DRUG INTERACTIONS
Abciximab: (Moderate) Unless contraindicated, aspirin is used in combination with abciximab. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Abrocitinib: (Contraindicated) Concurrent use with daily aspirin doses higher than 81 mg is contraindicated during the first 3 months of abrocitinib therapy due to an increased risk of bleeding with thrombocytopenia.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Acetaminophen; Caffeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Acetaminophen; Caffeine; Dihydrocodeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Acetazolamide: (Major) Avoid the coadministration of high-dose salicylates and carbonic anhydrase inhibitors whenever possible. There were reports of anorexia, tachypnea, lethargy, metabolic acidosis, coma, and death with high-dose aspirin and acetazolamide. Two mechanisms could cause increased acetazolamide concentrations, resulting in CNS depression and metabolic acidosis: first, competition with aspirin for renal tubular secretion and, second, displacement by salicylates from plasma protein binding sites. Additionally, carbonic anhydrase inhibitors alkalinize urine and increase the excretion of normal doses of salicylates; decreased plasma salicylate concentrations may or may not be clinically significant.
Acetohexamide: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
Acidifying Agents: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Ado-Trastuzumab emtansine: (Moderate) Use caution if coadministration of aspirin with ado-trastuzumab emtansine is necessary due to reports of severe and sometimes fatal hemorrhage, including intracranial bleeding, with ado-trastuzumab emtansine therapy. Consider additional monitoring when concomitant use is medically necessary. While some patients who experienced bleeding during ado-trastuzumab therapy were also receiving anticoagulation therapy, others had no known additional risk factors
Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Alkalinizing Agents: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Alogliptin: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Alogliptin; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Alogliptin; Pioglitazone: (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria. (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Alpha-glucosidase Inhibitors: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Amiloride: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia. (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Aminoglycosides: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
Amlodipine; Benazepril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Amlodipine; Celecoxib: (Major) Concomitant use of analgesic doses of aspirin and celecoxib is generally not recommended due to the increased risks of bleeding and nephrotoxicity. Concurrent use of aspirin with NSAIDs does not produce a greater analgesic effect compared to the use of NSAIDs alone. Celecoxib (200 to 400 mg daily) did not interfere with the cardioprotective antiplatelet effect of aspirin (100 to 325 mg) in 2 studies in healthy volunteers and in patients with osteoarthritis and established heart disease. Concurrent use does not produce greater therapeutic effect.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Amoxicillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Amoxicillin; Clavulanic Acid: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Amphotericin B cholesteryl sulfate complex (ABCD): (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Amphotericin B lipid complex (ABLC): (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Amphotericin B liposomal (LAmB): (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Amphotericin B: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity.
Ampicillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Ampicillin; Sulbactam: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Anagrelide: (Moderate) Use caution with the coadministration of aspirin and anagrelide. The coadministration of single or repeated doses of anagrelide and aspirin resulted in greater ex vivo anti-platelet aggregation effects than administration of aspirin alone. In an observational study, the concomitant use of anagrelide and aspirin increased the rate of major hemorrhagic events compared to patients receiving other cytoreductive therapy. Assess the risks and benefits of concomitant aspirin and anagrelide use, particularly in patients at high risk for hemorrhage. Monitor for bleeding during concomitant therapy.
Angiotensin-converting enzyme inhibitors: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Antithrombin III: (Moderate) Large doses of salicylates (more than 3 to 4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Patients taking large doses of salicylates and antithrombin III should be monitored closely for bleeding.
Apixaban: (Major) Large doses of salicylates (3 to 4 g/day or more) can cause hypoprothrombinemia, an additional risk factor for bleeding. Patients taking large doses of salicylates and apixaban should be monitored closely for bleeding.
Ardeparin: (Moderate) An additive risk of bleeding may be seen in patients receiving a low molecular weight heparin in combination with other agents known to increase the risk of bleeding such as salicylates. Monitor clinical and laboratory response closely during concurrent use.
Ascorbic Acid, Vitamin C: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Aspirin, ASA; Caffeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Aspirin, ASA; Caffeine; Dihydrocodeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Aspirin, ASA; Dipyridamole: (Moderate) Although aspirin may be used in combination with dipyridamole, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Atenolol; Chlorthalidone: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Azilsartan; Chlorthalidone: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, including salicylates. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
Barbiturates: (Moderate) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as barbiturates. An enhanced effect of the displaced drug may occur.
Benazepril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Bendroflumethiazide; Nadolol: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Beta-blockers: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Betrixaban: (Major) Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and aspirin are used concomitantly. Coadministration of betrixaban and aspirin may increase the risk of bleeding.
Bismuth Subsalicylate: (Major) Concomitant use of aspirin with repeated or maximum doses of bismuth subsalicylate-containing preparations may contribute to elevated serum salicylate levels and should be avoided. Consider replacing aspirin therapy with an alternative non-steroidal anti-inflammatory agent that is not salicylate based where appropriate.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of aspirin with repeated or maximum doses of bismuth subsalicylate-containing preparations may contribute to elevated serum salicylate levels and should be avoided. Consider replacing aspirin therapy with an alternative non-steroidal anti-inflammatory agent that is not salicylate based where appropriate.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Bisphosphonates: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
Bromocriptine: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects.
Bumetanide: (Moderate) Salicylates may decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of renal prostaglandin synthesis. Patients receiving loop diuretics and salicylates should be monitored for changes in the effectiveness of their diuretic therapy.
Bupivacaine; Meloxicam: (Major) Additive adverse gastrointestinal (GI) effects are possible if meloxicam is used with salicylates (e.g., aspirin). The concurrent use of aspirin and a nonsteroidal anti-inflammatory drug (NSAID) does increase the risk of serious gastrointestinal events. Concomitant administration of aspirin, ASA (3000 mg/day) to healthy volunteers increased the meloxicam AUC by 10% and increased the meloxicam peak plasma concentrations by 24%. Because of its lack of platelet effects, meloxicam is not a substitute for aspirin for cardiovascular prophylaxis.
Buspirone: (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.
