NAPROXEN AND ESOMEPRAZOLE MAGNESIUM
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.
Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin synthesis. Esomeprazole magnesium is a proton pump inhibitor (PPI) that irreversibly inhibits the H+/K+ ATPase pump in gastric parietal cells, decreasing gastric acid secretion.
| Metabolism | Naproxen is primarily metabolized by hepatic CYP1A2 and CYP2C9 to 6-O-desmethylnaproxen and other metabolites. Esomeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4 to hydroxy, desmethyl, and sulfone metabolites. |
| Excretion | Naproxen: ~95% renal (as unchanged drug and conjugates), ~5% fecal. Esomeprazole: ~80% renal (as metabolites), ~20% fecal. |
| Half-life | Naproxen: ~12-17 hours (allows twice-daily dosing). Esomeprazole: ~1-1.5 hours (no accumulation). |
| Protein binding | Naproxen: >99% bound to albumin. Esomeprazole: 97% bound to albumin. |
| Volume of Distribution | Naproxen: 0.16 L/kg (low, mainly in plasma). Esomeprazole: 0.22 L/kg (moderate, extracellular fluid). |
| Bioavailability | Naproxen: ~95% oral. Esomeprazole: ~64% oral (first-pass metabolism). |
| Onset of Action | Naproxen: 1-2 hours oral (analgesic effect). Esomeprazole: ~1 hour oral (acid suppression). |
| Duration of Action | Naproxen: 8-12 hours (immediate release). Esomeprazole: ~24 hours (once daily acid suppression). |
One tablet (naproxen 500 mg / esomeprazole 20 mg) orally twice daily.
| Dosage form | TABLET, DELAYED RELEASE |
| Renal impairment | Contraindicated in patients with creatinine clearance <30 mL/min. For CrCl 30-89 mL/min, no dose adjustment; use with caution. |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh A or B): no adjustment. Severe hepatic impairment (Child-Pugh C): avoid use. |
| Pediatric use | Not recommended for patients <18 years of age; safety and efficacy not established. |
| Geriatric use | Use the lowest effective dose for the shortest duration. Consider renal function; avoid in CrCl <30 mL/min. Monitor for GI bleeding and renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
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 |
| Breastfeeding | Naproxen transfers into breast milk (M/P ratio ~0.01–0.05, relative infant dose 1–3% of maternal weight-adjusted dose). Esomeprazole is poorly excreted (M/P ratio not well-defined; estimated <1% of maternal dose). Both are generally considered compatible with breastfeeding, but use lowest effective dose and monitor infant for gastrointestinal effects or drowsiness. |
| Teratogenic Risk |
■ FDA Black Box Warning
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. Naproxen is contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Common Effects | erosive esophagitis |
| Serious Effects |
Hypersensitivity to naproxen, esomeprazole, or any component of the formulation; history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs; peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery; patients with severe renal impairment (CrCl <30 mL/min); patients with severe hepatic impairment (Child-Pugh Class C); patients with known history of gastric cancer or Barrett's esophagus; patients receiving rilpivirine-containing products.
| Precautions | Cardiovascular thrombotic events; gastrointestinal bleeding, ulceration, and perforation; elevation of liver enzymes; renal toxicity; hypertension; exacerbation of asthma; anemia; fluid retention; masking of inflammation; photosensitivity; risk of Clostridium difficile-associated diarrhea; hypomagnesemia; vitamin B12 deficiency; osteoporosis-related fractures; decreased gastric acidity leading to increased risk of gastrointestinal infections. |
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| First trimester: NSAID use associated with increased risk of spontaneous abortion and cardiac defects (relative risk 1.8–2.0). Second trimester: Generally low risk, but avoid prolonged use. Third trimester: NSAIDs (naproxen) cause premature closure of ductus arteriosus, oligohydramnios, and fetal renal impairment; esomeprazole has no known major teratogenic risk, but proton pump inhibitors (PPIs) have weak association with congenital anomalies (odds ratio ~1.1–1.2). Overall, avoid in third trimester; use lowest effective dose in first and second trimesters if necessary. |
| Fetal Monitoring | Assess maternal renal function (serum creatinine, BUN) and hepatic function (LFTs) at baseline and periodically. Monitor for signs of gastrointestinal bleeding (CBC, stool guaiac). Fetal ultrasound to assess ductus arteriosus patency and amniotic fluid volume if prolonged use in third trimester. Monitor infant for adverse effects if breastfeeding. |
| Fertility Effects | Naproxen may impair female fertility through inhibition of prostaglandin synthesis, potentially delaying or preventing ovulation (reversible upon discontinuation). Esomeprazole has no known significant effect on fertility. Use in women attempting to conceive should be avoided or minimized. |