip
M16.10	Unilateral primary osteoarthritis, unspecified hip
M16.11	Unilateral primary osteoarthritis, right hip
M16.12	Unilateral primary osteoarthritis, left hip
M16.2	Bilateral osteoarthritis resulting from hip dysplasia
M16.3	Unilateral osteoarthritis resulting from hip dysplasia
M16.30	Unilateral osteoarthritis resulting from hip dysplasia, unspecified hip
M16.31	Unilateral osteoarthritis resulting from hip dysplasia, right hip
M16.32	Unilateral osteoarthritis resulting from hip dysplasia, left hip
M16.4	Bilateral post-traumatic osteoarthritis of hip
M16.5	Unilateral post-traumatic osteoarthritis of hip
M16.50	Unilateral post-traumatic osteoarthritis, unspecified hip
M16.51	Unilateral post-traumatic osteoarthritis, right hip
M16.52	Unilateral post-traumatic osteoarthritis, left hip
M16.6	Other bilateral secondary osteoarthritis of hip
M16.7	Other unilateral secondary osteoarthritis of hip
M16.9	Osteoarthritis of hip, unspecified
M17	Osteoarthritis of knee
M17.0	Bilateral primary osteoarthritis of knee
M17.1	Unilateral primary osteoarthritis of knee
M17.10	Unilateral primary osteoarthritis, unspecified knee
M17.11	Unilateral primary osteoarthritis, right knee
M17.12	Unilateral primary osteoarthritis, left knee
M17.2	Bilateral post-traumatic osteoarthritis of knee
M17.3	Unilateral post-traumatic osteoarthritis of knee
M17.30	Unilateral post-traumatic osteoarthritis, unspecified knee
M17.31	Unilateral post-traumatic osteoarthritis, right knee
M17.32	Unilateral post-traumatic osteoarthritis, left knee
M17.4	Other bilateral secondary osteoarthritis of knee
M17.5	Other unilateral secondary osteoarthritis of knee
M17.9	Osteoarthritis of knee, unspecified
M18	Osteoarthritis of first carpometacarpal joint
M18.0	Bilateral primary osteoarthritis of first carpometacarpal joints
M18.1	Unilateral primary osteoarthritis of first carpometacarpal joint
M18.10	Unilateral primary osteoarthritis of first carpometacarpal joint, unspecified hand
M18.11	Unilateral primary osteoarthritis of first carpometacarpal joint, right hand
M18.12	Unilateral primary osteoarthritis of first carpometacarpal joint, left hand
M18.2	Bilateral post-traumatic osteoarthritis of first carpometacarpal joints
M18.3	Unilateral post-traumatic osteoarthritis of first carpometacarpal joint
M18.30	Unilateral post-traumatic osteoarthritis of first carpometacarpal joint, unspecified hand
M18.31	Unilateral post-traumatic osteoarthritis of first carpometacarpal joint, right hand
M18.32	Unilateral post-traumatic osteoarthritis of first carpometacarpal joint, left hand
M18.4	Other bilateral secondary osteoarthritis of first carpometacarpal joints
M18.5	Other unilateral secondary osteoarthritis of first carpometacarpal joint
M18.50	Other unilateral secondary osteoarthritis of first carpometacarpal joint, unspecified hand
M18.51	Other unilateral secondary osteoarthritis of first carpometacarpal joint, right hand
M18.52	Other unilateral secondary osteoarthritis of first carpometacarpal joint, left hand
M18.9	Osteoarthritis of first carpometacarpal joint, unspecified
M19	Other and unspecified osteoarthritis
M19.0	Primary osteoarthritis of other joints
M19.01	Primary osteoarthritis, shoulder
M19.011	Primary osteoarthritis, right shoulder
M19.012	Primary osteoarthritis, left shoulder
M19.019	Primary osteoarthritis, unspecified shoulder
M19.02	Primary osteoarthritis, elbow
M19.021	Primary osteoarthritis, right elbow
M19.022	Primary osteoarthritis, left elbow
M19.029	Primary osteoarthritis, unspecified elbow
M19.03	Primary osteoarthritis, wrist
M19.031	Primary osteoarthritis, right wrist
M19.032	Primary osteoarthritis, left wrist
M19.039	Primary osteoarthritis, unspecified wrist
M19.04	Primary osteoarthritis, hand
M19.041	Primary osteoarthritis, right hand
M19.042	Primary osteoarthritis, left hand
M19.049	Primary osteoarthritis, unspecified hand
M19.07	Primary osteoarthritis ankle and foot
M19.071	Primary osteoarthritis, right ankle and foot
M19.072	Primary osteoarthritis, left ankle and foot
M19.079	Primary osteoarthritis, unspecified ankle and foot
M19.09	Primary osteoarthritis, other specified site
M19.1	Post-traumatic osteoarthritis of other joints
M19.11	Post-traumatic osteoarthritis, shoulder
M19.111	Post-traumatic osteoarthritis, right shoulder
M19.112	Post-traumatic osteoarthritis, left shoulder
M19.119	Post-traumatic osteoarthritis, unspecified shoulder
M19.12	Post-traumatic osteoarthritis, elbow
M19.121	Post-traumatic osteoarthritis, right elbow
M19.122	Post-traumatic osteoarthritis, left elbow
M19.129	Post-traumatic osteoarthritis, unspecified elbow
M19.13	Post-traumatic osteoarthritis, wrist
M19.131	Post-traumatic osteoarthritis, right wrist
M19.132	Post-traumatic osteoarthritis, left wrist
M19.139	Post-traumatic osteoarthritis, unspecified wrist
M19.14	Post-traumatic osteoarthritis, hand
M19.141	Post-traumatic osteoarthritis, right hand
M19.142	Post-traumatic osteoarthritis, left hand
M19.149	Post-traumatic osteoarthritis, unspecified hand
M19.17	Post-traumatic osteoarthritis, ankle and foot
M19.171	Post-traumatic osteoarthritis, right ankle and foot
M19.172	Post-traumatic osteoarthritis, left ankle and foot
M19.179	Post-traumatic osteoarthritis, unspecified ankle and foot
M19.19	Post-traumatic osteoarthritis, other specified site
M19.2	Secondary osteoarthritis of other joints
M19.21	Secondary osteoarthritis, shoulder
M19.211	Secondary osteoarthritis, right shoulder
M19.212	Secondary osteoarthritis, left shoulder
M19.219	Secondary osteoarthritis, unspecified shoulder
M19.22	Secondary osteoarthritis, elbow
M19.221	Secondary osteoarthritis, right elbow
M19.222	Secondary osteoarthritis, left elbow
M19.229	Secondary osteoarthritis, unspecified elbow
M19.23	Secondary osteoarthritis, wrist
M19.231	Secondary osteoarthritis, right wrist
M19.232	Secondary osteoarthritis, left wrist
M19.239	Secondary osteoarthritis, unspecified wrist
M19.24	Secondary osteoarthritis, hand
M19.241	Secondary osteoarthritis, right hand
M19.242	Secondary osteoarthritis, left hand
M19.249	Secondary osteoarthritis, unspecified hand
M19.27	Secondary osteoarthritis, ankle and foot
