Bosentan

TRACLEER is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1): in adults to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with WHO Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%). in pediatric patients aged 3 years and older with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR), which is expected to result in an improvement in exercise ability. TRACLEER is an endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1): in adults to improve exercise ability and to decrease clinical worsening.

Bosentan is a specific and competitive antagonist at endothelin receptor types ET A and ET B. Bosentan has a slightly higher affinity for ET A receptors than for ET B receptors. The clinical impact of dual endothelin blockage is unknown. Endothelin-1 (ET-1) is a neurohormone, the effects of which are mediated by binding to ET A and ET B receptors in the endothelium and vascular smooth muscle. ET-1 concentrations are elevated in plasma and lung tissue of patients with PAH, suggesting a pathogenic role for ET-1 in this disease.

Patients older than 12 years of age: initiate at 62.5 mg orally twice daily, for patients weighing greater than 40 kg, increase to 125 mg orally twice daily after 4 weeks. Patients 12 years of age and younger: dosage is based on weight, see Table 1. Reduce the dose and closely monitor patients developing aminotransferase elevations more than 3×Upper Limit of Normal (ULN).

Pregnancy. Use with Cyclosporine A. Use with Glyburide. Hypersensitivity. Pregnancy Use of TRACLEER is contraindicated in females who are pregnant.

Boxed warning (risks of hepatotoxicity and embryo-fetal toxicity): Because of the risk of hepatotoxicity, TRACLEER is available only through a restricted program called the Bosentan Risk Evaluation and Mitigation Strategy (REMS). Under the Bosentan REMS, prescribers, patients, and pharmacies must enroll in the program. Fluid retention: May require intervention. Pulmonary veno-occlusive disease (PVOD): If signs of pulmonary edema occur, consider the diagnosis of associated PVOD and consider discontinuing TRACLEER. Decreased sperm counts. Decreases in hemoglobin and hematocrit: Monitor hemoglobin levels after 1 and 3 months of treatment, then every 3 months thereafter.

The following important adverse reactions are described elsewhere in the labeling: Hepatotoxicity Embryo-fetal Toxicity Fluid Retention Common adverse reactions (≥3% more than placebo) for the film-coated tablet are respiratory tract infection and anemia. Common adverse reactions (≥15%) for the dispersible tablet are upper respiratory tract infections and pyrexia.

Cytochrome P450: Coadministration of TRACLEER with drugs metabolized by CYP2C9 and CYP3A can increase exposure to TRACLEER and/or the coadministered drug. Hormonal contraceptives: TRACLEER use decreases contraceptive exposure and reduces effectiveness.

Store at 20 ºC to 25 ºC (68 ºF to 77 ºF). Excursions are permitted between 15 °C and 30 °C (59 °F and 86 °F). These storage temperatures apply to both film-coated and dispersible tablets. Divided dispersible tablets should be stored under the same conditions and used within 7 days. Tablet pieces may be returned to the opened blister and stored there out of reach of children for up to 7 days.