Butalbital; Acetaminophen; Caffeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Butalbital; Acetaminophen; Caffeine; Codeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Caffeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Caffeine; Sodium Benzoate: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Canagliflozin: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Canagliflozin; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Caplacizumab: (Major) Avoid concomitant use of caplacizumab and aspirin when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Capreomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including salicylates, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Captopril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Carbenicillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Cefixime: (Minor) In vitro, salicylates have displaced cefixime from its protein-binding sites, resulting in a 50% increase in free cefixime levels. The clinical significance of this effect is unclear at this time.
Cefotetan: (Minor) Cefotetan has been associated with hypoprothrombinemia and may cause additive effects when given concurrently with salicylates.
Celecoxib: (Major) Concomitant use of analgesic doses of aspirin and celecoxib is generally not recommended due to the increased risks of bleeding and nephrotoxicity. Concurrent use of aspirin with NSAIDs does not produce a greater analgesic effect compared to the use of NSAIDs alone. Celecoxib (200 to 400 mg daily) did not interfere with the cardioprotective antiplatelet effect of aspirin (100 to 325 mg) in 2 studies in healthy volunteers and in patients with osteoarthritis and established heart disease. Concurrent use does not produce greater therapeutic effect.
Celecoxib; Tramadol: (Major) Concomitant use of analgesic doses of aspirin and celecoxib is generally not recommended due to the increased risks of bleeding and nephrotoxicity. Concurrent use of aspirin with NSAIDs does not produce a greater analgesic effect compared to the use of NSAIDs alone. Celecoxib (200 to 400 mg daily) did not interfere with the cardioprotective antiplatelet effect of aspirin (100 to 325 mg) in 2 studies in healthy volunteers and in patients with osteoarthritis and established heart disease. Concurrent use does not produce greater therapeutic effect.
Chlorothiazide: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Concomitant use of analgesic doses of aspirin with ibuprofen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of ibuprofen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of ibuprofen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to ibuprofen interference with the antiplatelet effect of aspirin. A decrease in antiplatelet activity (53%) was observed at 24 hours after 6 days of ibuprofen 400 mg/day given 2 hours before immediate-release aspirin 81 mg/day. An interaction was still observed, but minimized, when ibuprofen 400 mg/day was given as early as 8 hours before immediate-release aspirin (90.7%). There was no interaction when ibuprofen 400 mg/day was given 2 hours after the immediate-release aspirin dose (99.2%). In a study with enteric-coated aspirin, subjects given aspirin 81 mg/day with ibuprofen 400 mg 3 times daily (2, 7, and 12 hours after aspirin dose) for 6 days, there was an interaction with antiplatelet activity at 24 hours after the day 6 aspirin dose (67%). An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs' ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with routine as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure.
Chlorpropamide: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
Chlorthalidone: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Chlorthalidone; Clonidine: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Cidofovir: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Cilostazol: (Moderate) Use caution with the coadministration of aspirin and cilostazol. Although the short-term (<= 4 days) coadministration of aspirin and cilostazol increased the inhibition of ADP-induced platelet aggregation by 22% to 37% compared to aspirin or cilostazol use alone, no clinically significant effect on PT, aPTT, or bleeding time was observed compared to aspirin alone. In clinical trials, there was no apparent increase in hemorrhagic adverse effects in patients taking cilostazol and aspirin compared to aspirin alone. The effects of long-term coadministration are unknown. Monitor for bleeding during concomitant therapy.
Citalopram: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Clomipramine: (Moderate) Clomipramine may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. This may increase the risk for an upper GI bleed.
Clopidogrel: (Moderate) Although aspirin may be used in combination with clopidogrel, both drugs are associated with bleeding. In clinical trials, bleeding rates with concomitant use of aspirin and clopidogrel vs. placebo vary from similar to increased bleeding with coadministration. Monitor for bleeding during concomitant therapy.
Colistimethate, Colistin, Polymyxin E: (Major) Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including salicylates, may increase serum concentrations of either drug.
Colistin: (Major) Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including salicylates, may increase serum concentrations of either drug.
Collagenase: (Moderate) Cautious use of injectable collagenase by patients taking more than 150 mg/day of aspirin is advised. The efficacy and safety of administering injectable collagenase to a patient taking more than 150 mg/day of aspirin within 7 days before the injection are unknown. Receipt of injectable collagenase may cause an ecchymosis or bleeding at the injection site.
Corticosteroids: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
Cyclosporine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like cyclosporine may lead to additive nephrotoxicity.
Dabigatran: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy.
Dalteparin: (Moderate) An additive risk of bleeding may be seen in patients receiving a low molecular weight heparin in combination with other agents known to increase the risk of bleeding such as salicylates. Monitor clinical and laboratory response closely during concurrent use.
Danazol: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Dapagliflozin: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Dapagliflozin; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Dapagliflozin; Saxagliptin: (Moderate) Salicylates can indirectly increase insulin secretion, decreasing blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving saxagliptin. (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Daratumumab; Hyaluronidase: (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates.
Defibrotide: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Dextrin: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Dichlorphenamide: (Major) Dichlorphenamide is contraindicated with the concomitant use of high dose aspirin, ASA and should be used cautiously in patients receiving low dose aspirin. Dichlorphenamide may cause an elevation in salicylate concentrations in patients receiving aspirin. Adverse reactions including anorexia, tachypnea, lethargy, and coma have been reported with the concomitant use of dichlorphenamide and high dose aspirin.
Diclofenac: (Major) Increased adverse gastrointestinal effects, including gastric ulceration or blood loss, are possible if diclofenac is used with salicylates. The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function.
Diclofenac; Misoprostol: (Major) Increased adverse gastrointestinal effects, including gastric ulceration or blood loss, are possible if diclofenac is used with salicylates. The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function.
Dicloxacillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Diflunisal: (Major) The concurrent use of diflunisal and salicylates is not recommended due to the increased risk of gastrointestinal toxicity with little or no increase in anti-inflammatory efficacy.
