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Drug overview for DISALCID (salsalate):
Generic name: SALSALATE (SAL-suh-late)
Drug class: Non-Steroidal Anti-Inflammatory (NSAID) and Salicylates
Therapeutic class: Analgesic, Anti-inflammatory or Antipyretic
Salsalate, a prototypical nonsteroidal anti-inflammatory agent (NSAIA), is the salicylate ester of salicylic acid; in vivo, the drug hydrolyzes to 2 molecules of salicylate.
Salsalate is used for anti-inflammatory and analgesic effects in the symptomatic treatment of rheumatoid arthritis, osteoarthritis, and related inflammatory conditions. There are few controlled comparative studies of salsalate and aspirin, but the anti-inflammatory and analgesic effects of salsalate are generally considered to be comparable to those of aspirin. In one study, the anti-inflammatory and analgesic effects of salsalate (1 g 3 times daily) in the treatment of rheumatoid arthritis were about equal to those of indomethacin (25 mg 3 times daily).
Further comparative studies of salsalate in the treatment of rheumatoid arthritis or osteoarthritis are needed to determine the relative efficacy of the drug. Salsalate may be particularly useful in patients with GI intolerance to aspirin or in patients in whom interference with normal platelet function by aspirin or other NSAIAs is considered undesirable. There is insufficient evidence that salsalate has antipyretic activity. Since salsalate does not inhibit platelet aggregation, the drug should not be substituted for aspirin in the prophylaxis of thrombosis.
Generic name: SALSALATE (SAL-suh-late)
Drug class: Non-Steroidal Anti-Inflammatory (NSAID) and Salicylates
Therapeutic class: Analgesic, Anti-inflammatory or Antipyretic
Salsalate, a prototypical nonsteroidal anti-inflammatory agent (NSAIA), is the salicylate ester of salicylic acid; in vivo, the drug hydrolyzes to 2 molecules of salicylate.
Salsalate is used for anti-inflammatory and analgesic effects in the symptomatic treatment of rheumatoid arthritis, osteoarthritis, and related inflammatory conditions. There are few controlled comparative studies of salsalate and aspirin, but the anti-inflammatory and analgesic effects of salsalate are generally considered to be comparable to those of aspirin. In one study, the anti-inflammatory and analgesic effects of salsalate (1 g 3 times daily) in the treatment of rheumatoid arthritis were about equal to those of indomethacin (25 mg 3 times daily).
Further comparative studies of salsalate in the treatment of rheumatoid arthritis or osteoarthritis are needed to determine the relative efficacy of the drug. Salsalate may be particularly useful in patients with GI intolerance to aspirin or in patients in whom interference with normal platelet function by aspirin or other NSAIAs is considered undesirable. There is insufficient evidence that salsalate has antipyretic activity. Since salsalate does not inhibit platelet aggregation, the drug should not be substituted for aspirin in the prophylaxis of thrombosis.
DRUG IMAGES
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The following indications for DISALCID (salsalate) have been approved by the FDA:
Indications:
Osteoarthritis
Rheumatoid arthritis
Professional Synonyms:
Arthritis deformans
Arthrosis deformans
Degenerative arthritis
Degenerative joint disease
Degenerative polyarthritis
Hypertrophic arthritis
Nodose rheumatism
Osteoarthrosis
Rheumatic arthritis
Rheumatic gout
Indications:
Osteoarthritis
Rheumatoid arthritis
Professional Synonyms:
Arthritis deformans
Arthrosis deformans
Degenerative arthritis
Degenerative joint disease
Degenerative polyarthritis
Hypertrophic arthritis
Nodose rheumatism
Osteoarthrosis
Rheumatic arthritis
Rheumatic gout
The following dosing information is available for DISALCID (salsalate):
For the symptomatic treatment of rheumatoid arthritis, osteoarthritis, or related inflammatory conditions, the usual initial adult dosage of salsalate is 3 g daily, given in 2 or 3 divided doses. Dosage should be adjusted according to the patient's response, tolerance, and serum salicylate concentration. The usual maintenance dosage of salsalate is 2-4 g daily.
Salsalate is administered orally. The drug should usually be administered with food or a large quantity (240 mL) of water or milk.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| DISALCID 500 MG TABLET | Maintenance | Adults take 1 tablet (500 mg) by oral route 2 times per day |
| DISALCID 750 MG TABLET | Maintenance | Adults take 2 tablets (1,500 mg) by oral route 2 times per day |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| SALSALATE 750 MG TABLET | Maintenance | Adults take 2 tablets (1,500 mg) by oral route 2 times per day |
| SALSALATE 500 MG TABLET | Maintenance | Adults take 1 tablet (500 mg) by oral route 2 times per day |
The following drug interaction information is available for DISALCID (salsalate):
There are 4 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Ketorolac (Non-Injection)/NSAID; Aspirin (Greater Than 300 mg); Salicylates SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Possible additive or synergistic side effects.(1,2) CLINICAL EFFECTS: Concurrent use of multiple doses of ketorolac with other non-steroidal anti-inflammatory agents (NSAIDs), salicylates or aspirin may result in an increase in NSAID-related side effects such as bleeding or renal impairment.(1-3) PREDISPOSING FACTORS: Patients with pre-existing renal impairment may be at an increased risk of adverse effects from this interaction. The risk for bleeding episodes may be greater in patients with multiple disease-associated factors (e.g. thrombocytopenia, advanced liver disease). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g., anticoagulants, antiplatelets, corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Risk of GI bleed may be increased in patients who are of older age, in poor health status, or who use alcohol or smoke. Risk may also be increased with longer duration of NSAID use and prior history of peptic ulcer disease and/or GI bleeding. PATIENT MANAGEMENT: Manufacturers of ketorolac state that concurrent use of ketorolac with either other NSAIDs or aspirin is contraindicated.(1,2) If concurrent therapy is deemed medically necessary, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Conduct periodic monitoring of renal function, especially in patients with renal impairment. Instruct patients to report any signs and symptoms of bleeding, such as unusual bruising; red or black, tarry stools; acute abdominal or joint pain and/or swelling. DISCUSSION: Based upon similar pharmacodynamic effects and potentially cumulative risks of serious NSAID-related adverse events, manufacturers of ketorolac state the concurrent administration of ketorolac with other NSAIDs or aspirin is contraindicated.(1,2) |
KETOROLAC TROMETHAMINE, SPRIX |
| Ketorolac (Injectable)/NSAIDs; Aspirin (Greater Than 300 mg); Salicylates SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Possible additive or synergistic side effects.(1) CLINICAL EFFECTS: Concurrent use of multiple doses of ketorolac with other non-steroidal anti-inflammatory agents (NSAIDs), salicylates or aspirin may result in an increase in NSAID-related side effects such as bleeding or renal impairment.(1-3) PREDISPOSING FACTORS: Patients with pre-existing renal impairment may be at an increased risk of adverse effects from this interaction. The risk for bleeding episodes may be greater in patients with multiple disease-associated factors (e.g. thrombocytopenia, advanced liver disease). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g., anticoagulants, antiplatelets, corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Risk of GI bleed may be increased in patients who are of older age, in poor health status, or who use alcohol or smoke. Risk may also be increased with longer duration of NSAID use and prior history of peptic ulcer disease and/or GI bleeding. PATIENT MANAGEMENT: The manufacturer of ketorolac states that concurrent use of ketorolac with either other NSAIDs, salicylates or aspirin is contraindicated.(1) If concurrent therapy is deemed medically necessary, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: Manufacturers of ketorolac state that concurrent use of ketorolac with either other NSAIDs, salicylates or aspirin is contraindicated.(1,2) If concurrent therapy is deemed medically necessary, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Conduct periodic monitoring of renal function, especially in patients with renal impairment. |
BUPIVACAINE-KETOROLAC-KETAMINE, KETOROLAC TROMETHAMINE, R.E.C.K.(ROPIV-EPI-CLON-KETOR), ROPIVACAINE-CLONIDINE-KETOROLC, ROPIVACAINE-KETOROLAC-KETAMINE, TORONOVA II SUIK, TORONOVA SUIK |
| Dichlorphenamide/Aspirin (Greater Than 325 mg); Salicylates SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Dichlorphenamide 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 dichlorphenamide 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 |
| Selected Nephrotoxic Agents/Bacitracin 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: Bacitracin may cause renal failure due to glomerular and tubular necrosis. Concurrent administration of other nephrotoxic agents may result in additive renal toxicity.(1-3) CLINICAL EFFECTS: Concurrent use of bacitracin with other potentially nephrotoxic agents may result in renal toxicity.(1-3) PREDISPOSING FACTORS: Dehydration and high-dose bacitracin may predispose to adverse renal effects.(1) PATIENT MANAGEMENT: Health Canada states that bacitracin is contraindicated in patients with renal impairment, including those taking other nephrotoxic drugs.(1) The Canadian and US manufacturers of bacitracin state that concomitant use of bacitracin with other potentially nephrotoxic agents should be avoided.(2,3) DISCUSSION: Renal impairment is a major toxicity of bacitracin. Cases of nephrotoxicity have been reported when bacitracin was used off-label.(1-3) |
BACITRACIN, BACITRACIN MICRONIZED, BACITRACIN ZINC |
There are 12 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 |
|---|---|
| Methotrexate (low strength injection, oral)/Select Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. 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 salicylates 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 salicylates and low dose 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 in patients with renal impairment or near the time of methotrexate dosage (in patients receiving weekly therapy). 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 not linked to this interaction. Other lower-strength aspirin formulations (e.g. headache, cough & cold, opioid combinations) which could be consumed multiple times a day remain linked to this interaction. |
JYLAMVO, METHOTREXATE, OTREXUP, RASUVO, TREXALL, XATMEP |
