Bismuth subsalicylate (BSS) is an oral colloidal bismuth salt belonging to the salicylate class. It is used to relieve occasional diarrhea or heartburn and stomach upset. Products for non-prescription (OTC) use are approved for adults and children 12 years of age and older. Use of BSS in younger children is not recommended or approved OTC; consult a qualified health care provider. As with other salicylates, including aspirin, individuals who are pregnant, breast-feeding, or with bleeding risks should also not use BSS without health care provider approval. BSS is part of established prevention and treatment strategies for traveler's diarrhea. BSS can also be used as a component of quadruple-drug therapy (as first-line or rescue therapy) to eradicate Helicobacter pylori (H. pylori) gastrointestinal infection, and usually includes BSS plus 2 antimicrobials and a proton pump inhibitor.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Clinical studies of bismuth have utilized different salts, each containing differing amounts of bismuth. In the US, bismuth subsalicylate is commercially available. Each tablet or caplet or tablespoonful (i.e., 15 mL) contains 262 mg of bismuth subsalicylate (BSS) which is equivalent to 151 mg elemental bismuth. One tablespoonful (15 mL) of maximum strength liquid contains 525 mg of bismuth subsalicylate (BSS) which is equivalent to 303 mg elemental bismuth.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Tablets can be chewed or dissolved in the mouth.
-Caplets are to be swallowed whole with a drink of water.
Oral Liquid Formulations
-Shake suspension well before administration; measure dosage with calibrated oral syringe or cup.
Adverse reactions to bismuth subsalicylate are generally related to excessive doses. At recommended dosage, adverse effects are uncommon. A common, albeit harmless, adverse effect of bismuth ingestion is stool discoloration as a result of the formation of bismuth sulfide, a highly insoluble black salt. Dark brown or black stools are common during administration of bismuth subsalicylate. Tongue discoloration is also possible. Use of bismuth subsalicylate can cause constipation.
Bismuth subsalicylate is hydrolyzed by gastric acid to produce bismuth oxychloride and salicylic acid. Salicylic acid is absorbed systemically. Excessive use of bismuth subsalicylate or use with other salicylate (e.g., aspirin) containing products can produce symptoms of salicylate toxicity, especially in young children, elderly, or patients with renal impairment. Symptoms of salicylate toxicity include abdominal pain, diaphoresis, dizziness, drowsiness, headache, hearing loss, polydipsia, nausea, vomiting, and tinnitus.
Overdose of bismuth subsalicylate can produce signs of bismuth encephalopathy including anxiety, confusion, severe headache, lethargy, myasthenia, tremor or uncontrollable body movements.
Bismuth subsalicylate is hydrolyzed by gastric acid to produce bismuth oxychloride and salicylic acid. Salicylic acid is absorbed systemically. Use of bismuth subsalicylate or use with other salicylate (e.g., aspirin) containing products could lead to Reye's Syndrome. Reye's syndrome, a potentially fatal disease, has been associated with aspirin use in children following active varicella infection or other viral illnesses. Reye's syndrome has been reported in children of all ages; however, most of the reported cases have occurred in children 5-10 years of age. Data are not strong to support a dose-dependent association with Reyes's syndrome ; however, one case-controlled study reported that patients who developed Reye's syndrome (n = 27) had received larger doses for a longer duration compared with controls who did not develop Reye's syndrome. Of the patients who developed Reye's syndrome, 67% were receiving > 20 mg/kg/day of salicylates compared with only 22% of controls. Reye's syndrome is a multisystem disorder evidenced by persistent vomiting, altered sensorium, elevated hepatic enzymes, hypoprothrombinemia, hyperammonemia, convulsions, and encephalopathy.
Because systemic concentrations of salicylic acid are detectable during therapy with bismuth subsalicylate, its use is contraindicated in patients with salicylate hypersensitivity. Repeated doses of bismuth subsalicylate for durations in excess of recommendations should be avoided to avoid salicylate toxicity. Advise patients to discontinue use of the product and seek medical attention if tinnitus or hearing impairment occur during treatment as these may be signs of toxicity. Avoid concurrent treatment with bismuth subsalicylate and other salicylates, including aspirin.
