Pantoprazole

Generic Name: Pantoprazole
Brand Names: Protonix (US), Pantoloc, Somac, Pantecta, Zurcal, among others

Drug Class: Proton Pump Inhibitor (PPI)
Pharmaceutical Category: Gastrointestinal acid suppressor
Formulations:
– Delayed-release tablets (20 mg, 40 mg)
– Intravenous injection (40 mg vial)
– Granules for oral suspension (20 mg, limited availability)
Route of Administration: Oral and intravenous

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1. Mechanism of Action

Pantoprazole is a proton pump inhibitor that selectively inhibits the H⁺/K⁺ ATPase enzyme (the proton pump) located on the secretory surface of gastric parietal cells.
It blocks the final step in gastric acid production, leading to a profound and long-lasting reduction in gastric acid secretion, both basal and stimulated.

Pantoprazole acts irreversibly by forming a covalent bond with the H⁺/K⁺ ATPase, requiring new enzyme synthesis for acid secretion to resume.

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2. Therapeutic Indications

Approved Uses:

• Gastroesophageal reflux disease (GERD), including erosive esophagitis

• Zollinger-Ellison syndrome and other pathological hypersecretory conditions

• Peptic ulcer disease (PUD) – gastric and duodenal ulcers

• Helicobacter pylori eradication (in triple therapy with antibiotics)

• NSAID-induced ulcer prophylaxis or healing

• Stress ulcer prophylaxis (especially IV use in hospitalized patients)

• Barrett's esophagus (symptom control and acid suppression)

Off-label/Investigational:

• Functional dyspepsia

• Laryngopharyngeal reflux

• Eosinophilic esophagitis

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3. Dosage and Administration

Standard Oral Dosing (Adults):

Indication	Dose	Frequency	Duration
GERD (acute)	40 mg	Once daily	4–8 weeks
Maintenance (GERD)	20–40 mg	Once daily	As needed
Peptic ulcer (gastric/duodenal)	40 mg	Once daily	4–8 weeks
H. pylori eradication	40 mg	Twice daily	7–14 days (with antibiotics)
Zollinger-Ellison syndrome	Initial: 40 mg BID	Adjust as needed	Long-term
NSAID-induced ulcer prophylaxis	20–40 mg	Once daily	During NSAID therapy

IV Use (when oral route not possible):

• 40 mg once daily (IV injection or infusion over 15 minutes)

Timing:

• Take before meals, usually 30–60 minutes before breakfast

• Do not crush or chew the tablets (delayed-release formulation)

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4. Pharmacokinetics

• Absorption: Well absorbed orally, bioavailability ~77%

• Peak Plasma Time: ~2.5 hours

• Protein Binding: ~98%

• Metabolism: Hepatic via CYP2C19 and CYP3A4

• Elimination: Renal (~80% as metabolites), feces (~20%)

• Half-life: 1 hour (effect on acid secretion lasts up to 24 hours)

Note: Genetic polymorphisms (e.g., CYP2C19 poor metabolizers) may prolong drug effects.

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5. Contraindications

• Known hypersensitivity to pantoprazole, substituted benzimidazoles, or any excipients

• Coadministration with rilpivirine (HIV drug) due to reduced absorption

• Caution in severe hepatic impairment

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6. Warnings and Precautions

• Long-term PPI use risks:

  • Clostridium difficile infection (esp. in hospitalized patients)

  • Bone fractures (hip, spine, wrist) with prolonged use

  • Hypomagnesemia (may lead to tetany, arrhythmias)

  • Vitamin B12 deficiency (especially after >2 years)

  • Kidney disease (interstitial nephritis, rare but serious)

  • Gastric polyps (fundic gland type, benign)

  • Rebound acid hypersecretion upon withdrawal

• Masking of gastric cancer: PPIs may reduce ulcer symptoms while delaying diagnosis of underlying malignancy

• Use with caution in liver disease – monitor LFTs

• Monitor electrolytes (Mg²⁺, Ca²⁺) in long-term therapy

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7. Adverse Effects

Common (≥1%)

• Headache

• Diarrhea

• Abdominal pain

• Nausea

• Flatulence

• Vomiting

• Dizziness

Uncommon (0.1–1%)

• Pruritus, rash

• Arthralgia, myalgia

• Sleep disturbances

• Elevated liver enzymes

Rare (<0.1%)

• Interstitial nephritis

• Pancytopenia or thrombocytopenia

• Severe hepatic injury

• Anaphylaxis, angioedema

• Hypomagnesemia, seizures

• Stevens-Johnson syndrome

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8. Drug Interactions

Due to gastric pH elevation, pantoprazole may affect absorption of some drugs:

Decreased Absorption:

• Ketoconazole, itraconazole, posaconazole (antifungals)

• Atazanavir, rilpivirine (HIV medications)

• Iron salts

• Erlotinib (tyrosine kinase inhibitor)

Other Interactions:

• Clopidogrel: Less interaction compared to omeprazole, but monitor for antiplatelet efficacy

• Methotrexate: High-dose MTX may accumulate → toxicity

• Warfarin: Monitor INR, rare potentiation

• Digoxin: Hypomagnesemia from PPI may increase digoxin toxicity

• Tacrolimus: ↑ levels possible

• CYP2C19 inhibitors/inducers: May alter pantoprazole metabolism (e.g., fluvoxamine, rifampin)

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9. Use in Special Populations

Pregnancy:

• Category B (US): Animal studies show no fetal risk; limited human data

• Use if clearly needed

Lactation:

• Excreted in breast milk (minimal levels); use with caution or avoid if alternatives available

Pediatrics:

• Approved for children ≥5 years old with GERD

• Dosage is weight-based; consult pediatric guidelines

Elderly:

• No dosage adjustment necessary

• Monitor for bone density loss, electrolyte imbalance

Renal Impairment:

• No dose adjustment needed

Hepatic Impairment:

• Mild to moderate: no adjustment

• Severe: caution, monitor LFTs

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10. Comparative Features vs. Other PPIs

Feature	Pantoprazole	Omeprazole	Esomeprazole	Lansoprazole	Rabeprazole
CYP interaction	Less with clopidogrel	More CYP2C19	Moderate	Moderate	Less
Acid suppression	High	High	Highest	High	High
Food interaction	Less affected	Delayed with food	Delayed	Affected	Slightly affected
Generic availability	Yes	Yes	Yes	Yes	Yes

Pantoprazole is preferred when minimal CYP2C19 interaction is desired (e.g., in patients on clopidogrel).

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11. Patient Counseling Points

• Take 30–60 minutes before a meal, usually before breakfast

• Do not crush or chew delayed-release tablets

• Inform prescriber of persistent symptoms, weight loss, dysphagia, or GI bleeding

• Do not discontinue abruptly if on long-term therapy—taper to avoid rebound acid secretion

• Long-term users should have periodic magnesium and B12 level checks