| Selected Immunosuppressants/NSAIDs; Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Cyclosporine increases the production of prostaglandin E2 and I2. Prostaglandin E2 has been shown to prevent cyclosporine -induced renal toxicity in animals. NSAIDS and salicylates may increase cyclosporine-induced renal toxicity by blocking the formation of prostaglandins. Concurrent use of everolimus, sirolimus or tacrolimus with NSAIDs or salicylates may result in additive nephrotoxicity. CLINICAL EFFECTS: Concurrent administration of cyclosporine, everolimus, sirolimus, or tacrolimus and a NSAID or salicylate may result in a decrease in renal function, with or without an alteration in immunosuppressant levels. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If possible, avoid the concurrent use of NSAIDs or salicylates in patients maintained on cyclosporine, everolimus, sirolimus, or tacrolimus. If concurrent therapy is warranted, patients should be monitored for a decrease in renal function. The NSAID or salicylate may need to be discontinued. DISCUSSION: A decrease in renal function has been reported with concurrent cyclosporine and diclofenac, sulindac, mefenamic acid, ketoprofen, piroxicam, and naproxen. Decreasing the cyclosporine dose without discontinuing the NSAID does not appear to improve renal function. The use of agents which decrease renal function concurrently with everolimus, sirolimus or tacrolimus should be approached with caution. An observational study of 63 inpatient encounters for 57 transplant patients evaluated concurrent use between calcineurin inhibitor (CNI) therapy and NSAID use. Patients were matched to 126 transplant patients on CNI therapy without NSAID use. Patients who received at least one dose of NSAID had a 12.2% rate of treatment emergent acute kidney injury (AKI). The relative risk ratio for AKI in patient exposed to NSAID therapy was 2.20 (95% CI 0.74-6.54). An increase in 48 hour post NSAID exposure serum creatinine above baseline was documented in 65.9% of patients compared to 46% in the non NSAID group (p=0.016). Multivariate analysis revealed changes in serum creatinine at 48 hours after admission were independently associated with age (p=0.008) and NSAID use (p=0.026).(12) |
AFINITOR, AFINITOR DISPERZ, ASTAGRAF XL, CYCLOSPORINE, CYCLOSPORINE MODIFIED, ENVARSUS XR, EVEROLIMUS, FYARRO, GENGRAF, NEORAL, PROGRAF, SANDIMMUNE, SIROLIMUS, TACROLIMUS, TACROLIMUS XL, TORPENZ, ZORTRESS |
| Selected Anticoagulants (Vit K antagonists)/NSAIDs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. Some NSAIDs may displace anticoagulants from plasma protein binding sites. NSAIDs also have the potential to produce gastrointestinal ulceration and bleeding. Some NSAIDs may impair platelet function and prolong bleeding times. CLINICAL EFFECTS: Concurrent use of anticoagulants and NSAIDs may increase the risk for bleeding. PREDISPOSING FACTORS: Bleeding risk may be increased in patients with renal impairment and in patients older than 75 years. 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., other anticoagulants, antiplatelets, corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Risk of GI bleed may be increased in patients who are of older age, in poor health status, or who use alcohol or smoke. Risk may also be increased with longer duration of NSAID use and prior history of peptic ulcer disease and/or GI bleeding. PATIENT MANAGEMENT: If concurrent therapy with anticoagulants and NSAIDs is warranted, patients should be closely monitored 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: The effects of NSAIDs on the hypoprothrombinemic response to anticoagulants appears to vary between patients as well as with different NSAIDs. Documentation is frequently contradictory - while studies have shown several NSAIDs to have no effect on the pharmacokinetics of warfarin, case reports have documented increased effects with and without bleeding when these same NSAIDs were administered concurrently with warfarin. While celecoxib has been shown not to affect platelet aggregation or bleeding times and had no effects on the anticoagulant effect of warfarin in healthy subjects, increased prothrombin times and bleeding episodes, some of which were fatal, have been reported, predominantly in the elderly, in patients receiving concurrent therapy with celecoxib and warfarin. Rofecoxib has been shown to increase prothrombin times in subjects who received concurrent warfarin therapy. A post hoc analysis of nonselective NSAIDs in the RE-LY study (compared dabigatran 150 and 110 mg twice daily with warfarin in atrial fibrillation) assessed clinical outcomes by comparing nonselective NSAID use (at least once during trial) with no NSAID use in 2279 patients. The use of NSAIDs was associated an increased risk of major bleeding (hazard ratio (HR) 1.68), gastrointestinal major bleeding (HR 1.81), stroke or systemic embolism (HR 1.50), and hospitalization (HR 1.64).(22) 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 sulindac resulted in a ratio of rate ratios (RR) (95% CI) of 3.7 (1.79-7.62); warfarin and etodolac ratio of RR 2.61 (1.6-4.25); warfarin and ibuprofen ratio of RR 1.94 (1.5-2.5); warfarin and naproxen ratio of RR 1.72 (1.35-2.19); warfarin and indomethacin ratio of RR 1.62 (1.03-2.55); warfarin and diclofenac ratio of RR 1.43 (1.07-1.92; warfarin and celecoxib ratio of RR 1.24 (1.02-1.53); and warfarin and meloxicam ratio of RR 1.23 (1.02-1.47).(23) 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. 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 8 of those studies found a higher rate of clinically significant bleeding in patients on warfarin and NSAIDs (OR=1.83; 95% CI 1.29-2.59). Increased bleeding risk was seen in subgroup analyses with non-selective NSAIDs (OR=1.86; 95% CI 1.10-3.17) and COX-2 inhibitors (OR=1.81; 95% CI 1.3-2.52).(24) If concurrent therapy with anticoagulants and NSAIDs is warranted, it would be prudent to monitor patients closely for increased anticoagulant effects. |
ANISINDIONE, DICUMAROL, JANTOVEN, WARFARIN SODIUM |
| Influenza Virus Vaccine Live/Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Use of salicylates during influenza infection has been associated with Reye's Syndrome.(1,2) CLINICAL EFFECTS: Use of the live influenza virus vaccine in children and adolescents (patients age 2-17 years) receiving salicylate therapy may increase the risk of Reye's Syndrome.(1,2) Symptoms of Reye's syndrome include drowsiness, confusion, seizures, coma. In severe cases, Reye's syndrome can result in death. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The use of live influenza virus vaccine in children and adolescents (patients age 2-17 years) receiving salicylate therapy is contraindicated.(1,2) Use of salicylates should be avoided for 4 weeks after administration of live influenza vaccine.(1) DISCUSSION: Because the use of salicylates during influenza infection has been associated with Reye's Syndrome, the use of live influenza virus vaccine in children and adolescents (patients age 2-17 years) receiving salicylate therapy is contraindicated.(1,2) |
FLUMIST TRIVALENT 2024-2025 |
| Selected Platelet Aggregation Inhibitors/NSAIDs; Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Abciximab, cangrelor, cilostazol, clopidogrel, dipyridamole, eptifibatide, prasugrel, ticagrelor, vorapaxar and NSAIDs or salicylates inhibit platelet aggregation. CLINICAL EFFECTS: Concurrent use of platelet aggregation inhibitors and NSAIDs or salicylates may increase the risk of 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, other antiplatelets, corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Risk of GI bleed may be increased in patients who are of older age, in poor health status, or who use alcohol or smoke. Risk may also be increased with longer duration of NSAID use and prior history of peptic ulcer disease and/or GI bleeding. Risk increases as the number of risk factors increases. PATIENT MANAGEMENT: Use caution when administering platelet aggregation inhibitors with NSAIDs or salicylates.(1-5) It would be prudent to monitor patients more closely during concurrent therapy and to use the lowest NSAID or salicylate dose possible. If concurrent therapy is warranted, monitor patients 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 2010 ACCF/ACG/AHA Consensus guidelines recommend the use of proton pump inhibitors (PPIs) in patients with multiple risk factors for GI bleeding who require antiplatelet therapy. However, esomeprazole and omeprazole should be avoided with clopidogrel as they are expected to reduce the effectiveness of clopidogrel. Use of other PPIs should be approached with caution, as they may reduce the effectiveness of clopidogrel. DISCUSSION: Because of the increased risk of bleeding, caution is warranted when using this combination. 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. |
ASPIRIN-DIPYRIDAMOLE ER, BRILINTA, CILOSTAZOL, CLOPIDOGREL, CLOPIDOGREL BISULFATE, DIPYRIDAMOLE, EFFIENT, EPTIFIBATIDE, KENGREAL, PLAVIX, PRASUGREL HCL, TICAGRELOR, ZONTIVITY |
| Colistimethate/Selected Nephrotoxic Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Colistimethate can cause nephrotoxicity.(1,2) Concurrent administration of other nephrotoxic agents may result in an increased risk of nephrotoxicity.(1) It is suspected that cephalothin interferes with the excretion of colistimethate resulting in enhanced nephrotoxicity.(2,3) CLINICAL EFFECTS: Concurrent use of colistimethate with other nephrotoxic agents may result in additive nephrotoxic effects. PREDISPOSING FACTORS: Factors predisposing to nephrotoxicity include higher cumulative doses of colistimethate, longer treatment duration, hypovolemia, and critical illness. PATIENT MANAGEMENT: Concurrent use of potentially nephrotoxic agents with colistimethate should be avoided.(1,2) If concurrent use is necessary, it should be undertaken with great caution.(1) DISCUSSION: In a case control study of 42 patients on intravenous colistimethate sodium, NSAIDs were identified as an independent risk factor for nephrotoxicity (OR 40.105, p=0.044).(4) In 4 case reports, patients developed elevated serum creatinine and blood urea nitrogen following concurrent colistimethate and cephalothin (3 patients) or when colistimethate followed cephalothin therapy (1 patient).(3) A literature review found that individual nephrotoxic agents, including aminoglycosides, vancomycin, amphotericin, IV contrast, diuretics, ACE inhibitors, ARBs, NSAIDs, and calcineurin inhibitors, were not consistently associated with additive nephrotoxicity when used with colistimethate. However, when multiple agents (at least 2 additional potential nephrotoxins) were used concurrently, there was a significant correlation to colistimethate nephrotoxicity.(5) |
COLISTIMETHATE, COLISTIMETHATE SODIUM, COLY-MYCIN M PARENTERAL |
| 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 |
| Dabigatran/NSAIDs; Salicylates 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 and/or other clotting factors increased bleeding episodes can occur.(1,2) CLINICAL EFFECTS: Concurrent use of dabigatran with NSAIDs or salicylates may result in additive or synergistic effects resulting in unwanted bleeding episodes.(1) PREDISPOSING FACTORS: Factors associated with an increased risk for bleeding include renal impairment, concomitant use of P-glycoprotein inhibitors, patient older than 74 years, coexisting conditions (e.g. recent trauma, thrombocytopenia, advanced liver disease), use of drugs associated with bleeding risk (e.g. other anticoagulants, antiplatelets, corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs)), and patient weight less than 50 kg. (1-3) Risk of GI bleed may be increased in patients who are of older age, in poor health status, who use alcohol or smoke, with longer duration of NSAID use, and with prior history of peptic ulcer disease and/or GI bleeding. PATIENT MANAGEMENT: Monitor patients receiving concurrent therapy for signs of blood loss and promptly evaluate patients with any symptoms. Discontinue dabigatran in patients with active pathological 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 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: 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) A post hoc analysis of nonselective NSAIDs in the RE-LY study (compared dabigatran 150 and 110 mg twice daily with warfarin in atrial fibrillation) assessed clinical outcomes by comparing nonselective NSAID use (at least once during trial) with no NSAID use in 2279 patients. The use of NSAIDs was associated an increased risk of major bleeding (hazard ratio (HR) 1.68), gastrointestinal major bleeding (HR 1.81), stroke or systemic embolism (HR 1.50), and hospitalization (HR 1.64).(22) |
DABIGATRAN ETEXILATE, PRADAXA |
| Apixaban; Betrixaban; Edoxaban; Rivaroxaban/NSAIDs; Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of apixaban(1-4), betrixaban(7), edoxaban(5), or rivaroxaban(6) and nonsteroidal antiinflammatory agents (NSAIDs) or salicylates may result in additive increased risk of bleeding. CLINICAL EFFECTS: Concurrent use of apixaban(1), betrixaban(7), edoxaban(5), or rivaroxaban(2) with NSAIDs or salicylates may result in unwanted bleeding episodes. PREDISPOSING FACTORS: Bleeding risk may be increased in patients with renal impairment and in patients older than 75 years. 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., other anticoagulants, antiplatelets, corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Risk of GI bleed may be increased in patients who are of older age, in poor health status, or who use alcohol or smoke. Risk may also be increased with longer duration of NSAID use and prior history of peptic ulcer disease and/or GI bleeding. PATIENT MANAGEMENT: Approach concurrent therapy with apixaban(1-4), betrixaban(7), edoxaban(5), or rivaroxaban(6) with caution. 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: In a study, naproxen (500 mg) increased apixaban (10 mg) area-under-curve (AUC) and maximum concentration (Cmax) by 1.5-fold an 1.6-fold, respectively, with corresponding increases in clotting tests. There were no changes in the effect of naproxen on arachidonic acid-induced platelet aggregation, no clinically relevant changes in bleeding times, or naproxen pharmacokinetics.(1) In a single dose study, there were no pharmacokinetic or pharmacodynamic interactions between rivaroxaban and naproxen.(6) Although effects seen in the above studies were limited, NSAIDs are known to increase bleeding and may further increase the risk of bleeding with these agents.(1-6) In edoxaban clinical studies, concomitant use of low-dose aspirin (less than or equal to 100 mg/day) or thienopyridines, and NSAIDs was permitted and resulted in increased rates of clinically relevant bleeding.(5) In a study of 34 healthy subjects administered edoxaban 60 mg daily and naproxen 500 mg daily, bleeding time increased by 2.08-fold from baseline on the combination, compared to a 1.23-fold increase with naproxen alone and 1.7-fold increase on edoxaban alone.(8) 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 ibuprofen resulted in a ratio of rate ratios (RR) (95% CI) of 5.16 (3.0-8.85); apixaban and celecoxib ratio of RR 1.8 (1.06-3.06); rivaroxaban and etodolac ratio of RR 2.47 (1.18-4.22); rivaroxaban and naproxen ratio of RR 1.89 (1.12-1.43); and rivaroxaban and ibuprofen ratio of RR 1.68 (1.29-4.44).(9) |
ELIQUIS, RIVAROXABAN, SAVAYSA, XARELTO |
| Methotrexate (Oncology-Injection)/Selected Salicylates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. 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 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 in patients with renal impairment or near the time of methotrexate dosage (in patients receiving weekly therapy). 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 not linked to this interaction. Other lower-strength aspirin formulations (e.g. headache, cough & cold, opioid combinations) which could be consumed multiple times a day remain linked to this interaction. |
METHOTREXATE, METHOTREXATE SODIUM |
| 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 23 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 |
|---|---|
| Heparin/Selected Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Additive prolongation of bleeding time. CLINICAL EFFECTS: Increased risk of bleeding which may extend for several days beyond discontinuation of salicylates. 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. If this combination is used, monitor patients 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. A non-acetylated salicylate may be used to avoid antiplatelet activity. 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. Single ingredient aspirin or buffered aspirin products with strengths < or = 325 mg and combination aspirin products which are used to treat cardiovascular disease (e.g. aspirin+statins, aspirin+dipyridamole) are not included in this interaction. DISCUSSION: This interaction is likely to occur. |
ARIXTRA, ELMIRON, ENOXAPARIN SODIUM, ENOXILUV, FONDAPARINUX SODIUM, FRAGMIN, HEPARIN SODIUM, HEPARIN SODIUM IN 0.45% NACL, HEPARIN SODIUM-0.45% NACL, HEPARIN SODIUM-0.9% NACL, HEPARIN SODIUM-D5W, LOVENOX, PENTOSAN POLYSULFATE SODIUM |
| Uricosurics/Aspirin (Greater Than 100 mg); Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Not clearly established. Protein binding displacement is a possibility. CLINICAL EFFECTS: May observe hyperuricemia and gout resulting from reduced uricosuric response. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid chronic, moderate to high doses of salicylates. DISCUSSION: This interaction is well documented. Occasional small doses of salicylates do not appear to inhibit the action of uricosurics. |
DUZALLO, PROBENECID, PROBENECID-COLCHICINE |
| NSAIDs; Salicylates/Loop Diuretics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: During concurrent administration of a loop diuretic and a nonsteroidal anti-inflammatory drug (NSAID), patients may retain sodium as a result of NSAID-induced prostaglandin inhibition. CLINICAL EFFECTS: The pharmacological effects of loop diuretics may be decreased due to reduced antihypertensive and diuretic actions. Concurrent use of NSAIDs with loop diuretics and renin-angiotensin system (RAS) inhibitors may result in increased risk of acute kidney injury (AKI). PREDISPOSING FACTORS: Low water intake/dehydration, drug sensitivity, greater than 75 years of age, and renal impairment may increase an individuals susceptibility to AKI. PATIENT MANAGEMENT: Monitor patients for a decrease in the effects of the loop diuretic. It may be necessary to administer a higher dose of the diuretic or an alternative anti-inflammatory agent. Concurrent use of NSAIDs with loop diuretics and RAS inhibitors should be used with caution and monitored closely for signs of AKI. DISCUSSION: In a computational study, the risk of AKI using triple therapy with a diuretic, RAS inhibitor, and NSAID was assessed. The study found the following factors may increase an individual's susceptibility to AKI: low water intake, drug sensitivity, greater than 75 years of age, and renal impairment.(19,20) In an observational study, current use of a triple therapy with a diuretic, RAS inhibitor, and NSAID, was associated with an increased rate of acute kidney injury (rate ratio (RR) 1.31, 95% confidence interval (CI) 1.12-1.53). The highest risk of AKI associated with triple therapy were observed in the first 30 days of use (RR 1.82, CI 1.35-2.46). (21) Administration of indomethacin alone has been reported to decrease sodium excretion and increase blood pressure. In patients receiving a loop diuretic (e.g., bumetanide, furosemide), these effects interfere with clinical management. Several NSAIDs have been shown to interact with loop diuretics interfering with the pharmacological effects of the diuretic. In volunteers on sodium restricted diets, ibuprofen and indomethacin inhibited furosemide diuresis. |
BUMETANIDE, EDECRIN, ETHACRYNATE SODIUM, ETHACRYNIC ACID, FUROSCIX, FUROSEMIDE, FUROSEMIDE-0.9% NACL, LASIX, SOAANZ, TORSEMIDE |
| Antidiabetics, Oral/Aspirin (Greater Than 100 mg); Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Complex. Salicylates appear to have intrinsic glucose lowering properties via several proposed mechanisms. Also, salicylates may cause protein binding displacement of antidiabetics. Decreased renal clearance may also occur. CLINICAL EFFECTS: Potentiation of hypoglycemic effects may be observed. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Hypoglycemic signs and blood glucose levels should be monitored. Adjust the antidiabetic dose as needed. Particular caution should be taken when salicylates are started or stopped in patients previously stabilized on antidiabetics. DISCUSSION: Additional documentation is necessary to confirm this potential interaction. |
DUETACT, GLIMEPIRIDE, GLIPIZIDE, GLIPIZIDE ER, GLIPIZIDE XL, GLIPIZIDE-METFORMIN, GLUCOTROL XL, GLYBURIDE, GLYBURIDE MICRONIZED, GLYBURIDE-METFORMIN HCL, NATEGLINIDE, PIOGLITAZONE-GLIMEPIRIDE |
| NSAIDs; Salicylates/Lithium SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Decreased renal excretion of lithium, possibly resulting from NSAID-induced prostaglandin inhibition. CLINICAL EFFECTS: May observe increased lithium toxicity. PREDISPOSING FACTORS: Risk factors for lithium toxicity include: renal impairment or worsening of existing renal disease, dehydration, low sodium diet, and concomitant use of multiple medications which may impair renal elimination of lithium (e.g. ARBs, ACE Inhibitors, NSAIDs, diuretics). Patients who require higher therapeutic lithium levels to maintain symptom control are particularly susceptible to these factors. PATIENT MANAGEMENT: The magnitude of this interaction is highly variable. Patients with predisposing factors, e.g. dehydration, renal impairment, or concurrent use of other agents which may impair lithium elimination, are expected to have a higher risk for lithium toxicity. If both drugs are administered, monitor plasma lithium levels and observe the patient for signs and symptoms of lithium toxicity or changes in renal function. Full effects of the addition or an increase in NSAID dose may not be seen for one to two weeks. Adjust the dose of lithium accordingly. If lithium is to be started in a patient stabilized on chronic NSAID therapy, consider starting with a lower lithium dose and titrate slowly as half-life may be prolonged. Monitor lithium concentrations until stabilized on the combination. Counsel the patient to contact their prescriber before starting an OTC NSAID. Assure that patients are familiar with signs and symptoms of lithium toxicity (e.g. new or worsening tremor, nausea/vomiting, diarrhea, ataxia, or altered mental status) and to report signs and symptoms of toxicity. DISCUSSION: Numerous studies and case reports have been documented that administration of a NSAID to a patient stabilized on lithium therapy may result in increased serum lithium levels and possible toxicity. Full effects may take 1 to 2 weeks to develop and may persist for a week after the NSAID is discontinued. |
