Comparative Pharmacology
Head-to-head clinical analysis: ACIPHEX versus PREVACID NAPRAPAC 375 COPACKAGED.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ACIPHEX versus PREVACID NAPRAPAC 375 COPACKAGED.
ACIPHEX vs PREVACID NAPRAPAC 375 (COPACKAGED)
Head-to-head clinical comparison of therapeutic indices and safety profiles.
Rabeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+ ATPase enzyme system at the secretory surface of gastric parietal cells.
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.
Healing of erosive esophagitisMaintenance of healed erosive esophagitisTreatment of symptomatic gastroesophageal reflux disease (GERD)Helicobacter pylori eradication to reduce duodenal ulcer recurrence (in combination with amoxicillin and clarithromycin)Treatment of pathological hypersecretory conditions including Zollinger-Ellison syndrome
FDA: Relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitisFDA: Decrease the risk of developing NSAID-associated gastric ulcers in patients with a history of documented gastric ulcer who require the use of an NSAIDOff-label: Juvenile idiopathic arthritis, acute gout, dysmenorrhea, tendinitis, bursitis
20 mg orally once daily; duration: 4-8 weeks for erosive esophagitis, 4 weeks for GERD, 24 weeks for H. pylori eradication (triple therapy: AcipHex 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg twice daily for 7 days), 4 weeks for duodenal ulcer, up to 12 months for pathological hypersecretory conditions.
One tablet (naproxen 375 mg / lansoprazole 15 mg) orally twice daily.
None Documented
None Documented
Plasma half-life 1-2 hours, but pharmacodynamic half-life (acid suppression) >24 hours due to accumulation in parietal cell canaliculi.
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.
Primarily hepatic via CYP2C19 and CYP3A4; metabolites include thioether and sulfone; renal excretion of metabolites.
Naproxen is primarily metabolized by CYP2C9 and CYP1A2 to inactive metabolites. Lansoprazole is extensively metabolized by CYP2C19 and CYP3A4 to active and inactive metabolites.
Hepatic metabolism, primarily via CYP2C19 and CYP3A4; ~90% eliminated as metabolites in urine, <1% unchanged; remainder in feces.
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%).
96-98% bound to plasma proteins, primarily albumin and alpha1-acid glycoprotein.
Naproxen: >99% bound to albumin. Lansoprazole: ~97% bound to albumin.
Vd ~0.5 L/kg, indicating distribution primarily into extracellular fluid; small distribution into total body water.
Naproxen: 0.16 L/kg. Lansoprazole: 0.3-0.5 L/kg.
Oral bioavailability ~52%, increases with multiple dosing (no clinically relevant accumulation); food delays absorption but does not reduce extent.
Naproxen: 95% oral. Lansoprazole: 80-91% oral (increases after multiple doses).
No dose adjustment required for mild to moderate renal impairment. Severe renal impairment (CrCl <30 mL/min): maximum dose 20 mg once daily.
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.
Child-Pugh Class A or B: no adjustment. Child-Pugh Class C: maximum dose 20 mg once daily.
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.
GERD: 12 years and older: 20 mg once daily for 4-8 weeks. Erosive esophagitis: 12 years and older: 20 mg once daily for 4-8 weeks. Safety and efficacy not established in children under 12 years.
Safety and efficacy in pediatric patients (<18 years) have not been established; not recommended.
No dose adjustment needed based on age alone. However, monitor for increased risk of hip fracture, Clostridium difficile infection, and vitamin B12 deficiency with long-term 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.
No 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.
["Gastric malignancy: symptomatic response does not preclude presence of gastric malignancy","Acute interstitial nephritis observed","Clostridium difficile-associated diarrhea: increased risk with PPI use","Bone fracture: long-term use may increase risk of osteoporosis-related fractures","Cutaneous lupus erythematosus and systemic lupus erythematosus: reported","Cyanocobalamin (Vitamin B12) deficiency: long-term use may impair absorption","Hypomagnesemia: reported with prolonged use, especially with concomitant diuretics","Increased risk of fundic gland polyps with long-term use","Interference with secretin stimulation test and chromogranin A levels"]
["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"]
["Hypersensitivity to rabeprazole, substituted benzimidazoles, or any component of the formulation","Concomitant use with rilpivirine-containing products"]
["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"]
Data Pending Review
Data Pending Review
ACIPHEX can be taken with or without food, but for best results, take it before a meal (food slightly increases absorption). Avoid excessive alcohol and spicy or acidic foods that may exacerbate symptoms. No specific food-drug interactions; however, PPIs may reduce absorption of certain nutrients like vitamin B12, calcium, and magnesium with long-term use.
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.
FDA Pregnancy Category B. No evidence of teratogenicity in animal studies at doses up to 13 times the human dose. Limited human data; however, studies have not shown an increased risk of major birth defects. Use only if clearly needed.
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.
Rabeprazole is excreted in human milk; the M/P ratio is unknown. Because of the potential for adverse reactions in nursing infants, caution should be exercised; consider alternative agents or discontinue nursing if no suitable alternative.
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.
No specific dose adjustment recommended for pregnancy. Use the lowest effective dose for the shortest duration. Pharmacokinetic changes in pregnancy may reduce plasma concentrations, but no dose adjustment is mandated.
No specific dose adjustment recommended for lansoprazole. Naproxen: Avoid in third trimester; consider lowest effective dose and short duration in earlier trimesters due to increased renal clearance and potential for premature labor inhibition.
Category C
Category C
ACIPHEX (rabeprazole) is a proton pump inhibitor (PPI) with rapid onset of action; it can be taken without regard to meals but for optimal acid suppression, take before breakfast. Avoid concurrent use with clopidogrel due to possible reduced antiplatelet effect; consider alternative PPI if needed. Monitor for hypomagnesemia, vitamin B12 deficiency, and increased risk of Clostridioides difficile infection with long-term use. Short-term use (≤8 weeks) is recommended for initial therapy of GERD; reassess need for continued therapy.
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.
Take ACIPHEX exactly as prescribed, usually once daily before a meal (preferably breakfast).Do not crush, chew, or split the delayed-release tablets; swallow them whole with a glass of water.Inform your doctor if you have liver disease, osteoporosis, or low magnesium levels.Common side effects include headache, diarrhea, and nausea; contact your doctor if you experience severe diarrhea, rash, or signs of low magnesium (muscle cramps, irregular heartbeat).Long-term use may increase risk of bone fractures, vitamin B12 deficiency, and kidney problems; discuss with your doctor if you need treatment beyond 8 weeks.Do not take other acid reducers (e.g., antacids, H2 blockers) without consulting your doctor.
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.