Bosentan

What it is and how it works

Mechanism of Action 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.

Indications

Bosentan tablets are 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. Bosentan tablets are 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.

Dosage and administration (summary)

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 X Upper Limit of Normal (ULN) . Required Monitoring Healthcare professionals who prescribe bosentan must enroll in the Bosentan REMS and must comply with the required monitoring to minimize the risks associated with bosentan . Measure liver aminotransferase levels prior to initiation of treatment and then monthly .

Contraindications

Pregnancy Use with Cyclosporine A Use with Glyburide Hypersensitivity Pregnancy Use of bosentan is contraindicated in females who are pregnant . Use with Cyclosporine A Coadministration of cyclosporine A and bosentan resulted in markedly increased plasma concentrations of bosentan. Therefore, concomitant use of bosentan and cyclosporine A is contraindicated . Use with Glyburide An increased risk of liver enzyme elevations was observed in patients receiving glyburide concomitantly with bosentan.

Warnings and precautions

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 bosentan . Decreased sperm counts . Decreases in hemoglobin and hematocrit: Monitor hemoglobin levels after 1 and 3 months of treatment, then every 3 months thereafter . Hepatotoxicity ALT or AST > 3 x ULN were observed in 11% of bosentan-treated patients (n = 658) compared to 2% of placebo-treated patients (n = 280).

Pregnancy

Pregnancy Risk Summary Based on data from animal reproduction studies, bosentan may cause fetal harm, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy .

Storage and supply

62.5 mg tablets: Peach to light pink colored, coated, round, biconvex, tablets debossed with '446' on one side and plain on other side. NDC 68382-446-14 in bottle of 60 tablets with child-resistant closure NDC 68382-446-01 in bottle of 100 tablets NDC 68382-446-28 in bottle of 180 tablets NDC 68382-446-05 in bottle of 500 tablets NDC 68382-446-77 i…

Source: Bosentan (Bosentan) — US FDA prescribing information, 2026-06-02, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.