LITHIUM CARBONATE, LITHIUM CARBONATE ER, LITHIUM CITRATE, LITHIUM CITRATE TETRAHYDRATE, LITHOBID |
| Angiotensin II Receptor Blocker (ARB)/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Angiotensin II receptor blockers (ARBs) can cause vasodilation of the efferent renal arteriole which may result in decreased glomerular filtration rate. NSAIDs inhibit prostaglandin synthesis which can lead to afferent arteriolar vasoconstriction and may negate any decrease in blood pressure. CLINICAL EFFECTS: Concurrent use of ARBs with NSAIDs may result in decreased antihypertensive effects. In patients with existing renal impairment, the use of these agents together may also result in further deterioration of renal clearance caused by renal hypoperfusion. Concurrent use of ARBs with NSAIDs and diuretics may result in increased risk of acute kidney injury (AKI). PREDISPOSING FACTORS: Low water intake/dehydration, drug sensitivity, greater than 75 years of age, and use of diuretics can lead to hypovolemia and increased risk of AKI. PATIENT MANAGEMENT: Patients maintained on ARBs should be monitored for a loss of blood pressure control and a change in renal function if an NSAID is added to their regimen. Patients receiving concurrent therapy may require higher doses of ARBs. If blood pressure control cannot be achieved or if the patient's renal function deteriorates, the NSAID may need to be discontinued. Patients should be monitored for hypotension if NSAIDs are withdrawn from concurrent ARB therapy. Concurrent use of ARBs with NSAIDs and diuretics should be used with caution and monitored for signs of AKI. DISCUSSION: In a computational study, the risk of AKI using triple therapy with a diuretic, renin-angiotensin system (RAS) inhibitor, and NSAID was assessed. The study found the following factors may increase an individual's susceptibility to AKI: low water intake, drug sensitivity, greater than 75 years of age, and renal impairment.(22,23) In an observational study, current use of a triple therapy combination was associated with an increased rate of acute kidney injury (rate ratio (RR) 1.31, 95% confidence interval (CI) 1.12-1.53). The highest risk of AKI associated with triple therapy were observed in the first 30 days of use (RR 1.82, CI 1.35-2.46).(24) In a population based cohort study, the concurrent use of NSAIDs with renin-angiotensin system (RAS) inhibitors in 5,710 hypertensive patients stabilized on antihypertensive therapy required hypertension treatment intensification. Adjusted hazard ratios (HR) for hypertension treatment intensification were 1.34 [95% CI 1.05-1.71] for NSAIDs in general, 1.79 (95% CI 1.15-2.78) for diclofenac and 2.02 (95% CI 1.09-3.77) for piroxicam. There were significant interactions between NSAIDs and angiotensin converting enzyme inhibitors (ACE inhibitors; HR 4.09, 95% CI 2.02-8.27) or angiotensin receptor blockers (ARBs; HR 3.62, 95% CI 1.80-7.31), but not with other antihypertensive drugs. |
AMLODIPINE-OLMESARTAN, AMLODIPINE-VALSARTAN, AMLODIPINE-VALSARTAN-HCTZ, ARBLI, ATACAND, ATACAND HCT, AVALIDE, AVAPRO, AZOR, BENICAR, BENICAR HCT, CANDESARTAN CILEXETIL, CANDESARTAN-HYDROCHLOROTHIAZID, COZAAR, DIOVAN, DIOVAN HCT, EDARBI, EDARBYCLOR, ENTRESTO, ENTRESTO SPRINKLE, EPROSARTAN MESYLATE, EXFORGE, EXFORGE HCT, HYZAAR, IRBESARTAN, IRBESARTAN-HYDROCHLOROTHIAZIDE, LOSARTAN POTASSIUM, LOSARTAN-HYDROCHLOROTHIAZIDE, MICARDIS, MICARDIS HCT, OLMESARTAN MEDOXOMIL, OLMESARTAN-AMLODIPINE-HCTZ, OLMESARTAN-HYDROCHLOROTHIAZIDE, TELMISARTAN, TELMISARTAN-AMLODIPINE, TELMISARTAN-HYDROCHLOROTHIAZID, TRIBENZOR, VALSARTAN, VALSARTAN-HYDROCHLOROTHIAZIDE |
| NSAIDs; Aspirin (Non-Cardioprotective)/Beta-Blockers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unknown; however, possibly related to inhibition of prostaglandin by NSAIDs. CLINICAL EFFECTS: The antihypertensive action of beta-blockers may be decreased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor patient's blood pressure and adjust the dose of the beta-blocker as needed. DISCUSSION: Concurrent administration of beta-blockers and NSAIDs has been associated with a clinically significant loss in antihypertensive response. The magnitude of the effect of NSAIDs on control of blood pressure by beta-blockers needs to be determined for each anti-inflammatory agent. 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. |
ACEBUTOLOL HCL, ATENOLOL, ATENOLOL-CHLORTHALIDONE, BETAPACE, BETAPACE AF, BETAXOLOL HCL, BISOPROLOL FUMARATE, BISOPROLOL-HYDROCHLOROTHIAZIDE, BREVIBLOC, BYSTOLIC, CARVEDILOL, CARVEDILOL ER, COREG, COREG CR, CORGARD, ESMOLOL HCL, ESMOLOL HCL-SODIUM CHLORIDE, ESMOLOL HCL-WATER, HEMANGEOL, INDERAL LA, INDERAL XL, INNOPRAN XL, LABETALOL HCL, LABETALOL HCL-WATER, NADOLOL, NEBIVOLOL HCL, PINDOLOL, PROPRANOLOL HCL, PROPRANOLOL HCL ER, PROPRANOLOL-HYDROCHLOROTHIAZID, RAPIBLYK, SOTALOL, SOTALOL AF, SOTALOL HCL, SOTYLIZE, TENORETIC 100, TENORETIC 50, TENORMIN, TIMOLOL MALEATE |
| Acetazolamide; Methazolamide/Aspirin (Greater Than 100 mg); Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Acetazolamide and methazolamide may reduce blood pH, causing a shift of salicylates from plasma into tissues (eg, central nervous system). Alternatively, toxicity may be due to salicylate-induced displacement of the carbonic anhydrase inhibitor from its protein binding sites and inhibition of renal tubular secretion. CLINICAL EFFECTS: An increase in the pharmacologic effects of salicylates with possible toxicity may occur. PREDISPOSING FACTORS: High doses of salicylates, low body weight. PATIENT MANAGEMENT: Avoid the combination if possible. If it is necessary to administer these drugs concurrently, monitor salicylate levels and monitor the patient for symptoms of toxicity. Adjust the dose as needed. DISCUSSION: Two young patients with unimpaired renal and hepatic function were found to have developed metabolic acidosis after treatment for glaucoma and joint pain with a combination of salicylates and carbonic anhydrase inhibitors in normal doses.(1) A 67-year old woman and a 75-year old woman taking carbonic anhydrase inhibitors for therapy of glaucoma and high doses of aspirin for arthritis developed severe acid-base imbalance and salicylate intoxication.(2) Neither patient exhibited ill effects when taking high aspirin doses without a carbonic anhydrase inhibitor. Carbonic anhydrase inhibitor-induced acidemia increases the risk of developing salicylate intoxication in patients receiving high aspirin doses. Two elderly patients, who were chronically receiving aspirin developed lethargy, incontinence, and confusion after dosing with acetazolamide.(3) These effects could have been due to either drug (see mechanism). |
ACETAZOLAMIDE, ACETAZOLAMIDE ER, ACETAZOLAMIDE SODIUM, METHAZOLAMIDE |
| Triamterene; Amiloride/Selected NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown; however, nonsteroidal anti-inflammatory (NSAID) inhibition of prostaglandins may allow triamterene or amiloride- induced nephrotoxicity or hyperkalemia to occur in some patients. CLINICAL EFFECTS: Possible renal failure or hyperkalemia. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: When possible, avoid concurrent therapy with triamterene or amiloride with NSAIDs. If these agents are used concurrently, monitor renal function and serum electrolytes. If decreased renal function or hyperkalemia develops, discontinue both agents. DISCUSSION: Although acute renal failure and hyperkalemia have only been reported in studies and case reports involving indomethacin, diclofenac, flurbiprofen, and ibuprofen with either triamterene or amiloride, the proposed mechanism suggests that all nonsteroidal anti-inflammatory agents may be capable of this interaction. Patients receiving diuretics are at an increased risk of NSAID-induced renal failure. |
AMILORIDE HCL, AMILORIDE-HYDROCHLOROTHIAZIDE, DYRENIUM, TRIAMTERENE, TRIAMTERENE-HYDROCHLOROTHIAZID |
| Valproic Acid/Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Multiple mechanisms appear to be involved. Salicylates may displace valproic acid from plasma protein binding sites. Salicylates may also affect the metabolism of valproate by increasing conjugation and decreasing oxidation of valproic acid. CLINICAL EFFECTS: Concurrent use of salicylates may increase the unbound fraction of serum valproic acid concentration, resulting in toxicity. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving concurrent salicylate therapy should be observed for signs of valproic acid toxicity (e.g., ataxia, drowsiness, nystagmus, tremor). The dosage of valproic acid may need to be adjusted. DISCUSSION: In two studies involving 6 epileptic children taking valproic acid, concurrent aspirin led to an increase in serum valproic acid free fraction and an increased half-life. Renal clearance of free valproic acid was found to decrease.(1,2) In another study involving 5 children, concurrent valproic acid and aspirin resulted in a decrease in free valproic acid clearance although total valproic acid levels did not change significantly.(3) However, one study reported that the concurrent use of valproic acid and aspirin leads to an increased excretion of valproic acid and a decreased total salicylate excretion.(4) In 3 case reports, aspirin given to children taking valproic acid resulted in valproic acid toxicity (tremor, nystagmus, truncal ataxia). There was an increase in free valproic acid levels in two cases, however, a reduction in the free fraction and the total valproic acid levels occurred in the third patient.(5) In another case report, a patient was maintained on divalproex sodium (2500 mg/day) and aspirin (325 mg/day) with a trough valproate level of 24.7 ng/ml and a total valproate level of 64.0 ng/ml. Five days after aspirin was discontinued for a procedure, trough valproate levels fell to 3.9 ng/ml and a total valproate level fell to 36.0 ng/ml with no change in divalproex dosing.(6) In a study in 7 healthy males, concurrent diflunisal (250 mg twice daily) increased the unbound fraction of valproic acid (200 mg twice daily) by 20%. The area-under-curve (AUC) of 3-oxo-valproic acid increased by 35%. There were no effects on diflunisal levels.(7) |
DEPAKOTE, DEPAKOTE ER, DEPAKOTE SPRINKLE, DIVALPROEX SODIUM, DIVALPROEX SODIUM ER, SODIUM VALPROATE, VALPROATE SODIUM, VALPROIC ACID |
