PREVACID NAPRAPAC 500 (COPACKAGED)
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PREVACID NAPRAPAC 500 (COPACKAGED) (PREVACID NAPRAPAC 500 (COPACKAGED)).
Lansoprazole inhibits gastric acid secretion by irreversibly binding to the H+/K+ ATPase (proton pump) in gastric parietal cells. Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2), reducing prostaglandin synthesis.
| Metabolism | Lansoprazole is extensively metabolized in the liver via CYP2C19 and CYP3A4; naproxen is metabolized in the liver via CYP1A2 and CYP2C9, with less than 1% excreted unchanged. |
| Excretion | Naproxen: 95% renal (primarily as unchanged drug and metabolites, including 6-O-desmethyl naproxen), <5% biliary/fecal. Esomeprazole: 80% renal (as metabolites, primarily hydroxyesomeprazole and desmethyl-esomeprazole, with ~1% unchanged), 20% fecal (via bile). |
| Half-life | Naproxen: 12–17 hours (mean ~14 h), prolonged with renal impairment. Esomeprazole: 1–1.5 hours (increase to 2–3 h with CYP2C19 poor metabolizers or hepatic impairment). |
| Protein binding | Naproxen: >99% bound to albumin. Esomeprazole: 97% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Naproxen: 0.16 L/kg (low, indicating minimal distribution into tissues; primarily confined to plasma). Esomeprazole: 0.22 L/kg (distributes into body water; apparent Vd about 15 L). |
| Bioavailability | Naproxen: Oral bioavailability ~95% (well absorbed, minimal first-pass). Esomeprazole: Oral bioavailability 64% (first-pass effect; decreased with food, take at least 1 hour before meals). |
| Onset of Action | Naproxen: Oral onset within 1 hour (analgesia), measurable in plasma within 30 min. Esomeprazole: 1 hour for gastric acid suppression (max effect at 1–2 hours). |
| Duration of Action | Naproxen: Up to 7–8 hours for analgesia (dosing interval q8–12h). Esomeprazole: Acid suppression for ~24 hours (duration commensurate with once-daily dosing). |
| Molecular Weight | Naproxen: 230.26 Da; Lansoprazole: 369.36 Da |
One tablet of naproxen 500 mg and one capsule of lansoprazole 15 mg taken together orally once daily. Naproxen component: 500 mg orally twice daily. Lansoprazole component: 15 mg orally once daily.
| Dosage form | CAPSULE, DELAYED REL PELLETS, TABLET |
| Renal impairment | Naproxen: GFR <30 mL/min: contraindicated. GFR 30-60 mL/min: reduce dose and avoid long-term use. Lansoprazole: no adjustment necessary. |
| Liver impairment | Naproxen: mild to moderate hepatic impairment: reduce dose; severe impairment: contraindicated. Lansoprazole: Child-Pugh class A/B: maximum 30 mg/day; Child-Pugh class C: maximum 15 mg/day. |
| Pediatric use | Not recommended for use in pediatric patients due to lack of safety and efficacy data. |
| Geriatric use | Use lowest effective dose for shortest duration; monitor renal function and GI bleeding risk; avoid in patients with GFR <30 mL/min. |
| 1st trimester | Avoid in first trimester; naproxen may inhibit prostaglandin synthesis leading to increased risk of spontaneous abortion (Miscarriage) and cardiac defects. Lansoprazole: limited data suggests low risk. |
| 2nd trimester | Avoid in second trimester; naproxen use associated with oligohydramnios and fetal renal dysfunction. Lansoprazole: consider if benefit outweighs risk. |
| 3rd trimester | Contraindicated in third trimester due to risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal renal impairment from naproxen. Lansoprazole: avoid unless necessary. |
Clinical note
Comprehensive clinical and safety monograph for PREVACID NAPRAPAC 500 (COPACKAGED) (PREVACID NAPRAPAC 500 (COPACKAGED)).
| Placental transfer | Naproxen readily crosses placenta; lansoprazole likely crosses to a lesser extent. Both demonstrate measurable placental transfer. |
| Breastfeeding | Naproxen is excreted in small amounts; lansoprazole likely enters milk but data limited. Avoid if possible, especially with prolonged use or in neonates with jaundice or G6PD deficiency. Monitor infant for diarrhea, drowsiness, rash. |
■ FDA Black Box Warning
Naproxen, a component of this product, increases the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk increases with duration of use and in patients with cardiovascular risk factors. Naproxen is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Common Effects | Increased bleeding tendency Abdominal pain Indigestion Bruise Nosebleeds Gastrointestinal bleeding Weakness Headache Muscle pain Diarrhea Nausea |
| Serious Effects |
History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsKnown hypersensitivity to naproxen, lansoprazole, or any component of the formulationPatients with severe renal impairment (CrCl < 30 mL/min) or worsening renal functionActive peptic ulcer disease, GI bleeding, or perforationThird trimester of pregnancy (due to NSAID component)
| Precautions | Cardiovascular thrombotic events, Gastrointestinal bleeding, ulceration, and perforation, Renal toxicity including acute interstitial nephritis, Hepatic toxicity, Anaphylactoid reactions, Exacerbation of asthma, Hypertension, Heart failure, Fluid retention, Masking of signs of infection, Hematologic toxicity (anemia, prolonged bleeding time), Photosensitivity |
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| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | Naproxen: NSAID exposure during first trimester is associated with increased risk of miscarriage and cardiac defects. During second and third trimesters, NSAIDs may cause premature closure of ductus arteriosus, oligohydramnios, and fetal renal impairment. Avoid after 30 weeks gestation due to risk of premature ductus arteriosus closure. Lansoprazole: Proton pump inhibitors are generally considered low risk; large cohort studies show no consistent increase in major birth defects. However, some data suggest a small increased risk of congenital malformations with first trimester use. |
| Fetal Monitoring | Monitor for signs of premature ductus arteriosus closure (fetal echocardiography) and oligohydramnios (ultrasound) if used after 30 weeks. Assess maternal renal function, blood pressure, and evidence of gastrointestinal bleeding. In neonates, monitor for respiratory depression and hypotonia if used near term. |
| Fertility Effects | Naproxen may impair female fertility through inhibition of prostaglandin synthesis, affecting ovulation and implantation. Reversible upon discontinuation. No known adverse effects on male fertility. |
| Food/Dietary | Naproxen should be taken with food or milk to reduce GI irritation. Lansoprazole may be taken with or without food; however, it is best taken before a meal (e.g., breakfast) for maximal effect. Avoid high-fat meals as they may delay absorption of naproxen. No specific food restrictions for lansoprazole. |
| Clinical Pearls | This copackaged product contains lansoprazole (a proton pump inhibitor) and naproxen (an NSAID). Use lowest effective dose for shortest duration to minimize GI and cardiovascular risks. Contraindicated in patients with history of aspirin/NSAID-induced asthma, urticaria, or other allergic reactions. Monitor renal function, blood pressure, and for signs of GI bleeding. Coadministration with warfarin, clopidogrel, or methotrexate requires caution. Avoid use with other NSAIDs or aspirin. |
| Patient Advice | Take naproxen with food or milk to reduce stomach upset. · Do not take with other NSAIDs or aspirin unless directed by your doctor. · Swallow lansoprazole capsules whole; do not crush or chew. If you have trouble swallowing, open capsule and sprinkle contents on applesauce. · Avoid alcohol while taking this medication as it may increase risk of stomach bleeding. · Report signs of stomach bleeding (e.g., black/tarry stools, vomit that looks like coffee grounds), chest pain, weakness, or slurred speech immediately. · Do not use this medication for more than 10 days for pain without consulting a doctor. |