A FDA rule, effective April 17, 2004, eliminated labeling for the non-prescription (OTC) administration of bismuth subsalicylate in neonates, infants and children < 12 years old due to lack of adequate data to support use in this age group. Because systemic concentrations of salicylate are detectable during therapy with bismuth subsalicylate, any use of bismuth subsalicylate should be avoided in febrile pediatric patients until the possibility of influenza-like or varicella infection has been eliminated due to the risk of Reye's syndrome. Current evidence suggests that acetylated salicylates such as aspirin are associated with this complication; aspirin has been associated with the occurrence of Reye's syndrome when given to pediatric patients with varicella zoster (chickenpox) or influenza (flu). Although a causal relationship has not been confirmed, most authorities advise against the use of salicylates in pediatric patients with varicella, influenza, or other viral infection. It is also recommended that pediatric patients not be given salicylates for 6 weeks after receiving varicella vaccination.
Due to an increased risk of bleeding, bismuth subsalicylate therapy is contraindicated in patients with hematological disease (i.e., conditions that increases risk of bleeding) for example: hypoprothrombinemia, vitamin K deficiency, coagulopathy (e.g., hemophilia), severe hepatic impairment due to hepatic disease, thrombotic thrombocytopenic purpura (TTP), or in patients receiving warfarin anticoagulant therapy. Significant systemic absorption of salicylic acid may occur during chronic treatment or with large doses of bismuth subsalicylate. However, the risk of bleeding with non-acetylated salicylates is less than that of aspirin due to the lack of platelet effects. Since 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.
Bismuth subsalicylate is contraindicated in the presence of GI bleeding and in peptic ulcer disease. Chronic or high-dose bismuth subsalicylate therapy should be given with caution in patients with a history of or active GI disease including erosive gastritis and esophagitis. Such patients should be monitored closely, with special caution in tobacco smoking patients or in patients with alcoholism.
Prolonged use, or large doses of bismuth subsalicylate can increase the hypoglycemic effect of insulin, or oral hypoglycemics. Patients with diabetes mellitus should be treated with caution and warned of possible changes in blood glucose evaluations.
Patients with renal impairment (renal disease, renal failure) may be at risk for developing salicylate toxicity when receiving large doses of or chronic treatment with bismuth subsalicylate. Geriatric patients may be at increased risk of salicylate toxicity possibly due to decreased renal function associated with increased age.
Although bismuth subsalicylate has been shown to be effective in the treatment of traveler's diarrhea, it is not suitable as a single agent for the treatment of dysentery. Diarrhea accompanied by bloody stools and fever can indicate dysentery and patients should be referred to a physician.
Patient suffering from dehydration should be treated with caution. Bismuth subsalicylate will not address the problem of dehydration associated with diarrhea. Adequate administration of fluids is essential, especially to children.
Patients with gout should receive bismuth subsalicylate with caution. The salicylate content of bismuth subsalicylate can interfere with uricosuric antigout agents, and can also affect serum uric acid concentrations.
Bismuth subsalicylate is classified in FDA pregnancy risk category C; however, salicylates, including bismuth subsalicylate, should be avoided during pregnancy. The potential for premature closure of the ductus arteriosis, decreased birth weight, jaundice (due to competition with bilirubin for albumin binding), teratogenicity, perinatal mortality, and fetal or maternal hemorrhage exists. Early in pregnancy, occasional use of small doses of salicylates (60-80 mg/day) may be safe, but the risk for bleeding is still present. In general, salicylates should be avoided if possible in pregnancy. Excessive use of bismuth subsalicylate during the third trimester may also result in prolonged labor and obstetric delivery complications.
In general, salicylates are excreted into breast-milk and are potentially harmful to a nursing infant. Bismuth subsalicylate is considered possibly toxic in lactation and should be avoided during breast-feeding. If attempting to treat diarrhea, loperamide may be considered a preferable alternative (see Loperamide monograph); if treating dyspepsia or pyrosis, consider antacids and H2 blockers (see respective monographs).
Administration of bismuth subsalicylate may result in laboratory test interference. Bismuth preparations are known to suppress H. pylori; thus, ingestion of these preparations within 4 weeks of performing diagnostic tests for H. pylori may lead to false negative results. At a minimum, instruct the patient to avoid the use of these agents in the 4 weeks prior to the test.
For over-the-counter (non-prescription) treatment of nonspecific diarrhea:
Oral dosage:
Adults: 524 mg PO every 30 minutes or 1,050 mg PO every 1 hour as needed for diarrhea. Do not exceed 4,200 mg/day. May give until diarrhea stops or no more than 2 days.
