Pregel

Approved Indications

• Gastroesophageal Reflux Disease (GERD): Short-term treatment (up to 8 weeks) of erosive esophagitis associated with GERD; may repeat for an additional 8 weeks if healing is incomplete.
• Maintenance of Healing of Erosive Esophagitis: To maintain healing and reduce relapse in GERD patients with a history of erosive esophagitis.
• Pathological Hypersecretory Conditions: Long-term treatment of pathological hypersecretory conditions such as Zollinger–Ellison Syndrome and other conditions involving excessive gastric acid secretion.
• Peptic Ulcer Disease (PUD): Used as part of a combination regimen for Helicobacter pylori eradication therapy in patients with duodenal ulcers (not FDA-labeled but standard practice).

Important Off-Label Uses

• Prevention of NSAID-Associated Ulcers: Prevention of gastric ulceration in patients on chronic NSAIDs, especially those at high risk.
• Stress Ulcer Prophylaxis: Off-label IV use in critically ill hospitalized patients at high risk for stress-related mucosal bleeding.
• Upper GI Bleeding: Off-label IV use for acute peptic ulcer bleeding to reduce rebleeding risk.
• Barrett’s Esophagus: Long-term acid suppression in patients with Barrett’s esophagus (off-label).

Erosive Esophagitis (Adults)

• Oral: 40 mg once daily for up to 8 weeks. A second 8-week course may be considered if needed.
• IV: 40 mg once daily for 7–10 days if oral therapy is not possible.

Maintenance of Erosive Esophagitis (Adults)

• Oral: 40 mg once daily for maintenance to prevent relapse; duration individualized.

Pathological Hypersecretory Conditions (e.g., Zollinger–Ellison Syndrome)

• Oral/IV: 40 mg twice daily initially; adjust dose according to individual needs, sometimes up to 240 mg/day in divided doses, guided by gastric acid output.

H. pylori Eradication (Off-Label Triple Therapy)

• Oral: 40 mg twice daily for 7–14 days, in combination with clarithromycin and either amoxicillin or metronidazole.

Stress Ulcer Prophylaxis (Off-Label)

• IV: 40 mg IV once daily in ICU patients with significant risk factors.

Pediatric GERD (5–16 Years)

• Oral: 20 mg once daily for children <40 kg; 40 mg once daily for children ≥40 kg for up to 8 weeks.
• Not approved for children under 5 years.

Elderly

• No dose adjustment generally required but monitor for adverse effects due to increased sensitivity.

Renal Impairment

• No dose adjustment needed.

Hepatic Impairment

• Mild–moderate impairment: No adjustment needed.
• Severe impairment: Use cautiously; long-term high doses should be used with clinical monitoring.

Administration Instructions

• Tablets should be swallowed whole; do not split, crush, or chew.
• Should be taken before meals, usually once daily in the morning.
• For IV: Reconstitute as per labeling, administer as IV push over 2–15 minutes or as an infusion over ~15 minutes.

Pantoprazole Sodium is a proton pump inhibitor (PPI) that suppresses final gastric acid secretion by binding irreversibly to the H⁺/K⁺ ATPase enzyme system (proton pump) on gastric parietal cells. This inhibition blocks the final step of gastric acid production, effectively reducing both basal and stimulated acid output. The result is sustained acid suppression that promotes healing of acid-induced lesions in the esophagus, stomach, or duodenum and controls acid hypersecretion in conditions like Zollinger–Ellison Syndrome.

Absorption:

• Rapidly absorbed after oral dosing; absolute bioavailability ~77%.
• Peak plasma concentration (Tmax): ~2–2.5 hours.
• Food may slightly delay Tmax but does not significantly affect overall bioavailability.

Distribution:

• Highly protein-bound (~98%).
• Apparent volume of distribution: ~11–23 L.

Metabolism:

• Extensively metabolized in the liver, mainly via CYP2C19 (major) and CYP3A4 (minor).
• Main metabolites are inactive sulfone and sulfide derivatives.

