Bosentan

Indications

Bosentan is used for: Pulmonary Arterial Hypertension (PAH)

Adult Dose

Oral Pulmonary hypertension Adult: >12 yr <40 kg: Initial and maintenance dose is 62.5 mg bid; >40 kg: Initially, 62.5 mg bid for 4 wk, then increased to a maintenance dose of 125 mg bid. Elderly: No dosage adjustment needed. Hepatic impairment: Mild: No dosage adjustment needed. Moderate and severe: Contraindicated.

Child Dose

Renal Dose

Renal impairment: No dosage adjustment needed in renal impairment or dialysis patients.

Administration

Bosentan should be administered in the morning and evening with or without food.

Contra Indications

Patients with WHO Class II symptoms showed reduction in the rate of clinical deterioration and a trend for improvement in walk distance. Physicians should consider whether these benefits are sufficient to offset the risk of hepatotoxicity in WHO Class II patients, which may preclude future use as their disease progresses.

Precautions

Hepatotoxicity and teratogenicity. Elevations of AST or ALT associated with Bosentan are dose-dependent, occur both early and late in treatment, usually progress slowly, are typically asymptomatic, and usually have been reversible after treatment interruption or cessation. Aminotransferase elevations also may reverse spontaneously while continuing treatment with Tracleer. Liver aminotransferase levels must be measured prior to initiation of treatment and then monthly and therapy adjusted accordingly .Discontinue Bosentan if liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin > 2 Lactation: Not known if excreted in breast milk; not recommended

Pregnancy-Lactation

Interactions

Increased bosentan levels w/ CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, diltiazem), CYP2C9 inhibitors (e.g. amiodarone, fluconazole), tacrolimus. Rifampicin initially increases but subsequently decreases bosentan concentration. May decrease plasma levels of warfarin, statins (e.g. simvastatin, lovastatin), hormonal contraceptives, sildenafil, tadalafil. Potentially Fatal: Increased risk of hepatotoxicity may occur w/ glibenclamide. Ciclosporin markedly increases bosentan concentration.

Adverse Effects

Side effects of Bosentan : >10% Hgb decreased; >1 g/dL (57%),Inhibition of spermatogenesis (25%),Headache (16-22%),Nasopharyngitis (11%),Transaminses increased (12%),Respiratory tract infection (22%),Increased transaminases (12%) 1-10% Edema, lower limb (5-8%),Flushing (7-9%),Hypotension (7%),Hepatic abnormalities (4%),Palpitations (4%),Anemia (3%),Dyspepsia (4%),Edema, general (4%),Fatigue (2%),Pruritus (4%) <1% Hyperbilirubinemia,Vasculitis,Jaundice,Leukopenia,Thrombocytopenia,Leukocytoplastic

Mechanism of Action

Competitive antagonist of endothelin-1; blocks endothelin receptors on vascular endothelium and smooth muscle resulting in inhibition of vasoconstriction