Rabifast

Approved Indications

• Gastroesophageal Reflux Disease (GERD):
• Treatment of erosive or ulcerative GERD
• Maintenance of healing of erosive GERD
• Treatment of non-erosive (symptomatic) GERD
• Duodenal Ulcers:
• Short-term treatment of active duodenal ulcers
• Zollinger-Ellison Syndrome:
• Long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome
• Helicobacter pylori Eradication (in combination therapy):
• As part of triple therapy with amoxicillin and clarithromycin for the eradication of H. pylori in patients with active duodenal ulcer disease or a history of duodenal ulcers
• NSAID-Associated Ulcers:
• Treatment and prevention of gastric ulcers or duodenal ulcers associated with NSAID use

Clinically Accepted Off-Label Uses

• Functional dyspepsia
• Barrett’s esophagus (as part of acid suppression therapy)
• Stress ulcer prophylaxis in critically ill hospitalized patients
• Eosinophilic esophagitis (in combination with dietary modifications)

Adults

• GERD (erosive or ulcerative):
  20 mg once daily for 4 to 8 weeks; may continue for another 8 weeks if not healed
• GERD (maintenance):
  20 mg once daily as needed
• Symptomatic GERD (non-erosive):
  20 mg once daily for 4 weeks
• Duodenal Ulcers:
  20 mg once daily before breakfast for 4 weeks; some may need up to 8 weeks
• Zollinger-Ellison Syndrome:
  Initial dose: 60 mg once daily; titrate as needed
  Doses up to 100 mg once daily or 60 mg twice daily have been used
• H. pylori Eradication (Triple Therapy):
  Rabeprazole 20 mg + Amoxicillin 1000 mg + Clarithromycin 500 mg, all twice daily for 7–14 days
• NSAID-associated Ulcers:
  20 mg once daily for 4–8 weeks; prevention: 20 mg once daily

Pediatric Use

• GERD (ages 1 to 11 years):
• 5 mg once daily for <15 kg
• 10 mg once daily for ≥15 kg
• Up to 12 weeks of use
• GERD (ages 12–16 years):
  20 mg once daily for up to 8 weeks

Elderly

• No dose adjustment required
• Monitor for fracture risk, electrolyte imbalances, and B12 deficiency with long-term use

Renal Impairment

• No dose adjustment necessary

Hepatic Impairment

• Use with caution in moderate hepatic dysfunction
• No dose adjustment needed for mild impairment

Administration Notes

• Take orally, preferably before meals
• Do not crush or chew the delayed-release tablets
• Swallow whole with water

Rabeprazole is a proton pump inhibitor (PPI) that blocks the final step in acid production by irreversibly inhibiting the H⁺/K⁺ ATPase enzyme system (proton pump) in the gastric parietal cells. This suppression of gastric acid secretion reduces both basal and stimulated acid output. The drug accumulates in the acidic canaliculi of the parietal cells, becomes protonated, and covalently binds to cysteine residues on the proton pump, leading to long-lasting inhibition. This action allows for healing of acid-related gastrointestinal lesions and symptom relief in GERD and ulcer diseases.

• Absorption:
• Rapid, with peak plasma concentrations in 2–5 hours
• Not significantly affected by food, but better taken before meals
• Bioavailability:
• Approx. 52% after oral administration; increases slightly on repeated dosing
• Distribution:
• Plasma protein binding ~96.3%
• Volume of distribution is moderate
• Metabolism:
• Extensively metabolized in the liver via non-enzymatic reduction, CYP3A4, and CYP2C19
• Half-life:
• ~1–2 hours, but acid suppression lasts much longer due to irreversible binding
• Excretion:
• Mainly through urine (90%), rest via feces
• Primarily excreted as inactive metabolites

• Pregnancy:
• FDA Pregnancy Category B
• Animal studies do not indicate direct or indirect harmful effects on pregnancy or fetal development
• No adequate controlled studies in pregnant women; use only if clearly needed
• Lactation:
• Unknown whether rabeprazole is excreted in human breast milk
• Due to potential for serious adverse effects in the nursing infant, caution is advised
• Consider discontinuing breastfeeding or the drug, depending on clinical need

• Primary Class: Proton Pump Inhibitor (PPI)
• Subclassification: Substituted benzimidazole derivative
• Generation: Second-generation PPI with rapid onset and long-lasting acid suppression

• Known hypersensitivity to rabeprazole, other PPIs (e.g., omeprazole, esomeprazole), or any component of the formulation
• Co-administration with rilpivirine (due to risk of loss of virologic response)
• History of hypersensitivity reactions to substituted benzimidazoles

• Long-term Use Risks:
• Bone fractures (hip, wrist, spine) due to decreased calcium absorption
• Hypomagnesemia with chronic use >1 year
• Vitamin B12 deficiency with prolonged use
• Chronic atrophic gastritis, especially with H. pylori
• C. difficile-associated diarrhea:
• Risk increases with long-term or broad-spectrum antimicrobial use
• Lupus erythematosus:
• Both systemic and cutaneous forms have been reported (rare)
• Hepatic Impairment:
• Use caution in moderate-to-severe liver dysfunction
• Gastric Malignancy Masking:
• Acid suppression may delay diagnosis of gastric cancer

Common Side Effects

• Gastrointestinal: Diarrhea, nausea, vomiting, abdominal pain, flatulence, constipation
• Neurologic: Headache, dizziness
• Musculoskeletal: Back pain
• Infection: Upper respiratory tract infections, pharyngitis

Less Common / Serious Side Effects

• Hematologic: Thrombocytopenia, neutropenia (rare)
• Hepatic: Elevated liver enzymes, hepatitis (rare)
• Metabolic: Hypomagnesemia, hyponatremia (long-term use)
• Renal: Interstitial nephritis (rare)
• Allergic: Anaphylaxis, angioedema, Stevens-Johnson syndrome (very rare)

• Drugs affected by gastric pH:
• ↓ Absorption of ketoconazole, itraconazole, erlotinib, and iron salts
• ↓ Activation of clopidogrel (controversial; rabeprazole has lower interaction compared to omeprazole)
• CYP450 interactions:
• Rabeprazole is metabolized by CYP3A4 and CYP2C19, but has low potential for significant drug interactions
• No clinically significant effect on warfarin, theophylline, diazepam, or phenytoin
• Methotrexate:
• Delayed clearance of methotrexate at high doses may occur
• Rilpivirine:
• Contraindicated due to reduced efficacy caused by increased gastric pH

• FDA and EMA reviews (2023):
• Reaffirmed the class warning for PPI-related hypomagnesemia and fracture risk
• Recommended routine magnesium monitoring for chronic users, especially those on diuretics or digoxin
• Clinical practice guidelines (AGA, 2022):
• Recommend shortest effective duration for PPI therapy
• Use on-demand or intermittent therapy in non-erosive GERD
• Updated GERD management recommendations:
• Rabeprazole is among first-line PPIs due to potent acid suppression, fast onset, and good tolerability

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C
• Humidity: Keep in a dry place, away from moisture
• Light Protection: Store in original container; protect from light
• Handling:
• Do not crush or split tablets
• Keep out of reach of children
• No refrigeration required