Diphenhydramine; Ibuprofen: (Major) Concomitant use of analgesic doses of aspirin with ibuprofen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of ibuprofen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of ibuprofen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to ibuprofen interference with the antiplatelet effect of aspirin. A decrease in antiplatelet activity (53%) was observed at 24 hours after 6 days of ibuprofen 400 mg/day given 2 hours before immediate-release aspirin 81 mg/day. An interaction was still observed, but minimized, when ibuprofen 400 mg/day was given as early as 8 hours before immediate-release aspirin (90.7%). There was no interaction when ibuprofen 400 mg/day was given 2 hours after the immediate-release aspirin dose (99.2%). In a study with enteric-coated aspirin, subjects given aspirin 81 mg/day with ibuprofen 400 mg 3 times daily (2, 7, and 12 hours after aspirin dose) for 6 days, there was an interaction with antiplatelet activity at 24 hours after the day 6 aspirin dose (67%). An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs' ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with routine as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure.
Diphenhydramine; Naproxen: (Major) Concomitant use of analgesic doses of aspirin with naproxen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of naproxen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of naproxen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to naproxen interference with the antiplatelet effect of aspirin during the washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with immediate-release aspirin 81 mg/day vs. aspirin alone [(93.1% (naproxen and aspirin) vs. 98.7% (aspirin alone)]. The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). The interaction may also be present with the use of prescription doses of naproxen or with enteric-coated, low-dose aspirin; however, peak interference with aspirin function may occur later due to a longer washout period.
Dipyridamole: (Moderate) Although aspirin may be used in combination with dipyridamole, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Drotrecogin Alfa: (Major) Treatment with drotrecogin alfa should be carefully considered in patients who are receiving or have received salicylates within 7 days. These patients are at increased risk of bleeding during drotrecogin alfa therapy. Caution should be used when drotrecogin alfa is used with any other drugs that affect hemostasis.
Edoxaban: (Major) Monitor for bleeding in patients who require chronic treatment with aspirin. Concomitant use of edoxaban with drugs that affect hemostasis, such as aspirin, may increase the risk of bleeding. The coadministration of aspirin (100 mg or 325 mg) and edoxaban increased bleeding time relative to that seen with either drug alone.
Efavirenz; Emtricitabine; Tenofovir: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Empagliflozin: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Empagliflozin; Linagliptin: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents, such as linagliptin. (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Empagliflozin; Linagliptin; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents, such as linagliptin. (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Empagliflozin; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Emtricitabine; Tenofovir disoproxil fumarate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Enalapril, Enalaprilat: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Enalapril; Felodipine: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Enoxaparin: (Moderate) An additive risk of bleeding may be seen in patients receiving a low molecular weight heparin in combination with other agents known to increase the risk of bleeding such as salicylates. Monitor clinical and laboratory response closely during concurrent use.
Epoprostenol: (Moderate) When used concurrently with platelet inhibitors, epoprostenol may increase the risk of bleeding.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Eptifibatide: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Ergotamine; Caffeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin.
Ertugliflozin; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control.
Ertugliflozin; Sitagliptin: (Moderate) Salicylates can indirectly increase insulin secretion, decreasing blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Escitalopram: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Ethacrynic Acid: (Moderate) Salicylates may decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of renal prostaglandin synthesis. Patients receiving loop diuretics and salicylates should be monitored for changes in the effectiveness of their diuretic therapy.
Ethanol: (Major) Concomitant ingestion of alcohol with salicylates, especially aspirin, ASA, increases the risk of developing gastric irritation and GI mucosal bleeding. Alcohol and salicylates are mucosal irritants and aspirin decreases platelet aggregation. Routine ingestion of alcohol and aspirin can cause significant GI bleeding, which may or may not be overt. Even occasional concomitant use of salicylates and alcohol should be avoided. Chronic ingestion of alcohol is often associated with hypoprothrombinemia and this condition increases the risk of salicylate-induced bleeding. Patients should be warned regarding the potential for increased risk of GI bleeding if alcohol-containing beverages are taken concurrently with salicylates. (Major) Concomitant ingestion of ethanol with salicylates, especially aspirin, ASA, increases the risk of developing gastric irritation and GI mucosal bleeding. Ethanol and salicylates are mucosal irritants and aspirin decreases platelet aggregation. Routine ingestion of ethanol and aspirin can cause significant GI bleeding, which may or may not be overt. Even occasional concomitant use of salicylates and ethanol should be avoided. Chronic alcoholism is often associated with hypoprothrombinemia and this condition increases the risk of salicylate-induced bleeding. Patients should be warned regarding the potential for increased risk of GI bleeding if alcohol-containing beverages are taken concurrently with salicylates.
Ethotoin: (Minor) Large doses of salicylates can displace hydantoins from plasma protein-binding sites. Although increased serum concentrations of unbound phenytoin may lead to phenytoin toxicity, the liver may also more rapidly clear unbound drug.
Etodolac: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity.
Famotidine; Ibuprofen: (Major) Concomitant use of analgesic doses of aspirin with ibuprofen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of ibuprofen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of ibuprofen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to ibuprofen interference with the antiplatelet effect of aspirin. A decrease in antiplatelet activity (53%) was observed at 24 hours after 6 days of ibuprofen 400 mg/day given 2 hours before immediate-release aspirin 81 mg/day. An interaction was still observed, but minimized, when ibuprofen 400 mg/day was given as early as 8 hours before immediate-release aspirin (90.7%). There was no interaction when ibuprofen 400 mg/day was given 2 hours after the immediate-release aspirin dose (99.2%). In a study with enteric-coated aspirin, subjects given aspirin 81 mg/day with ibuprofen 400 mg 3 times daily (2, 7, and 12 hours after aspirin dose) for 6 days, there was an interaction with antiplatelet activity at 24 hours after the day 6 aspirin dose (67%). An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs' ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with routine as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure.
Fenoprofen: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased.
Flavocoxid, Flavocoxid; Citrated Zinc Bisglycinate: (Major) Because flavocoxid has been associated with isolated cases of occult GI bleeding, additive pharmacodynamic effects may be seen in patients receiving salicylates. Avoid the concurrent use of flavocoxid with salicylates until further data are available.
Fluoxetine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Flurbiprofen: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity.
Fluvoxamine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Fondaparinux: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors (e.g. aspirin, ASA) in combination with fondaparinux. Data on the concomitant use of fondaparinux with aspirin are lacking; however, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Foscarnet: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents, such as foscarnet, may lead to additive nephrotoxicity.