Children and Adolescents 12 to 17 years: 524 mg PO every 30 minutes or 1,050 mg PO every 1 hour as needed for diarrhea. Do not exceed 4,200 mg/day. May give until diarrhea stops or no more than 2 days.
For over-the-counter (non-prescription) relief of gastric distress, including dyspepsia and pyrosis (heartburn) and related symptoms (e.g., nausea):
Oral dosage:
Adults: 262 mg to 524 mg PO every 30 minutes as needed. Do not exceed 4,200 mg/day. Do not use for more than 2 days; if symptoms persist consult health care provider.
Children and Adolescents 12 to 17 years: 262 mg to 524 mg PO every 30 minutes as needed. Do not exceed 4,200 mg/day. Do not use for more than 2 days; if symptoms persist consult health care provider.
For Helicobacter pylori (H. pylori) eradication*:
-for Helicobacter pylori (H. pylori) eradication* as part of initial bismuth-based quadruple therapy:
Oral dosage:
Adults: 524 mg PO 4 times daily in combination with metronidazole, tetracycline, and a proton pump inhibitor (PPI) for 10 to 14 days.
Children and Adolescents 11 to 17 years: 524 mg PO 4 times daily in combination with metronidazole, tetracycline, and a proton pump inhibitor (PPI) for 14 days.
Children 9 to 10 years: 262 mg PO 4 times daily in combination with metronidazole, tetracycline, and a proton pump inhibitor (PPI) for 14 days.
Children 1 to 8 years: 262 mg PO 4 times daily in combination with metronidazole, amoxicillin, and a proton pump inhibitor (PPI) for 14 days.
-for Helicobacter pylori (H. pylori) eradication* as part of salvage bismuth-based quadruple therapy:
Oral dosage:
Adults: 524 mg PO 4 times daily in combination with metronidazole, tetracycline, and a proton pump inhibitor (PPI) for 14 days.
Children and Adolescents 11 to 17 years: 524 mg PO 4 times daily in combination with metronidazole, tetracycline, and a proton pump inhibitor (PPI) for 14 days.
Children 9 to 10 years: 262 mg PO 4 times daily in combination with metronidazole, tetracycline, and a proton pump inhibitor (PPI) for 14 days.
Children 1 to 8 years: 262 mg PO 4 times daily in combination with metronidazole, amoxicillin, and a proton pump inhibitor (PPI) for 14 days.
-for Helicobacter pylori (H. pylori) eradication* as part of an alternative bismuth-based quadruple therapy:
Oral dosage:
Adults: 524 mg PO 4 times daily in combination with a proton pump inhibitor (PPI) plus 2 antibiotics for 10 to 14 days. Antibiotic combinations may include 2 of the following: amoxicillin, clarithromycin, levofloxacin, metronidazole, and tetracycline.
For the treatment of traveler's diarrhea*:
Oral dosage:
Adults: 524 mg PO 4 times daily or every 30 to 60 minutes until diarrhea subsides or 8 doses have been taken per 24 hours. May be considered in the treatment of mild traveler's diarrhea.
Children and Adolescents 12 years and older: 524 mg PO 4 times daily or every 30 to 60 minutes until diarrhea subsides or 8 doses have been taken per 24 hours. May be considered in the treatment of mild traveler's diarrhea.
Children 10 to 11 years: 262 mg PO every 30 to 60 minutes until diarrhea subsides or 8 doses have been taken per 24 hours. May be considered in the treatment of mild traveler's diarrhea.
Children 6 to 9 years: 175 mg PO every 30 to 60 minutes until diarrhea subsides or 8 doses have been taken per 24 hours. May be considered in the treatment of mild traveler's diarrhea.
Children 3 to 5 years: 87 mg PO every 30 to 60 minutes until diarrhea subsides or 8 doses have been taken per 24 hours. May be considered in the treatment of mild traveler's diarrhea.
For traveler's diarrhea prophylaxis*:
Oral dosage:
Adults: 2.1 or 4.2 g/day PO in 4 divided doses for any traveler. Start 1 day before departure and continue for 2 days after returning. There is no data on use beyond 4 weeks.
Maximum Dosage Limits:
-Adults
4.2 g/day PO.
