Sitaxentan-induced hepatic failure in two patients with pulmonary arterial hypertension

To the Editor: Sitaxentan sodium is an endothelin receptor antagonist (ERA) recently approved for the management of pulmonary arterial hypertension (PAH) 1. While hepatotoxicity is a recognised side-effect of treatment with the ERA bosentan, it is considered to be less common with sitaxentan 2–4. We recently admitted two patients with severe hepatotoxicity on sitaxentan to the Pulmonary Hypertension Unit at the Mater Misericordiae University Hospital (Dublin, Ireland). The first patient was a 47-yr-old male with PAH associated with congenital heart disease. He had a past history of ventricular septal defect closure at 12 yrs of age and was referred to our service with a history of gradual diminishing exercise capacity. His right heart catherisation demonstrated a pulmonary artery systolic pressure of 80 mmHg and a normal pulmonary capillary wedge pressure. He was commenced on sitaxentan 100 mg q.d. Initial liver function tests (LFTs) were normal, and the patient continued to undergo monthly LFT monitoring. At 3 months, he was experiencing an improvement in his symptoms and 6-min walking distance. However, 1 month later, he became generally unwell, with nausea, vomitting, anorexia and weight loss. He denied abdominal pain or pruritis. …