Fosinopril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Fosphenytoin: (Minor) Large doses of salicylates can displace phenytoin from plasma protein-binding sites. Although increased serum concentrations of unbound phenytoin may lead to phenytoin toxicity, the liver may also more rapidly clear unbound drug. Fosphenytoin is converted to phenytoin in vivo, so this interaction may also occur with fosphenytoin.
Furosemide: (Moderate) Salicylates may decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of renal prostaglandin synthesis. Patients receiving loop diuretics and salicylates should be monitored for changes in the effectiveness of their diuretic therapy.
Gallium Ga 68 Dotatate: (Major) In general, avoid use of mannitol and salicylates. Concomitant administration of nephrotoxic drugs, such as the salicylates, increases the risk of renal failure after administration of mannitol. However, mannitol promotes the urinary excretion of salicylates, and may be used as an adjunct in salicylate intoxication.
Garlic, Allium sativum: (Moderate) Garlic, Allium sativum may produce clinically-significant antiplatelet effects; until more data are available, garlic should be used cautiously in patients receiving drugs with a potential risk for bleeding such as aspirin, ASA.
Ginger, Zingiber officinale: (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available.
Ginkgo, Ginkgo biloba: (Moderate) Monitor for signs or symptoms of bleeding with coadministration of ginkgo biloba and aspirin as an increased bleeding risk may occur. Although data are mixed, ginkgo biloba is reported to inhibit platelet aggregation and several case reports describe bleeding complications with ginkgo biloba, with or without concomitant drug therapy.
Glimepiride: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
Glimepiride; Rosiglitazone: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria.
Glipizide: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
Glipizide; Metformin: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control.
Glyburide: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
Glyburide; Metformin: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control.
Green Tea: (Moderate) Green tea should be used cautiously in patients taking aspirin; there may be an increased risk of bleeding. Monitoring clinical and/or laboratory parameters is warranted. Green tea has demonstrated antiplatelet and fibrinolytic actions in animals.
Griseofulvin: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended.
Heparin: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors (e.g. aspirin, ASA). Despite the potential drug-drug interaction between aspirin and heparin, heparin is frequently administered in combination with low-dose aspirin therapy to patients who have had an acute myocardial infarction and in other disease states. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Hyaluronidase: (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Hydrocodone; Ibuprofen: (Major) Concomitant use of analgesic doses of aspirin with ibuprofen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of ibuprofen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of ibuprofen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to ibuprofen interference with the antiplatelet effect of aspirin. A decrease in antiplatelet activity (53%) was observed at 24 hours after 6 days of ibuprofen 400 mg/day given 2 hours before immediate-release aspirin 81 mg/day. An interaction was still observed, but minimized, when ibuprofen 400 mg/day was given as early as 8 hours before immediate-release aspirin (90.7%). There was no interaction when ibuprofen 400 mg/day was given 2 hours after the immediate-release aspirin dose (99.2%). In a study with enteric-coated aspirin, subjects given aspirin 81 mg/day with ibuprofen 400 mg 3 times daily (2, 7, and 12 hours after aspirin dose) for 6 days, there was an interaction with antiplatelet activity at 24 hours after the day 6 aspirin dose (67%). An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs' ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with routine as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure.
Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with drugs that interfere with platelet function such as aspirin; the risk of bleeding may be increased. If coadministration with asprin is necessary, monitor platelet counts more frequently for evidence of thrombocytopenia. (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels. (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Ibrutinib: (Moderate) The concomitant use of ibrutinib and antiplatelet agents such as aspirin may increase the risk of bleeding; monitor patients for signs of bleeding. Severe bleeding events have occurred with ibrutinib therapy including intracranial hemorrhage, GI bleeding, hematuria, and post procedural hemorrhage; some events were fatal. The mechanism for bleeding with ibrutinib therapy is not well understood. Also, aspirin may mask signs of infection such as fever and in patients following treatment with antineoplastic agents or immunosuppressives.
Ibuprofen: (Major) Concomitant use of analgesic doses of aspirin with ibuprofen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of ibuprofen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of ibuprofen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to ibuprofen interference with the antiplatelet effect of aspirin. A decrease in antiplatelet activity (53%) was observed at 24 hours after 6 days of ibuprofen 400 mg/day given 2 hours before immediate-release aspirin 81 mg/day. An interaction was still observed, but minimized, when ibuprofen 400 mg/day was given as early as 8 hours before immediate-release aspirin (90.7%). There was no interaction when ibuprofen 400 mg/day was given 2 hours after the immediate-release aspirin dose (99.2%). In a study with enteric-coated aspirin, subjects given aspirin 81 mg/day with ibuprofen 400 mg 3 times daily (2, 7, and 12 hours after aspirin dose) for 6 days, there was an interaction with antiplatelet activity at 24 hours after the day 6 aspirin dose (67%). An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs' ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with routine as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure.
Ibuprofen; Oxycodone: (Major) Concomitant use of analgesic doses of aspirin with ibuprofen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of ibuprofen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of ibuprofen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to ibuprofen interference with the antiplatelet effect of aspirin. A decrease in antiplatelet activity (53%) was observed at 24 hours after 6 days of ibuprofen 400 mg/day given 2 hours before immediate-release aspirin 81 mg/day. An interaction was still observed, but minimized, when ibuprofen 400 mg/day was given as early as 8 hours before immediate-release aspirin (90.7%). There was no interaction when ibuprofen 400 mg/day was given 2 hours after the immediate-release aspirin dose (99.2%). In a study with enteric-coated aspirin, subjects given aspirin 81 mg/day with ibuprofen 400 mg 3 times daily (2, 7, and 12 hours after aspirin dose) for 6 days, there was an interaction with antiplatelet activity at 24 hours after the day 6 aspirin dose (67%). An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs' ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with routine as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure.