M19.271	Secondary osteoarthritis, right ankle and foot
M19.272	Secondary osteoarthritis, left ankle and foot
M19.279	Secondary osteoarthritis, unspecified ankle and foot
M19.29	Secondary osteoarthritis, other specified site
M19.9	Osteoarthritis, unspecified site
M19.90	Unspecified osteoarthritis, unspecified site
M19.91	Primary osteoarthritis, unspecified site
M19.92	Post-traumatic osteoarthritis, unspecified site
M19.93	Secondary osteoarthritis, unspecified site
Pain
G43	Migraine
G43.0	Migraine without aura
G43.00	Migraine without aura, not intractable
G43.001	Migraine without aura, not intractable, with status migrainosus
G43.009	Migraine without aura, not intractable, without status migrainosus
G43.01	Migraine without aura, intractable
G43.011	Migraine without aura, intractable, with status migrainosus
G43.019	Migraine without aura, intractable, without status migrainosus
G43.1	Migraine with aura
G43.10	Migraine with aura, not intractable
G43.101	Migraine with aura, not intractable, with status migrainosus
G43.109	Migraine with aura, not intractable, without status migrainosus
G43.11	Migraine with aura, intractable
G43.111	Migraine with aura, intractable, with status migrainosus
G43.119	Migraine with aura, intractable, without status migrainosus
G43.4	Hemiplegic migraine
G43.40	Hemiplegic migraine, not intractable
G43.401	Hemiplegic migraine, not intractable, with status migrainosus
G43.409	Hemiplegic migraine, not intractable, without status migrainosus
G43.41	Hemiplegic migraine, intractable
G43.411	Hemiplegic migraine, intractable, with status migrainosus
G43.419	Hemiplegic migraine, intractable, without status migrainosus
G43.5	Persistent migraine aura without cerebral infarction
G43.50	Persistent migraine aura without cerebral infarction, not intractable
G43.501	Persistent migraine aura without cerebral infarction, not intractable, with status migrainosus
G43.509	Persistent migraine aura without cerebral infarction, not intractable, without status migrainosus
G43.51	Persistent migraine aura without cerebral infarction, intractable
G43.511	Persistent migraine aura without cerebral infarction, intractable, with status migrainosus
G43.519	Persistent migraine aura without cerebral infarction, intractable, without status migrainosus
G43.6	Persistent migraine aura with cerebral infarction
G43.60	Persistent migraine aura with cerebral infarction, not intractable
G43.601	Persistent migraine aura with cerebral infarction, not intractable, with status migrainosus
G43.609	Persistent migraine aura with cerebral infarction, not intractable, without status migrainosus
G43.61	Persistent migraine aura with cerebral infarction, intractable
G43.611	Persistent migraine aura with cerebral infarction, intractable, with status migrainosus
G43.619	Persistent migraine aura with cerebral infarction, intractable, without status migrainosus
G43.7	Chronic migraine without aura
G43.70	Chronic migraine without aura, not intractable
G43.701	Chronic migraine without aura, not intractable, with status migrainosus
G43.709	Chronic migraine without aura, not intractable, without status migrainosus
G43.71	Chronic migraine without aura, intractable
G43.711	Chronic migraine without aura, intractable, with status migrainosus
G43.719	Chronic migraine without aura, intractable, without status migrainosus
G43.8	Other migraine
G43.80	Other migraine, not intractable
G43.801	Other migraine, not intractable, with status migrainosus
G43.809	Other migraine, not intractable, without status migrainosus
G43.81	Other migraine, intractable
G43.811	Other migraine, intractable, with status migrainosus
G43.819	Other migraine, intractable, without status migrainosus
G43.82	Menstrual migraine, not intractable
G43.821	Menstrual migraine, not intractable, with status migrainosus
G43.829	Menstrual migraine, not intractable, without status migrainosus
G43.83	Menstrual migraine, intractable
G43.831	Menstrual migraine, intractable, with status migrainosus
G43.839	Menstrual migraine, intractable, without status migrainosus
G43.9	Migraine, unspecified
G43.90	Migraine, unspecified, not intractable
G43.901	Migraine, unspecified, not intractable, with status migrainosus
G43.909	Migraine, unspecified, not intractable, without status migrainosus
G43.91	Migraine, unspecified, intractable
G43.911	Migraine, unspecified, intractable, with status migrainosus
G43.919	Migraine, unspecified, intractable, without status migrainosus
G43.B	Ophthalmoplegic migraine
G43.B0	Ophthalmoplegic migraine, not intractable
G43.B1	Ophthalmoplegic migraine, intractable
G43.C	Periodic headache syndromes in child or adult
G43.C0	Periodic headache syndromes in child or adult, not intractable
G43.C1	Periodic headache syndromes in child or adult, intractable
G43.D	Abdominal migraine
G43.D0	Abdominal migraine, not intractable
G43.D1	Abdominal migraine, intractable
G43.E	Chronic migraine with aura
G43.E0	Chronic migraine with aura, not intractable
G43.E01	Chronic migraine with aura, not intractable, with status migrainosus
G43.E09	Chronic migraine with aura, not intractable, without status migrainosus
G43.E1	Chronic migraine with aura, intractable
G43.E11	Chronic migraine with aura, intractable, with status migrainosus
G43.E19	Chronic migraine with aura, intractable, without status migrainosus
G44	Other headache syndromes
G44.00	Cluster headache syndrome, unspecified
G44.001	Cluster headache syndrome, unspecified, intractable
G44.009	Cluster headache syndrome, unspecified, not intractable
G44.01	Episodic cluster headache
G44.011	Episodic cluster headache, intractable
G44.019	Episodic cluster headache, not intractable
G44.02	Chronic cluster headache
G44.021	Chronic cluster headache, intractable
G44.029	Chronic cluster headache, not intractable
G44.03	Episodic paroxysmal hemicrania
G44.031	Episodic paroxysmal hemicrania, intractable
G44.039	Episodic paroxysmal hemicrania, not intractable
G44.04	Chronic paroxysmal hemicrania
G44.041	Chronic paroxysmal hemicrania, intractable
G44.049	Chronic paroxysmal hemicrania, not intractable
G44.05	Short lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCt)
G44.051	Short lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCt), intractable
G44.059	Short lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCt), not intractable
G44.1	Vascular headache, not elsewhere classified
G44.2	Tension-type headache
G44.20	Tension-type headache, unspecified
G44.201	Tension-type headache, unspecified, intractable
G44.209	Tension-type headache, unspecified, not intractable
G44.21	Episodic tension-type headache
G44.211	Episodic tension-type headache, intractable
G44.219	Episodic tension-type headache, not intractable
G44.22	Chronic tension-type headache
G44.221	Chronic tension-type headache, intractable
G44.229	Chronic tension-type headache, not intractable
G44.3	Post-traumatic headache
G44.30	Post-traumatic headache, unspecified
G44.301	Post-traumatic headache, unspecified, intractable
G44.309	Post-traumatic headache, unspecified, not intractable
G44.31	Acute post-traumatic headache
G44.311	Acute post-traumatic headache, intractable
G44.319	Acute post-traumatic headache, not intractable
G44.32	Chronic post-traumatic headache
G44.321	Chronic post-traumatic headache, intractable
G44.329	Chronic post-traumatic headache, not intractable
G44.4	Drug-induced headache, not elsewhere classified
G44.40	Drug-induced headache, not elsewhere classified, not intractable
G44.41	Drug-induced headache, not elsewhere classified, intractable
G44.5	Complicated headache syndromes
G44.51	Hemicrania continua
G44.52	New daily persistent headache (NDPh)
G44.53	Primary thunderclap headache
G44.59	Other complicated headache syndrome
G44.8	Other specified headache syndromes
G44.81	Hypnic headache
G44.82	Headache associated with sexual activity
G44.83	Primary cough headache
G44.84	Primary exertional headache
G44.85	Primary stabbing headache
G44.86	Cervicogenic headache
G44.89	Other headache syndrome
G50.1	Atypical facial pain
G89	Pain, not elsewhere classified
G89.0	Central pain syndrome
G89.1	Acute pain, not elsewhere classified
G89.11	Acute pain due to trauma
G89.12	Acute post-thoracotomy pain
G89.18	Other acute postprocedural pain
G89.2	Chronic pain, not elsewhere classified
G89.21	Chronic pain due to trauma
G89.22	Chronic post-thoracotomy pain
G89.28	Other chronic postprocedural pain
G89.29	Other chronic pain
G89.3	Neoplasm related pain (acute) (chronic)
G89.4	Chronic pain syndrome
G90.5	Complex regional pain syndrome I (CRPS i)
G90.50	Complex regional pain syndrome i, unspecified
G90.51	Complex regional pain syndrome I of upper limb
G90.511	Complex regional pain syndrome I of right upper limb
G90.512	Complex regional pain syndrome I of left upper limb
G90.513	Complex regional pain syndrome I of upper limb, bilateral
G90.519	Complex regional pain syndrome I of unspecified upper limb
G90.52	Complex regional pain syndrome I of lower limb
G90.521	Complex regional pain syndrome I of right lower limb
G90.522	Complex regional pain syndrome I of left lower limb
G90.523	Complex regional pain syndrome I of lower limb, bilateral
G90.529	Complex regional pain syndrome I of unspecified lower limb
G90.59	Complex regional pain syndrome I of other specified site
H57.1	Ocular pain
H57.10	Ocular pain, unspecified eye
H57.11	Ocular pain, right eye
H57.12	Ocular pain, left eye
H57.13	Ocular pain, bilateral
H92	Otalgia and effusion of ear
H92.0	Otalgia
H92.01	Otalgia, right ear
H92.02	Otalgia, left ear
H92.03	Otalgia, bilateral
H92.09	Otalgia, unspecified ear
K14.6	Glossodynia
M25.5	Pain in joint
M25.50	Pain in unspecified joint
M25.51	Pain in shoulder
M25.511	Pain in right shoulder
M25.512	Pain in left shoulder
M25.519	Pain in unspecified shoulder
M25.52	Pain in elbow
M25.521	Pain in right elbow
M25.522	Pain in left elbow
M25.529	Pain in unspecified elbow
M25.53	Pain in wrist
M25.531	Pain in right wrist
M25.532	Pain in left wrist
M25.539	Pain in unspecified wrist
M25.54	Pain in joints of hand
M25.541	Pain in joints of right hand
M25.542	Pain in joints of left hand
M25.549	Pain in joints of unspecified hand
M25.55	Pain in hip
M25.551	Pain in right hip
M25.552	Pain in left hip
M25.559	Pain in unspecified hip
M25.56	Pain in knee
M25.561	Pain in right knee
M25.562	Pain in left knee
M25.569	Pain in unspecified knee
M25.57	Pain in ankle and joints of foot
M25.571	Pain in right ankle and joints of right foot
M25.572	Pain in left ankle and joints of left foot
M25.579	Pain in unspecified ankle and joints of unspecified foot
M25.59	Pain in other specified joint
M26.62	Arthralgia of temporomandibular joint
M26.621	Arthralgia of right temporomandibular joint
M26.622	Arthralgia of left temporomandibular joint
M26.623	Arthralgia of bilateral temporomandibular joint
M26.629	Arthralgia of temporomandibular joint, unspecified side
M54	Dorsalgia
M54.2	Cervicalgia
M54.4	Lumbago with sciatica
M54.40	Lumbago with sciatica, unspecified side
M54.41	Lumbago with sciatica, right side
M54.42	Lumbago with sciatica, left side
M54.5	Low back pain
M54.50	Low back pain, unspecified
M54.51	Vertebrogenic low back pain
M54.59	Other low back pain
M54.6	Pain in thoracic spine
M54.8	Other dorsalgia
M54.89	Other dorsalgia
M54.9	Dorsalgia, unspecified
M77.4	Metatarsalgia
M77.40	Metatarsalgia, unspecified foot
M77.41	Metatarsalgia, right foot
M77.42	Metatarsalgia, left foot
M79.1	Myalgia
M79.10	Myalgia, unspecified site
M79.11	Myalgia of mastication muscle
M79.12	Myalgia of auxiliary muscles, head and neck
M79.18	Myalgia, other site
M79.6	Pain in limb, hand, foot, fingers and toes
M79.60	Pain in limb, unspecified
M79.601	Pain in right arm
M79.602	Pain in left arm
M79.603	Pain in arm, unspecified
M79.604	Pain in right leg
M79.605	Pain in left leg
M79.606	Pain in leg, unspecified
M79.609	Pain in unspecified limb
M79.62	Pain in upper arm
M79.621	Pain in right upper arm
M79.622	Pain in left upper arm
M79.629	Pain in unspecified upper arm
M79.63	Pain in forearm
M79.631	Pain in right forearm
M79.632	Pain in left forearm
M79.639	Pain in unspecified forearm
M79.64	Pain in hand and fingers
M79.641	Pain in right hand
M79.642	Pain in left hand
M79.643	Pain in unspecified hand
M79.644	Pain in right finger(s)
M79.645	Pain in left finger(s)
