RABEPRAZOLE SODIUM
Clinical safety rating: safe
Animal studies have demonstrated safety
Rabeprazole is a proton pump inhibitor (PPI) that inhibits the gastric H+/K+-ATPase enzyme at the secretory surface of gastric parietal cells, thereby suppressing basal and stimulated gastric acid secretion. It is a substituted benzimidazole that accumulates in the acidic environment of the parietal cell and is protonated, forming a covalent disulfide bond with cysteine residues of the proton pump, leading to irreversible inhibition.
| Metabolism | Rabeprazole is extensively metabolized in the liver primarily via non-enzymatic reduction and to a lesser extent by cytochrome P450 (CYP) isoenzymes CYP2C19 and CYP3A4. The major metabolites are rabeprazole thioether (via non-enzymatic reduction) and desmethylrabeprazole (via CYP2C19). Conjugation with glutathione also occurs. |
| Excretion | Primarily renal (approx. 90% as metabolites, <1% unchanged) and fecal (approx. 10%) |
| Half-life | 1-2 hours in most individuals, but pharmacodynamic half-life is longer (24-48 hours) due to irreversible binding to proton pumps; clearance is reduced in hepatic impairment (half-life up to 12 hours) |
| Protein binding | Approximately 96-97%, primarily to albumin and alpha1-acid glycoprotein |
| Volume of Distribution | Approximately 0.34 L/kg (range 0.28-0.42 L/kg), indicating limited extravascular distribution consistent with low tissue penetration except in parietal cells |
| Bioavailability | Oral: ~52% (with high interindividual variability, range 30-90%) due to first-pass metabolism; food delays but does not significantly reduce extent of absorption |
| Onset of Action | Oral: inhibition of acid secretion begins within 1 hour; maximal effect at 2-4 hours |
| Duration of Action | Duration of acid suppression persists for 24-48 hours after a single dose, with recovery of acid secretion over 3-5 days after cessation |
| Action Class | Proton pump inhibitors |
| Brand Substitutes | Cyra 20mg Tablet, Pepcia 20 Tablet, Dgrab 20mg Tablet, Rabium 20 Tablet, Rabicip 20 Tablet |
Oral: 20 mg once daily; duodenal ulcer: 20 mg once daily for up to 4 weeks; erosive esophagitis: 20 mg once daily for 4 to 8 weeks; GERD: 20 mg once daily for 4 to 8 weeks; Helicobacter pylori eradication: 20 mg twice daily in combination with antibiotics.
| Dosage form | TABLET, DELAYED RELEASE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (CrCl < 30 mL/min), limited data; consider maximum dose of 20 mg daily. |
| Liver impairment | Child-Pugh Class A or B: No adjustment. Child-Pugh Class C: Maximum dose 20 mg daily; monitor for adverse effects. |
| Pediatric use | For GERD or erosive esophagitis in children 1-11 years (≥15 kg): 10 mg once daily; >15 kg: 20 mg once daily. For adolescents 12-16 years: 20 mg once daily. Duration: up to 8 weeks. |
| Geriatric use | No specific dose adjustment; initiate at the lower end of dosing range (20 mg daily) due to potential for decreased hepatic or renal function and increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Can reduce absorption of drugs requiring gastric pH for absorption (eg ketoconazole) May increase risk of Clostridium difficile-associated diarrhea and bone fractures with long-term use.
| Breastfeeding | Rabeprazole is excreted in human milk in low concentrations. The milk-to-plasma ratio is unknown. Because of the potential for tumorigenicity shown in animal studies, caution is advised. Consider alternative agents with more safety data, such as omeprazole or lansoprazole. |
| Teratogenic Risk | Rabeprazole is classified as Pregnancy Category B. Animal studies have not shown fetal harm, but adequate human studies are lacking. No increased risk of major congenital malformations has been reported in first trimester exposure. Fetal risk cannot be completely excluded; use only if clearly needed. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to rabeprazole, other benzimidazole PPIs, or any component of the formulation","Concurrent use with rilpivirine-containing products","Severe hepatic impairment (Child-Pugh C) - relative caution"]
| Precautions | ["Gastric malignancy: Symptomatic response does not preclude presence of gastric malignancy.","Atrophic gastritis: Long-term use may lead to atrophic gastritis.","Bone fracture: Long-term or high-dose use may increase risk of osteoporosis-related fractures of hip, wrist, or spine.","Hypomagnesemia: Prolonged use (>1 year) may cause symptomatic hypomagnesemia; monitor magnesium levels if on diuretics or with prolonged treatment.","Vitamin B12 deficiency: Chronic use may impair absorption of cyanocobalamin.","Clostridium difficile infection: Long-term use may increase risk of C. difficile-associated diarrhea.","Acute interstitial nephritis: Discontinue if signs of renal injury occur.","Severe cutaneous adverse reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis; discontinue at first signs.","CYP2C19 poor metabolizers: May have higher systemic exposure due to reduced clearance."] |
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| Fetal Monitoring | No specific fetal monitoring required. Monitor maternal clinical response and adverse effects. In late pregnancy, monitor for potential maternal vitamin B12 deficiency with long-term use. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies showed no impairment of fertility at doses up to 30 mg/kg/day (about 6 times the human dose). |