Ibuprofen; Pseudoephedrine: (Major) Concomitant use of analgesic doses of aspirin with ibuprofen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of ibuprofen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of ibuprofen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to ibuprofen interference with the antiplatelet effect of aspirin. A decrease in antiplatelet activity (53%) was observed at 24 hours after 6 days of ibuprofen 400 mg/day given 2 hours before immediate-release aspirin 81 mg/day. An interaction was still observed, but minimized, when ibuprofen 400 mg/day was given as early as 8 hours before immediate-release aspirin (90.7%). There was no interaction when ibuprofen 400 mg/day was given 2 hours after the immediate-release aspirin dose (99.2%). In a study with enteric-coated aspirin, subjects given aspirin 81 mg/day with ibuprofen 400 mg 3 times daily (2, 7, and 12 hours after aspirin dose) for 6 days, there was an interaction with antiplatelet activity at 24 hours after the day 6 aspirin dose (67%). An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs' ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with routine as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure.
Iloprost: (Moderate) When used concurrently with platelet inhibitors, inhaled iloprost may increase the risk of bleeding.
Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Incretin Mimetics: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
Indapamide: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics because salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance.
Indomethacin: (Major) The concurrent use of salicylates and indomethacin is not recommended. Combined use does not produce any greater therapeutic effect than indomethacin monotherapy. Also, a significantly greater incidence of gastrointestinal adverse effects with concurrent use has been observed. Because NSAIDs can cause GI bleeding, inhibit platelet aggregation, and prolong bleeding time, additive effects may be seen in patients receiving platelet inhibitors (e.g., aspirin), anticoagulants, or thrombolytic agents.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and salicylates due to the risk of glomerulonephritis and nephrotoxicity as well as the potential risk of bleeding from thrombocytopenia. Consider discontinuation of salicylates in a patient taking inotersen with a platelet count of less than 50,000 per microliter.
Insulins: (Moderate) Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia.
Intravenous Lipid Emulsions: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Iron Sucrose, Sucroferric Oxyhydroxide: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
Ketoprofen: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity.
Ketorolac: (Contraindicated) Ketorolac is contraindicated in patients currently receiving salicylates due to increased risk of serious NSAID-related adverse events, including gastrointestinal bleeding, ulceration, and perforation.
Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Lansoprazole; Naproxen: (Major) Concomitant use of analgesic doses of aspirin with naproxen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of naproxen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of naproxen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to naproxen interference with the antiplatelet effect of aspirin during the washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with immediate-release aspirin 81 mg/day vs. aspirin alone [(93.1% (naproxen and aspirin) vs. 98.7% (aspirin alone)]. The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). The interaction may also be present with the use of prescription doses of naproxen or with enteric-coated, low-dose aspirin; however, peak interference with aspirin function may occur later due to a longer washout period.
Lesinurad: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad.
Lesinurad; Allopurinol: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad.
Linagliptin: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents, such as linagliptin.
Linagliptin; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents, such as linagliptin.
Lisinopril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Loop diuretics: (Moderate) Salicylates may decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of renal prostaglandin synthesis. Patients receiving loop diuretics and salicylates should be monitored for changes in the effectiveness of their diuretic therapy.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Low Molecular Weight Heparins: (Moderate) An additive risk of bleeding may be seen in patients receiving a low molecular weight heparin in combination with other agents known to increase the risk of bleeding such as salicylates. Monitor clinical and laboratory response closely during concurrent use.
Macimorelin: (Major) Avoid use of macimorelin with drugs that directly affect pituitary growth hormone secretion, such as salicylates. Healthcare providers are advised to discontinue salicylate therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
Mannitol: (Major) In general, avoid use of mannitol and salicylates. Concomitant administration of nephrotoxic drugs, such as the salicylates, increases the risk of renal failure after administration of mannitol. However, mannitol promotes the urinary excretion of salicylates, and may be used as an adjunct in salicylate intoxication.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) No adverse events associated with the use of salicylates after varicella vaccination have been reported. However, the manufacturer of varicella virus vaccine live recommends the avoidance of salicylates or aspirin, ASA use for 6 weeks after vaccination. Reye's syndrome, which exclusively affects children under 15 years old, has been associated with aspirin use following active varicella infection. Vaccination with close clinical monitoring is recommended for children who require therapeutic aspirin, ASA therapy; according to the CDC the use of attenuated, live varicella virus vaccine is thought to present less risk than natural varicella disease to such children.
Meclofenamate Sodium: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity.
Mefenamic Acid: (Major) Increased adverse gastrointestinal (GI) effects are possible if mefenamic acid is used with salicylates. In addition, concomitant administration of salicylates and mefenamic acid may result in an increase in unbound plasma concentrations of either drug, which could result in greater adverse effects. In general, concomitant use of aspirin and mefenamic acid is not recommended.
Meglitinides: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of antidiabetic agents. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose or use of greater than maximum recommended daily dosages, salicylates can cause either hypoglycemia or hyperglycemia. Large doses of aspirin should be used cautiously in patients who receive antidiabetic agents.
Meloxicam: (Major) Additive adverse gastrointestinal (GI) effects are possible if meloxicam is used with salicylates (e.g., aspirin). The concurrent use of aspirin and a nonsteroidal anti-inflammatory drug (NSAID) does increase the risk of serious gastrointestinal events. Concomitant administration of aspirin, ASA (3000 mg/day) to healthy volunteers increased the meloxicam AUC by 10% and increased the meloxicam peak plasma concentrations by 24%. Because of its lack of platelet effects, meloxicam is not a substitute for aspirin for cardiovascular prophylaxis.
Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control.
Metformin; Repaglinide: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of antidiabetic agents. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose or use of greater than maximum recommended daily dosages, salicylates can cause either hypoglycemia or hyperglycemia. Large doses of aspirin should be used cautiously in patients who receive antidiabetic agents.
Metformin; Rosiglitazone: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria.
Metformin; Saxagliptin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. (Moderate) Salicylates can indirectly increase insulin secretion, decreasing blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving saxagliptin.
Metformin; Sitagliptin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. (Moderate) Salicylates can indirectly increase insulin secretion, decreasing blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Methazolamide: (Major) Avoid the coadministration of high-dose salicylates and carbonic anhydrase inhibitors, like methazolamide, whenever possible. The combination yielded reports of anorexia, tachypnea, lethargy, metabolic acidosis, coma, and death. The mechanism appears to be accumulation of the carbonic anhydrase inhibitor, resulting in increased CNS depression and metabolic acidosis. The acidosis may allow greater CNS penetration of the salicylate.
