Protonix Side Effects & Drug Interactions

Drug Library
Protonix - Side Effects & Drug Interactions [pantoprazole sodium]

In the liver, treatment at 0.5 to 200 mg/ kg/ day produced dose-related increases in the incidences of hepatocellular adenomas and carcinomas. In the thyroid gland, treatment at 200 mg/ kg/ day produced increased incidences of follicular cell adenomas and carcinomas for both male and female rats.

Sporadic occurrences of hepatocellular adenomas and a hepatocellular carcinoma were observed in Sprague-Dawley rats exposed to pantoprazole in 6-month and 12-month toxicity studies. In a 24-month carcinogenicity study, Fischer 344 rats were treated orally with doses of 5 to 50 mg/ kg/ day, approximately 1 to 10 times the recommended human dose based on body surface area. In the gastric fundus, treatment at 5 to 50 mg/ kg/ day produced enterochromaffin-like (ECL) cell hyperplasia and benign and malignant neuroendocrine cell tumors. Dose selection for this study may not have been adequate to comprehensively evaluate the carcinogenic potential of pantoprazole.

In a 24-month carcinogenicity study, B6C3F1 mice were treated orally with doses of 5 to 150 mg/ kg/ day, 0.5 to 15 times the recommended human dose based on body surface area. In the liver, treatment at 150 mg/ kg/ day produced increased incidences of hepatocellular adenomas and carcinomas in female mice. Treatment at 5 to 150 mg/ kg/ day also produced gastric fundic ECL cell hyperplasia.

A 26-week p53 + /-transgenic mouse carcinogenicity study was not positive. Pantoprazole was positive in the in vitro human lymphocyte chromosomal aberration assays, in one of two mouse micronucleus tests for clastogenic effects, and in the in vitro Chinese hamster ovarian cell/ HGPRT forward mutation assay for mutagenic effects. Equivocal results were observed in the in vivo rat liver DNA covalent binding assay. Pantoprazole was negative in the in vitro Ames mutation assay, the in vitro unscheduled DNA synthesis (UDS) assay with rat hepatocytes, the in vitro AS52/ GPT mammalian cell-forward gene mutation assay, the in vitro thymidine kinase mutation test with mouse lymphoma L5178Y cells, and the in vivo rat bone marrow cell chromosomal aberration assay.