Pantoprazole

Article Author:
Michelle Bernshteyn
Article Editor:
Umair Masood
Updated:
5/12/2019 3:19:30 PM
PubMed Link:
Pantoprazole

Indications

Pantoprazole is a proton-pump inhibitor (PPI) widely used in hospitals and outpatient settings. Pantoprazole is approved by the Food and Drug Administration Agency (FDA) for treatment of various disease processes including treatment of 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 is also utilized for various off-label uses including eradication of Helicobacter pylori bacteria and prevention of peptic ulcer re-bleeding and/or NSAID-induced ulcers[2]. Patients who are critically ill may be given Pantoprazole as stress ulcer prophylaxis [3]. This medication can be safely administered 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 2 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, and therefore, it makes sense that this medication would work best in the stomach which is 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 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, a correct diagnosis needs to be made. This is because there are different administration protocols based on what is being 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 can be administered orally or intravenously. 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 be continued for up to 12 months. Intravenously, 40 mg of pantoprazole is administered daily for 7 to 10 days. For Zollinger-Ellison syndrome, Pantoprazole can also be administered orally or intravenously. For oral administration, treatment is typically 40 mg twice daily. There is an option of titrating up to 240 mg if need be. Intravenously, it is recommended to administer 80 mg of pantoprazole every 12 hours. As mentioned, pantoprazole is also utilized for 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, it is recommended to administer 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, it is recommended to administer a 20 to 40 mg oral dose daily [9]. Pantoprazole is administered with or without food but it is preferred that it is taken 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 this risk was recently acknowledged in December of 2017 by Health Canada. In the geriatric population specifically, treatment with pantoprazole for 8 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].

Contraindications

Pantoprazole is contraindicated in patients with a history of hypersensitivity to the drug itself, to 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[13]. If a hypersensitivity reaction were to occur following administration of pantoprazole, the infusion should be stopped 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 should be monitored 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 be considered. 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 should be monitored, and appropriate changes should be made. 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 cannot be removed from the body via hemodialysis. As a result, treatment in Pantoprazole overdose is focused 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 usually prescribed by the nurse practitioner, primary care provider, internist and gastroenterologist. While the drug s effective for peptic ulcer disease, there have been many reports regarding overdose. 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.


References

[1] Maintenance therapy with pantoprazole 20 mg prevents relapse of reflux oesophagitis., Escourrou J,Deprez P,Saggioro A,Geldof H,Fischer R,Maier C,, Alimentary pharmacology & therapeutics, 1999 Nov     [PubMed PMID: 10571605]
[2] Guidelines for prevention of NSAID-related ulcer complications., Lanza FL,Chan FK,Quigley EM,, The American journal of gastroenterology, 2009 Mar     [PubMed PMID: 19240698]
[3] Randomized clinical trial: the impact of gastrointestinal risk factor screening and prophylactic proton pump inhibitor therapy in patients receiving dual antiplatelet therapy., Jensen BES,Hansen JM,Larsen KS,Junker AB,Lassen JF,Jensen SE,Schaffalitzky de Muckadell OB,, European journal of gastroenterology & hepatology, 2017 Jul 3     [PubMed PMID: 28678044]
[4] International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding., Barkun AN,Bardou M,Kuipers EJ,Sung J,Hunt RH,Martel M,Sinclair P,, Annals of internal medicine, 2010 Jan 19     [PubMed PMID: 20083829]
[5] Pantoprazole 20 mg is effective for relief of symptoms and healing of lesions in mild reflux oesophagitis., Dettmer A,Vogt R,Sielaff F,Lühmann R,Schneider A,Fischer R,, Alimentary pharmacology & therapeutics, 1998 Sep     [PubMed PMID: 9768529]
[6] 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., Bianchi Porro G,Lazzaroni M,Imbesi V,Montrone F,Santagada T,, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 2000 Apr     [PubMed PMID: 10975769]
[7] Clarithromycin versus Gemifloxacin in Quadruple Therapeutic Regimens for <i>Helicobacter Pylori</i> Infection Eradication., Mansour-Ghanaei F,Pedarpour Z,Shafaghi A,Joukar F,, Middle East journal of digestive diseases, 2017 Apr     [PubMed PMID: 28638586]
[8] Pantoprazole infusion as adjuvant therapy to endoscopic treatment in patients with peptic ulcer bleeding: prospective randomized controlled trial., Zargar SA,Javid G,Khan BA,Yattoo GN,Shah AH,Gulzar GM,Sodhi JS,Mujeeb SA,Khan MA,Shah NA,Shafi HM,, Journal of gastroenterology and hepatology, 2006 Apr     [PubMed PMID: 16677158]
[9] Prevention of NSAID-associated gastrointestinal lesions: a comparison study pantoprazole versus omeprazole., Regula J,Butruk E,Dekkers CP,de Boer SY,Raps D,Simon L,Terjung A,Thomas KB,Lühmann R,Fischer R,, The American journal of gastroenterology, 2006 Aug     [PubMed PMID: 16817839]
[10] Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency., Lam JR,Schneider JL,Zhao W,Corley DA,, JAMA, 2013 Dec 11     [PubMed PMID: 24327038]
[11] Linder L,Tamboue C,Clements JN, Drug-Induced Vitamin B{sub}12{/sub} Deficiency: A Focus on Proton Pump Inhibitors and Histamine-2 Antagonists. Journal of pharmacy practice. 2017 Dec;     [PubMed PMID: 27520327]
[12] Comparison of Two Versions of the Beers Criteria and Adverse Outcomes in Older Hospitalized Patients., Ozalas SM,Huang V,Brunetti L,Reilly T,, The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists, 2017 Dec 1     [PubMed PMID: 29467068]
[13] A case of pantoprazole anaphylaxis with cross reactivity to all proton pump inhibitors: finding a safe alternative., Türedi Ö,Sözener ZÇ,Kendirlinan R,Bavbek S,, Current drug safety, 2017 Jul 11     [PubMed PMID: 28699491]