Methotrexate: (Major) Do not administer salicylates before or concomitantly with high doses of methotrexate, such as used in the treatment of osteosarcoma. Concomitant administration of some NSAIDs with high dose methotrexate therapy has been reported to elevate and prolong serum methotrexate concentrations, resulting in deaths from severe hematologic and gastrointestinal toxicity. Use caution when salicylates are administered concomitantly with lower doses of methotrexate. Salicylates have been reported to reduce the tubular secretion of methotrexate in an animal model and may enhance its toxicity. Methotrexate is partially bound to serum albumin, and toxicity may be increased because of displacement by salicylates.
Methyclothiazide: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Methylsulfonylmethane, MSM: (Moderate) It would be prudent for patients who take aspirin to avoid methylsulfonylmethane, MSM. Monitor patients who choose to take MSM while on aspirin therapy for bleeding. Patients taking MSM and anticoagulant drugs have reported increased anticoagulant effects such as increased bruising or blood in the stool.
Metoclopramide: (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
Metolazone: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Moexipril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Mycophenolate: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Nabumetone: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity.
Nafcillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Naproxen: (Major) Concomitant use of analgesic doses of aspirin with naproxen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of naproxen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of naproxen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to naproxen interference with the antiplatelet effect of aspirin during the washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with immediate-release aspirin 81 mg/day vs. aspirin alone [(93.1% (naproxen and aspirin) vs. 98.7% (aspirin alone)]. The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). The interaction may also be present with the use of prescription doses of naproxen or with enteric-coated, low-dose aspirin; however, peak interference with aspirin function may occur later due to a longer washout period.
Naproxen; Esomeprazole: (Major) Concomitant use of analgesic doses of aspirin with naproxen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of naproxen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of naproxen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to naproxen interference with the antiplatelet effect of aspirin during the washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with immediate-release aspirin 81 mg/day vs. aspirin alone [(93.1% (naproxen and aspirin) vs. 98.7% (aspirin alone)]. The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). The interaction may also be present with the use of prescription doses of naproxen or with enteric-coated, low-dose aspirin; however, peak interference with aspirin function may occur later due to a longer washout period.
Naproxen; Pseudoephedrine: (Major) Concomitant use of analgesic doses of aspirin with naproxen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of naproxen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of naproxen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to naproxen interference with the antiplatelet effect of aspirin during the washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with immediate-release aspirin 81 mg/day vs. aspirin alone [(93.1% (naproxen and aspirin) vs. 98.7% (aspirin alone)]. The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). The interaction may also be present with the use of prescription doses of naproxen or with enteric-coated, low-dose aspirin; however, peak interference with aspirin function may occur later due to a longer washout period.
Nateglinide: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of antidiabetic agents. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose or use of greater than maximum recommended daily dosages, salicylates can cause either hypoglycemia or hyperglycemia. Large doses of aspirin should be used cautiously in patients who receive antidiabetic agents.
Nitazoxanide: (Moderate) The active metabolite of nitazoxanide, tizoxanide, is highly bound to plasma proteins. Caution should be exercised when administering nitazoxanide concurrently with other highly plasma protein-bound drugs with narrow therapeutic indices because competition for binding sites may occur.
Nitroglycerin: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised.
Olanzapine; Fluoxetine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Omacetaxine: (Major) Avoid the concomitant use of omacetaxine and aspirin, ASA when the platelet count is less than 50,000 cells/microliter due to an increased risk of bleeding. Also, aspirin may mask signs of infection such as fever and pain in patients following treatment with antineoplastic agents or immunosuppressives. Aspirin, ASA should be used with caution in patients receiving immunosuppressive therapy. Special consideration should be given to myelosuppressed patients prior to receiving aspirin.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Omeprazole; Sodium Bicarbonate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Oxacillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Oxaprozin: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity.
Paroxetine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Penicillin G Benzathine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Penicillin G Benzathine; Penicillin G Procaine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Penicillin G Procaine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Penicillin G: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Penicillin V: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Penicillins: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Pentosan: (Moderate) Pentosan is a weak anticoagulant. Pentosan has 1/15 the anticoagulant activity of heparin. An additive risk of bleeding may be seen in patients receiving other platelet inhibitors (e.g. aspirin, ASA) in combination with pentosan. Also, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Pentoxifylline: (Moderate) The concomitant administration of platelet inhibitor with pentoxifylline in the treatment of intermittent claudication has not been evaluated and should be approached with caution, due to the potential for synergistic effects.
Perindopril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Perindopril; Amlodipine: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Pertuzumab; Trastuzumab; Hyaluronidase: (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Phentermine; Topiramate: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation.
Phenytoin: (Minor) Large doses of salicylates can displace phenytoin from plasma protein-binding sites. Although increased serum concentrations of unbound phenytoin may lead to phenytoin toxicity, the liver may also more rapidly clear unbound drug. Displacement of phenytoin from binding sites can lead to a decrease in the total phenytoin serum concentration. Close monitoring for excessive phenytoin toxicity or decreased phenytoin efficacy is recommended.
Phosphorated Carbohydrate Solution: (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels.
Phosphorus: (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels.
Photosensitizing agents (topical): (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Pioglitazone: (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria.
Pioglitazone; Glimepiride: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria.
Pioglitazone; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria.
Piperacillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Piperacillin; Tazobactam: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Piroxicam: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity.
Pneumococcal Vaccine, Polyvalent: (Moderate) Concomitant administration of antipyretics, such as aspirin, ASA, may decrease an individual's immunological response to the pneumococcal vaccine. A post-marketing study conducted in Poland using a non-US vaccination schedule (2, 3, 4, and 12 months of age) evaluated the impact of prophylactic oral acetaminophen on antibody responses to Prevnar 13. Data show that acetaminophen, given at the time of vaccination and then dosed at 6 to 8 hour intervals for 3 doses on a scheduled basis, reduced the antibody response to some serotypes after the third dose of Prevnar 13 when compared to the antibody responses of infants who only received antipyretics 'as needed' for treatment. However, reduced antibody responses were not observed after the fourth dose of Prevnar 13 with prophylactic acetaminophen.