| Selected Nephrotoxic Agents/Cisplatin SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The nephrotoxic effects of aminoglycosides or non-steroidal anti-inflammatory drugs (NSAIDs) may be additive to those of cisplatin. CLINICAL EFFECTS: The concurrent administration of amikacin, gentamicin, tobramycin, or NSAIDs with cisplatin may result in additive nephrotoxic effects.(1,2,5,6) PREDISPOSING FACTORS: Pre-existing renal insufficiency, advanced age, dehydration may increase the risk of nephrotoxicity.(1,5,6) PATIENT MANAGEMENT: The US labeling for aminoglycosides and cisplatin states that the concurrent use of aminoglycosides and cisplatin should be avoided.(1,3,4,6) Inform patients that concurrent cisplatin and aminoglycosides or NSAIDs can cause nephrotoxicity and that renal function and electrolyte monitoring during treatment is necessary.(2) DISCUSSION: The US manufacturers of amikacin, gentamicin and tobramycin state that since the nephrotoxic effects of these medications may be additive, avoid concurrent or sequential use of other neurotoxic and/or nephrotoxic agents including cisplatin.(1,3,6) |
CISPLATIN, KEMOPLAT |
| Drospirenone/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Drospirenone has antimineralocorticoid activity and may cause hyperkalemia. NSAIDs may also increase potassium levels.(1) CLINICAL EFFECTS: Concurrent use of drospirenone and NSAIDs may result in hyperkalemia.(1) PREDISPOSING FACTORS: Renal insufficiency, hepatic dysfunction, adrenal insufficiency, and use of potassium supplements, ACE inhibitors, angiotensin II receptor antagonists, heparin, and potassium-sparing diuretics may increase potassium levels.(1) PATIENT MANAGEMENT: Patients receiving drospirenone with a NSAID should have their serum potassium level checked during the first treatment cycle.(1) DISCUSSION: Drospirenone has antimineralocorticoid activity comparable to 25 mg of spironolactone and may result in hyperkalemia. Concurrent use of NSAIDs may also increase potassium levels.(1) Occasional or chronic use of NSAIDs was not restricted in clinical trials of drospirenone.(1) |
ANGELIQ, BEYAZ, DROSPIRENONE-ETH ESTRA-LEVOMEF, DROSPIRENONE-ETHINYL ESTRADIOL, JASMIEL, LO-ZUMANDIMINE, LORYNA, NEXTSTELLIS, NIKKI, OCELLA, SAFYRAL, SLYND, SYEDA, VESTURA, YASMIN 28, YAZ, ZARAH, ZUMANDIMINE |
| 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 |
| Aldosterone Receptor Antagonists/NSAIDs; Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown; however, nonsteroidal anti-inflammatory (NSAID) inhibition of prostaglandins may allow eplerenone, finerenone, or spironolactone-induced nephrotoxicity or hyperkalemia to occur in some patients.(1-3) In some patients, NSAIDs may reduce the diuretic, natriuretic and antihypertensive effects of eplerenone, finerenone, or spironolactone.(1-3) CLINICAL EFFECTS: Concurrent use of eplerenone, finerenone, or spironolactone with NSAIDs may result in renal failure or hyperkalemia. The effects of the diuretic, natriuretic, or antihypertensive effects of eplerenone, finerenone, or spironolactone may be decreased.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: When possible, avoid concurrent therapy with eplerenone, finerenone, or spironolactone with NSAIDs. If these agents are used concurrently, monitor renal function and serum electrolytes. If decreased renal function or hyperkalemia develops, discontinue both agents. The manufacturer of eplerenone recommends checking serum potassium and serum creatinine within 3-7 days of concurrent therapy with NSAIDs.(1) The manufacturer of spironolactone states concurrent use with NSAIDs may lead to severe hyperkalemia and extreme caution should be used during concurrent therapy.(2) DISCUSSION: Although acute renal failure and hyperkalemia have only been reported in studies and case reports involving indomethacin, diclofenac, flurbiprofen, and ibuprofen with either triamterene or amiloride, the proposed mechanism suggests that all nonsteroidal anti-inflammatory agents may be capable of this interaction with all potassium-sparing diuretics. Patients receiving diuretics are at an increased risk of NSAID-induced renal failure. |
ALDACTONE, CAROSPIR, EPLERENONE, INSPRA, KERENDIA, SPIRONOLACTONE, SPIRONOLACTONE-HCTZ |
| 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 |
| ACE Inhibitors/Acemetacin; Proglumetacin; Salsalate 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 an ACE inhibitor, whose hypotensive effects may be related to the increase in hypotensive prostaglandins, may negate any decrease in blood pressure. CLINICAL EFFECTS: Concurrent use of ACE inhibitors 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 ACE inhibitors 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 ACE inhibitors. 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 ACE inhibitor 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. 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 |
| 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; Aspirin (Non-Cardioprotective)/Metoprolol SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unknown; however, possibly related to inhibition of prostaglandin by NSAIDs. CLINICAL EFFECTS: The antihypertensive action of metoprolol may be decreased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor patient's blood pressure and adjust the dose of metoprolol as needed. DISCUSSION: Concurrent administration of metoprolol and NSAIDs has been associated with a clinically significant loss in antihypertensive response. The magnitude of the effect of NSAIDs on control of blood pressure by beta-blockers needs to be determined for each anti-inflammatory agent. 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. |
KAPSPARGO SPRINKLE, LOPRESSOR, METOPROLOL SUCCINATE, METOPROLOL TARTRATE, METOPROLOL-HYDROCHLOROTHIAZIDE, TOPROL XL |
| 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 |
The following contraindication information is available for DISALCID (salsalate):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 7 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Aspirin exacerbated respiratory disease |
| Gastrointestinal hemorrhage |
| Hemolytic anemia from pyruvate kinase and g6PD deficiencies |
| Hemophilia |
| Increased risk of bleeding due to coagulation disorder |
| Lactation |
| Pregnancy |
There are 8 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Gastritis |
| Gastroesophageal reflux disease |
| Gastrointestinal ulcer |
| Hypoprothrombinemia |
| Increased risk of bleeding |
| Nasal polyp |
| Thrombotic thrombocytopenic purpura |
| Vitamin K deficiency |
There are 7 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Anemia |
| Diabetes mellitus |
| Disease of liver |
| Edema |
| Kidney disease with reduction in glomerular filtration rate (GFr) |
| Severe hepatic disease |
| Thyrotoxicosis |
The following adverse reaction information is available for DISALCID (salsalate):
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 24 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Tinnitus |
Gastrointestinal ulcer Hypertension |
| Rare/Very Rare |
|---|
|
Acute myocardial infarction Anaphylaxis Anemia Angioedema Bronchospastic pulmonary disease Cerebrovascular accident Chronic heart failure Edema Gastrointestinal hemorrhage Gastrointestinal perforation Hepatitis Hypotension Interstitial nephritis Kidney disease with reduction in glomerular filtration rate (GFr) Renal failure Renal papillary necrosis Stevens-johnson syndrome Thrombocytopenic disorder Thrombotic disorder Toxic epidermal necrolysis Urticaria |
There are 6 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Hearing loss Nausea Skin rash Vertigo |
None. |
| Rare/Very Rare |
|---|
|
Abnormal hepatic function tests Diarrhea |
The following precautions are available for DISALCID (salsalate):
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 DISALCID (salsalate):
WARNING: Nonsteroidal anti-inflammatory drugs (including salsalate) may rarely increase the risk for a heart attack or stroke. This effect does not apply to low-dose aspirin. (See Drug Interactions section.) This effect can happen at any time while taking this drug but is more likely if you take it for a long time.
The risk may be greater if you have heart disease or increased risk for heart disease (for example, due to smoking, family history of heart disease, or conditions such as high blood pressure or diabetes). Do not take this drug right before or after heart bypass surgery (CABG). Also, this drug may rarely cause serious (rarely fatal) bleeding from the stomach or intestines.
This bleeding can occur without warning symptoms at any time during treatment. Stop taking this medication and get medical help right away if you notice any of the following rare but very serious side effects: stomach/abdominal pain that doesn't go away, chest pain, severe dizziness, weakness on one side of the body, sudden vision changes, trouble speaking, black stools, vomit that looks like coffee grounds. (See also Precautions section.) Talk with your doctor or pharmacist about the risks and benefits of treatment with this medication.
WARNING: Nonsteroidal anti-inflammatory drugs (including salsalate) may rarely increase the risk for a heart attack or stroke. This effect does not apply to low-dose aspirin. (See Drug Interactions section.) This effect can happen at any time while taking this drug but is more likely if you take it for a long time.
The risk may be greater if you have heart disease or increased risk for heart disease (for example, due to smoking, family history of heart disease, or conditions such as high blood pressure or diabetes). Do not take this drug right before or after heart bypass surgery (CABG). Also, this drug may rarely cause serious (rarely fatal) bleeding from the stomach or intestines.
This bleeding can occur without warning symptoms at any time during treatment. Stop taking this medication and get medical help right away if you notice any of the following rare but very serious side effects: stomach/abdominal pain that doesn't go away, chest pain, severe dizziness, weakness on one side of the body, sudden vision changes, trouble speaking, black stools, vomit that looks like coffee grounds. (See also Precautions section.) Talk with your doctor or pharmacist about the risks and benefits of treatment with this medication.
The following icd codes are available for DISALCID (salsalate)'s list of indications:
| Osteoarthritis | |
| M15 | Polyosteoarthritis |
| M15.0 | Primary generalized (osteo)arthritis |
| M15.1 | Heberden's nodes (with arthropathy) |
| M15.2 | Bouchard's nodes (with arthropathy) |
| M15.3 | Secondary multiple arthritis |
| M15.4 | Erosive (osteo)arthritis |
| M15.8 | Other polyosteoarthritis |
| M15.9 | Polyosteoarthritis, unspecified |
| M16 | Osteoarthritis of hip |
| M16.0 | Bilateral primary osteoarthritis of hip |
| M16.1 | Unilateral primary osteoarthritis of hip |
| M16.10 | Unilateral primary osteoarthritis, unspecified hip |
| M16.11 | Unilateral primary osteoarthritis, right hip |
| M16.12 | Unilateral primary osteoarthritis, left hip |
| M16.2 | Bilateral osteoarthritis resulting from hip dysplasia |
| M16.3 | Unilateral osteoarthritis resulting from hip dysplasia |
| M16.30 | Unilateral osteoarthritis resulting from hip dysplasia, unspecified hip |
| M16.31 | Unilateral osteoarthritis resulting from hip dysplasia, right hip |
| M16.32 | Unilateral osteoarthritis resulting from hip dysplasia, left hip |
| M16.4 | Bilateral post-traumatic osteoarthritis of hip |
| M16.5 | Unilateral post-traumatic osteoarthritis of hip |
| M16.50 | Unilateral post-traumatic osteoarthritis, unspecified hip |
| M16.51 | Unilateral post-traumatic osteoarthritis, right hip |
| M16.52 | Unilateral post-traumatic osteoarthritis, left hip |
