CONTRAINDICATIONS / PRECAUTIONS
Angina, cardiac disease, cerebrovascular disease, dehydration, edema, heart failure, hypertension, hypovolemia, myocardial infarction, peripheral vascular disease, renal disease, renal failure, renal impairment, stroke, systemic lupus erythematosus (SLE), thromboembolism
Salsalate, like all nonsteroidal anti-inflammatory drugs (NSAIDs), may exacerbate hypertension and congestive heart failure (see Adverse Reactions) and may cause an increased risk of serious cardiovascular thromboembolism, myocardial infarction, and stroke, which can be fatal. The risk may increase with duration of use, and patients with cardiovascular disease or risk factors for cardiovascular disease (e.g., high blood pressure) may be at greater risk. Caution is recommended when administering salsalate to patients with cardiac disease, angina, peripheral vascular disease, cerebrovascular disease (e.g., stroke, transient ischemic attack), pre-existing renal disease, fluid retention, hypertension, or edema. Salicylates should be used with caution in patients with renal impairment and with extreme caution, if at all, in patients with advanced, chronic renal failure, as salicylic acid and its metabolites are excreted in the urine (see Pharmacokinetics). Patients with renal impairment may be at increased risk of developing nephrotoxicity due to salicylate therapy. Renal function should be monitored periodically in patients receiving prolonged or high-dose salicylate therapy, as nephrotoxicity may occur. Prolonged exposure to high doses of salicylates may cause hypokalemia due to both renal and extrarenal losses. Salicylates should be used cautiously in patients with renal disease or systemic lupus erythematosus (SLE) due to the risk of decreased glomerular filtration rate in these patients. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with renal impairment, renal failure, heart failure, liver dysfunction, hypovolemia (dehydration), those taking diuretics and ACE inhibitors, or older patients. Discontinuation of NSAID therapy is usually followed by recovery.
Coronary artery bypass graft surgery (CABG)
Salsalate, like other NSAIDS, is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft surgery (CABG). An increased incidence of myocardial infarction and stroke was found through analysis of data regarding the use of a COX-2 selective NSAID for the treatment of pain in the first 10—14 days after CABG surgery.
Acute bronchospasm, asthma, nasal polyps, NSAID hypersensitivity, salicylate hypersensitivity
Salsalate is contraindicated in patients with salicylate hypersensitivity or NSAID hypersensitivity who have experienced asthma, urticaria, or other allergic reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactoid reactions to salsalate have been reported in such patients. Salsalate should not be used in patients with aspirin-sensitive asthma or the aspirin triad because of the approximate 5% cross-sensitivity that occurs between aspirin and NSAIDs. The triad typically occurs in patients with asthma who experience rhinitis with or without nasal polyps or who experience severe, potentially fatal, acute bronchospasm after taking aspirin or other NSAIDs. However, salsalate is less likely than aspirin to induce asthma in aspirin-sensitive patients. Among 10 patients with confirmed asthmatic reactions to aspirin, 2 had an asthmatic reaction after 2000 mg PO of salsalate; the reaction was confirmed by a second salsalate challenge.
Alcoholism, anemia, anticoagulant therapy, corticosteroid therapy, esophagitis, gastritis, GI bleeding, GI disease, GI perforation, peptic ulcer disease, tobacco smoking
Salsalate can cause gastritis, ulceration with or without GI perforation, and/or GI bleeding, which can occur at any time, often without preceding symptoms. Non-acetylated salicylates should be used with extreme caution in patients with a history of or active GI disease including erosive gastritis, esophagitis, GI bleeding, peptic ulcer disease, or previous NSAID-induced bleeding. Patients at increased risk for NSAID-induced GI bleeding include those receiving concurrent myelosuppressive chemotherapy, corticosteroid therapy, or anticoagulant therapy, tobacco smoking patients, and patients with alcoholism. Older patients seem to tolerate GI ulceration or bleeding less well than younger patients. Most fatal GI events occur in older or debilitated patients. In patients who develop gastric or duodenal ulcers during salicylate treatment, the drug should be discontinued due to an increased risk of bleeding and/or perforation. Anemia may be exacerbated during salicylate therapy due to GI blood loss. Hematocrit should be monitored periodically in patients receiving prolonged or high-dose salicylate therapy, as iron deficiency anemia may occur. Patients should not receive salicylates if they consume 3 or more alcoholic beverages per day because of the potential increased risk for GI bleeding. Closely monitor all patients for potential GI ulceration and bleeding (see Adverse Reactions).
