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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PREVACID NAPRAPAC 375 (COPACKAGED) (PREVACID NAPRAPAC 375 (COPACKAGED)).
| Breastfeeding | Lansoprazole: Present in breast milk at low levels (M/P ratio unknown); considered compatible. Naproxen: Excreted in breast milk (M/P ratio ~0.01); use with caution due to potential adverse effects in infants. |
| 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. |
■ 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 |
["Hypersensitivity to naproxen, lansoprazole, or any component of the product","History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs","In the setting of coronary artery bypass graft (CABG) surgery","Advanced renal disease (unless benefit outweighs risk)","History of GI bleeding or perforation related to prior NSAID therapy","Active peptic ulcer disease or active GI bleeding"]
| 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"] |
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| 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. |