Pantoprazole Delayed-Release Tablets (Protonix—Wyeth Laboratories)

By William T. Elliott, MD, FACP and James Chan, PharmD, PhD

With astrazeneca’s omeprazole (prilosec) holding firm as the best-selling medication in the world, other pharmaceutical companies are rushing to develop their own proton pump inhibitors (PPIs). The latest entry into the market is pantoprazole (Protonix—Wyeth Laboratories), the fourth PPI to be approved by the FDA for use in this country. Pantoprazole is a benzimidazole derivative chemically similar to omeprazole and lansoprazole. The drug is licensed from Byk Gulden Pharmaceuticals in Germany and marketed as Protonix by Wyeth. The drug was approved for the treatment of reflux esophagitis. A parenteral form is awaiting FDA approval.

Indications

Pantoprazole is approved for short-term treatment in the healing and symptomatic relief of erosive esophagitis. The recommended course of treatment is up to eight weeks. If healing has not been achieved after eight weeks, an additional eight-week course may be considered.1

Dosage

Pantoprazole is available as 40-mg delayed-release (enteric-coated) tablets. The recommended adult dose is 40 mg daily for up to eight weeks. It may be taken without regard to meals or antacids.1 No dosage adjustment is needed for patients with mild to severe renal impairment, mild or moderate hepatic impairment, or in elderly patients. The tablets should not be split, chewed, or crushed, as an enteric coating protects the acid labile pantoprazole from the low gastric pH.

Potential Advantages

Pantoprazole has low affinity for cytochrome P450 isoenzymes. Clinically significant drug interactions necessitating dose adjustments have not been reported with any of the following drugs: theophylline, cisapride, carbamazepine, diazepam, diclofenac, digoxin, glyburide, levonorgestrel/estradiol, metoprolol, nifedipine, phenytoin, or warfarin.1,2

Potential Disadvantages

As with other antisecretory drugs, pantoprazole may interfere with the absorption of drugs that depend on gastric acid for absorption (e.g., ketoconazole, iron salts). Maintenance use of pantoprazole beyond 16 weeks has not been established.1 Clinical experience is limited with pantoprazole.

Comments

Pantoprazole is the newest PPI to be approved by the FDA. It is only approved for the healing and symptomatic relief of erosive esophagitis. Similar to omeprazole and lansoprazole, it is an irreversible inhibitor of the parietal cell H+, K+ ATPase. In a U.S. multicenter, double-blind, placebo-controlled trial, pantoprazole produced a healing rate of 75% at four weeks and 92.6% at eight weeks compared to 14.3% and 39.7% for placebo.1 A comparative trial with omeprazole indicated comparable efficacy in healing and symptom relief of reflux esophagitis.2 Although pantoprazole is not FDA approved for the treatment of gastric ulcers, duodenal ulcers, or the eradication of H. pylori, data suggest that its efficacy in these conditions is similar to other PPIs. PPIs also have similar side effect profiles, with diarrhea and headache as the most frequent side effects among the various agents.3

Pantoprazole is chemically more stable than omeprazole or lansoprazole in a weakly acidic condition (pH 3.5-7.4), which may improve its selectivity for parietal cell H+, K+ ATPase and less stable for less acidic compartments such as lysosomes and chromaffin granules.2,3 The clinical relevance of this is not known.

Pantoprazole is expected to be available in the second quarter of 2000. Cost is currently not available.

Clinical Implications

Pantoprazole represents the fourth entry into the competitive PPI market where efficacy and side effect profiles are similar among the various agents.4 Pantoprazole may have two advantages among these agents in that it may be the least likely to interact with other drugs although drug interactions have generally not been problematic for these drugs).

It will also likely be the first PPI to be available in a parenteral form, which is awaiting FDA approval. The oral and intravenous forms have been reported to be equivalent, on a mg basis, in gastric acid suppression in patients with gastroesophageal reflux disease.5

References

1. Protonix Product Information. Wyeth Laboratories. February 2000.

2. Fitton A, Wiseman L. Drugs 1996;51:460-482.

3. Richardson P, et al. Drugs 1998;56:307-335.

4. Byrne MF, Murray FE. Pharmacoeconomics 1999;16: 225-246.

5. Metz DC, et al. Am J Gastroenterol 2000;95:626-633.

Which is not true about pantoprazole?

a. It is approved for the treatment of peptic ulcer disease and Zollinger-Ellison syndrome.

b. It is taken once a day.

c. It has a low incidence of drug interactions.

d. There is a parenteral form of the drug that is awaiting approval.