Continuing Education Activity

Pantoprazole is a proton-pump inhibitor (PPI) widely used in hospitals and outpatient settings. Pantoprazole has approval from the Food and Drug Administration Agency (FDA) to treat various disease processes, including treatment of erosive esophagitis associated with gastroesophageal reflux disease and the treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome. It is also FDA approved for the healing maintenance of erosive esophagitis. Pantoprazole also has various off-label uses, including eradicating Helicobacter pylori bacteria and preventing peptic ulcer re-bleeding and/or NSAID-induced ulcers. Patients who are critically ill may be given pantoprazole as stress ulcer prophylaxis. This medication is safe for administration in adult and pediatric populations. This activity reviews the uses of pantoprazole and highlights the role of the interprofessional team in the management of patients with peptic ulcer disease.

Objectives:

• Identify the mechanism of action of pantoprazole.
• Describe the adverse effects of pantoprazole.
• Outline the contraindications of pantoprazole.
• Explain the interprofessional team strategies for improving care coordination and communication to advance the treatment of peptic ulcer disease and improve outcomes.

Indications

Pantoprazole is a proton-pump inhibitor (PPI) widely used in hospitals and outpatient settings. Pantoprazole has approval from the Food and Drug Administration Agency (FDA) for the treatment of various disease processes, including therapy for erosive esophagitis associated with gastroesophageal reflux disease and the treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.[1] It is also FDA approved for the healing maintenance of erosive esophagitis. Pantoprazole also has various off-label uses, including eradicating Helicobacter pylori bacteria and preventing peptic ulcer re-bleeding and/or NSAID-induced ulcers.[2] Patients who are critically ill may be given Pantoprazole as stress ulcer prophylaxis.[3] The administration of this medication is safe in adult and pediatric populations.

Mechanism of Action

There are two groups of PPIs: the benzimidazole group and the imidazopyridine group. Pantoprazole falls in the benzimidazole group of PPIs. The difference between these two groups is that benzimidazoles have an extended rate of metabolism resulting in a shorter presence in plasma. Regarding the mechanism of action, pantoprazole irreversibly inhibits the H+/K+ ATP pumps. There is an increased rate of pantoprazole degradation with decreased environmental pH. Therefore, it makes sense that this medication would work best in the stomach, where the H+/K+ ATP pumps are located (specifically within the parietal cells of the stomach lining). This step is the final step in gastric acid production. As a result, the binding of pantoprazole to these pumps prevents acid secretion for up to 24 hours. After 24 hours, new pumps have been created, and thus a subsequent dose of pantoprazole is required to inhibit their action. The onset of action is rapid, and the maximal effect occurs between 2 and 6 hours after drug administration. Pantoprazole is also metabolized in the liver, predominantly by CYP2C19 demethylation and sulfation. These metabolites are not known to be of any significance.

Administration

To correctly dose pantoprazole requires correct diagnosis since there are different administration protocols based on the condition treated. There are a handful of disease processes that pantoprazole helps treat.[4] These include erosive esophagitis associated with gastroesophageal reflux disease, healing maintenance of erosive esophagitis, and pathological hypersecretory conditions such as Zollinger-Ellison syndrome. For erosive esophagitis associated with gastroesophageal reflux disease, pantoprazole administration can be oral or intravenous. For oral administration, treatment is typically 40 mg daily or 20 mg daily for milder cases, for a total of 8 weeks.[5] There is an optional “maintenance” period in which the same dose can continue for up to 12 months. Intravenously, 40 mg of pantoprazole is administered daily for 7 to 10 days. For Zollinger-Ellison syndrome, pantoprazole administration can also be oral or intravenous. For oral administration, treatment is typically 40 mg twice daily. There is an option of titrating up to 240 mg if need be. Intravenously, the recommendation is to administer 80 mg of pantoprazole every 12 hours. As mentioned, pantoprazole also has various off-label uses.[6] 

For the eradication of Helicobacter pylori bacterial infections, pantoprazole can be incorporated into drug regimens, which include different types of antibiotics.[7] For all of these regimens, the recommended dosing is 40 mg of pantoprazole twice daily. For peptic ulcer re-bleeding prevention, a loading dose of 80 mg followed by an 8 mg per hour infusion is recommended.[8] For NSAID-induced ulcers, the recommended dosing is 20 to 40 mg oral each day.[9] Pantoprazole administration can be with or without food, but it is preferable to take it 30 minutes before a meal. The tablet should be swallowed whole and should not be crushed or chewed. The absorption of pantoprazole is not affected by the concomitant administration of antacids. It has a bioavailability of 77% when taken orally.

