Bosentan Tablets

Because of the risks of hepatotoxicity and birth defects, Bosentan Tablets is available only through a restricted program called the Bosentan REMS Program. Under the Bosentan REMS, prescribers, patients, and pharmacies must enroll in the program [see Warnings and Precautions (5.3)].

Hepatotoxicity
In clinical studies, Bosentan Tablets caused at least 3-fold upper limit of normal (ULN) elevation of liver aminotransferases (ALT and AST) in about 11% of patients, accompanied by elevated bilirubin in a small number of cases. Because these changes are a marker for potential serious hepatotoxicity, serum aminotransferase levels must be measured prior to initiation of treatment and then monthly [see Dosage and Administration (2.4), Warnings and Precautions (5.1)]. In the postmarketing period, in the setting of close monitoring, rare cases of unexplained hepatic cirrhosis were reported after prolonged (> 12 months) therapy with Bosentan Tablets in patients with multiple comorbidities and drug therapies. There have also been reports of liver failure. The contribution of Bosentan Tablets in these cases could not be excluded.

In at least one case, the initial presentation (after > 20 months of treatment) included pronounced elevations in aminotransferases and bilirubin levels accompanied by non-specific symptoms, all of which resolved slowly over time after discontinuation of Bosentan Tablets. This case reinforces the importance of strict adherence to the monthly monitoring schedule for the duration of treatment and the treatment algorithm, which include...