M79.646	Pain in unspecified finger(s)
M79.65	Pain in thigh
M79.651	Pain in right thigh
M79.652	Pain in left thigh
M79.659	Pain in unspecified thigh
M79.66	Pain in lower leg
M79.661	Pain in right lower leg
M79.662	Pain in left lower leg
M79.669	Pain in unspecified lower leg
M79.67	Pain in foot and toes
M79.671	Pain in right foot
M79.672	Pain in left foot
M79.673	Pain in unspecified foot
M79.674	Pain in right toe(s)
M79.675	Pain in left toe(s)
M79.676	Pain in unspecified toe(s)
N23	Unspecified renal colic
N64.4	Mastodynia
N94	Pain and other conditions associated with female genital organs and menstrual cycle
N94.0	Mittelschmerz
N94.3	Premenstrual tension syndrome
N94.4	Primary dysmenorrhea
N94.5	Secondary dysmenorrhea
N94.6	Dysmenorrhea, unspecified
R07	Pain in throat and chest
R07.0	Pain in throat
R07.1	Chest pain on breathing
R07.2	Precordial pain
R07.81	Pleurodynia
R07.82	Intercostal pain
R07.89	Other chest pain
R07.9	Chest pain, unspecified
R10	Abdominal and pelvic pain
R10.0	Acute abdomen
R10.1	Pain localized to upper abdomen
R10.10	Upper abdominal pain, unspecified
R10.11	Right upper quadrant pain
R10.12	Left upper quadrant pain
R10.2	Pelvic and perineal pain
R10.3	Pain localized to other parts of lower abdomen
R10.30	Lower abdominal pain, unspecified
R10.31	Right lower quadrant pain
R10.32	Left lower quadrant pain
R10.33	Periumbilical pain
R10.8	Other abdominal pain
R10.83	Colic
R10.84	Generalized abdominal pain
R10.9	Unspecified abdominal pain
R51	Headache
R51.0	Headache with orthostatic component, not elsewhere classified
R51.9	Headache, unspecified
R52	Pain, unspecified
R68.84	Jaw pain
T82.84	Pain due to cardiac and vascular prosthetic devices, implants and grafts
T82.847	Pain due to cardiac prosthetic devices, implants and grafts
T82.847A	Pain due to cardiac prosthetic devices, implants and grafts, initial encounter
T82.847D	Pain due to cardiac prosthetic devices, implants and grafts, subsequent encounter
T82.848	Pain due to vascular prosthetic devices, implants and grafts
T82.848A	Pain due to vascular prosthetic devices, implants and grafts, initial encounter
T82.848D	Pain due to vascular prosthetic devices, implants and grafts, subsequent encounter
T83.84	Pain due to genitourinary prosthetic devices, implants and grafts
T83.84xA	Pain due to genitourinary prosthetic devices, implants and grafts, initial encounter
T83.84xD	Pain due to genitourinary prosthetic devices, implants and grafts, subsequent encounter
T84.84	Pain due to internal orthopedic prosthetic devices, implants and grafts
T84.84xA	Pain due to internal orthopedic prosthetic devices, implants and grafts, initial encounter
T84.84xD	Pain due to internal orthopedic prosthetic devices, implants and grafts, subsequent encounter
T85.84	Pain due to internal prosthetic devices, implants and grafts, not elsewhere classified
T85.840	Pain due to nervous system prosthetic devices, implants and grafts
T85.840A	Pain due to nervous system prosthetic devices, implants and grafts, initial encounter
T85.840D	Pain due to nervous system prosthetic devices, implants and grafts, subsequent encounter
T85.848	Pain due to other internal prosthetic devices, implants and grafts
T85.848A	Pain due to other internal prosthetic devices, implants and grafts, initial encounter
T85.848D	Pain due to other internal prosthetic devices, implants and grafts, subsequent encounter
Rheumatoid arthritis
M05	Rheumatoid arthritis with rheumatoid factor
M05.0	Felty's syndrome
M05.00	Felty's syndrome, unspecified site
M05.01	Felty's syndrome, shoulder
M05.011	Felty's syndrome, right shoulder
M05.012	Felty's syndrome, left shoulder
M05.019	Felty's syndrome, unspecified shoulder
M05.02	Felty's syndrome, elbow
M05.021	Felty's syndrome, right elbow
M05.022	Felty's syndrome, left elbow
M05.029	Felty's syndrome, unspecified elbow
M05.03	Felty's syndrome, wrist
M05.031	Felty's syndrome, right wrist
M05.032	Felty's syndrome, left wrist
M05.039	Felty's syndrome, unspecified wrist
M05.04	Felty's syndrome, hand
M05.041	Felty's syndrome, right hand
M05.042	Felty's syndrome, left hand
M05.049	Felty's syndrome, unspecified hand
M05.05	Felty's syndrome, hip
M05.051	Felty's syndrome, right hip
M05.052	Felty's syndrome, left hip
M05.059	Felty's syndrome, unspecified hip
M05.06	Felty's syndrome, knee
M05.061	Felty's syndrome, right knee
M05.062	Felty's syndrome, left knee
M05.069	Felty's syndrome, unspecified knee
M05.07	Felty's syndrome, ankle and foot
M05.071	Felty's syndrome, right ankle and foot
M05.072	Felty's syndrome, left ankle and foot
M05.079	Felty's syndrome, unspecified ankle and foot
M05.09	Felty's syndrome, multiple sites
M05.1	Rheumatoid lung disease with rheumatoid arthritis
M05.10	Rheumatoid lung disease with rheumatoid arthritis of unspecified site
M05.11	Rheumatoid lung disease with rheumatoid arthritis of shoulder
M05.111	Rheumatoid lung disease with rheumatoid arthritis of right shoulder
M05.112	Rheumatoid lung disease with rheumatoid arthritis of left shoulder
M05.119	Rheumatoid lung disease with rheumatoid arthritis of unspecified shoulder
M05.12	Rheumatoid lung disease with rheumatoid arthritis of elbow
M05.121	Rheumatoid lung disease with rheumatoid arthritis of right elbow
M05.122	Rheumatoid lung disease with rheumatoid arthritis of left elbow
M05.129	Rheumatoid lung disease with rheumatoid arthritis of unspecified elbow
M05.13	Rheumatoid lung disease with rheumatoid arthritis of wrist
M05.131	Rheumatoid lung disease with rheumatoid arthritis of right wrist
M05.132	Rheumatoid lung disease with rheumatoid arthritis of left wrist
M05.139	Rheumatoid lung disease with rheumatoid arthritis of unspecified wrist
M05.14	Rheumatoid lung disease with rheumatoid arthritis of hand
M05.141	Rheumatoid lung disease with rheumatoid arthritis of right hand
M05.142	Rheumatoid lung disease with rheumatoid arthritis of left hand
M05.149	Rheumatoid lung disease with rheumatoid arthritis of unspecified hand
M05.15	Rheumatoid lung disease with rheumatoid arthritis of hip
M05.151	Rheumatoid lung disease with rheumatoid arthritis of right hip
M05.152	Rheumatoid lung disease with rheumatoid arthritis of left hip
