ASPIRIN; OMEPRAZOLE
Clinical safety rating: safe
Can reduce absorption of drugs requiring gastric pH for absorption (eg ketoconazole) May increase risk of Clostridium difficile-associated diarrhea and bone fractures with long-term use.
Aspirin irreversibly acetylates cyclooxygenase (COX-1 and COX-2), inhibiting thromboxane A2 synthesis and platelet aggregation. Omeprazole is a proton pump inhibitor that irreversibly binds to H+/K+-ATPase in gastric parietal cells, reducing gastric acid secretion.
| Metabolism | Aspirin: Rapidly hydrolyzed to salicylate by esterases in liver and plasma; salicylate is conjugated with glycine (salicyluric acid) and glucuronic acid; minor oxidation. Omeprazole: Primarily metabolized by CYP2C19 and CYP3A4 to inactive metabolites. |
| Excretion | Aspirin: renal elimination of salicylate and its metabolites (salicyluric acid, salicyl phenolic glucuronide, salicyl acyl glucuronide, gentisic acid); ~10% excreted unchanged in urine; dose-dependent due to saturable metabolism. Omeprazole: ~80% eliminated as metabolites in urine, ~20% in feces via biliary excretion. |
| Half-life | Aspirin: 15-20 minutes for parent drug; salicylate half-life 2-3 hours at low doses, increasing to >20 hours at high doses due to saturable hepatic metabolism; clinically, dosing interval adjusted for antiplatelet effect (low dose) vs anti-inflammatory (high dose). Omeprazole: 0.5-1 hour; no accumulation on repeated dosing; metabolized via CYP2C19 and CYP3A4. |
| Protein binding | Aspirin: 80-90% bound to albumin; salicylate binding is saturable and decreases with high concentrations. Omeprazole: 95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Aspirin: Vd 0.15-0.2 L/kg for salicylate; increases in acidosis as drug distributes into tissues. Omeprazole: Vd 0.3-0.4 L/kg; distributes into gastric parietal cells. |
| Bioavailability | Aspirin: oral immediate-release: 50-75% (presystemic hydrolysis); enteric-coated: 40-50%; rectal: 80-100%. Omeprazole: oral immediate-release: 30-40% (first-pass metabolism); delayed-release: ~50%; bioavailability increases with repeated dosing. |
| Onset of Action | Aspirin: oral immediate-release: 5-30 minutes for analgesia/antiplatelet effect; enteric-coated: delayed 1-2 hours. Omeprazole: oral: 1-2 hours for acid suppression; maximal effect after 4 days. |
| Duration of Action | Aspirin: antiplatelet effect persists for lifespan of platelet (7-10 days) due to irreversible COX-1 inhibition; analgesic/antipyretic duration 3-6 hours. Omeprazole: acid suppression lasts 24-72 hours after single dose; requires daily dosing for sustained effect. |
| Molecular Weight | 180.16 |
Aspirin 81 mg orally once daily plus omeprazole 20 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No adjustment needed for GFR >30 mL/min. For GFR 10-30 mL/min, use aspirin with caution; omeprazole no adjustment. For GFR <10 mL/min, aspirin generally contraindicated. |
| Liver impairment | Omeprazole: Child-Pugh A: no adjustment; Child-Pugh B: maximum 20 mg daily; Child-Pugh C: avoid or reduce dose. Aspirin: avoid in severe hepatic impairment. |
| Pediatric use | Aspirin: not recommended for analgesia/anti-inflammatory in children due to Reye's syndrome risk. For specific indications (e.g., Kawasaki disease): 30-50 mg/kg/day divided every 6 hours, followed by low dose 3-5 mg/kg/day once daily. Omeprazole: 1-2 mg/kg/day once daily; max 20 mg daily for <16 years. |
| Geriatric use | Aspirin: use lowest effective dose (e.g., 81 mg daily) due to increased bleeding risk. Omeprazole: 20 mg daily; consider short-term therapy and monitor for increased fracture risk and vitamin B12 deficiency. |
| 1st trimester | Avoid; associated with increased risk of miscarriage and congenital malformations (e.g., gastroschisis). Omeprazole use limited data but considered low risk in standard doses. |
| 2nd trimester | Avoid; NSAIDs may cause oligohydramnios and fetal renal impairment. Omeprazole generally considered safe if needed. |
| 3rd trimester | Contraindicated; risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal complications. Omeprazole safe if necessary. |
Clinical note
Can reduce absorption of drugs requiring gastric pH for absorption (eg ketoconazole) May increase risk of Clostridium difficile-associated diarrhea and bone fractures with long-term use.