-Geriatric
4.2 g/day PO.
-Adolescents
4.2 g/day PO.
-Children
12 years: 4.2 g/day PO.
11 years: Safety and efficacy have not been established; however, doses up to 2.1 g/day PO have been used off-label.
1 to 10 years: Safety and efficacy have not been established; however, doses up to 1.05 g/day PO have been used off-label.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; use intermittently with caution since any absorbed salicylate component is dependent on renal excretion.
*non-FDA-approved indication
Acarbose: (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.
Acebutolol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor for salicylate-related adverse effects, including salicylate toxicity, if concomitant use of aspirin and bismuth subsalicylate is necessary. Adverse reactions, such as bleeding, renal impairment, and tinnitus, may occur.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor for salicylate-related adverse effects, including salicylate toxicity, if concomitant use of aspirin and bismuth subsalicylate is necessary. Adverse reactions, such as bleeding, renal impairment, and tinnitus, may occur.
Acetaminophen; Aspirin: (Moderate) Monitor for salicylate-related adverse effects, including salicylate toxicity, if concomitant use of aspirin and bismuth subsalicylate is necessary. Adverse reactions, such as bleeding, renal impairment, and tinnitus, may occur.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for salicylate-related adverse effects, including salicylate toxicity, if concomitant use of aspirin and bismuth subsalicylate is necessary. Adverse reactions, such as bleeding, renal impairment, and tinnitus, may occur.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Acetaminophen; Codeine: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Acetaminophen; Hydrocodone: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Acetaminophen; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Acetaminophen; Oxycodone: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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.
Acetohydroxamic Acid: (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.
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.
Albuterol; Budesonide: (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.
Alfentanil: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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.
Alosetron: (Moderate) Use alosetron with caution and monitoring in patients taking additional medications that may reduce gastric motility, including antidiarrheals, due to increased risk for serious complications of constipation.
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.
Alteplase: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Amantadine: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of amantadine may produce additive effects.
Amikacin: (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.
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.
Aminolevulinic Acid: (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.
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) Avoid concomitant use of celecoxib with salicylates, such as bismuth subsalicylate, due to an increased risk of gastrointestinal toxicity, with little or no increase in efficacy.
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.
Amobarbital: (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.
Amoxapine: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of amoxapine may produce additive effects.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) Coadministration of bismuth subcitrate potassium and omeprazole resulted in a significant increase in the systemic absorption of bismuth. However, when administered in the FDA-approved dosage regimen, bismuth subcitrate potassium; metronidazole; tetracycline capsules (Pylera) is administered with omeprazole for 10 days. The manufacturer does not feel that short-term exposure to bismuth concentrations > 50 mcg/L will increase the risk of neurotoxicity; health care practitioners should be aware of this potential adverse effect.
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.
Argatroban: (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.
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: (Moderate) Monitor for salicylate-related adverse effects, including salicylate toxicity, if concomitant use of aspirin and bismuth subsalicylate is necessary. Adverse reactions, such as bleeding, renal impairment, and tinnitus, may occur.
Aspirin, ASA; Butalbital; Caffeine: (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. (Moderate) Monitor for salicylate-related adverse effects, including salicylate toxicity, if concomitant use of aspirin and bismuth subsalicylate is necessary. Adverse reactions, such as bleeding, renal impairment, and tinnitus, may occur.
Aspirin, ASA; Caffeine: (Moderate) Monitor for salicylate-related adverse effects, including salicylate toxicity, if concomitant use of aspirin and bismuth subsalicylate is necessary. Adverse reactions, such as bleeding, renal impairment, and tinnitus, may occur.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor for salicylate-related adverse effects, including salicylate toxicity, if concomitant use of aspirin and bismuth subsalicylate is necessary. Adverse reactions, such as bleeding, renal impairment, and tinnitus, may occur.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. (Moderate) Monitor for salicylate-related adverse effects, including salicylate toxicity, if concomitant use of aspirin and bismuth subsalicylate is necessary. Adverse reactions, such as bleeding, renal impairment, and tinnitus, may occur.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Monitor for salicylate-related adverse effects, including salicylate toxicity, if concomitant use of aspirin and bismuth subsalicylate is necessary. Adverse reactions, such as bleeding, renal impairment, and tinnitus, may occur. (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
Aspirin, ASA; Dipyridamole: (Moderate) Monitor for salicylate-related adverse effects, including salicylate toxicity, if concomitant use of aspirin and bismuth subsalicylate is necessary. Adverse reactions, such as bleeding, renal impairment, and tinnitus, may occur.
