Pantoprazole

MECHANISM OF ACTION

Pantoprazole is a proton pump inhibitor (PPI) that works by irreversibly inhibiting the H⁺/K⁺-ATPase enzyme (proton pump) in gastric parietal cells, blocking the final step of gastric acid secretion. This leads to a long-lasting reduction in stomach acid production, helping to treat conditions like GERD, peptic ulcers, and Zollinger-Ellison syndrome by promoting healing and relieving acid-related symptoms.

PHARMACOKINETICS

Absorption:

• Well absorbed after oral administration.
• Peak plasma concentration (Tmax) occurs in 2–3 hours.
• Bioavailability is approximately 77% (not significantly affected by food).

Distribution:

• Plasma protein binding: 98% (mainly to albumin).
• Volume of distribution (Vd): 11-23.6 L.

Metabolism:

• Extensively metabolized in the liver via CYP2C19 (major pathway) and CYP3A4 (minor).
• Main metabolite: Desmethylpantoprazole, which is inactive.

Excretion:

• Urine (71%) as metabolites
• Feces (18%) via bile
• Half-life (t½): 1-1.5 hours (longer in liver impairment)

DOSAGE AND ADMINISTRATION

Gastroesophageal Reflux Disease (GERD)

• Mild to Moderate GERD (Short-term treatment):

Oral: 40 mg once daily for 4–8 weeks.

• Erosive Esophagitis (Healing phase):

Oral: 40 mg once daily for 8 weeks (may extend if needed).

• Maintenance therapy (to prevent relapse):

Oral: 40 mg once daily.

Peptic Ulcer Disease (PUD)

• Gastric or duodenal ulcers:

Oral: 40 mg once daily for 4–8 weeks.

• H. pylori eradication (as part of triple therapy):

Oral: 40 mg twice daily for 7–14 days, with clarithromycin and amoxicillin (or metronidazole).

Zollinger-Ellison Syndrome (Hypersecretory conditions)

• Initial dose: 40–80 mg twice daily (adjust as needed).
• Severe cases: Up to 240 mg/day, divided into two doses.

IV Administration (For patients unable to take oral medication)

• IV Dose: 40 mg once daily (over 15 minutes).
• Severe acid hypersecretion (e.g., Zollinger-Ellison): Higher doses may be required, given every 8–12 hours.

Administration 

• Oral: Take before meals (preferably in the morning).
• Do not crush or chew enteric-coated tablets.
• IV: Administer as a slow injection over 15 minutes.

DRUG INTERACTIONS

• Reduced absorption: Ketoconazole, Itraconazole, Atazanavir, Iron salts.
• CYP2C19 inhibition: Increases Diazepam, Phenytoin, Warfarin levels.
• Clopidogrel: May reduce antiplatelet effect.
• Methotrexate: Increases toxicity risk.
• Tacrolimus/Mycophenolate: Increases Tacrolimus levels, decreases Mycophenolate absorption.

CONTRAINDICATIONS

• Hypersensitivity → Allergy to pantoprazole, other PPIs, or excipients.
• Severe liver disease → Use with caution in hepatic impairment.
• Concomitant use with Rilpivirine → Reduces effectiveness of the HIV drug.
• Gastric cancer masking → Long-term use may delay diagnosis.
• Osteoporosis-related fractures → Caution in high-risk patients.
• Hypomagnesemia risk → Monitor with prolonged use.

SIDE EFFECTS

Common Side Effects

• Headache
• Nausea, vomiting
• Diarrhea, constipation
• Abdominal pain, bloating
• Dizziness

Serious Side Effects

• Long-term use risks: Vitamin B12 deficiency, Osteoporosis-related fractures, Hypomagnesemia (muscle spasms, irregular heartbeat)
• Kidney issues: Interstitial nephritis (rare but serious)
• Gastric polyps: Benign but can increase with prolonged use
• Clostridium difficile infection: Risk of severe diarrhea

TOXICITY

Symptoms of Overdose

• Confusion, dizziness
• Blurred vision
• Nausea, vomiting
• Increased heart rate (tachycardia)
• Sweating
• Drowsiness

Serious Toxic Effects (Rare, High Doses)

• Electrolyte imbalances (hypomagnesemia, hypocalcemia)
• Kidney damage (acute interstitial nephritis)
• Liver dysfunction (elevated liver enzymes)
• Severe metabolic alkalosis (rare)

Management

• Supportive care (symptom management)
• Activated charcoal if recently ingested
• Monitor electrolytes and kidney function
• No specific antidote; dialysis not effective