Rabeprazole

Generic Name: Rabeprazole
Brand Names: AcipHex (US), Pariet (EU/UK/Asia), Rabecid, Rabez, Rabicip, Rabium
Drug Class: Proton Pump Inhibitor (PPI)
Formulations:
– Oral delayed-release tablets: 10 mg, 20 mg
– Enteric-coated granules or capsules (some regional brands)
Route of Administration: Oral (by mouth)

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Therapeutic Indications and Clinical Use

Rabeprazole is a proton pump inhibitor used to treat conditions associated with excessive gastric acid secretion. It suppresses gastric acid production effectively and is commonly prescribed for both short-term symptom relief and long-term maintenance therapy.

Approved Indications:

1. Gastroesophageal Reflux Disease (GERD)
   – Symptomatic GERD
   – Erosive esophagitis
   – Maintenance of healed erosive esophagitis

2. Peptic Ulcer Disease (PUD)
   – Duodenal ulcers
   – Gastric ulcers
   – NSAID-induced gastric ulcers (treatment and prevention)

3. Helicobacter pylori eradication (as part of triple therapy)
   – Used with amoxicillin and clarithromycin

4. Zollinger-Ellison Syndrome and other hypersecretory conditions

5. Dyspepsia (off-label or regional approval)
   – Symptom control in non-ulcer indigestion

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Mechanism of Action

Rabeprazole is a prodrug that becomes active in the acidic environment of gastric parietal cells. It binds irreversibly to the H⁺/K⁺ ATPase enzyme system (proton pump) on the gastric parietal cell membrane.

Key effects:

• Inhibits the final step of gastric acid secretion

• Reduces both basal and stimulated acid production

• Provides longer acid suppression than H2 blockers

Distinctive Features:

• Slightly faster onset compared to other PPIs

• Less dependence on CYP2C19 metabolism compared to omeprazole or lansoprazole

• More acid-stable → faster action

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Dosing and Administration

1. GERD and Erosive Esophagitis:

• Healing phase: 20 mg once daily for 4–8 weeks

• Maintenance: 10–20 mg once daily (individualized)

2. Duodenal Ulcer:

• 20 mg once daily for 4 weeks (may extend to 8 weeks)

3. Gastric Ulcer:

• 20 mg once daily for 6 weeks (up to 12 weeks if needed)

4. NSAID-Associated Ulcers:

• Treatment: 20 mg once daily for 4–8 weeks

• Prevention: 20 mg once daily with NSAID

5. H. pylori Eradication (Triple Therapy):

• Rabeprazole 20 mg twice daily, with:
  – Amoxicillin 1000 mg BID
  – Clarithromycin 500 mg BID
  – Duration: 7–14 days

6. Zollinger-Ellison Syndrome:

• Initial dose: 60 mg once daily

• Titrated as needed (up to 100 mg BID in rare cases)

Administration Notes:

• Take tablets whole, do not crush or chew

• Usually taken before meals, particularly breakfast

• Can be taken without regard to meals (but best acid suppression when taken before eating)

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Pharmacokinetics

• Bioavailability: ~52% (increases slightly with repeated dosing)

• Time to peak concentration: ~3.5 hours

• Protein binding: ~96.3%

• Metabolism: Primarily non-enzymatic reduction; partly via CYP3A4 and CYP2C19

• Half-life: ~1–2 hours (but effect lasts >24 hours due to irreversible pump binding)

• Excretion:
  – Urine: ~90% as metabolites
  – Feces: <10%

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Contraindications

• Known hypersensitivity to rabeprazole, substituted benzimidazoles, or excipients

• Co-administration with rilpivirine (due to significant pH-dependent absorption issues)

• Suspected gastric malignancy without full diagnostic workup (risk of symptom masking)

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Warnings and Precautions

1. Vitamin B12 Deficiency (Long-term use):
   – Gastric acid required for B12 release from food
   – Monitor in patients on prolonged therapy (>1 year)

2. Hypomagnesemia:
   – Reported with long-term use; symptoms may include muscle cramps, seizures, and arrhythmias

3. Bone Fracture Risk:
   – Increased risk of hip, wrist, and spine fractures with long-term PPI use
   – Especially in high doses or elderly patients