Coagulopathy, G6PD deficiency, hemophilia, hepatic disease, hypoprothrombinemia, jaundice, thrombolytic therapy, thrombotic thrombocytopenic purpura (TTP), vitamin K deficiency
Carefully monitor patients with hypoprothrombinemia, vitamin K deficiency, coagulopathy (e.g., hemophilia), severe hepatic impairment due to hepatic disease, thrombotic thrombocytopenic purpura (TTP), or patients receiving anticoagulant therapy or thrombolytic therapy (see Drug Interactions) who take salsalate. If salicylate therapy is required, non-acetylated salicylates are preferred in these patients because of the lack of platelet effects. No changes in bleeding time or in platelet aggregation response to adenosine diphosphate or collagen occurred in either healthy patients or patients with hemophilia A who got salsalate. As salicylates may cause or aggravate hemolysis in patients with pyruvate kinase deficiency or rare variants of G6PD deficiency, these drugs should be avoided in these patients. Because of an increased risk of hepatotoxicity, liver function tests should be monitored in patients who are receiving high doses of salicylates and have juvenile arthritis, rheumatic fever, or pre-existing hepatic disease/impairment. Salsalate should be discontinued if elevated hepatic enzymes persist or worsen or if signs or symptoms of hepatic disease such as jaundice develop (see Adverse Reactions).
Bone marrow suppression, immunosuppression, infection, neutropenia
Salsalate should be used with caution in patients with immunosuppression or neutropenia following myelosuppressive chemotherapy. Salicylates may mask the signs of infection such as fever or pain in patients with bone marrow suppression.
Geriatric
Geriatric patients may be at increased risk of salicylate toxicity possibly due to decreased renal function. Elderly patients seem to tolerate GI ulceration or bleeding less well than younger individuals and many spontaneous reports of fatal GI events are in this population. Elderly patients at the highest risk for the development of gastric or duodenal ulcers are those using both NSAIDs and corticosteroids, with a prior history of peptic ulcer disease or NSAID-related GI bleeding, high-dose NSAID therapy, complaints of dyspepsia, and those with concurrent disease states that increase their risk of mortality from a GI bleed or perforation. Elderly patients are more likely to have concomitant disease states that may exacerbate salicylate-induced renal changes. Use the lowest effective dose in patients at risk. Monitor the geriatric adult for the development of pedal edema, rales, blood pressure elevation, or changes in creatinine or BUN concentrations after initiating salsalate therapy. Consider monitoring of stool for occult blood, serum magnesium and potassium concentrations, and a complete blood count at baseline and periodically during chronic salicylate therapy. According to the Beers Criteria, nonacetylated salicylates are potentially inappropriate medications (PIMs) in geriatric patients with chronic kidney disease Stage IV or higher (CrCl less than 30 mL/minute); avoid use in this population due to the potential risk of acute kidney injury and further decline of renal function. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs); salicylates should be reserved for symptoms and/or inflammatory conditions for which lower risk analgesics (e.g., acetaminophen) have either failed or are not clinically indicated. Salicylates may cause GI bleeding in patients with a prior history of, or with increased risk for, GI bleeding. In addition, salicylates may cause or worsen renal failure, increase blood pressure, or exacerbate heart failure.
Ascites
Sodium-restricted patients or patients with hypovolemic states (e.g., ascites, dehydration, heart failure, hypertension, or hypovolemia) may be more susceptible to adverse renal effects of salicylate therapy, like salsalate. In patients with carditis, high doses of salicylates may precipitate congestive heart failure or pulmonary edema.
Acid/base imbalance, metabolic acidosis, metabolic alkalosis, respiratory acidosis, respiratory alkalosis
The respiratory effects of salicylates, such as salsalate, may contribute to serious acid/base imbalance in patients with underlying acid/base disorders (e.g., metabolic acidosis, metabolic alkalosis, respiratory acidosis, or respiratory alkalosis) or in overdose situations. Patients who are unable to compensate for salicylate-induced metabolic acidosis (i.e., respiratory response to CO2 is depressed) will develop respiratory acidosis and increased concentrations of plasma CO2.
Gout, hyperuricemia
In patients with gout, salsalate may increase serum uric acid concentrations, resulting in hyperuricemia, and interfere with the efficacy of uricosuric agents.
Children, influenza, varicella
Reye's Syndrome may develop in children who have chicken pox (varicella), influenza, or flu symptoms. Some studies suggest a possible association between the development of Reye's Syndrome and the use of medicines containing salicylate or aspirin. Salsalate contains a salicylate and therefore is not recommended for use in children with chicken pox, influenza, or flu symptoms.
Laboratory test interference
Salsalate may cause laboratory test interference. Salicylate competes with thyroid hormone for binding to plasma proteins, which may be reflected in a depressed plasma T4 value in some patients; thyroid function and basal metabolism are unaffected.
Pregnancy
Avoid salsalate use during the third trimester of pregnancy (starting at 30 weeks of gestation) due to the risk of premature closure of the fetal ductus arteriosus and persistent pulmonary hypertension in the neonate. If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs and follow up according to clinical practice. Use of NSAIDs around 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required. There are no adequate and well-controlled studies of salsalate in pregnant women.
Breast-feeding
Use caution when salsalate is administered to a breast-feeding woman. It is not known whether salsalate is excreted in human milk. The primary metabolite of salsalate, salicylic acid, is distributed into breast milk in concentrations approximating the maternal blood concentration. The infant of a mother receiving salsalate therapy may ingest in mother's milk 30% to 80% as much salicylate per kg of body weight as the mother is taking.
DRUG INTERACTIONS
Acetaminophen; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
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.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Alkalinizing Agents: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
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) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (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) Monitor blood glucose during concomitant thiazolidinedione and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. (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.
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) Concurrent use of salsalate and celecoxib is generally not recommended due to the increased risks of bleeding and nephrotoxicity. Concurrent use of salsalate and NSAIDs does not produce greater therapeutic effect compared to the use of NSAIDs alone.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
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.
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.
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. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
Atenolol; Chlorthalidone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Azilsartan; Chlorthalidone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Bendroflumethiazide; Nadolol: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Beta-blockers: (Moderate) Concurrent use of beta-blockers with salsalate 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.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
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) Avoid concomitant use of meloxicam with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Canagliflozin: (Moderate) Monitor blood glucose during concomitant canagliflozin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Canagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant canagliflozin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
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) Concurrent use of salsalate and celecoxib is generally not recommended due to the increased risks of bleeding and nephrotoxicity. Concurrent use of salsalate and NSAIDs does not produce greater therapeutic effect compared to the use of NSAIDs alone.
Celecoxib; Tramadol: (Major) Concurrent use of salsalate and celecoxib is generally not recommended due to the increased risks of bleeding and nephrotoxicity. Concurrent use of salsalate and NSAIDs does not produce greater therapeutic effect compared to the use of NSAIDs alone.
Chlorothiazide: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of ibuprofen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Chlorthalidone; Clonidine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Cidofovir: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs), such as salsalate, is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Citalopram: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis 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. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
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.
Corticosteroids: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
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.
Dapagliflozin: (Moderate) Monitor blood glucose during concomitant dapagliflozin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dapagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant dapagliflozin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant dapagliflozin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
Dichlorphenamide: (Moderate) Use dichlorphenamide and salsalate together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Major) Avoid concomitant use of diclofenac with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Diclofenac; Misoprostol: (Major) Avoid concomitant use of diclofenac with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
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) Avoid concomitant use of ibuprofen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Diphenhydramine; Naproxen: (Major) Avoid concomitant use of naproxen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
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.
