Background Bosentan and ambrisentan, endothelin receptor antagonists, are used as treatment for pulmonary arterial hypertension (PAH), alone or in combination. It is known that elevations in liver aminotransferases (AST/ALT) associated with bosentan and ambrisetan are dose dependent, and hence aminotransferases levels must be monitored.
Purpose To analyse hepatotoxicity in patients diagnosed with PAH treated with bosentan or ambrisentan.
Material and methods A retrospective observational study was conducted from 2010 to 2016. We included all patients receiving treatment with bosentan or ambrisentan for at least 2 months. We registered AST and ALT levels prior to initiation of treatment, at 2 and 8 weeks after initiation and then monthly. Based on the summary of product characteristics, we considered aminotransferases levels 3 times the upper limit of normal (ULN) as hepatotoxicity. Information was obtained from electronic medical records (SAP).
Results We enrolled 39 patients (37 women, 2 men) with a mean age of 57 years (20–85) at the start of treatment with bosentan. The mean period of treatment until the end of the study was 57.2 months (2–146). During the study period, we registered 3×ULN in 18% of patients; 57% required a reduced dose, 14% stop treatment and the rest did not required modification of treatment. 6 patients (5 women, 1 man), with a mean age of 51 years (45–77) (at the start of treatment) were treated with ambrisentan. At the end of period of study, mean time of treatment was 18.5 months. We registered 3×ULN in 33% of patients; in any case, medical prescription changed treatment.
Conclusion The hepatotoxicity results registered in our study were very similar to outcomes from clinical trials. The pharmacist must check the correct dose, based on AST/ALT level. Also, side effect are dose dependent and mainly asymptomatic, but nevertheless some cases of liver cirrhosis and liver failure have been reported.
No conflict of interest
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