| M16.6 | Other bilateral secondary osteoarthritis of hip |
| M16.7 | Other unilateral secondary osteoarthritis of hip |
| M16.9 | Osteoarthritis of hip, unspecified |
| M17 | Osteoarthritis of knee |
| M17.0 | Bilateral primary osteoarthritis of knee |
| M17.1 | Unilateral primary osteoarthritis of knee |
| M17.10 | Unilateral primary osteoarthritis, unspecified knee |
| M17.11 | Unilateral primary osteoarthritis, right knee |
| M17.12 | Unilateral primary osteoarthritis, left knee |
| M17.2 | Bilateral post-traumatic osteoarthritis of knee |
| M17.3 | Unilateral post-traumatic osteoarthritis of knee |
| M17.30 | Unilateral post-traumatic osteoarthritis, unspecified knee |
| M17.31 | Unilateral post-traumatic osteoarthritis, right knee |
| M17.32 | Unilateral post-traumatic osteoarthritis, left knee |
| M17.4 | Other bilateral secondary osteoarthritis of knee |
| M17.5 | Other unilateral secondary osteoarthritis of knee |
| M17.9 | Osteoarthritis of knee, unspecified |
| M18 | Osteoarthritis of first carpometacarpal joint |
| M18.0 | Bilateral primary osteoarthritis of first carpometacarpal joints |
| M18.1 | Unilateral primary osteoarthritis of first carpometacarpal joint |
| M18.10 | Unilateral primary osteoarthritis of first carpometacarpal joint, unspecified hand |
| M18.11 | Unilateral primary osteoarthritis of first carpometacarpal joint, right hand |
| M18.12 | Unilateral primary osteoarthritis of first carpometacarpal joint, left hand |
| M18.2 | Bilateral post-traumatic osteoarthritis of first carpometacarpal joints |
| M18.3 | Unilateral post-traumatic osteoarthritis of first carpometacarpal joint |
| M18.30 | Unilateral post-traumatic osteoarthritis of first carpometacarpal joint, unspecified hand |
| M18.31 | Unilateral post-traumatic osteoarthritis of first carpometacarpal joint, right hand |
| M18.32 | Unilateral post-traumatic osteoarthritis of first carpometacarpal joint, left hand |
| M18.4 | Other bilateral secondary osteoarthritis of first carpometacarpal joints |
| M18.5 | Other unilateral secondary osteoarthritis of first carpometacarpal joint |
| M18.50 | Other unilateral secondary osteoarthritis of first carpometacarpal joint, unspecified hand |
| M18.51 | Other unilateral secondary osteoarthritis of first carpometacarpal joint, right hand |
| M18.52 | Other unilateral secondary osteoarthritis of first carpometacarpal joint, left hand |
| M18.9 | Osteoarthritis of first carpometacarpal joint, unspecified |
| M19 | Other and unspecified osteoarthritis |
| M19.0 | Primary osteoarthritis of other joints |
| M19.01 | Primary osteoarthritis, shoulder |
| M19.011 | Primary osteoarthritis, right shoulder |
| M19.012 | Primary osteoarthritis, left shoulder |
| M19.019 | Primary osteoarthritis, unspecified shoulder |
| M19.02 | Primary osteoarthritis, elbow |
| M19.021 | Primary osteoarthritis, right elbow |
| M19.022 | Primary osteoarthritis, left elbow |
| M19.029 | Primary osteoarthritis, unspecified elbow |
| M19.03 | Primary osteoarthritis, wrist |
| M19.031 | Primary osteoarthritis, right wrist |
| M19.032 | Primary osteoarthritis, left wrist |
| M19.039 | Primary osteoarthritis, unspecified wrist |
| M19.04 | Primary osteoarthritis, hand |
| M19.041 | Primary osteoarthritis, right hand |
| M19.042 | Primary osteoarthritis, left hand |
| M19.049 | Primary osteoarthritis, unspecified hand |
| M19.07 | Primary osteoarthritis ankle and foot |
| M19.071 | Primary osteoarthritis, right ankle and foot |
| M19.072 | Primary osteoarthritis, left ankle and foot |
| M19.079 | Primary osteoarthritis, unspecified ankle and foot |
| M19.09 | Primary osteoarthritis, other specified site |
| M19.1 | Post-traumatic osteoarthritis of other joints |
| M19.11 | Post-traumatic osteoarthritis, shoulder |
| M19.111 | Post-traumatic osteoarthritis, right shoulder |
| M19.112 | Post-traumatic osteoarthritis, left shoulder |
| M19.119 | Post-traumatic osteoarthritis, unspecified shoulder |
| M19.12 | Post-traumatic osteoarthritis, elbow |
| M19.121 | Post-traumatic osteoarthritis, right elbow |
| M19.122 | Post-traumatic osteoarthritis, left elbow |
| M19.129 | Post-traumatic osteoarthritis, unspecified elbow |
| M19.13 | Post-traumatic osteoarthritis, wrist |
| M19.131 | Post-traumatic osteoarthritis, right wrist |
| M19.132 | Post-traumatic osteoarthritis, left wrist |
| M19.139 | Post-traumatic osteoarthritis, unspecified wrist |
| M19.14 | Post-traumatic osteoarthritis, hand |
| M19.141 | Post-traumatic osteoarthritis, right hand |
| M19.142 | Post-traumatic osteoarthritis, left hand |
| M19.149 | Post-traumatic osteoarthritis, unspecified hand |
| M19.17 | Post-traumatic osteoarthritis, ankle and foot |
| M19.171 | Post-traumatic osteoarthritis, right ankle and foot |
| M19.172 | Post-traumatic osteoarthritis, left ankle and foot |
| M19.179 | Post-traumatic osteoarthritis, unspecified ankle and foot |
| M19.19 | Post-traumatic osteoarthritis, other specified site |
| M19.2 | Secondary osteoarthritis of other joints |
| M19.21 | Secondary osteoarthritis, shoulder |
| M19.211 | Secondary osteoarthritis, right shoulder |
| M19.212 | Secondary osteoarthritis, left shoulder |
| M19.219 | Secondary osteoarthritis, unspecified shoulder |
| M19.22 | Secondary osteoarthritis, elbow |
| M19.221 | Secondary osteoarthritis, right elbow |
| M19.222 | Secondary osteoarthritis, left elbow |
| M19.229 | Secondary osteoarthritis, unspecified elbow |
| M19.23 | Secondary osteoarthritis, wrist |
| M19.231 | Secondary osteoarthritis, right wrist |
| M19.232 | Secondary osteoarthritis, left wrist |
| M19.239 | Secondary osteoarthritis, unspecified wrist |
| M19.24 | Secondary osteoarthritis, hand |
| M19.241 | Secondary osteoarthritis, right hand |
| M19.242 | Secondary osteoarthritis, left hand |
| M19.249 | Secondary osteoarthritis, unspecified hand |
| M19.27 | Secondary osteoarthritis, ankle and foot |
| M19.271 | Secondary osteoarthritis, right ankle and foot |
| M19.272 | Secondary osteoarthritis, left ankle and foot |
| M19.279 | Secondary osteoarthritis, unspecified ankle and foot |
| M19.29 | Secondary osteoarthritis, other specified site |
| M19.9 | Osteoarthritis, unspecified site |
| M19.90 | Unspecified osteoarthritis, unspecified site |
| M19.91 | Primary osteoarthritis, unspecified site |
| M19.92 | Post-traumatic osteoarthritis, unspecified site |
| M19.93 | Secondary osteoarthritis, unspecified site |
| Rheumatoid arthritis | |
| M05 | Rheumatoid arthritis with rheumatoid factor |
| M05.0 | Felty's syndrome |
| M05.00 | Felty's syndrome, unspecified site |
| M05.01 | Felty's syndrome, shoulder |
| M05.011 | Felty's syndrome, right shoulder |
| M05.012 | Felty's syndrome, left shoulder |
| M05.019 | Felty's syndrome, unspecified shoulder |
| M05.02 | Felty's syndrome, elbow |
| M05.021 | Felty's syndrome, right elbow |
| M05.022 | Felty's syndrome, left elbow |
| M05.029 | Felty's syndrome, unspecified elbow |
| M05.03 | Felty's syndrome, wrist |
| M05.031 | Felty's syndrome, right wrist |
| M05.032 | Felty's syndrome, left wrist |
| M05.039 | Felty's syndrome, unspecified wrist |
| M05.04 | Felty's syndrome, hand |
| M05.041 | Felty's syndrome, right hand |
| M05.042 | Felty's syndrome, left hand |
| M05.049 | Felty's syndrome, unspecified hand |
| M05.05 | Felty's syndrome, hip |
| M05.051 | Felty's syndrome, right hip |
| M05.052 | Felty's syndrome, left hip |
| M05.059 | Felty's syndrome, unspecified hip |
| M05.06 | Felty's syndrome, knee |
| M05.061 | Felty's syndrome, right knee |
| M05.062 | Felty's syndrome, left knee |
| M05.069 | Felty's syndrome, unspecified knee |
| M05.07 | Felty's syndrome, ankle and foot |
| M05.071 | Felty's syndrome, right ankle and foot |
| M05.072 | Felty's syndrome, left ankle and foot |
| M05.079 | Felty's syndrome, unspecified ankle and foot |
| M05.09 | Felty's syndrome, multiple sites |
| M05.1 | Rheumatoid lung disease with rheumatoid arthritis |
| M05.10 | Rheumatoid lung disease with rheumatoid arthritis of unspecified site |
| M05.11 | Rheumatoid lung disease with rheumatoid arthritis of shoulder |
| M05.111 | Rheumatoid lung disease with rheumatoid arthritis of right shoulder |
| M05.112 | Rheumatoid lung disease with rheumatoid arthritis of left shoulder |
| M05.119 | Rheumatoid lung disease with rheumatoid arthritis of unspecified shoulder |
| M05.12 | Rheumatoid lung disease with rheumatoid arthritis of elbow |
| M05.121 | Rheumatoid lung disease with rheumatoid arthritis of right elbow |
| M05.122 | Rheumatoid lung disease with rheumatoid arthritis of left elbow |
| M05.129 | Rheumatoid lung disease with rheumatoid arthritis of unspecified elbow |
| M05.13 | Rheumatoid lung disease with rheumatoid arthritis of wrist |
| M05.131 | Rheumatoid lung disease with rheumatoid arthritis of right wrist |
| M05.132 | Rheumatoid lung disease with rheumatoid arthritis of left wrist |
| M05.139 | Rheumatoid lung disease with rheumatoid arthritis of unspecified wrist |
| M05.14 | Rheumatoid lung disease with rheumatoid arthritis of hand |
| M05.141 | Rheumatoid lung disease with rheumatoid arthritis of right hand |
| M05.142 | Rheumatoid lung disease with rheumatoid arthritis of left hand |
| M05.149 | Rheumatoid lung disease with rheumatoid arthritis of unspecified hand |
| M05.15 | Rheumatoid lung disease with rheumatoid arthritis of hip |
| M05.151 | Rheumatoid lung disease with rheumatoid arthritis of right hip |
| M05.152 | Rheumatoid lung disease with rheumatoid arthritis of left hip |
| M05.159 | Rheumatoid lung disease with rheumatoid arthritis of unspecified hip |
| M05.16 | Rheumatoid lung disease with rheumatoid arthritis of knee |
| M05.161 | Rheumatoid lung disease with rheumatoid arthritis of right knee |
| M05.162 | Rheumatoid lung disease with rheumatoid arthritis of left knee |
| M05.169 | Rheumatoid lung disease with rheumatoid arthritis of unspecified knee |
| M05.17 | Rheumatoid lung disease with rheumatoid arthritis of ankle and foot |
| M05.171 | Rheumatoid lung disease with rheumatoid arthritis of right ankle and foot |
| M05.172 | Rheumatoid lung disease with rheumatoid arthritis of left ankle and foot |
| M05.179 | Rheumatoid lung disease with rheumatoid arthritis of unspecified ankle and foot |
| M05.19 | Rheumatoid lung disease with rheumatoid arthritis of multiple sites |
| M05.2 | Rheumatoid vasculitis with rheumatoid arthritis |
| M05.20 | Rheumatoid vasculitis with rheumatoid arthritis of unspecified site |
| M05.21 | Rheumatoid vasculitis with rheumatoid arthritis of shoulder |
| M05.211 | Rheumatoid vasculitis with rheumatoid arthritis of right shoulder |
| M05.212 | Rheumatoid vasculitis with rheumatoid arthritis of left shoulder |
| M05.219 | Rheumatoid vasculitis with rheumatoid arthritis of unspecified shoulder |
| M05.22 | Rheumatoid vasculitis with rheumatoid arthritis of elbow |
| M05.221 | Rheumatoid vasculitis with rheumatoid arthritis of right elbow |
| M05.222 | Rheumatoid vasculitis with rheumatoid arthritis of left elbow |
| M05.229 | Rheumatoid vasculitis with rheumatoid arthritis of unspecified elbow |
| M05.23 | Rheumatoid vasculitis with rheumatoid arthritis of wrist |
| M05.231 | Rheumatoid vasculitis with rheumatoid arthritis of right wrist |