Aspirin, ASA; Omeprazole: (Moderate) Monitor for salicylate-related adverse effects, including salicylate toxicity, if concomitant use of aspirin and bismuth subsalicylate is necessary. Adverse reactions, such as bleeding, renal impairment, and tinnitus, may occur. (Minor) Coadministration of bismuth subcitrate potassium and omeprazole resulted in a significant increase in the systemic absorption of bismuth. However, when administered in the FDA-approved dosage regimen, bismuth subcitrate potassium; metronidazole; tetracycline capsules (Pylera) is administered with omeprazole for 10 days. The manufacturer does not feel that short-term exposure to bismuth concentrations > 50 mcg/L will increase the risk of neurotoxicity; health care practitioners should be aware of this potential adverse effect.
Aspirin, ASA; Oxycodone: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. (Moderate) Monitor for salicylate-related adverse effects, including salicylate toxicity, if concomitant use of aspirin and bismuth subsalicylate is necessary. Adverse reactions, such as bleeding, renal impairment, and tinnitus, may occur.
Atenolol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
Atenolol; Chlorthalidone: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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. (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.
Atropine; Difenoxin: (Moderate) Diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with bismuth may increase the risk of serious GI related adverse events.
Azelastine; Fluticasone: (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.
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.
Beclomethasone: (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.
Belladonna; Opium: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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.
Benzhydrocodone; Acetaminophen: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Benztropine: (Moderate) Both antidiarrheals and anticholinergics, such as benztropine, decrease GI motility. Use of these drugs together may produce additive effects on the GI track; thereby increasing the risk for toxic megacolon.
Beta-blockers: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
Betamethasone: (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.
Betaxolol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
Bethanechol: (Moderate) Pharmacodynamic interactions between loperamide and drugs that enhance peristalsis are theoretically possible. It is wise to avoid use loperamide in patients who require bethanechol.
Bictegravir; Emtricitabine; 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.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
Bisoprolol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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) Concurrent use of beta-blockers with bismuth subsalicylate 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. (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.
Bivalirudin: (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.
Brimonidine; Timolol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
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.
Budesonide: (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.
Budesonide; Formoterol: (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.
Budesonide; Glycopyrrolate; Formoterol: (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.
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 bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Butalbital; Acetaminophen: (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.
Butalbital; Acetaminophen; Caffeine: (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.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. (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.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. (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. (Moderate) Monitor for salicylate-related adverse effects, including salicylate toxicity, if concomitant use of aspirin and bismuth subsalicylate is necessary. Adverse reactions, such as bleeding, renal impairment, and tinnitus, may occur.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Minor) H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.
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.
Carteolol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
Carvedilol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
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) Avoid concomitant use of celecoxib with salicylates, such as bismuth subsalicylate, due to an increased risk of gastrointestinal toxicity, with little or no increase in efficacy.
Celecoxib; Tramadol: (Major) Avoid concomitant use of celecoxib with salicylates, such as bismuth subsalicylate, due to an increased risk of gastrointestinal toxicity, with little or no increase in efficacy. (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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; Codeine: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Chlorpheniramine; Hydrocodone: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of ibuprofen with bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Chlorpromazine: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of phenothiazines may produce additive effects.
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.
Ciclesonide: (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.
Cidofovir: (Major) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents may lead to additive nephrotoxicity. Salicylates should be given with caution to patients taking cidofovir.
Cimetidine: (Minor) H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.
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.
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.
Clozapine: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of clozapine may produce additive effects.
Codeine: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Codeine; Guaifenesin: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Codeine; Phenylephrine; Promethazine: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Codeine; Promethazine: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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.
Cortisone: (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.
Crofelemer: (Moderate) Pharmacodynamic interactions between crofelemer and other antidiarrheals are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking antidiarrheal medications that decrease GI motility may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. During clinical trials with crofelemer, patients were excluded if they were actively using other antidiarrheal medications. Use caution and monitor GI symptoms during coadministration.
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.
Darunavir; Cobicistat; Emtricitabine; 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.
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.
Deflazacort: (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.
