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). |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PREVACID NAPRAPAC 500 (COPACKAGED) (PREVACID NAPRAPAC 500 (COPACKAGED)).
| Breastfeeding | Naproxen: Enters breast milk in small amounts; M/P ratio approximately 0.01. Avoid use due to potential adverse effects on infant cardiovascular and renal systems. Lansoprazole: Excreted into breast milk; no M/P ratio available. Use caution; consider alternatives. |
| 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. |
■ 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 NSAIDs","History of gastrointestinal bleeding or perforation related to previous NSAID therapy","Active peptic ulcer disease or significant upper gastrointestinal bleeding","Severe renal impairment (CrCl <30 mL/min)","Severe hepatic impairment","Concomitant use with another NSAID or aspirin (except low-dose aspirin for cardiovascular prophylaxis under physician supervision)","Pregnancy (third trimester) due to risk of premature closure of ductus arteriosus","Hypersensitivity to any component of the product"]
| Precautions |
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| 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. |
| ["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"] |