Adverse Effects

Even though pantoprazole is a relatively benign medication, there is still a risk of adverse effects.[10] The primary adverse effects of pantoprazole include diarrhea, headache, upper respiratory tract infection, and abdominal pain. Long-term complications of pantoprazole use include diarrhea attributed to Clostridium difficile or microscopic colitis, small-intestinal bacterial overgrowth, vitamin B12 deficiency, iron deficiency, calcium deficiency, magnesium deficiency, bone demineralization, interstitial nephritis, and diminished absorption of medications such as clopidogrel.[11] There is a rarely associated risk of subacute cutaneous lupus erythematosus in association with pantoprazole, and in December of 2017, Health Canada recently acknowledged this risk. In the geriatric population specifically, treatment with pantoprazole for eight or more weeks is not recommended. The Beers Criteria classifies pantoprazole as an inappropriate medication for the elderly population due to an associated increased risk of Clostridium difficile infection and bone density loss.[12][13]

Contraindications

Pantoprazole is contraindicated in patients with a history of hypersensitivity to the drug itself, components of the formulation, and/or other benzimidazole PPIs, including omeprazole, lansoprazole, rabeprazole, esomeprazole, or dexlansoprazole. Hypersensitivity reactions would include, but at not limited to, anaphylactic shock, pulmonary effects such as bronchospasm, angioedema, and urticaria.[14] If a hypersensitivity reaction were to occur following the administration of pantoprazole, the infusion should stop immediately. Furthermore, pantoprazole should not be taken with rilpivirine (which is a non-nucleoside reverse transcriptase inhibitor) as it may reduce the drug’s serum concentration.

Monitoring

Patients who are prescribed pantoprazole require monitoring for signs and symptoms of gastroesophageal reflux disease and peptic ulcer disease. If symptoms of these conditions arise, an increase in dosage or medication change should merit clinician consideration. Pantoprazole can decrease the concentration or increase the absorption of other medications such as CYP2C19 inducers, bisphosphonate derivatives, amphetamines, fluconazole, and methotrexate, to name a few. Therefore, the affected efficacy of these medications also requires vigilance, and appropriate changes made when necessary. Finally, pantoprazole sounds and looks similar to the antipsychotic aripiprazole. Prescribing healthcare professionals and patients should acknowledge this and be cautious to avoid mistakes.

Toxicity

There have not been a significant number of pantoprazole overdoses, which have led to serious medical consequences. There is no specific antidote for an event such as this. Furthermore, pantoprazole is not removable from the body via hemodialysis. As a result, treatment in Pantoprazole overdose focuses on symptomatic relief. In laboratory studies have shown that single doses ranging from 709 mg/kg to 887 mg/kg caused death in animal subjects (mice, rats, and dogs). Acutely, there was evidence of hypoactivity, tremor, and ataxia in these animals.

Enhancing Healthcare Team Outcomes

Pantoprazole is often prescribed by the primary care provider (including mid-level practitioners), internist, and gastroenterologist. While the drug is effective for peptic ulcer disease, there have been many reports regarding overdose. The pharmacist should also perform a complete medication reconciliation when starting pantoprazole. Healthcare workers should avoid writing prescriptions for many months and educate patients on drug safety, including storing the medication in a locked cabinet away from the reach of children.

All members of the interprofessional healthcare team need to work collaboratively when patients are taking pantoprazole. This includes open information sharing and coordinating therapeutic interventions, so the patient receives optimal care with the fewest possible adverse events. [Level 5]

Review Questions

• Access free multiple choice questions on this topic.
• Comment on this article.

References

1.

Escourrou J, Deprez P, Saggioro A, Geldof H, Fischer R, Maier C. Maintenance therapy with pantoprazole 20 mg prevents relapse of reflux oesophagitis. Aliment Pharmacol Ther. 1999 Nov;13(11):1481-91. [PubMed: 10571605]

2.