M05.159	Rheumatoid lung disease with rheumatoid arthritis of unspecified hip
M05.16	Rheumatoid lung disease with rheumatoid arthritis of knee
M05.161	Rheumatoid lung disease with rheumatoid arthritis of right knee
M05.162	Rheumatoid lung disease with rheumatoid arthritis of left knee
M05.169	Rheumatoid lung disease with rheumatoid arthritis of unspecified knee
M05.17	Rheumatoid lung disease with rheumatoid arthritis of ankle and foot
M05.171	Rheumatoid lung disease with rheumatoid arthritis of right ankle and foot
M05.172	Rheumatoid lung disease with rheumatoid arthritis of left ankle and foot
M05.179	Rheumatoid lung disease with rheumatoid arthritis of unspecified ankle and foot
M05.19	Rheumatoid lung disease with rheumatoid arthritis of multiple sites
M05.2	Rheumatoid vasculitis with rheumatoid arthritis
M05.20	Rheumatoid vasculitis with rheumatoid arthritis of unspecified site
M05.21	Rheumatoid vasculitis with rheumatoid arthritis of shoulder
M05.211	Rheumatoid vasculitis with rheumatoid arthritis of right shoulder
M05.212	Rheumatoid vasculitis with rheumatoid arthritis of left shoulder
M05.219	Rheumatoid vasculitis with rheumatoid arthritis of unspecified shoulder
M05.22	Rheumatoid vasculitis with rheumatoid arthritis of elbow
M05.221	Rheumatoid vasculitis with rheumatoid arthritis of right elbow
M05.222	Rheumatoid vasculitis with rheumatoid arthritis of left elbow
M05.229	Rheumatoid vasculitis with rheumatoid arthritis of unspecified elbow
M05.23	Rheumatoid vasculitis with rheumatoid arthritis of wrist
M05.231	Rheumatoid vasculitis with rheumatoid arthritis of right wrist
M05.232	Rheumatoid vasculitis with rheumatoid arthritis of left wrist
M05.239	Rheumatoid vasculitis with rheumatoid arthritis of unspecified wrist
M05.24	Rheumatoid vasculitis with rheumatoid arthritis of hand
M05.241	Rheumatoid vasculitis with rheumatoid arthritis of right hand
M05.242	Rheumatoid vasculitis with rheumatoid arthritis of left hand
M05.249	Rheumatoid vasculitis with rheumatoid arthritis of unspecified hand
M05.25	Rheumatoid vasculitis with rheumatoid arthritis of hip
M05.251	Rheumatoid vasculitis with rheumatoid arthritis of right hip
M05.252	Rheumatoid vasculitis with rheumatoid arthritis of left hip
M05.259	Rheumatoid vasculitis with rheumatoid arthritis of unspecified hip
M05.26	Rheumatoid vasculitis with rheumatoid arthritis of knee
M05.261	Rheumatoid vasculitis with rheumatoid arthritis of right knee
M05.262	Rheumatoid vasculitis with rheumatoid arthritis of left knee
M05.269	Rheumatoid vasculitis with rheumatoid arthritis of unspecified knee
M05.27	Rheumatoid vasculitis with rheumatoid arthritis of ankle and foot
M05.271	Rheumatoid vasculitis with rheumatoid arthritis of right ankle and foot
M05.272	Rheumatoid vasculitis with rheumatoid arthritis of left ankle and foot
M05.279	Rheumatoid vasculitis with rheumatoid arthritis of unspecified ankle and foot
M05.29	Rheumatoid vasculitis with rheumatoid arthritis of multiple sites
M05.3	Rheumatoid heart disease with rheumatoid arthritis
M05.30	Rheumatoid heart disease with rheumatoid arthritis of unspecified site
M05.31	Rheumatoid heart disease with rheumatoid arthritis of shoulder
M05.311	Rheumatoid heart disease with rheumatoid arthritis of right shoulder
M05.312	Rheumatoid heart disease with rheumatoid arthritis of left shoulder
M05.319	Rheumatoid heart disease with rheumatoid arthritis of unspecified shoulder
M05.32	Rheumatoid heart disease with rheumatoid arthritis of elbow
M05.321	Rheumatoid heart disease with rheumatoid arthritis of right elbow
M05.322	Rheumatoid heart disease with rheumatoid arthritis of left elbow
M05.329	Rheumatoid heart disease with rheumatoid arthritis of unspecified elbow
M05.33	Rheumatoid heart disease with rheumatoid arthritis of wrist
M05.331	Rheumatoid heart disease with rheumatoid arthritis of right wrist
M05.332	Rheumatoid heart disease with rheumatoid arthritis of left wrist
M05.339	Rheumatoid heart disease with rheumatoid arthritis of unspecified wrist
M05.34	Rheumatoid heart disease with rheumatoid arthritis of hand
M05.341	Rheumatoid heart disease with rheumatoid arthritis of right hand
M05.342	Rheumatoid heart disease with rheumatoid arthritis of left hand
M05.349	Rheumatoid heart disease with rheumatoid arthritis of unspecified hand
M05.35	Rheumatoid heart disease with rheumatoid arthritis of hip
M05.351	Rheumatoid heart disease with rheumatoid arthritis of right hip
M05.352	Rheumatoid heart disease with rheumatoid arthritis of left hip
M05.359	Rheumatoid heart disease with rheumatoid arthritis of unspecified hip
M05.36	Rheumatoid heart disease with rheumatoid arthritis of knee
M05.361	Rheumatoid heart disease with rheumatoid arthritis of right knee
M05.362	Rheumatoid heart disease with rheumatoid arthritis of left knee
M05.369	Rheumatoid heart disease with rheumatoid arthritis of unspecified knee
M05.37	Rheumatoid heart disease with rheumatoid arthritis of ankle and foot
M05.371	Rheumatoid heart disease with rheumatoid arthritis of right ankle and foot
M05.372	Rheumatoid heart disease with rheumatoid arthritis of left ankle and foot
M05.379	Rheumatoid heart disease with rheumatoid arthritis of unspecified ankle and foot
M05.39	Rheumatoid heart disease with rheumatoid arthritis of multiple sites
M05.4	Rheumatoid myopathy with rheumatoid arthritis
M05.40	Rheumatoid myopathy with rheumatoid arthritis of unspecified site
M05.41	Rheumatoid myopathy with rheumatoid arthritis of shoulder
M05.411	Rheumatoid myopathy with rheumatoid arthritis of right shoulder
M05.412	Rheumatoid myopathy with rheumatoid arthritis of left shoulder
M05.419	Rheumatoid myopathy with rheumatoid arthritis of unspecified shoulder
M05.42	Rheumatoid myopathy with rheumatoid arthritis of elbow
M05.421	Rheumatoid myopathy with rheumatoid arthritis of right elbow
M05.422	Rheumatoid myopathy with rheumatoid arthritis of left elbow
M05.429	Rheumatoid myopathy with rheumatoid arthritis of unspecified elbow
M05.43	Rheumatoid myopathy with rheumatoid arthritis of wrist
M05.431	Rheumatoid myopathy with rheumatoid arthritis of right wrist
M05.432	Rheumatoid myopathy with rheumatoid arthritis of left wrist
M05.439	Rheumatoid myopathy with rheumatoid arthritis of unspecified wrist
M05.44	Rheumatoid myopathy with rheumatoid arthritis of hand
M05.441	Rheumatoid myopathy with rheumatoid arthritis of right hand
M05.442	Rheumatoid myopathy with rheumatoid arthritis of left hand
M05.449	Rheumatoid myopathy with rheumatoid arthritis of unspecified hand
M05.45	Rheumatoid myopathy with rheumatoid arthritis of hip
M05.451	Rheumatoid myopathy with rheumatoid arthritis of right hip
M05.452	Rheumatoid myopathy with rheumatoid arthritis of left hip
M05.459	Rheumatoid myopathy with rheumatoid arthritis of unspecified hip
M05.46	Rheumatoid myopathy with rheumatoid arthritis of knee
M05.461	Rheumatoid myopathy with rheumatoid arthritis of right knee
M05.462	Rheumatoid myopathy with rheumatoid arthritis of left knee
M05.469	Rheumatoid myopathy with rheumatoid arthritis of unspecified knee
M05.47	Rheumatoid myopathy with rheumatoid arthritis of ankle and foot
M05.471	Rheumatoid myopathy with rheumatoid arthritis of right ankle and foot
M05.472	Rheumatoid myopathy with rheumatoid arthritis of left ankle and foot
M05.479	Rheumatoid myopathy with rheumatoid arthritis of unspecified ankle and foot
M05.49	Rheumatoid myopathy with rheumatoid arthritis of multiple sites
M05.5	Rheumatoid polyneuropathy with rheumatoid arthritis
M05.50	Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified site
M05.51	Rheumatoid polyneuropathy with rheumatoid arthritis of shoulder
M05.511	Rheumatoid polyneuropathy with rheumatoid arthritis of right shoulder
M05.512	Rheumatoid polyneuropathy with rheumatoid arthritis of left shoulder
M05.519	Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified shoulder
M05.52	Rheumatoid polyneuropathy with rheumatoid arthritis of elbow
M05.521	Rheumatoid polyneuropathy with rheumatoid arthritis of right elbow
M05.522	Rheumatoid polyneuropathy with rheumatoid arthritis of left elbow
M05.529	Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified elbow
M05.53	Rheumatoid polyneuropathy with rheumatoid arthritis of wrist
M05.531	Rheumatoid polyneuropathy with rheumatoid arthritis of right wrist
M05.532	Rheumatoid polyneuropathy with rheumatoid arthritis of left wrist
M05.539	Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified wrist
M05.54	Rheumatoid polyneuropathy with rheumatoid arthritis of hand
M05.541	Rheumatoid polyneuropathy with rheumatoid arthritis of right hand
M05.542	Rheumatoid polyneuropathy with rheumatoid arthritis of left hand
M05.549	Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified hand
M05.55	Rheumatoid polyneuropathy with rheumatoid arthritis of hip
M05.551	Rheumatoid polyneuropathy with rheumatoid arthritis of right hip
M05.552	Rheumatoid polyneuropathy with rheumatoid arthritis of left hip
M05.559	Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified hip
M05.56	Rheumatoid polyneuropathy with rheumatoid arthritis of knee
M05.561	Rheumatoid polyneuropathy with rheumatoid arthritis of right knee
M05.562	Rheumatoid polyneuropathy with rheumatoid arthritis of left knee
M05.569	Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified knee
M05.57	Rheumatoid polyneuropathy with rheumatoid arthritis of ankle and foot
M05.571	Rheumatoid polyneuropathy with rheumatoid arthritis of right ankle and foot
M05.572	Rheumatoid polyneuropathy with rheumatoid arthritis of left ankle and foot
M05.579	Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified ankle and foot
M05.59	Rheumatoid polyneuropathy with rheumatoid arthritis of multiple sites
M05.6	Rheumatoid arthritis with involvement of other organs and systems
M05.60	Rheumatoid arthritis of unspecified site with involvement of other organs and systems
M05.61	Rheumatoid arthritis of shoulder with involvement of other organs and systems
M05.611	Rheumatoid arthritis of right shoulder with involvement of other organs and systems
M05.612	Rheumatoid arthritis of left shoulder with involvement of other organs and systems
M05.619	Rheumatoid arthritis of unspecified shoulder with involvement of other organs and systems
M05.62	Rheumatoid arthritis of elbow with involvement of other organs and systems
M05.621	Rheumatoid arthritis of right elbow with involvement of other organs and systems
M05.622	Rheumatoid arthritis of left elbow with involvement of other organs and systems
M05.629	Rheumatoid arthritis of unspecified elbow with involvement of other organs and systems
M05.63	Rheumatoid arthritis of wrist with involvement of other organs and systems
M05.631	Rheumatoid arthritis of right wrist with involvement of other organs and systems
M05.632	Rheumatoid arthritis of left wrist with involvement of other organs and systems
M05.639	Rheumatoid arthritis of unspecified wrist with involvement of other organs and systems
M05.64	Rheumatoid arthritis of hand with involvement of other organs and systems
M05.641	Rheumatoid arthritis of right hand with involvement of other organs and systems
M05.642	Rheumatoid arthritis of left hand with involvement of other organs and systems
M05.649	Rheumatoid arthritis of unspecified hand with involvement of other organs and systems
M05.65	Rheumatoid arthritis of hip with involvement of other organs and systems
M05.651	Rheumatoid arthritis of right hip with involvement of other organs and systems
M05.652	Rheumatoid arthritis of left hip with involvement of other organs and systems
M05.659	Rheumatoid arthritis of unspecified hip with involvement of other organs and systems
M05.66	Rheumatoid arthritis of knee with involvement of other organs and systems
M05.661	Rheumatoid arthritis of right knee with involvement of other organs and systems
M05.662	Rheumatoid arthritis of left knee with involvement of other organs and systems
M05.669	Rheumatoid arthritis of unspecified knee with involvement of other organs and systems
M05.67	Rheumatoid arthritis of ankle and foot with involvement of other organs and systems
M05.671	Rheumatoid arthritis of right ankle and foot with involvement of other organs and systems
