Pantoprazole

Pantoprazole is a medication that reduces stomach acid by inhibiting the proton pump. It is used to treat conditions such as GERD, peptic ulcers, and Zollinger-Ellison syndrome. Pantoprazole was approved by the U.S. Food and Drug Administration (FDA) in 2000 for the treatment of gastroesophageal reflux disease (GERD) and related conditions. Since then, it has been approved for various uses, including the treatment of peptic ulcers and Zollinger-Ellison syndrome. It is widely prescribed and available in many countries worldwide.

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