Potassium Bicarbonate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Potassium Chloride: (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Potassium Citrate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Potassium Citrate; Citric Acid: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Potassium Phosphate: (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels.
Potassium Phosphate; Sodium Phosphate: (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels.
Pramlintide: (Moderate) Salicylates can indirectly increase insulin secretion, and thus decrease blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Prasterone, dehydroepiandrosterone, DHEA appears to have antiplatelet effects, which may prolong bleeding times. Because of these potential, varied effects on coagulation, patients receiving DHEA concurrently with aspirin, should be monitored for side effects or the need for dosage adjustments.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Prasterone, dehydroepiandrosterone, DHEA appears to have antiplatelet effects, which may prolong bleeding times. Because of these potential, varied effects on coagulation, patients receiving DHEA concurrently with aspirin, should be monitored for side effects or the need for dosage adjustments.
Prasugrel: (Moderate) Although indicated for concomitant use, both prasugrel and aspirin are associated with bleeding. Aspirin 150 mg did not alter prasugrel-mediated inhibition of platelet aggregation; however, bleeding time was increased compared to either drug alone. Monitor for bleeding during concomitant therapy.
Probenecid: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Probenecid; Colchicine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Psyllium: (Moderate) Psyllium can interfere with the absorption of certain oral drugs if administered concomitantly. For example, psyllium fiber can adsorb salicylates. Per the psyllium manufacturers, administration of other prescribed oral drugs should be separated from the administration of psyllium by at least 2 hours.
Quinapril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Ramipril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Repaglinide: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of antidiabetic agents. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose or use of greater than maximum recommended daily dosages, salicylates can cause either hypoglycemia or hyperglycemia. Large doses of aspirin should be used cautiously in patients who receive antidiabetic agents.
Rituximab; Hyaluronidase: (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Rivaroxaban: (Major) Salicylates such as aspirin are known to increase bleeding, and bleeding risk may be increased when these drugs are used concomitantly with rivaroxaban. The safety of long-term concomitant use of these drugs has not been studied. Promptly evaluate any signs or symptoms of bleeding or blood loss if patients are treated concomitantly with salicylates. In a single-dose drug interaction study, no pharmacokinetic interactions were observed after concomitant administration of acetylsalicylic acid (aspirin, ASA) with rivaroxaban.
Rosiglitazone: (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria.
Salicylic Acid: (Moderate) Concomitant use of salicylic acid with other drugs which may contribute to elevated serum salicylate levels (e.g., oral aspirin or other oral salicylates and other salicylate containing medications, such as sports injury creams) should be avoided. Concurrent use may result in excessive exposure to salicylic acid. Consider replacing aspirin therapy with an alternative non-steroidal anti-inflammatory agent that is not salicylate based where appropriate.
Saxagliptin: (Moderate) Salicylates can indirectly increase insulin secretion, decreasing blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving saxagliptin.
Selective serotonin reuptake inhibitors: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Serotonin norepinephrine reuptake inhibitors: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving aspirin, ASA or other salicylates which affect hemostasis. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with medications which impair platelet function and to promptly report any bleeding events to the practitioner.
Sertraline: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Sibutramine: (Moderate) Bleeding events have occurred in patients receiving sibutramine. Serotonin reuptake inhibitors, like sibutramine, may inhibit serotonin uptake by platelets, impairing platelet function. Aspirin has antiplatelet effects that may be additive. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Simvastatin; Sitagliptin: (Moderate) Salicylates can indirectly increase insulin secretion, decreasing blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Sitagliptin: (Moderate) Salicylates can indirectly increase insulin secretion, decreasing blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Sodium Bicarbonate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Sodium Citrate; Citric Acid: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Sodium Lactate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Sodium Thiosulfate; Salicylic Acid: (Moderate) Concomitant use of salicylic acid with other drugs which may contribute to elevated serum salicylate levels (e.g., oral aspirin or other oral salicylates and other salicylate containing medications, such as sports injury creams) should be avoided. Concurrent use may result in excessive exposure to salicylic acid. Consider replacing aspirin therapy with an alternative non-steroidal anti-inflammatory agent that is not salicylate based where appropriate.
Spironolactone: (Moderate) Concomitant use of aspirin and spironolactone may decrease the efficacy of spironolactone due to possible inhibition of tubular secretion of canrenone. Monitor patient closely during coadministration for desired effect; a higher maintenance dose may be necessary. In drug interaction studies, a single dose of 600 mg of aspirin inhibited the natriuretic effect of spironolactone. Salicylates can also increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. This combination may cause hyperkalemia.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of aspirin and spironolactone may decrease the efficacy of spironolactone due to possible inhibition of tubular secretion of canrenone. Monitor patient closely during coadministration for desired effect; a higher maintenance dose may be necessary. In drug interaction studies, a single dose of 600 mg of aspirin inhibited the natriuretic effect of spironolactone. Salicylates can also increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. This combination may cause hyperkalemia. (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Sulfinpyrazone: (Major) Salicylates should not be used concurrently with probenecid or sulfinpyrazone when these are used to treat hyperuricemia or gout because the uricosuric effect can be decreased. In addition, probenecid and sulfinpyrazone can decrease salicylic acid excretion leading to increased plasma concentration.
Sulfonamides: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Sulfonylureas: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
Sulindac: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity.
Sumatriptan; Naproxen: (Major) Concomitant use of analgesic doses of aspirin with naproxen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of naproxen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of naproxen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to naproxen interference with the antiplatelet effect of aspirin during the washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with immediate-release aspirin 81 mg/day vs. aspirin alone [(93.1% (naproxen and aspirin) vs. 98.7% (aspirin alone)]. The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). The interaction may also be present with the use of prescription doses of naproxen or with enteric-coated, low-dose aspirin; however, peak interference with aspirin function may occur later due to a longer washout period.
