Overview
Bosentan is an endothelin receptor antagonist used to treat pulmonary arterial hypertension (PAH) by blocking endothelin-1 receptors, reducing vasoconstriction and vascular remodeling.
Mechanism of Action
Competitive antagonist of endothelin-1 at endothelin-A (ETA) and endothelin-B (ETB) receptors, inhibiting vasoconstriction and cell proliferation in pulmonary vasculature.
Indications
- Pulmonary arterial hypertension (PAH) WHO Group 1 to improve exercise ability and reduce clinical worsening
- Treatment of digital ulcers in systemic sclerosis
Dosage
Initial: 62.5 mg twice daily for 4 weeks, then increase to maintenance dose of 125 mg twice daily. Lower doses may be used in patients with hepatic impairment or drug interactions.
Contraindications
- Pregnancy (Category X)
- Concomitant use with cyclosporine or glyburide
- Hypersensitivity to bosentan or any component
- Moderate to severe hepatic impairment
Side Effects
- Headache
- Flushing
- Edema
- Nasopharyngitis
- Elevated liver enzymes
- Anemia
- Palpitations
- Dyspepsia
- Fatigue
Interactions
- Cyclosporine (contraindicated)
- Glyburide (contraindicated)
- Strong CYP3A4 inhibitors (ketoconazole, ritonavir) - increase bosentan levels
- Hormonal contraceptives - reduced efficacy
- Warfarin - monitor INR
- Statins - reduced efficacy