| FDA category | Animal |
| Placental transfer | Aspirin crosses placenta readily; omeprazole crosses placenta but fetal levels are low. |
■ FDA Black Box Warning
Reye's syndrome: Do not use aspirin in children or teenagers with viral infections due to risk of Reye's syndrome.
| Common Effects | erosive esophagitis |
| Serious Effects |
Hypersensitivity to aspirin or omeprazoleHistory of asthma, rhinitis, or urticaria precipitated by NSAIDsActive peptic ulcer disease or GI bleedingSevere hepatic or renal impairmentThird trimester of pregnancyConcomitant use of methotrexate (≥15 mg/week) or anticoagulants
| Precautions | Bleeding risk: Aspirin increases risk of gastrointestinal and intracranial bleeding; use with caution in patients with bleeding disorders or on anticoagulants., GI toxicity: Despite omeprazole, long-term use of aspirin may cause GI ulcers, bleeding, or perforation., Renal impairment: Aspirin may reduce renal function; avoid in severe renal impairment., Hypersensitivity: Aspirin may cause urticaria, angioedema, or bronchospasm, especially in asthmatics., Hepatic impairment: Use aspirin with caution in severe liver disease., Bone marrow suppression: Omeprazole may cause vitamin B12 deficiency with long-term use., Clostridioides difficile infection: Increased risk with omeprazole., Hypomagnesemia: Omeprazole may cause low magnesium levels with prolonged use., Avoid abrupt discontinuation of aspirin in patients with cardiovascular disease due to rebound thrombotic risk. |
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| Breastfeeding |
| Aspirin (high dose) enters breast milk and may cause Reye's syndrome; avoid or use low dose (<100 mg/day) with monitoring. Omeprazole is excreted in low amounts and is considered compatible with breastfeeding. |
| Lactation Rating | L3 (Moderately Safe) for low-dose aspirin; L2 (Probably Safe) for omeprazole per LactMed. |
| Teratogenic Risk | Aspirin (high dose): First trimester – possible increased risk of miscarriage and congenital malformations (e.g., gastroschisis); third trimester – risk of premature closure of ductus arteriosus, oligohydramnios, and periventricular hemorrhage. Low-dose aspirin (≤100 mg/day) generally considered safe. Omeprazole: Studies show no consistent evidence of major malformations; however, some data suggest a small increased risk of congenital heart defects. Use only if clearly needed. |
| Fetal Monitoring | Monitor for signs of bleeding (e.g., bruising, petechiae) and renal function. In third trimester, monitor fetal ultrasound for ductus arteriosus patency and amniotic fluid index. For omeprazole, no specific monitoring required; monitor maternal gastrointestinal symptoms and gastric pH if needed. |
| Fertility Effects | Aspirin: Low-dose aspirin may improve pregnancy outcomes in women with antiphospholipid syndrome or recurrent pregnancy loss, but no direct effect on fertility. High-dose aspirin may inhibit ovulation via prostaglandin synthesis inhibition. Omeprazole: No known direct effect on fertility. Limited data suggest no impact. |
| Food/Dietary | Avoid alcohol. Aspirin absorption is delayed by food; take on an empty stomach. Omeprazole absorption may be reduced when taken with acidic beverages (e.g., fruit juice) or high-fat meals. No specific food restrictions, but maintain a balanced diet. |
| Clinical Pearls | Aspirin/omeprazole combination (e.g., Yosprala) is indicated for patients requiring aspirin for cardiovascular or cerebrovascular prophylaxis who are at risk of developing gastric ulcers. Omeprazole enteric coating may be compromised if tablet is crushed or chewed. Use with caution in patients with CYP2C19 poor metabolizers, as omeprazole efficacy may be reduced. Monitor for signs of GI bleeding, renal impairment, and hypomagnesemia with prolonged use. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily with a full glass of water. · Swallow the tablet whole; do not crush, chew, or break it. · Take the medication at least 60 minutes before a meal. · Avoid alcohol, as it may increase the risk of stomach bleeding. · Inform your doctor if you experience black or bloody stools, vomit that looks like coffee grounds, or unusual bruising/bleeding. · Do not use over-the-counter pain relievers (NSAIDs) without consulting your doctor. · Report any signs of low magnesium (muscle cramps, irregular heartbeat, seizures) or kidney problems (change in urine output). · Store at room temperature away from moisture and heat. |