M05.672	Rheumatoid arthritis of left ankle and foot with involvement of other organs and systems
M05.679	Rheumatoid arthritis of unspecified ankle and foot with involvement of other organs and systems
M05.69	Rheumatoid arthritis of multiple sites with involvement of other organs and systems
M05.7	Rheumatoid arthritis with rheumatoid factor without organ or systems involvement
M05.70	Rheumatoid arthritis with rheumatoid factor of unspecified site without organ or systems involvement
M05.71	Rheumatoid arthritis with rheumatoid factor of shoulder without organ or systems involvement
M05.711	Rheumatoid arthritis with rheumatoid factor of right shoulder without organ or systems involvement
M05.712	Rheumatoid arthritis with rheumatoid factor of left shoulder without organ or systems involvement
M05.719	Rheumatoid arthritis with rheumatoid factor of unspecified shoulder without organ or systems involvement
M05.72	Rheumatoid arthritis with rheumatoid factor of elbow without organ or systems involvement
M05.721	Rheumatoid arthritis with rheumatoid factor of right elbow without organ or systems involvement
M05.722	Rheumatoid arthritis with rheumatoid factor of left elbow without organ or systems involvement
M05.729	Rheumatoid arthritis with rheumatoid factor of unspecified elbow without organ or systems involvement
M05.73	Rheumatoid arthritis with rheumatoid factor of wrist without organ or systems involvement
M05.731	Rheumatoid arthritis with rheumatoid factor of right wrist without organ or systems involvement
M05.732	Rheumatoid arthritis with rheumatoid factor of left wrist without organ or systems involvement
M05.739	Rheumatoid arthritis with rheumatoid factor of unspecified wrist without organ or systems involvement
M05.74	Rheumatoid arthritis with rheumatoid factor of hand without organ or systems involvement
M05.741	Rheumatoid arthritis with rheumatoid factor of right hand without organ or systems involvement
M05.742	Rheumatoid arthritis with rheumatoid factor of left hand without organ or systems involvement
M05.749	Rheumatoid arthritis with rheumatoid factor of unspecified hand without organ or systems involvement
M05.75	Rheumatoid arthritis with rheumatoid factor of hip without organ or systems involvement
M05.751	Rheumatoid arthritis with rheumatoid factor of right hip without organ or systems involvement
M05.752	Rheumatoid arthritis with rheumatoid factor of left hip without organ or systems involvement
M05.759	Rheumatoid arthritis with rheumatoid factor of unspecified hip without organ or systems involvement
M05.76	Rheumatoid arthritis with rheumatoid factor of knee without organ or systems involvement
M05.761	Rheumatoid arthritis with rheumatoid factor of right knee without organ or systems involvement
M05.762	Rheumatoid arthritis with rheumatoid factor of left knee without organ or systems involvement
M05.769	Rheumatoid arthritis with rheumatoid factor of unspecified knee without organ or systems involvement
M05.77	Rheumatoid arthritis with rheumatoid factor of ankle and foot without organ or systems involvement
M05.771	Rheumatoid arthritis with rheumatoid factor of right ankle and foot without organ or systems involvement
M05.772	Rheumatoid arthritis with rheumatoid factor of left ankle and foot without organ or systems involvement
M05.779	Rheumatoid arthritis with rheumatoid factor of unspecified ankle and foot without organ or systems involvement
M05.79	Rheumatoid arthritis with rheumatoid factor of multiple sites without organ or systems involvement
M05.7A	Rheumatoid arthritis with rheumatoid factor of other specified site without organ or systems involvement
M05.8	Other rheumatoid arthritis with rheumatoid factor
M05.80	Other rheumatoid arthritis with rheumatoid factor of unspecified site
M05.81	Other rheumatoid arthritis with rheumatoid factor of shoulder
M05.811	Other rheumatoid arthritis with rheumatoid factor of right shoulder
M05.812	Other rheumatoid arthritis with rheumatoid factor of left shoulder
M05.819	Other rheumatoid arthritis with rheumatoid factor of unspecified shoulder
M05.82	Other rheumatoid arthritis with rheumatoid factor of elbow
M05.821	Other rheumatoid arthritis with rheumatoid factor of right elbow
M05.822	Other rheumatoid arthritis with rheumatoid factor of left elbow
M05.829	Other rheumatoid arthritis with rheumatoid factor of unspecified elbow
M05.83	Other rheumatoid arthritis with rheumatoid factor of wrist
M05.831	Other rheumatoid arthritis with rheumatoid factor of right wrist
M05.832	Other rheumatoid arthritis with rheumatoid factor of left wrist
M05.839	Other rheumatoid arthritis with rheumatoid factor of unspecified wrist
M05.84	Other rheumatoid arthritis with rheumatoid factor of hand
M05.841	Other rheumatoid arthritis with rheumatoid factor of right hand
M05.842	Other rheumatoid arthritis with rheumatoid factor of left hand
M05.849	Other rheumatoid arthritis with rheumatoid factor of unspecified hand
M05.85	Other rheumatoid arthritis with rheumatoid factor of hip
M05.851	Other rheumatoid arthritis with rheumatoid factor of right hip
M05.852	Other rheumatoid arthritis with rheumatoid factor of left hip
M05.859	Other rheumatoid arthritis with rheumatoid factor of unspecified hip
M05.86	Other rheumatoid arthritis with rheumatoid factor of knee
M05.861	Other rheumatoid arthritis with rheumatoid factor of right knee
M05.862	Other rheumatoid arthritis with rheumatoid factor of left knee
M05.869	Other rheumatoid arthritis with rheumatoid factor of unspecified knee
M05.87	Other rheumatoid arthritis with rheumatoid factor of ankle and foot
M05.871	Other rheumatoid arthritis with rheumatoid factor of right ankle and foot
M05.872	Other rheumatoid arthritis with rheumatoid factor of left ankle and foot
M05.879	Other rheumatoid arthritis with rheumatoid factor of unspecified ankle and foot
M05.89	Other rheumatoid arthritis with rheumatoid factor of multiple sites
M05.8A	Other rheumatoid arthritis with rheumatoid factor of other specified site
M05.9	Rheumatoid arthritis with rheumatoid factor, unspecified
M06	Other rheumatoid arthritis
M06.0	Rheumatoid arthritis without rheumatoid factor