4. Clostridium difficile–associated diarrhea (CDAD):
   – Acid suppression may predispose to intestinal infections

5. Gastric Carcinoid Tumors (in animal models):
   – Due to chronic hypergastrinemia
   – Relevance to humans uncertain

6. Lupus erythematosus (Drug-induced):
   – Rare, reversible; mostly cutaneous

7. Renal Effects:
   – Acute interstitial nephritis reported with all PPIs
   – Monitor renal function if symptoms occur

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Adverse Effects

Common (≥1%):

• Headache

• Diarrhea

• Nausea

• Abdominal pain

• Flatulence

• Constipation

• Dizziness

Less Common to Rare (<1%):

• Skin rash or pruritus

• Dry mouth

• Insomnia

• Back pain

• Myalgia

• Peripheral edema

• Hypomagnesemia

• Fractures (long-term)

• Interstitial nephritis

• Subacute cutaneous lupus erythematosus

• Anemia or leukopenia (rare hematologic effects)

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Drug Interactions

1. Drugs requiring acidic environment for absorption:
   – ↓ Absorption of ketoconazole, itraconazole, atazanavir, rilpivirine, erlotinib
   – Avoid co-administration with rilpivirine (contraindicated)

2. Clopidogrel:
   – Rabeprazole has minimal interaction compared to omeprazole
   – Safer in patients requiring antiplatelet therapy

3. Methotrexate:
   – High-dose methotrexate clearance may be delayed
   – Temporary PPI discontinuation recommended during high-dose methotrexate

4. Warfarin:
   – Monitor INR during co-use (rare reports of increased INR)

5. Cyclosporine:
   – Slight increase in levels possible; monitor closely

6. Digoxin and Tacrolimus:
   – Acid suppression may increase systemic exposure

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Monitoring Parameters

• Symptom improvement (heartburn, indigestion, ulcer healing)

• Magnesium levels (especially with long-term use or if on diuretics)

• Renal function if symptoms of nephritis appear

• Vitamin B12 levels after long-term use

• Bone health (DEXA scan if high fracture risk)

• Monitor for new GI symptoms that could indicate malignancy

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Use in Special Populations

Pregnancy:
– Category B (US); generally considered safe
– Use only if clearly needed

Lactation:
– Not well studied; avoid or use alternative acid suppressants if breastfeeding

Pediatrics:
– Safety and efficacy not well established in children under 12 in most regions

Geriatrics:
– No specific dose adjustments; monitor renal and hepatic function

Renal Impairment:
– No dosage adjustment needed

Hepatic Impairment:
– Use with caution in moderate-severe liver dysfunction

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Patient Counseling Points

• Take medication at the same time each day, preferably before meals

• Do not crush or chew the tablet

• May take several days for full effect in GERD or ulcer treatment

• Do not use as immediate symptom relief for heartburn; not like an antacid

• Inform your doctor of any unexplained weight loss, dysphagia, persistent vomiting, or black stools

• Notify your provider if symptoms persist beyond 2 weeks of OTC use

• Inform providers if taking antiretrovirals, antifungals, methotrexate, or other chronic medications

• Do not stop abruptly if on long-term therapy—may lead to rebound acid hypersecretion

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Comparison with Other Proton Pump Inhibitors (PPIs)

PPI	Onset	Metabolism	CYP2C19 Impact	Acid Stability	Clopidogrel Interaction
Rabeprazole	Fast (~1 hr)	CYP3A4, non-enzymatic	Low	High	Minimal (preferred)
Omeprazole	Moderate	CYP2C19, CYP3A4	High	Moderate	High (avoid)
Esomeprazole	Moderate	CYP2C19, CYP3A4	Moderate	High	Moderate
Pantoprazole	Slower	CYP2C19	Low	High	Minimal
Lansoprazole	Moderate	CYP2C19	High	Moderate	Moderate

Storage and Stability

• Store below 25°C

• Protect from moisture and light

• Do not use if tablets are damaged or discolored

• Keep out of reach of children

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Availability and Regulatory Status

• Prescription-only medication in most regions

• Available as generics and branded forms

• Listed on WHO Model List of Essential Medicines

• Approved by FDA, EMA, MHRA, TGA, and other national bodies