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Drug overview for DURLAZA (aspirin):
Generic name: ASPIRIN (AS-pir-in)
Drug class: Non-Steroidal Anti-Inflammatory (NSAID) and Salicylates
Therapeutic class: Hematological Agents
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.)
Generic name: ASPIRIN (AS-pir-in)
Drug class: Non-Steroidal Anti-Inflammatory (NSAID) and Salicylates
Therapeutic class: Hematological Agents
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
DURLAZA ER 162.5 MG CAPSULE
The following indications for DURLAZA (aspirin) have been approved by the FDA:
Indications:
Cerebral thromboembolism prevention
Myocardial infarction prevention
Myocardial reinfarction prevention
Prevention of transient ischemic attack
Professional Synonyms:
Acute MI prophylaxis
Acute myocardial infarction prophylaxis
AMI prophylaxis
Cardiac infarct prophylaxis
Cardiac infarction prophylaxis
MI prophylaxis
Myocardial infarct prophylaxis
Myocardial infarction prophylaxis
Myocardial reinfarction prophylaxis
Stroke thromboembolism prophylaxis
TIA prophylaxis
TIAs prophylaxis
Transient ischemic attack prophylaxis
Indications:
Cerebral thromboembolism prevention
Myocardial infarction prevention
Myocardial reinfarction prevention
Prevention of transient ischemic attack
Professional Synonyms:
Acute MI prophylaxis
Acute myocardial infarction prophylaxis
AMI prophylaxis
Cardiac infarct prophylaxis
Cardiac infarction prophylaxis
MI prophylaxis
Myocardial infarct prophylaxis
Myocardial infarction prophylaxis
Myocardial reinfarction prophylaxis
Stroke thromboembolism prophylaxis
TIA prophylaxis
TIAs prophylaxis
Transient ischemic attack prophylaxis
The following dosing information is available for DURLAZA (aspirin):
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.
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.
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.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| DURLAZA ER 162.5 MG CAPSULE | Maintenance | Adults take 1 capsule (162.5 mg) by oral route once daily at the same time each day |
No generic dosing information available.
The following drug interaction information is available for DURLAZA (aspirin):
There are 1 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 |
|---|---|
| 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 |
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 2025-2026, FLUMIST HOME 2025-2026 |
| 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 24 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, 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, SACUBITRIL-VALSARTAN, 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 |
| 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, 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Obinutuzumab/Anticoagulants; Antiplatelets SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Severe and life-threatening thrombocytopenia has been reported during obinutuzumab therapy.(1) Anticoagulants and antiplatelets may have an additive risk of bleeding. CLINICAL EFFECTS: Concurrent use of obinutuzumab with anticoagulants or antiplatelet agents may result in additive or synergistic effects, including fatal and non-fatal 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: Monitor all patients frequently for thrombocytopenia and signs of bleeding. Consider withholding concomitant anticoagulants and antiplatelets, especially during the first cycle of obinutuzumab.(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 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: Obinutuzumab with chemotherapy has been reported to cause severe and life-threatening thrombocytopenia. Fatal hemorrhagic events have occurred in patients with NHL and CLL during obinutuzumab therapy, including during Cycle 1.(1) |
GAZYVA |
The following contraindication information is available for DURLAZA (aspirin):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 5 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Aspirin exacerbated respiratory disease |
| Gastrointestinal hemorrhage |
| Hemolytic anemia from pyruvate kinase and g6PD deficiencies |
| Hemorrhage |
| 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 DURLAZA (aspirin):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
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 |
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 DURLAZA (aspirin):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
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 prioritized warning is available for DURLAZA (aspirin):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for DURLAZA (aspirin)'s list of indications:
| Cerebral thromboembolism prevention | |
| Z86.73 | Personal history of transient ischemic attack (TIa), and cerebral infarction without residual deficits |
| 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 |
Formulary Reference Tool