M06.00	Rheumatoid arthritis without rheumatoid factor, unspecified site
M06.01	Rheumatoid arthritis without rheumatoid factor, shoulder
M06.011	Rheumatoid arthritis without rheumatoid factor, right shoulder
M06.012	Rheumatoid arthritis without rheumatoid factor, left shoulder
M06.019	Rheumatoid arthritis without rheumatoid factor, unspecified shoulder
M06.02	Rheumatoid arthritis without rheumatoid factor, elbow
M06.021	Rheumatoid arthritis without rheumatoid factor, right elbow
M06.022	Rheumatoid arthritis without rheumatoid factor, left elbow
M06.029	Rheumatoid arthritis without rheumatoid factor, unspecified elbow
M06.03	Rheumatoid arthritis without rheumatoid factor, wrist
M06.031	Rheumatoid arthritis without rheumatoid factor, right wrist
M06.032	Rheumatoid arthritis without rheumatoid factor, left wrist
M06.039	Rheumatoid arthritis without rheumatoid factor, unspecified wrist
M06.04	Rheumatoid arthritis without rheumatoid factor, hand
M06.041	Rheumatoid arthritis without rheumatoid factor, right hand
M06.042	Rheumatoid arthritis without rheumatoid factor, left hand
M06.049	Rheumatoid arthritis without rheumatoid factor, unspecified hand
M06.05	Rheumatoid arthritis without rheumatoid factor, hip
M06.051	Rheumatoid arthritis without rheumatoid factor, right hip
M06.052	Rheumatoid arthritis without rheumatoid factor, left hip
M06.059	Rheumatoid arthritis without rheumatoid factor, unspecified hip
M06.06	Rheumatoid arthritis without rheumatoid factor, knee
M06.061	Rheumatoid arthritis without rheumatoid factor, right knee
M06.062	Rheumatoid arthritis without rheumatoid factor, left knee
M06.069	Rheumatoid arthritis without rheumatoid factor, unspecified knee
M06.07	Rheumatoid arthritis without rheumatoid factor, ankle and foot
M06.071	Rheumatoid arthritis without rheumatoid factor, right ankle and foot
M06.072	Rheumatoid arthritis without rheumatoid factor, left ankle and foot
M06.079	Rheumatoid arthritis without rheumatoid factor, unspecified ankle and foot
M06.08	Rheumatoid arthritis without rheumatoid factor, vertebrae
M06.09	Rheumatoid arthritis without rheumatoid factor, multiple sites
M06.0A	Rheumatoid arthritis without rheumatoid factor, other specified site
M06.8	Other specified rheumatoid arthritis
M06.80	Other specified rheumatoid arthritis, unspecified site
M06.81	Other specified rheumatoid arthritis, shoulder
M06.811	Other specified rheumatoid arthritis, right shoulder
M06.812	Other specified rheumatoid arthritis, left shoulder
M06.819	Other specified rheumatoid arthritis, unspecified shoulder
M06.82	Other specified rheumatoid arthritis, elbow
M06.821	Other specified rheumatoid arthritis, right elbow
M06.822	Other specified rheumatoid arthritis, left elbow
M06.829	Other specified rheumatoid arthritis, unspecified elbow
M06.83	Other specified rheumatoid arthritis, wrist
M06.831	Other specified rheumatoid arthritis, right wrist
M06.832	Other specified rheumatoid arthritis, left wrist
M06.839	Other specified rheumatoid arthritis, unspecified wrist
M06.84	Other specified rheumatoid arthritis, hand
M06.841	Other specified rheumatoid arthritis, right hand
M06.842	Other specified rheumatoid arthritis, left hand
M06.849	Other specified rheumatoid arthritis, unspecified hand
M06.85	Other specified rheumatoid arthritis, hip
M06.851	Other specified rheumatoid arthritis, right hip
M06.852	Other specified rheumatoid arthritis, left hip
M06.859	Other specified rheumatoid arthritis, unspecified hip
M06.86	Other specified rheumatoid arthritis, knee
M06.861	Other specified rheumatoid arthritis, right knee
M06.862	Other specified rheumatoid arthritis, left knee
M06.869	Other specified rheumatoid arthritis, unspecified knee
M06.87	Other specified rheumatoid arthritis, ankle and foot
M06.871	Other specified rheumatoid arthritis, right ankle and foot
M06.872	Other specified rheumatoid arthritis, left ankle and foot
M06.879	Other specified rheumatoid arthritis, unspecified ankle and foot
M06.88	Other specified rheumatoid arthritis, vertebrae
M06.89	Other specified rheumatoid arthritis, multiple sites
M06.8A	Other specified rheumatoid arthritis, other specified site
M06.9	Rheumatoid arthritis, unspecified
Thrombosis prevention after PCI
Z98.61	Coronary angioplasty status
Transient cerebral ischemia
G45.8	Other transient cerebral ischemic attacks and related syndromes
G45.9	Transient cerebral ischemic attack, unspecified
Unstable angina pectoris
I20.0	Unstable angina
I20.2	Refractory angina pectoris
I25.110	Atherosclerotic heart disease of native coronary artery with unstable angina pectoris
I25.112	Atherosclerotic heart disease of native coronary artery with refractory angina pectoris
I25.700	Atherosclerosis of coronary artery bypass graft(s), unspecified, with unstable angina pectoris
I25.702	Atherosclerosis of coronary artery bypass graft(s), unspecified, with refractory angina pectoris
I25.710	Atherosclerosis of autologous vein coronary artery bypass graft(s) with unstable angina pectoris
I25.712	Atherosclerosis of autologous vein coronary artery bypass graft(s) with refractory angina pectoris
I25.720	Atherosclerosis of autologous artery coronary artery bypass graft(s) with unstable angina pectoris
I25.722	Atherosclerosis of autologous artery coronary artery bypass graft(s) with refractory angina pectoris
I25.730	Atherosclerosis of nonautologous biological coronary artery bypass graft(s) with unstable angina pectoris
I25.732	Atherosclerosis of nonautologous biological coronary artery bypass graft(s) with refractory angina pectoris
I25.750	Atherosclerosis of native coronary artery of transplanted heart with unstable angina
I25.752	Atherosclerosis of native coronary artery of transplanted heart with refractory angina pectoris
I25.760	Atherosclerosis of bypass graft of coronary artery of transplanted heart with unstable angina
I25.762	Atherosclerosis of bypass graft of coronary artery of transplanted heart with refractory angina pectoris
I25.790	Atherosclerosis of other coronary artery bypass graft(s) with unstable angina pectoris
I25.792	Atherosclerosis of other coronary artery bypass graft(s) with refractory angina pectoris