Introduction
Protonix (pantoprazole sodium) is a proton pump inhibitor (PPI) that decreases gastric acid production through irreversible inhibition of hydrogen/potassium adenosine triphosphatase (H+/K+ ATPase) in gastric parietal cells. It is widely used for the management of acid-related gastrointestinal disorders and is available in both oral and intravenous formulations.
Mechanism of Action
Pantoprazole is a substituted benzimidazole that accumulates in the acidic compartment of parietal cells, where it undergoes conversion to its active form. The activated drug forms covalent bonds with cysteine residues of the H+/K+ ATPase enzyme system at the secretory surface of gastric parietal cells, resulting in irreversible inhibition of the final step of gastric acid production. This effect leads to prolonged suppression of both basal and stimulated acid secretion, regardless of the stimulus.
Indications
- Treatment and maintenance of healing of erosive esophagitis associated with gastroesophageal reflux disease (GERD)
- Pathological hypersecretory conditions including Zollinger-Ellison syndrome
- Short-term treatment (7-10 days) of duodenal ulcers
- Reduction of NSAID-associated gastric ulcer risk in patients requiring continued NSAID therapy
- IV formulation for patients unable to take oral medication with the above conditions
Dosage and Administration
Oral administration:- Erosive esophagitis: 40 mg once daily for 8 weeks
- Maintenance of healing: 40 mg once daily
- Hypersecretory conditions: Initial dose 80 mg twice daily; adjust based on acid output
- Duodenal ulcer: 40 mg once daily for 2-4 weeks
- 40 mg once daily by IV infusion over 15 minutes for 7-10 days
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Maximum dose 20 mg daily in severe impairment
- Geriatric patients: No dosage adjustment required
- Pediatric patients: Safety and effectiveness established for ages 5+ (dose based on weight)
Pharmacokinetics
Absorption: Rapidly absorbed with absolute bioavailability of 77% that is not affected by food Distribution: Volume of distribution approximately 11-23 L with 98% protein binding Metabolism: Extensively metabolized in the liver via cytochrome P450 system (CYP2C19 and CYP3A4) Elimination: Primarily renal excretion (80%) as metabolites with elimination half-life of approximately 1 hour (does not reflect duration of acid suppression) Onset/Duration: Onset within 1 hour with acid suppression lasting up to 24 hoursContraindications
- Hypersensitivity to pantoprazole, substituted benzimidazoles, or any component of the formulation
- Concomitant use with rilpivirine-containing products
- Patients taking atazanavir or nelfinavir
Warnings and Precautions
- Gastric malignancy: Symptomatic response does not preclude presence of gastric malignancy
- Bone fracture: Long-term and multiple daily dose PPI therapy may be associated with increased risk of osteoporosis-related fractures
- Hypomagnesemia: Reported with prolonged PPI use; monitor magnesium levels before initiation and periodically during treatment
- Clostridium difficile-associated diarrhea: PPI use may increase risk
- Cutaneous and systemic lupus erythematosus: New onset or exacerbation reported
- Vitamin B12 deficiency: Long-term therapy may lead to malabsorption
- Acute interstitial nephritis: May occur at any time during therapy
Drug Interactions
- Atazanavir and nelfinavir: PPIs significantly reduce absorption (contraindicated)
- Warfarin: Increased INR and PT with possible bleeding
- Methotrexate: May increase methotrexate levels
- Clopidogrel: Potential reduction in antiplatelet effect
- CYP2C19 substrates: May increase concentrations of drugs metabolized by CYP2C19
- Iron salts, ketoconazole, mycophenolate mofetil: Reduced absorption due to increased gastric pH
Adverse Effects
Common (≥1%):- Headache (2-6%)
- Diarrhea (2-4%)
- Nausea/vomiting (1-3%)
- Abdominal pain (1-3%)
- Flatulence (1-2%)
- Anaphylaxis and serious hypersensitivity reactions
- Acute interstitial nephritis
- Clostridium difficile-associated diarrhea
- Bone fracture
- Hypomagnesemia
- Vitamin B12 deficiency
- Cutaneous and systemic lupus erythematosus
Monitoring Parameters
- Symptom improvement and healing assessment
- Magnesium levels with prolonged therapy
- Vitamin B12 levels with long-term use
- Renal function in patients at risk
- Bone density assessment with long-term high-dose therapy
- Signs of hypersensitivity reactions
- Monitoring for signs of C. difficile infection with diarrhea
Patient Education
- Take tablet whole 30 minutes before food; do not crush, chew, or split
- Report any signs of allergic reaction (rash, swelling, difficulty breathing)
- Notify healthcare provider of persistent diarrhea
- Long-term use may increase risk of bone fractures; maintain adequate calcium and vitamin D intake
- Report symptoms of hypomagnesemia (muscle spasms, seizures, arrhythmias)
- Inform all healthcare providers of PPI use, especially before new prescriptions
- Do not stop medication abruptly without medical supervision
- Regular follow-up appointments recommended for long-term therapy
References
1. Protonix [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals Inc; 2021. 2. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108(3):308-328. 3. Strand DS, Kim D, Peura DA. 25 years of proton pump inhibitors: a comprehensive review. Gut Liver. 2017;11(1):27-37. 4. FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs. US Food and Drug Administration. 2011. 5. Moayyedi P, Leontiadis GI. The risks of PPI therapy. Nat Rev Gastroenterol Hepatol. 2012;9(3):132-139. 6. Savarino V, et al. The appropriate use of proton pump inhibitors. Minerva Med. 2018;109(5):386-399.