Demeclocycline: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
Desvenlafaxine: (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.
Dexamethasone: (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.
Diclofenac: (Major) Avoid concomitant use of diclofenac with bismuth subsalicylate 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 bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Dicyclomine: (Moderate) Both antidiarrheals and anticholinergics, such as dicyclomine, decrease GI motility. Use of these drugs together may produce additive effects on the GI track; thereby increasing the risk for toxic megacolon.
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 bismuth subsalicylate 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 bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Diphenoxylate; Atropine: (Moderate) Diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with bismuth may increase the risk of serious GI related adverse events.
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.
Dorzolamide; Timolol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
Doxycycline: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
Dulaglutide: (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.
Duloxetine: (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.
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.
Efgartigimod Alfa; 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.
Elvitegravir; Cobicistat; Emtricitabine; 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.
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 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.
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 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.
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.
Esmolol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
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.
Exenatide: (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.
Famotidine: (Minor) H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.
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.
Fentanyl: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Fludrocortisone: (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.
Flunisolide: (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.
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.
Fluphenazine: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of phenothiazines may produce additive effects.
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.
Fluticasone: (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.
Fluticasone; Salmeterol: (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.
Fluticasone; Umeclidinium; Vilanterol: (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.
Fluticasone; Vilanterol: (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.
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.
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.
Formoterol; Mometasone: (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.
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.
Gentamicin: (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.
Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and bismuth subsalicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glipizide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and bismuth subsalicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glipizide; 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 sulfonylurea and bismuth subsalicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glyburide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and bismuth subsalicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glyburide; 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 sulfonylurea and bismuth subsalicylate 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.
H2-blockers: (Minor) H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.
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.
Homatropine; Hydrocodone: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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.
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; 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: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Hydrocodone; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Hydrocortisone: (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.
Hydromorphone: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (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.
Ibritumomab Tiuxetan: (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. (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels. (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
Ibuprofen: (Major) Avoid concomitant use of ibuprofen with bismuth subsalicylate 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 bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. (Minor) H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.
Ibuprofen; Oxycodone: (Major) Avoid concomitant use of ibuprofen with bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of ibuprofen with bismuth subsalicylate 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.
Indomethacin: (Major) The concurrent use of salicylates and indomethacin is not recommended. Combined use does not produce any greater therapeutic effect than indomethacin monotherapy. Also, a significantly greater incidence of gastrointestinal adverse effects with concurrent use has been observed. Because NSAIDs can cause GI bleeding, inhibit platelet aggregation, and prolong bleeding time, additive effects may be seen in patients receiving platelet inhibitors (e.g., aspirin), anticoagulants, or thrombolytic agents.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and salicylates due to the risk of glomerulonephritis and nephrotoxicity as well as the potential risk of bleeding from thrombocytopenia. Consider discontinuation of salicylates in a patient taking inotersen with a platelet count of less than 50,000 per microliter.
Insulin Aspart: (Moderate) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Aspart; Insulin Aspart Protamine: (Moderate) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Degludec: (Moderate) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Degludec; Liraglutide: (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. (Moderate) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Detemir: (Moderate) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glargine: (Moderate) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glargine; Lixisenatide: (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. (Moderate) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glulisine: (Moderate) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Lispro: (Moderate) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Lispro; Insulin Lispro Protamine: (Moderate) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin, Inhaled: (Moderate) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
Labetalol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
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.
Levobunolol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
Levomilnacipran: (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.
Levorphanol: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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.
Liraglutide: (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.
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.
Lixisenatide: (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.
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.
Mafenide: (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.
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.
Maprotiline: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of maprotiline may produce additive effects.
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 bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
Meperidine: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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; 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.
Methadone: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (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.
Methohexital: (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.
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.
Methylprednisolone: (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.
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: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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. (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.
Miglitol: (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.
Milnacipran: (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.
Minocycline: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
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.
Mometasone: (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.
Morphine: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Morphine; Naltrexone: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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.
Nadolol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
Naproxen: (Major) Avoid concomitant use of naproxen with bismuth subsalicylate 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 bismuth subsalicylate 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 bismuth subsalicylate 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.
Nebivolol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
Nebivolol; Valsartan: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
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.
Nizatidine: (Minor) H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.
Olanzapine: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of olanzapine may produce additive effects.