Tacrolimus: (Moderate) Tacrolimus, in the absence of overt renal impairment, may adversely affect renal function. Care should be taken in using tacrolimus with other nephrotoxic drugs, such as salicylates.
Telavancin: (Minor) Concurrent or sequential use of telavancin with drugs that inhibit renal prostaglandins such as salicylates may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Tenofovir Alafenamide: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
Tenofovir, PMPA: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus.
Thiazide diuretics: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Thiazolidinediones: (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria.
Thrombin Inhibitors: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Thrombolytic Agents: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Ticagrelor: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding.
Ticarcillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Ticarcillin; Clavulanic Acid: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Ticlopidine: (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy.
Tinzaparin: (Moderate) An additive risk of bleeding may be seen in patients receiving a low molecular weight heparin in combination with other agents known to increase the risk of bleeding such as salicylates. Monitor clinical and laboratory response closely during concurrent use.
Tipranavir: (Moderate) Caution should be used when administering tipranavir to patients receiving platelet inhibitors. In clinical trials, there have been reports of intracranial bleeding, including fatalities, in HIV infected patients receiving tipranavir as part of combination antiretroviral therapy. In many of these reports, the patients had other medical conditions (CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or alcoholism/alcohol abuse) or were receiving concomitant medications, including platelet inhibitors, that may have caused or contributed to these events.
Tirofiban: (Moderate) Unless contraindicated, aspirin is used in combination with tirofiban. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
Tolazamide: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
Tolbutamide: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria.
Tolmetin: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity.
Topiramate: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation.
Torsemide: (Moderate) Salicylates may decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of renal prostaglandin synthesis. Patients receiving loop diuretics and salicylates should be monitored for changes in the effectiveness of their diuretic therapy.
Trandolapril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation.
Trandolapril; Verapamil: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. (Minor) In a few reported cases, coadministration of verapamil with aspirin, ASA has led to increased bleeding times greater than observed with aspirin alone. The exact mechanism and clinical significance of this interaction is unknown.
Trastuzumab; Hyaluronidase: (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Trazodone: (Moderate) The combined use of trazodone and salicylates that affect hemostasis may elevate the risk for an upper GI bleed. Trazodone may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of salicylates. Additionally, salicylates impair the gastric mucosa defenses by inhibiting prostaglandin formation. It would be prudent for clinicians to monitor the patient's clinical status closely if trazodone is added to or removed from the regimen of a patient stabilized on salicylate therapy.
Treprostinil: (Moderate) When used concurrently with anticoagulants or platelet inhibitors, treprostinil may increase the risk of bleeding.
Triamterene: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia. (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Tromethamine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid.
Valproic Acid, Divalproex Sodium: (Moderate) Concurrent salicylate therapy can increase the free-fraction of valproic acid, causing possible valproic acid toxicity. Valproic acid levels should be monitored when these agents are used concomitantly.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Vancomycin: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents, such as vancomycin, may lead to additive nephrotoxicity.
Varicella-Zoster Virus Vaccine, Live: (Major) No adverse events associated with the use of salicylates after varicella vaccination have been reported. However, the manufacturer of varicella virus vaccine live recommends the avoidance of salicylates or aspirin, ASA use for 6 weeks after vaccination. Reye's syndrome, which exclusively affects children under 15 years old, has been associated with aspirin use following active varicella infection. Vaccination with close clinical monitoring is recommended for children who require therapeutic aspirin, ASA therapy; according to the CDC the use of attenuated, live varicella virus vaccine is thought to present less risk than natural varicella disease to such children.
Verapamil: (Minor) In a few reported cases, coadministration of verapamil with aspirin, ASA has led to increased bleeding times greater than observed with aspirin alone. The exact mechanism and clinical significance of this interaction is unknown.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with aspirin is necessary due to the risk of decreased verteporfin efficacy. Verteporfin is a light-activated drug. Once activated, local damage to neovascular endothelium results in a release of procoagulant and vasoactive factors resulting in platelet aggregation, fibrin clot formation, and vasoconstriction. Concomitant use of drugs that decrease platelet aggregation like aspirin could decrease the efficacy of verteporfin therapy.
Vilazodone: (Moderate) Patients should be instructed to monitor for signs and symptoms of bleeding while taking vilazodone concurrently with salicylates or other platelet inhibitors and to promptly report any bleeding events to the practitioner. Platelet aggregation may be impaired by vilazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., aspirin, cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors).
Vorapaxar: (Moderate) Although indicated for concomitant use, both vorapaxar and aspirin are associated with bleeding. Monitor for bleeding during concomitant therapy.
Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving aspirin, ASA or other salicylates. Bleeding events related to drugs that inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be instructed to monitor for signs and symptoms of bleeding while taking vortioxetine concurrently with aspirin products and to promptly report any bleeding events to the practitioner.
Warfarin: (Major) Co-administration of aspirin and warfarin is associated with an increased risk of bleeding. Consider alternate therapy for aspirin for analgesic or antipyretic uses. If aspirin and warfarin are coadministered, monitor the patient for signs or symptoms of bleeding. Gastrointestinal irritation and impaired hemostasis secondary to platelet inhibition have been observed with relatively small doses of aspirin. In addition, aspirin may displace warfarin from protein binding sites leading to increased anticoagulation effects. Large doses (more than 3 to 4 g/day) of aspirin can cause hypoprothrombinemia, an additional risk factor for bleeding; hypoprothrombinemia has also been reported with aspirin doses less than 2 g/day. Lower doses (less than 100 mg) of aspirin are recommended for use in combination with aspirin for the prevention of cardiovascular events in specific cases, including in patients with mechanical mitral or aortic valve or atrial fibrillation after percutaneous coronary intervention or revascularization. The addition of warfarin to aspirin and a P2Y12 inhibitor in patients after ST-elevation myocardial infarction should be limited to situations where the risk of systemic or venous thromboembolism or stent thrombosis is considered to exceed that of bleeding. Data regarding the benefit vs. risk of combination therapy for other cardiovascular conditions remains unclear.
Zafirlukast: (Minor) Coadministration of aspirin may increase plasma concentrations of zafirlukast. The potential clinical sequelae of increased zafirlukast concentrations are not known.