| M05.232 | Rheumatoid vasculitis with rheumatoid arthritis of left wrist |
| M05.239 | Rheumatoid vasculitis with rheumatoid arthritis of unspecified wrist |
| M05.24 | Rheumatoid vasculitis with rheumatoid arthritis of hand |
| M05.241 | Rheumatoid vasculitis with rheumatoid arthritis of right hand |
| M05.242 | Rheumatoid vasculitis with rheumatoid arthritis of left hand |
| M05.249 | Rheumatoid vasculitis with rheumatoid arthritis of unspecified hand |
| M05.25 | Rheumatoid vasculitis with rheumatoid arthritis of hip |
| M05.251 | Rheumatoid vasculitis with rheumatoid arthritis of right hip |
| M05.252 | Rheumatoid vasculitis with rheumatoid arthritis of left hip |
| M05.259 | Rheumatoid vasculitis with rheumatoid arthritis of unspecified hip |
| M05.26 | Rheumatoid vasculitis with rheumatoid arthritis of knee |
| M05.261 | Rheumatoid vasculitis with rheumatoid arthritis of right knee |
| M05.262 | Rheumatoid vasculitis with rheumatoid arthritis of left knee |
| M05.269 | Rheumatoid vasculitis with rheumatoid arthritis of unspecified knee |
| M05.27 | Rheumatoid vasculitis with rheumatoid arthritis of ankle and foot |
| M05.271 | Rheumatoid vasculitis with rheumatoid arthritis of right ankle and foot |
| M05.272 | Rheumatoid vasculitis with rheumatoid arthritis of left ankle and foot |
| M05.279 | Rheumatoid vasculitis with rheumatoid arthritis of unspecified ankle and foot |
| M05.29 | Rheumatoid vasculitis with rheumatoid arthritis of multiple sites |
| M05.3 | Rheumatoid heart disease with rheumatoid arthritis |
| M05.30 | Rheumatoid heart disease with rheumatoid arthritis of unspecified site |
| M05.31 | Rheumatoid heart disease with rheumatoid arthritis of shoulder |
| M05.311 | Rheumatoid heart disease with rheumatoid arthritis of right shoulder |
| M05.312 | Rheumatoid heart disease with rheumatoid arthritis of left shoulder |
| M05.319 | Rheumatoid heart disease with rheumatoid arthritis of unspecified shoulder |
| M05.32 | Rheumatoid heart disease with rheumatoid arthritis of elbow |
| M05.321 | Rheumatoid heart disease with rheumatoid arthritis of right elbow |
| M05.322 | Rheumatoid heart disease with rheumatoid arthritis of left elbow |
| M05.329 | Rheumatoid heart disease with rheumatoid arthritis of unspecified elbow |
| M05.33 | Rheumatoid heart disease with rheumatoid arthritis of wrist |
| M05.331 | Rheumatoid heart disease with rheumatoid arthritis of right wrist |
| M05.332 | Rheumatoid heart disease with rheumatoid arthritis of left wrist |
| M05.339 | Rheumatoid heart disease with rheumatoid arthritis of unspecified wrist |
| M05.34 | Rheumatoid heart disease with rheumatoid arthritis of hand |
| M05.341 | Rheumatoid heart disease with rheumatoid arthritis of right hand |
| M05.342 | Rheumatoid heart disease with rheumatoid arthritis of left hand |
| M05.349 | Rheumatoid heart disease with rheumatoid arthritis of unspecified hand |
| M05.35 | Rheumatoid heart disease with rheumatoid arthritis of hip |
| M05.351 | Rheumatoid heart disease with rheumatoid arthritis of right hip |
| M05.352 | Rheumatoid heart disease with rheumatoid arthritis of left hip |
| M05.359 | Rheumatoid heart disease with rheumatoid arthritis of unspecified hip |
| M05.36 | Rheumatoid heart disease with rheumatoid arthritis of knee |
| M05.361 | Rheumatoid heart disease with rheumatoid arthritis of right knee |
| M05.362 | Rheumatoid heart disease with rheumatoid arthritis of left knee |
| M05.369 | Rheumatoid heart disease with rheumatoid arthritis of unspecified knee |
| M05.37 | Rheumatoid heart disease with rheumatoid arthritis of ankle and foot |
| M05.371 | Rheumatoid heart disease with rheumatoid arthritis of right ankle and foot |
| M05.372 | Rheumatoid heart disease with rheumatoid arthritis of left ankle and foot |
| M05.379 | Rheumatoid heart disease with rheumatoid arthritis of unspecified ankle and foot |
| M05.39 | Rheumatoid heart disease with rheumatoid arthritis of multiple sites |
| M05.4 | Rheumatoid myopathy with rheumatoid arthritis |
| M05.40 | Rheumatoid myopathy with rheumatoid arthritis of unspecified site |
| M05.41 | Rheumatoid myopathy with rheumatoid arthritis of shoulder |
| M05.411 | Rheumatoid myopathy with rheumatoid arthritis of right shoulder |
| M05.412 | Rheumatoid myopathy with rheumatoid arthritis of left shoulder |
| M05.419 | Rheumatoid myopathy with rheumatoid arthritis of unspecified shoulder |
| M05.42 | Rheumatoid myopathy with rheumatoid arthritis of elbow |
| M05.421 | Rheumatoid myopathy with rheumatoid arthritis of right elbow |
| M05.422 | Rheumatoid myopathy with rheumatoid arthritis of left elbow |
| M05.429 | Rheumatoid myopathy with rheumatoid arthritis of unspecified elbow |
| M05.43 | Rheumatoid myopathy with rheumatoid arthritis of wrist |
| M05.431 | Rheumatoid myopathy with rheumatoid arthritis of right wrist |
| M05.432 | Rheumatoid myopathy with rheumatoid arthritis of left wrist |
| M05.439 | Rheumatoid myopathy with rheumatoid arthritis of unspecified wrist |
| M05.44 | Rheumatoid myopathy with rheumatoid arthritis of hand |
| M05.441 | Rheumatoid myopathy with rheumatoid arthritis of right hand |
| M05.442 | Rheumatoid myopathy with rheumatoid arthritis of left hand |
| M05.449 | Rheumatoid myopathy with rheumatoid arthritis of unspecified hand |
| M05.45 | Rheumatoid myopathy with rheumatoid arthritis of hip |
| M05.451 | Rheumatoid myopathy with rheumatoid arthritis of right hip |
| M05.452 | Rheumatoid myopathy with rheumatoid arthritis of left hip |
| M05.459 | Rheumatoid myopathy with rheumatoid arthritis of unspecified hip |
| M05.46 | Rheumatoid myopathy with rheumatoid arthritis of knee |
| M05.461 | Rheumatoid myopathy with rheumatoid arthritis of right knee |
| M05.462 | Rheumatoid myopathy with rheumatoid arthritis of left knee |
| M05.469 | Rheumatoid myopathy with rheumatoid arthritis of unspecified knee |
| M05.47 | Rheumatoid myopathy with rheumatoid arthritis of ankle and foot |
| M05.471 | Rheumatoid myopathy with rheumatoid arthritis of right ankle and foot |
| M05.472 | Rheumatoid myopathy with rheumatoid arthritis of left ankle and foot |
| M05.479 | Rheumatoid myopathy with rheumatoid arthritis of unspecified ankle and foot |
| M05.49 | Rheumatoid myopathy with rheumatoid arthritis of multiple sites |
| M05.5 | Rheumatoid polyneuropathy with rheumatoid arthritis |
| M05.50 | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified site |
| M05.51 | Rheumatoid polyneuropathy with rheumatoid arthritis of shoulder |
| M05.511 | Rheumatoid polyneuropathy with rheumatoid arthritis of right shoulder |
| M05.512 | Rheumatoid polyneuropathy with rheumatoid arthritis of left shoulder |
| M05.519 | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified shoulder |
| M05.52 | Rheumatoid polyneuropathy with rheumatoid arthritis of elbow |
| M05.521 | Rheumatoid polyneuropathy with rheumatoid arthritis of right elbow |
| M05.522 | Rheumatoid polyneuropathy with rheumatoid arthritis of left elbow |
| M05.529 | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified elbow |
| M05.53 | Rheumatoid polyneuropathy with rheumatoid arthritis of wrist |
| M05.531 | Rheumatoid polyneuropathy with rheumatoid arthritis of right wrist |
| M05.532 | Rheumatoid polyneuropathy with rheumatoid arthritis of left wrist |
| M05.539 | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified wrist |
| M05.54 | Rheumatoid polyneuropathy with rheumatoid arthritis of hand |
| M05.541 | Rheumatoid polyneuropathy with rheumatoid arthritis of right hand |
| M05.542 | Rheumatoid polyneuropathy with rheumatoid arthritis of left hand |
| M05.549 | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified hand |
| M05.55 | Rheumatoid polyneuropathy with rheumatoid arthritis of hip |
| M05.551 | Rheumatoid polyneuropathy with rheumatoid arthritis of right hip |
| M05.552 | Rheumatoid polyneuropathy with rheumatoid arthritis of left hip |
| M05.559 | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified hip |
| M05.56 | Rheumatoid polyneuropathy with rheumatoid arthritis of knee |
| M05.561 | Rheumatoid polyneuropathy with rheumatoid arthritis of right knee |
| M05.562 | Rheumatoid polyneuropathy with rheumatoid arthritis of left knee |
| M05.569 | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified knee |
| M05.57 | Rheumatoid polyneuropathy with rheumatoid arthritis of ankle and foot |
| M05.571 | Rheumatoid polyneuropathy with rheumatoid arthritis of right ankle and foot |
| M05.572 | Rheumatoid polyneuropathy with rheumatoid arthritis of left ankle and foot |
| M05.579 | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified ankle and foot |
| M05.59 | Rheumatoid polyneuropathy with rheumatoid arthritis of multiple sites |
| M05.6 | Rheumatoid arthritis with involvement of other organs and systems |
| M05.60 | Rheumatoid arthritis of unspecified site with involvement of other organs and systems |
| M05.61 | Rheumatoid arthritis of shoulder with involvement of other organs and systems |
| M05.611 | Rheumatoid arthritis of right shoulder with involvement of other organs and systems |
| M05.612 | Rheumatoid arthritis of left shoulder with involvement of other organs and systems |
| M05.619 | Rheumatoid arthritis of unspecified shoulder with involvement of other organs and systems |
| M05.62 | Rheumatoid arthritis of elbow with involvement of other organs and systems |
| M05.621 | Rheumatoid arthritis of right elbow with involvement of other organs and systems |
| M05.622 | Rheumatoid arthritis of left elbow with involvement of other organs and systems |
| M05.629 | Rheumatoid arthritis of unspecified elbow with involvement of other organs and systems |
| M05.63 | Rheumatoid arthritis of wrist with involvement of other organs and systems |
| M05.631 | Rheumatoid arthritis of right wrist with involvement of other organs and systems |
| M05.632 | Rheumatoid arthritis of left wrist with involvement of other organs and systems |
| M05.639 | Rheumatoid arthritis of unspecified wrist with involvement of other organs and systems |
| M05.64 | Rheumatoid arthritis of hand with involvement of other organs and systems |
| M05.641 | Rheumatoid arthritis of right hand with involvement of other organs and systems |
| M05.642 | Rheumatoid arthritis of left hand with involvement of other organs and systems |
| M05.649 | Rheumatoid arthritis of unspecified hand with involvement of other organs and systems |
| M05.65 | Rheumatoid arthritis of hip with involvement of other organs and systems |
| M05.651 | Rheumatoid arthritis of right hip with involvement of other organs and systems |
| M05.652 | Rheumatoid arthritis of left hip with involvement of other organs and systems |
| M05.659 | Rheumatoid arthritis of unspecified hip with involvement of other organs and systems |
| M05.66 | Rheumatoid arthritis of knee with involvement of other organs and systems |
| M05.661 | Rheumatoid arthritis of right knee with involvement of other organs and systems |
| M05.662 | Rheumatoid arthritis of left knee with involvement of other organs and systems |
| M05.669 | Rheumatoid arthritis of unspecified knee with involvement of other organs and systems |
| M05.67 | Rheumatoid arthritis of ankle and foot with involvement of other organs and systems |