Edoxaban: (Moderate) Patients taking large doses of salicylates and edoxaban should be monitored closely for bleeding. Large doses of salicylates (3 g to 4 g/day or more) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Efavirenz; 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.
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) Monitor blood glucose during concomitant empagliflozin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant empagliflozin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant linagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant empagliflozin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant linagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant empagliflozin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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; 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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
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.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Ertugliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant sitagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Escitalopram: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis 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. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
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.
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.
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.
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.
Fluoxetine: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis 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. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
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 (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis 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. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
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.
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) Monitor blood glucose during concomitant thiazolidinedione and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Hydrocodone; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Ibritumomab Tiuxetan: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
Ibuprofen: (Major) Avoid concomitant use of ibuprofen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Ibuprofen; Famotidine: (Major) Avoid concomitant use of ibuprofen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Ibuprofen; Oxycodone: (Major) Avoid concomitant use of ibuprofen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of ibuprofen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
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) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
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) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
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; Naproxen: (Major) Avoid concomitant use of naproxen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Linagliptin: (Moderate) Monitor blood glucose during concomitant linagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant linagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Lithium: (Moderate) NSAIDs interfere with lithium excretion and may lead to elevated lithium serum concentrations. If NSAID therapy is started or stopped in a patient stabilized on lithium, monitor for evidence of lithium toxicity or decreased clinical effects, respectively.
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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
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) Avoid concomitant use of meloxicam with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Metformin: (Moderate) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Repaglinide: (Moderate) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (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) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant sitagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Metolazone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
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.
Naproxen: (Major) Avoid concomitant use of naproxen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Naproxen; Esomeprazole: (Major) Avoid concomitant use of naproxen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Naproxen; Pseudoephedrine: (Major) Avoid concomitant use of naproxen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
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.
Olanzapine; Fluoxetine: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis 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. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Omeprazole; Sodium Bicarbonate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
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 (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis 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. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
Penicillins: (Minor) Due to high protein binding, salicylates could be displaced from binding sites or could displace other highly protein-bound drugs such as penicillins. An enhanced effect of the displaced drug may occur.
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.
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.
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.
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) Monitor blood glucose during concomitant thiazolidinedione and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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) Monitor blood glucose during concomitant thiazolidinedione and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Pioglitazone; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
Potassium Bicarbonate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance. (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) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
Potassium Citrate; Citric Acid: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance. (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance.
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.
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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
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) Monitor blood glucose during concomitant thiazolidinedione and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Selective serotonin reuptake inhibitors: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis 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. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
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 (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis 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. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
Simvastatin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant sitagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sitagliptin: (Moderate) Monitor blood glucose during concomitant sitagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sodium Acetate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
Sodium Bicarbonate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
Sodium Citrate; Citric Acid: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
Sodium Lactate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
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) 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.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. (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.
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) Avoid concomitant use of naproxen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, 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 a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
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.
Thiazide diuretics: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Thiazolidinediones: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
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.
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.
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) Monitor for signs and symptoms of bleeding during concomitant trazodone and salicylate use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when serotonin norepinephrine reuptake inhibitors are coadministered with another anticoagulant.
Treprostinil: (Moderate) When used concurrently with anticoagulants or platelet inhibitors, treprostinil may increase the risk of bleeding.
Triamterene: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant triamterene and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant triamterene and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
Tromethamine: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant thiazide diuretic and salicylate use. Salicylate use decreases glomerular filtration rate and renal blood flow, and concomitant diuretic use may increase the risk of this reaction. Salicylates may diminish the effectiveness of diuretics due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.
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.
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).
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: (Moderate) Coadministration of salicylates and warfarin may result in an increased risk of bleeding. Salicylates may displace warfarin from protein binding sites leading to increased anticoagulation effects. Hypoprothrombinemia, an additional risk factor for bleeding, also has been reported with salicylates. Non-acetylated salicylates do not appear to affect platelet aggregation in the same manner as aspirin and are associated with a lower risk of bleeding when given currently with warfarin. If salicylates and warfarin are coadministered, monitor the patient for signs or symptoms of bleeding.