Aspirin/omeprazole

Contraindications

Known allergy to aspirin and other NSAIDs

Patients with the syndrome of asthma, rhinitis, and nasal polyps; aspirin may cause severe urticaria, angioedema, or bronchospasm

Known hypersensitivity to aspirin, omeprazole, substituted benzimidazoles, or any of the excipients in the formulation

Proton pump inhibitors (PPIs) are contraindicated with rilpivirine-containing products

Not indicated for pediatric patients (safety and efficacy not established); aspirin is contraindicated in children with suspected viral infections, with or without fever, because of the risk of Reye syndrome with concomitant use of aspirin in certain viral illnesses

Cautions

Aspirin

• Even low doses of aspirin can inhibit platelet function, leading to an increase in bleeding time; monitor for signs of bleeding
• Aspirin is associated with serious GI adverse reactions, including inflammation, bleeding ulceration, and perforation of the upper and lower GI tract; other adverse reactions with aspirin include stomach pain, heartburn, nausea, and vomiting
• Avoid with severe renal failure (GFR <10 mL/min); regular use of aspirin is associated with a dose-dependent increased risk of chronic renal failure; aspirin decreases GFR and renal blood flow, especially with preexisting renal disease
• Long-term moderate-to high doses of aspirin may result in elevations in serum ALT levels; avoid with any degree of hepatic impairment
• Aspirin may elevate hepatic enzymes, blood urea nitrogen, and serum creatinine; may cause hyperkalemia, proteinuria, and prolonged bleeding time
• NSAIDs, including aspirin, may cause premature closure of the fetal ductus arteriosus; avoid use in pregnant women starting at 30 weeks of gestation (see Pregnancy)

Omeprazole

• Avoid use in Asian patients with unknown CYP2C19 genotype or those who are known to be poor metabolizers (see Drug Interactions and Pharmacogenomics)
• Acute interstitial nephritis has been observed in patients taking PPIs
• PPIs are possibly associated with increased incidence of C difficile-associated diarrhea (CDAD); consider diagnosis of CDAD for patients taking PPIs who have diarrhea that does not improve
• Published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine, particularly with prolonged (>1 yr), high-dose therapy
• Daily long-term use (eg, >3 years) may lead to malabsorption or a deficiency of cyanocobalamin
• Cutaneous lupus erythematosus and systemic lupus erythematosus (SLE) have been reported with PPIs
• Hypomagnesemia may occur with prolonged use (>1 year); adverse effects may result and include tetany, arrhythmias, and seizures; in 25% of cases reviewed, magnesium supplementation alone did not improve low serum magnesium levels and the PPI had to be discontinued
• Decreased gastric acidity increases serum chromogranin A (CgA) levels and may cause false-positive diagnostic results for neuroendocrine tumors; temporarily discontinue PPIs before assessing CgA levels

Drug interaction overview

• Also see Interactions section and Drug Interaction Checker
• Aspirin
  • Because of its ability to inhibit platelet aggregation, low dose aspirin is often used in conjunction with anticoagulants for prevention of thrombotic CV events; closely monitor INR, and for signs and symptoms of bleeding
  • Maintenance doses of aspirin >100 mg reduce ticagrelor effect in preventing thrombotic cardiovascular events; avoid coadministration of ticagrelor with the 325-mg/40-mg tablet strength
  • Counsel patients who consume ≥3 alcoholic drinks/day about the bleeding risks involved with chronic, heavy alcohol use while taking aspirin
  • Aspirin may decrease antihypertensive effect of ACE-inhibitors, beta blockers, or diuretics
  • Moderate aspirin doses may increase effect of oral hypoglycemics
• Omeprazole
  • PPIs are contraindicated with rilpivirine-containing products
  • Omeprazole inhibits hepatic isoenzyme CYP2C19 and may decrease metabolism of drugs that are CYP2C19 substrates (eg, citalopram, cilostazol, phenytoin, diazepam, tacrolimus)
  • Coadministration of clopidogrel with 80-mg omeprazole reduces clopidogrel’s pharmacological activity, even when administered 12 hr apart; avoid coadministration; clopidogrel’s antiplatelet effect is entirely due to an active metabolite; the metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications (eg, omeprazole) that interfere with CYP2C19 activity
  • CYP2C19 or CYP3A4 inducers (eg, St John’s Wort or rifampin) can substantially decrease omeprazole concentrations; avoid coadministration
  • Coadministration of PPIs with methotrexate (primarily at high dose) may elevate and prolong methotrexate serum levels and/or its metabolite, possibly leading to toxicity
  • May increase exposure to digoxin; monitor digoxin concentrations and adjust dose as needed to maintain therapeutic serum concentrations
  • May reduce absorption of drugs that are dependent on gastric pH for absorption (eg, iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole)