PREVACID NAPRAPAC 375 (COPACKAGED)
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PREVACID NAPRAPAC 375 (COPACKAGED) (PREVACID NAPRAPAC 375 (COPACKAGED)).
Lansoprazole, a proton pump inhibitor, suppresses gastric acid secretion by inhibiting the gastric H+/K+-ATPase at the secretory surface of the gastric parietal cell. Naproxen, a nonsteroidal anti-inflammatory drug, inhibits cyclooxygenase (COX-1 and COX-2) reducing prostaglandin synthesis, which mediates inflammation, pain, and fever.
| Metabolism | Naproxen is primarily metabolized by CYP2C9 and CYP1A2 to inactive metabolites. Lansoprazole is extensively metabolized by CYP2C19 and CYP3A4 to active and inactive metabolites. |
| Excretion | Naproxen: Approximately 95% excreted in urine as unchanged naproxen (10%) and metabolites (~60% 6-O-desmethylnaproxen and conjugates); <5% in feces. Lansoprazole: Primarily metabolized in liver; metabolites excreted in urine (14-23%) and feces (~22%). |
| Half-life | Naproxen: 12-17 hours (mean 14 hours); allows twice-daily dosing. Lansoprazole: 1.5-2 hours (fast metabolizers) to 3-4 hours (slow metabolizers); clinically negligible due to irreversibly binding to proton pumps. |
| Protein binding | Naproxen: >99% bound to albumin. Lansoprazole: ~97% bound to albumin. |
| Volume of Distribution | Naproxen: 0.16 L/kg. Lansoprazole: 0.3-0.5 L/kg. |
| Bioavailability | Naproxen: 95% oral. Lansoprazole: 80-91% oral (increases after multiple doses). |
| Onset of Action | Naproxen: Oral, 1 hour for analgesia. Lansoprazole: Oral, 2-4 hours for gastric acid suppression; maximal effect after 3-4 days. |
| Duration of Action | Naproxen: 7-8 hours for analgesic effect (up to 12 hours in some patients). Lansoprazole: Acid suppression lasts 24-48 hours due to prolonged binding to H+/K+-ATPase. |
| Molecular Weight | Lansoprazole: 369.36 Da; Naproxen: 230.26 Da |
One tablet (naproxen 375 mg / lansoprazole 15 mg) orally twice daily.
| Dosage form | CAPSULE, DELAYED REL PELLETS, TABLET |
| Renal impairment | Contraindicated if creatinine clearance <30 mL/min. For CrCl 30-60 mL/min: limit naproxen dose to 375 mg twice daily. For CrCl <30 mL/min: avoid use. |
| Liver impairment | Severe hepatic impairment (Child-Pugh C): avoid naproxen; lansoprazole dose adjustment not required. Moderate impairment (Child-Pugh B): use with caution, consider reducing naproxen dose. |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established; not recommended. |
| Geriatric use | Use lowest effective dose; monitor renal function. Avoid in elderly with CrCl <30 mL/min. Increased risk of GI bleeding and renal impairment; consider alternative therapy if possible. |
| 1st trimester | Avoid use during first trimester due to potential teratogenic effects of NSAIDs (naproxen) and insufficient safety data for lansoprazole. |
| 2nd trimester | Use only if clearly needed; NSAIDs in second trimester may cause oligohydramnios and fetal renal dysfunction. |
| 3rd trimester | Contraindicated in third trimester due to risk of premature closure of ductus arteriosus and persistent pulmonary hypertension in the newborn from NSAIDs. |
Clinical note
Comprehensive clinical and safety monograph for PREVACID NAPRAPAC 375 (COPACKAGED) (PREVACID NAPRAPAC 375 (COPACKAGED)).
| Placental transfer | Both lansoprazole and naproxen cross the placenta. Naproxen reaches fetal concentrations approximately 1% of maternal plasma; lansoprazole transfer is minimal but not quantified. |
| Breastfeeding | Both lansoprazole and naproxen are excreted in breast milk in low amounts. Naproxen has a long half-life and may accumulate in infants; avoid use in breastfeeding due to potential adverse effects (e.g., gastrointestinal bleeding, renal impairment). |
■ 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 occur early in treatment and may increase with duration of use. NSAIDs are contraindicated 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 |
Known hypersensitivity to lansoprazole, naproxen, or any component of the productHistory of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsIn the setting of coronary artery bypass graft (CABG) surgeryThird trimester of pregnancyActive peptic ulcer disease or gastrointestinal bleedingSevere renal impairment (creatinine clearance <30 mL/min)
| Precautions | Cardiovascular thrombotic events (MI, stroke), Gastrointestinal bleeding, ulceration, and perforation, Renal toxicity including acute interstitial nephritis, Hepatic toxicity, Anaphylactic reactions, Exacerbation of asthma related to aspirin sensitivity, Hypertension and fluid retention, Photosensitivity, Corticosteroid-dependent patients (taper steroids slowly), Masking of signs of infection, Use with caution in patients with prior history of GI ulcer disease or bleeding, Concomitant use of aspirin or anticoagulants increases GI risk, PPI use associated with increased risk of Clostridium difficile diarrhea, osteoporosis-related fractures, hypomagnesemia, and vitamin B12 deficiency, Avoid prolonged use (>3 years) for hypomagnesemia risk |
Loading safety data…
| Lactation Rating | L4 (Hazardous) - Naproxen component contraindicated; lansoprazole considered compatible but overall risk high. |
| Teratogenic Risk | Lansoprazole: Pregnancy Category B. Animal studies show no fetal harm; no adequate human studies. Naproxen: Pregnancy Category C (1st/2nd trimester), Category D (3rd trimester). Avoid in 3rd trimester due to premature closure of ductus arteriosus and oligohydramnios. |
| Fetal Monitoring | Monitor for signs of premature ductus arteriosus closure, oligohydramnios, prolonged gestation, and maternal renal function in third trimester. Fetal echocardiography and ultrasound may be indicated. |
| Fertility Effects | Naproxen may impair female fertility via prostaglandin synthesis inhibition; reversible upon discontinuation. Lansoprazole no known effect on fertility. |
| Food/Dietary | Avoid high-fat meals as they may delay absorption of lansoprazole. Naproxen absorption is not significantly affected by food, but taking with food reduces GI irritation. Avoid alcohol and NSAIDs (e.g., aspirin, ibuprofen) to prevent additive GI toxicity. Cranberry juice may increase naproxen levels; limit intake. |
| Clinical Pearls | This copackaged product contains lansoprazole (PPI) and naproxen (NSAID). For patients with cardiovascular risk, naproxen's cardioprotective profile is relatively favorable among NSAIDs but not risk-free. Monitor renal function and electrolytes, especially in elderly or volume-depleted patients. Use lowest effective naproxen dose for shortest duration. PPI may mask symptoms of gastric malignancy; evaluate for alarm symptoms before initiation. |
| Patient Advice | Take lansoprazole at least 30 minutes before a meal, preferably breakfast. · Swallow capsules whole; do not crush or chew. · Naproxen may be taken with food or milk to reduce GI upset. · Avoid alcohol while taking naproxen to reduce risk of stomach bleeding. · Report black stools, coffee-ground vomit, or severe abdominal pain immediately. · Do not exceed prescribed doses; long-term use increases risk of kidney damage and GI events. · Inform all healthcare providers you are taking this medication. |