Olanzapine; Fluoxetine: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of olanzapine may produce additive effects. (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.
Olanzapine; Samidorphan: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of olanzapine may produce additive effects.
Oliceridine: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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.
Olopatadine; Mometasone: (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.
Omadacycline: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
Omeprazole: (Minor) Coadministration of bismuth subcitrate potassium and omeprazole resulted in a significant increase in the systemic absorption of bismuth. However, when administered in the FDA-approved dosage regimen, bismuth subcitrate potassium; metronidazole; tetracycline capsules (Pylera) is administered with omeprazole for 10 days. The manufacturer does not feel that short-term exposure to bismuth concentrations > 50 mcg/L will increase the risk of neurotoxicity; health care practitioners should be aware of this potential adverse effect.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Coadministration of bismuth subcitrate potassium and omeprazole resulted in a significant increase in the systemic absorption of bismuth. However, when administered in the FDA-approved dosage regimen, bismuth subcitrate potassium; metronidazole; tetracycline capsules (Pylera) is administered with omeprazole for 10 days. The manufacturer does not feel that short-term exposure to bismuth concentrations > 50 mcg/L will increase the risk of neurotoxicity; health care practitioners should be aware of this potential adverse effect.
Omeprazole; Sodium Bicarbonate: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance. (Minor) Coadministration of bismuth subcitrate potassium and omeprazole resulted in a significant increase in the systemic absorption of bismuth. However, when administered in the FDA-approved dosage regimen, bismuth subcitrate potassium; metronidazole; tetracycline capsules (Pylera) is administered with omeprazole for 10 days. The manufacturer does not feel that short-term exposure to bismuth concentrations > 50 mcg/L will increase the risk of neurotoxicity; health care practitioners should be aware of this potential adverse effect.
Opiate Agonists: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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.
Oxycodone: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Oxymorphone: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Paromomycin: (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.
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.
Pentobarbital: (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.
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.
Perphenazine: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of phenothiazines may produce additive effects.
Perphenazine; Amitriptyline: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of phenothiazines may produce additive effects.
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.
Phenobarbital: (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.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (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.
Phenytoin: (Minor) Large doses of salicylates can displace phenytoin from plasma protein-binding sites. Although increased serum concentrations of unbound phenytoin may lead to phenytoin toxicity, the liver may also more rapidly clear unbound drug. Displacement of phenytoin from binding sites can lead to a decrease in the total phenytoin serum concentration. Close monitoring for excessive phenytoin toxicity or decreased phenytoin efficacy is recommended.
Phosphorated Carbohydrate Solution: (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels.
Phosphorus: (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels.
Photosensitizing agents (topical): (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy.
Pindolol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
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) Monitor blood glucose during concomitant sulfonylurea and bismuth subsalicylate 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.
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.
Plazomicin: (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.
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.
Potassium Phosphate: (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels.
Potassium Phosphate; Sodium Phosphate: (Moderate) 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. (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels.
Pramlintide: (Moderate) Salicylates can indirectly increase insulin secretion, and thus decrease blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.
Prednisolone: (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.
Prednisone: (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.
Primidone: (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.
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.
Prochlorperazine: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of phenothiazines may produce additive effects.
Propranolol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
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.
Ranitidine: (Minor) H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.
Regular Insulin: (Moderate) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Regular Insulin; Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Remifentanil: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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.
Reteplase, r-PA: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
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.
Sarecycline: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
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.
Secobarbital: (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.
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.
Semaglutide: (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.
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.
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 Benzoate; Sodium Phenylacetate: (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.
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 Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (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.
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.
Sotalol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
Spironolactone: (Moderate) Monitor renal function periodically during concomitant use of spironolactone with bismuth subsalicylate. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and bismuth subsalicylate may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
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) Monitor renal function periodically during concomitant use of spironolactone with bismuth subsalicylate. In persons who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, coadministration of spironolactone and bismuth subsalicylate may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
Streptomycin: (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.
Sufentanil: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Sulfacetamide; Sulfur: (Moderate) Urinary alkalinizing agents may increase the excretion of salicylates by increasing renal clearance.
Sulfadiazine: (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.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (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.
Sulfasalazine: (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.
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) Monitor blood glucose during concomitant sulfonylurea and bismuth subsalicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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 bismuth subsalicylate 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.
Tapentadol: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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.