Excretion:

• Eliminated primarily as metabolites: ~71% renal, ~18% fecal.
• Terminal half-life: ~1 hour, but acid suppression lasts much longer due to irreversible pump binding.

Pregnancy:

• FDA Pregnancy Category B (historical). Animal studies show no evidence of harm; no adequate, well-controlled studies in pregnant women — use only if clearly needed.

Lactation:

• Pantoprazole is excreted in animal milk; likely low levels in human milk. Short-term use is generally considered compatible with breastfeeding, but monitor infant for potential GI effects (diarrhea, irritability).

• Primary Class: Proton Pump Inhibitor (PPI)
• Subclass: Benzimidazole derivative PPI

• Known hypersensitivity to Pantoprazole, other substituted benzimidazole PPIs, or any formulation component
• Documented severe hypersensitivity reactions to other PPIs
• Concurrent use with rilpivirine-containing antiretroviral products (due to significant reduction of rilpivirine plasma levels, risk of virologic failure)

• C. difficile Infection: Increased risk of Clostridioides difficile–associated diarrhea, especially with prolonged use.
• Bone Fracture Risk: Increased risk of hip, wrist, and spine fractures with long-term use, particularly in elderly patients and those receiving high-dose or multiple daily doses.
• Hypomagnesemia: May occur with prolonged use (>3 months); monitor magnesium, especially if used with digoxin or diuretics.
• Vitamin B12 Deficiency: Possible with prolonged use due to reduced gastric acid; consider monitoring if used >3 years.
• Acute Interstitial Nephritis (AIN): Rare but serious; discontinue if suspected.
• Fundic Gland Polyps: Long-term use may increase risk of benign gastric polyps.
• Masking Malignancy: May mask symptoms of gastric cancer; investigate unexplained weight loss, dysphagia, or persistent symptoms.
• Hepatic Disease: Use cautiously in severe hepatic impairment.

Common (by body system):

• Gastrointestinal: Diarrhea, nausea, abdominal pain, flatulence.
• Central Nervous System: Headache, dizziness.
• Dermatologic: Rash, pruritus.

Serious / Rare:

• Clostridioides difficile–associated diarrhea
• Hypomagnesemia (can cause arrhythmias, tetany, seizures)
• Bone fractures (long-term, high-dose use)
• Vitamin B12 deficiency (long-term use)
• Acute interstitial nephritis
• Severe cutaneous adverse reactions (rare)

Timing: Most common side effects appear early in therapy; long-term effects may develop after months or years.

• Drugs Needing Acid for Absorption: Decreased absorption of drugs requiring acidic pH (e.g., ketoconazole, atazanavir, rilpivirine).
• Methotrexate: High-dose methotrexate clearance may be delayed — risk of toxicity.
• Warfarin: Rarely affects INR; monitor if combined.
• CYP2C19 Substrates/Inhibitors: Metabolism may be altered in poor metabolizers or with strong CYP2C19 inhibitors.
• Clopidogrel: Pantoprazole has less interaction than omeprazole but may slightly reduce clopidogrel activation — clinical relevance minimal compared to other PPIs.

• Current FDA and EMA labeling emphasizes monitoring for long-term risks (fractures, C. difficile, hypomagnesemia).
• ACG and NICE guidelines continue to recommend PPIs, including Pantoprazole, as first-line therapy for GERD, PUD, H. pylori treatment, and prevention of NSAID-induced ulcers.
• Recent guidance increasingly focuses on deprescribing PPIs when no longer indicated.

• Store tablets at 20°C to 25°C (68°F–77°F); excursions permitted between 15°C and 30°C (59°F–86°F).
• Protect from moisture and light.
• Keep in original blister pack or container until use.
• IV vials: Store unopened vials at room temperature.
• Reconstituted IV solution: Prepare and use as directed; discard unused portion per manufacturer instructions.