| M05.671 | Rheumatoid arthritis of right ankle and foot with involvement of other organs and systems |
| M05.672 | Rheumatoid arthritis of left ankle and foot with involvement of other organs and systems |
| M05.679 | Rheumatoid arthritis of unspecified ankle and foot with involvement of other organs and systems |
| M05.69 | Rheumatoid arthritis of multiple sites with involvement of other organs and systems |
| M05.7 | Rheumatoid arthritis with rheumatoid factor without organ or systems involvement |
| M05.70 | Rheumatoid arthritis with rheumatoid factor of unspecified site without organ or systems involvement |
| M05.71 | Rheumatoid arthritis with rheumatoid factor of shoulder without organ or systems involvement |
| M05.711 | Rheumatoid arthritis with rheumatoid factor of right shoulder without organ or systems involvement |
| M05.712 | Rheumatoid arthritis with rheumatoid factor of left shoulder without organ or systems involvement |
| M05.719 | Rheumatoid arthritis with rheumatoid factor of unspecified shoulder without organ or systems involvement |
| M05.72 | Rheumatoid arthritis with rheumatoid factor of elbow without organ or systems involvement |
| M05.721 | Rheumatoid arthritis with rheumatoid factor of right elbow without organ or systems involvement |
| M05.722 | Rheumatoid arthritis with rheumatoid factor of left elbow without organ or systems involvement |
| M05.729 | Rheumatoid arthritis with rheumatoid factor of unspecified elbow without organ or systems involvement |
| M05.73 | Rheumatoid arthritis with rheumatoid factor of wrist without organ or systems involvement |
| M05.731 | Rheumatoid arthritis with rheumatoid factor of right wrist without organ or systems involvement |
| M05.732 | Rheumatoid arthritis with rheumatoid factor of left wrist without organ or systems involvement |
| M05.739 | Rheumatoid arthritis with rheumatoid factor of unspecified wrist without organ or systems involvement |
| M05.74 | Rheumatoid arthritis with rheumatoid factor of hand without organ or systems involvement |
| M05.741 | Rheumatoid arthritis with rheumatoid factor of right hand without organ or systems involvement |
| M05.742 | Rheumatoid arthritis with rheumatoid factor of left hand without organ or systems involvement |
| M05.749 | Rheumatoid arthritis with rheumatoid factor of unspecified hand without organ or systems involvement |
| M05.75 | Rheumatoid arthritis with rheumatoid factor of hip without organ or systems involvement |
| M05.751 | Rheumatoid arthritis with rheumatoid factor of right hip without organ or systems involvement |
| M05.752 | Rheumatoid arthritis with rheumatoid factor of left hip without organ or systems involvement |
| M05.759 | Rheumatoid arthritis with rheumatoid factor of unspecified hip without organ or systems involvement |
| M05.76 | Rheumatoid arthritis with rheumatoid factor of knee without organ or systems involvement |
| M05.761 | Rheumatoid arthritis with rheumatoid factor of right knee without organ or systems involvement |
| M05.762 | Rheumatoid arthritis with rheumatoid factor of left knee without organ or systems involvement |
| M05.769 | Rheumatoid arthritis with rheumatoid factor of unspecified knee without organ or systems involvement |
| M05.77 | Rheumatoid arthritis with rheumatoid factor of ankle and foot without organ or systems involvement |
| M05.771 | Rheumatoid arthritis with rheumatoid factor of right ankle and foot without organ or systems involvement |
| M05.772 | Rheumatoid arthritis with rheumatoid factor of left ankle and foot without organ or systems involvement |
| M05.779 | Rheumatoid arthritis with rheumatoid factor of unspecified ankle and foot without organ or systems involvement |
| M05.79 | Rheumatoid arthritis with rheumatoid factor of multiple sites without organ or systems involvement |
| M05.7A | Rheumatoid arthritis with rheumatoid factor of other specified site without organ or systems involvement |
| M05.8 | Other rheumatoid arthritis with rheumatoid factor |
| M05.80 | Other rheumatoid arthritis with rheumatoid factor of unspecified site |
| M05.81 | Other rheumatoid arthritis with rheumatoid factor of shoulder |
| M05.811 | Other rheumatoid arthritis with rheumatoid factor of right shoulder |
| M05.812 | Other rheumatoid arthritis with rheumatoid factor of left shoulder |
| M05.819 | Other rheumatoid arthritis with rheumatoid factor of unspecified shoulder |
| M05.82 | Other rheumatoid arthritis with rheumatoid factor of elbow |
| M05.821 | Other rheumatoid arthritis with rheumatoid factor of right elbow |
| M05.822 | Other rheumatoid arthritis with rheumatoid factor of left elbow |
| M05.829 | Other rheumatoid arthritis with rheumatoid factor of unspecified elbow |
| M05.83 | Other rheumatoid arthritis with rheumatoid factor of wrist |
| M05.831 | Other rheumatoid arthritis with rheumatoid factor of right wrist |
| M05.832 | Other rheumatoid arthritis with rheumatoid factor of left wrist |
| M05.839 | Other rheumatoid arthritis with rheumatoid factor of unspecified wrist |
| M05.84 | Other rheumatoid arthritis with rheumatoid factor of hand |
| M05.841 | Other rheumatoid arthritis with rheumatoid factor of right hand |
| M05.842 | Other rheumatoid arthritis with rheumatoid factor of left hand |
| M05.849 | Other rheumatoid arthritis with rheumatoid factor of unspecified hand |
| M05.85 | Other rheumatoid arthritis with rheumatoid factor of hip |
| M05.851 | Other rheumatoid arthritis with rheumatoid factor of right hip |
| M05.852 | Other rheumatoid arthritis with rheumatoid factor of left hip |
| M05.859 | Other rheumatoid arthritis with rheumatoid factor of unspecified hip |
| M05.86 | Other rheumatoid arthritis with rheumatoid factor of knee |
| M05.861 | Other rheumatoid arthritis with rheumatoid factor of right knee |
| M05.862 | Other rheumatoid arthritis with rheumatoid factor of left knee |
| M05.869 | Other rheumatoid arthritis with rheumatoid factor of unspecified knee |
| M05.87 | Other rheumatoid arthritis with rheumatoid factor of ankle and foot |
| M05.871 | Other rheumatoid arthritis with rheumatoid factor of right ankle and foot |
| M05.872 | Other rheumatoid arthritis with rheumatoid factor of left ankle and foot |
| M05.879 | Other rheumatoid arthritis with rheumatoid factor of unspecified ankle and foot |
| M05.89 | Other rheumatoid arthritis with rheumatoid factor of multiple sites |
| M05.8A | Other rheumatoid arthritis with rheumatoid factor of other specified site |
| M05.9 | Rheumatoid arthritis with rheumatoid factor, unspecified |
| M06 | Other rheumatoid arthritis |
| M06.0 | Rheumatoid arthritis without rheumatoid factor |
| M06.00 | Rheumatoid arthritis without rheumatoid factor, unspecified site |
| M06.01 | Rheumatoid arthritis without rheumatoid factor, shoulder |
| M06.011 | Rheumatoid arthritis without rheumatoid factor, right shoulder |
| M06.012 | Rheumatoid arthritis without rheumatoid factor, left shoulder |
| M06.019 | Rheumatoid arthritis without rheumatoid factor, unspecified shoulder |
| M06.02 | Rheumatoid arthritis without rheumatoid factor, elbow |
| M06.021 | Rheumatoid arthritis without rheumatoid factor, right elbow |
| M06.022 | Rheumatoid arthritis without rheumatoid factor, left elbow |
| M06.029 | Rheumatoid arthritis without rheumatoid factor, unspecified elbow |
| M06.03 | Rheumatoid arthritis without rheumatoid factor, wrist |
| M06.031 | Rheumatoid arthritis without rheumatoid factor, right wrist |
| M06.032 | Rheumatoid arthritis without rheumatoid factor, left wrist |
| M06.039 | Rheumatoid arthritis without rheumatoid factor, unspecified wrist |
| M06.04 | Rheumatoid arthritis without rheumatoid factor, hand |
| M06.041 | Rheumatoid arthritis without rheumatoid factor, right hand |
| M06.042 | Rheumatoid arthritis without rheumatoid factor, left hand |
| M06.049 | Rheumatoid arthritis without rheumatoid factor, unspecified hand |
| M06.05 | Rheumatoid arthritis without rheumatoid factor, hip |
| M06.051 | Rheumatoid arthritis without rheumatoid factor, right hip |
| M06.052 | Rheumatoid arthritis without rheumatoid factor, left hip |
| M06.059 | Rheumatoid arthritis without rheumatoid factor, unspecified hip |
| M06.06 | Rheumatoid arthritis without rheumatoid factor, knee |
| M06.061 | Rheumatoid arthritis without rheumatoid factor, right knee |
| M06.062 | Rheumatoid arthritis without rheumatoid factor, left knee |
| M06.069 | Rheumatoid arthritis without rheumatoid factor, unspecified knee |
| M06.07 | Rheumatoid arthritis without rheumatoid factor, ankle and foot |
| M06.071 | Rheumatoid arthritis without rheumatoid factor, right ankle and foot |
| M06.072 | Rheumatoid arthritis without rheumatoid factor, left ankle and foot |
| M06.079 | Rheumatoid arthritis without rheumatoid factor, unspecified ankle and foot |
| M06.08 | Rheumatoid arthritis without rheumatoid factor, vertebrae |
| M06.09 | Rheumatoid arthritis without rheumatoid factor, multiple sites |
| M06.0A | Rheumatoid arthritis without rheumatoid factor, other specified site |
| M06.8 | Other specified rheumatoid arthritis |
| M06.80 | Other specified rheumatoid arthritis, unspecified site |
| M06.81 | Other specified rheumatoid arthritis, shoulder |
| M06.811 | Other specified rheumatoid arthritis, right shoulder |
| M06.812 | Other specified rheumatoid arthritis, left shoulder |
| M06.819 | Other specified rheumatoid arthritis, unspecified shoulder |
| M06.82 | Other specified rheumatoid arthritis, elbow |
| M06.821 | Other specified rheumatoid arthritis, right elbow |
| M06.822 | Other specified rheumatoid arthritis, left elbow |
| M06.829 | Other specified rheumatoid arthritis, unspecified elbow |
| M06.83 | Other specified rheumatoid arthritis, wrist |
| M06.831 | Other specified rheumatoid arthritis, right wrist |
| M06.832 | Other specified rheumatoid arthritis, left wrist |
| M06.839 | Other specified rheumatoid arthritis, unspecified wrist |
| M06.84 | Other specified rheumatoid arthritis, hand |
| M06.841 | Other specified rheumatoid arthritis, right hand |
| M06.842 | Other specified rheumatoid arthritis, left hand |
| M06.849 | Other specified rheumatoid arthritis, unspecified hand |
| M06.85 | Other specified rheumatoid arthritis, hip |
| M06.851 | Other specified rheumatoid arthritis, right hip |
| M06.852 | Other specified rheumatoid arthritis, left hip |
| M06.859 | Other specified rheumatoid arthritis, unspecified hip |
| M06.86 | Other specified rheumatoid arthritis, knee |
| M06.861 | Other specified rheumatoid arthritis, right knee |
| M06.862 | Other specified rheumatoid arthritis, left knee |
| M06.869 | Other specified rheumatoid arthritis, unspecified knee |
| M06.87 | Other specified rheumatoid arthritis, ankle and foot |
| M06.871 | Other specified rheumatoid arthritis, right ankle and foot |
| M06.872 | Other specified rheumatoid arthritis, left ankle and foot |
| M06.879 | Other specified rheumatoid arthritis, unspecified ankle and foot |
| M06.88 | Other specified rheumatoid arthritis, vertebrae |
| M06.89 | Other specified rheumatoid arthritis, multiple sites |
| M06.8A | Other specified rheumatoid arthritis, other specified site |
| M06.9 | Rheumatoid arthritis, unspecified |
Formulary Reference Tool