Lanza FL, Chan FK, Quigley EM., Practice Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009 Mar;104(3):728-38. [PubMed: 19240698]

3.

Jensen BES, Hansen JM, Larsen KS, Junker AB, Lassen JF, Jensen SE, Schaffalitzky de Muckadell OB. Randomized clinical trial: the impact of gastrointestinal risk factor screening and prophylactic proton pump inhibitor therapy in patients receiving dual antiplatelet therapy. Eur J Gastroenterol Hepatol. 2017 Oct;29(10):1118-1125. [PubMed: 28678044]

4.

Barkun AN, Bardou M, Kuipers EJ, Sung J, Hunt RH, Martel M, Sinclair P., International Consensus Upper Gastrointestinal Bleeding Conference Group. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010 Jan 19;152(2):101-13. [PubMed: 20083829]

5.

Dettmer A, Vogt R, Sielaff F, Lühmann R, Schneider A, Fischer R. Pantoprazole 20 mg is effective for relief of symptoms and healing of lesions in mild reflux oesophagitis. Aliment Pharmacol Ther. 1998 Sep;12(9):865-72. [PubMed: 9768529]

6.

Bianchi Porro G, Lazzaroni M, Imbesi V, Montrone F, Santagada T. Efficacy of pantoprazole in the prevention of peptic ulcers, induced by non-steroidal anti-inflammatory drugs: a prospective, placebo-controlled, double-blind, parallel-group study. Dig Liver Dis. 2000 Apr;32(3):201-8. [PubMed: 10975769]

7.

Mansour-Ghanaei F, Pedarpour Z, Shafaghi A, Joukar F. Clarithromycin versus Gemifloxacin in Quadruple Therapeutic Regimens for Helicobacter Pylori Infection Eradication. Middle East J Dig Dis. 2017 Apr;9(2):100-106. [PMC free article: PMC5471100] [PubMed: 28638586]

8.

Zargar SA, Javid G, Khan BA, Yattoo GN, Shah AH, Gulzar GM, Sodhi JS, Mujeeb SA, Khan MA, Shah NA, Shafi HM. Pantoprazole infusion as adjuvant therapy to endoscopic treatment in patients with peptic ulcer bleeding: prospective randomized controlled trial. J Gastroenterol Hepatol. 2006 Apr;21(4):716-21. [PubMed: 16677158]

9.

Regula J, Butruk E, Dekkers CP, de Boer SY, Raps D, Simon L, Terjung A, Thomas KB, Lühmann R, Fischer R. Prevention of NSAID-associated gastrointestinal lesions: a comparison study pantoprazole versus omeprazole. Am J Gastroenterol. 2006 Aug;101(8):1747-55. [PubMed: 16817839]

10.

Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013 Dec 11;310(22):2435-42. [PubMed: 24327038]

11.

Linder L, Tamboue C, Clements JN. Drug-Induced Vitamin B₁₂ Deficiency: A Focus on Proton Pump Inhibitors and Histamine-2 Antagonists. J Pharm Pract. 2017 Dec;30(6):639-642. [PubMed: 27520327]

12.

Ozalas SM, Huang V, Brunetti L, Reilly T. Comparison of Two Versions of the Beers Criteria and Adverse Outcomes in Older Hospitalized Patients. Consult Pharm. 2017 Dec 01;32(12):752-763. [PubMed: 29467068]

13.

Staines KA, Myers K, Little K, Ralston SH, Farquharson C. Proton Pump Inhibitors Inhibit PHOSPHO1 Activity and Matrix Mineralisation In Vitro. Calcif Tissue Int. 2021 Dec;109(6):696-705. [PMC free article: PMC8531085] [PubMed: 34213594]

14.

Turedi O, Sozener ZC, Kendirlinan R, Bavbek S. A Case of Pantoprazole Anaphylaxis with Cross Reactivity to All Proton Pump Inhibitors: Finding a Safe Alternative. Curr Drug Saf. 2017;12(3):198-200. [PubMed: 28699491]

Disclosure: Michelle Bernshteyn declares no relevant financial relationships with ineligible companies.

Disclosure: Umair Masood declares no relevant financial relationships with ineligible companies.