Tenecteplase: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
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 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.
Tetracycline: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
Tetracyclines: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
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.
Thioridazine: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of phenothiazines may produce additive effects.
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.
Timolol: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate 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.
Tirzepatide: (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.
Tobramycin: (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.
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.
Tramadol: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Tramadol; Acetaminophen: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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.
Triamcinolone: (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.
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.
Trifluoperazine: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of phenothiazines may produce additive effects.
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.
Venlafaxine: (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.
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).
Vincristine Liposomal: (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.
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.
Bismuth subsalicylate (BSS) has antiinfective actions, a direct mucosal protective effect, and weak antacid properties. Hydrolysis of bismuth subsalicylate in the stomach produces salicylic acid, which can, in turn, inhibit prostaglandin synthesis. Because secretory diarrhea can be adversely affected by prostaglandins but may improve after administration of indomethacin, the antidiarrheal action of bismuth subsalicylate may be a result of its actions on prostaglandin synthesis. BSS has been shown to prevent attachment of microorganisms to intestinal mucosa, to inactivate enterotoxins, and to exert a direct antimicrobial effect. Antimicrobial actions of bismuth are short-lived and, since bismuth salts are highly insoluble, limited to the lumen of the GI tract. Thus, both bismuth and salicylic acid are responsible for the action of BSS, depending on the clinical setting.
Laboratory studies have demonstrated the effectiveness of bismuth subsalicylate in blocking the effect of toxins from E. coli and from V. cholera at the mucosal surface. Bismuth subsalicylate has apparent activity against both enterotoxigenic bacteria and the heat-labile toxin they produce. Normalization of fluid movement in the GI tract by BSS may be one mechanism by which diarrhea is alleviated. In vitro data showed that bismuth subsalicylate failed to protect against fluid accumulation once the toxin was bound to the intestinal mucosa. Bismuth subcarbonate did not exert a protective effect on isolated bowel mucosa as did bismuth subsalicylate, implicating salicylic acid as a significant part of the effectiveness of BSS. Thus, antidiarrheal effects could be due to the effect of salicylic acid on prostaglandin metabolism and/or the antibacterial actions of bismuth.
In peptic ulcer disease, bismuth subsalicylate exerts microbicidal activity against H. pylori. The pharmacologic actions of bismuth salts against H. pylori can be attributed specifically to bismuth. Changes in H. pylori are seen soon after administration of bismuth. Deposits, believed to be bismuth complexes, appear on the external surface and beneath the cell wall of the organism. The loss of adherence property loosens the organism from the antral epithelium. Distortion and vacuolization of the bacterial cell and its contents completes the process. It has been shown in vitro that bismuth can lyse H. pylori within 30-90 minutes. Adding certain antimicrobial agents produces a synergistic effect, and studies have demonstrated the efficacy of combination therapy in treating gastritis and healing duodenal ulcers by suppressing Helicobacter pylori. Ulcer healing also may depend on the cytoprotective effect of bismuth subsalicylate. Bismuth compounds might stimulate the production of prostaglandins, alter GI mucus, and/or modulate the immune response.
Bismuth subsalicylate (BSS) is administered orally. Insoluble bismuth salts are formed in the small intestine by reaction with bicarbonate and phosphate anions. The formation of bismuth sulfide can occur in the colon; this highly insoluble black salt produces dark stools. Salicylic acid is highly protein-bound. Excretion of the bismuth content is mainly fecal. Salicylic acid excretion is primarily renal, mostly as free salicylic acid and conjugated metabolites.
Affected cytochrome P450 isoenzymes and drug transporters: None known
-Route-Specific Pharmacokinetics
Oral Route
Hydrolysis of bismuth subsalicylate occurs in the stomach, producing bismuth oxychloride and salicylic acid. The salicylic acid is rapidly and almost completely (about 90%) absorbed. Following a single-60 mL dose of BSS, peak salicylate levels were about 40 +/- 17 mcg/mL. However, due to the non-linear pharmacokinetics of salicylic acid, BSS doses of 30 mL every 30 minutes for 8 doses produced mean peak plasma salicylate levels of 137 +/- 20 mcg/mL in adults. Accumulation of salicylic acid is possible with repeated dosing or with concurrent administration of other salicylates (e.g., aspirin). Absorption of bismuth is negligible with recommended doses.