bosentan monohydrate: clinical use

Prescribing considerations

• Initiation and monitoring should be undertaken by a clinician experienced in PAH or systemic sclerosis, as applicable.
• Assess baseline liver enzymes, haemoglobin, blood pressure, pregnancy status and contraception where relevant.
• In digital-ulcer disease, benefit concerns prevention of new ulcers rather than healing existing lesions.
• Monitor for fluid retention, particularly with left-ventricular systolic dysfunction, and consider pulmonary veno-occlusive disease if pulmonary oedema develops.

Contraindications and cautions

• Hypersensitivity to bosentan or an excipient
• Moderate or severe hepatic impairment
• Baseline ALT or AST above three times the upper limit of normal
• Concomitant ciclosporin A
• Pregnancy
• Child-bearing potential without reliable contraception

Monitoring

• Measure hepatic aminotransferases before and throughout treatment and after treatment changes as specified in the product information.
• Check haemoglobin before treatment, during the early treatment period and periodically thereafter.
• Arrange regular pregnancy testing for patients who could become pregnant.
• Monitor clinical status, blood pressure and signs of oedema, weight gain or worsening PAH.

Clinical pharmacology

Bosentan competitively antagonises ETA and ETB receptors. It is metabolised mainly by CYP2C9 and CYP3A4; it induces CYP2C9, CYP3A4 and possibly CYP2C19 and P-glycoprotein. Elimination is predominantly through bile after hepatic metabolism.

Formulation and product differences

• The selected product is an oval film-coated tablet with a functional break line and may be divided into equal halves.
• It may be taken with or without food and is essentially sodium-free.
• Alternative formulations may be more suitable for children, low body weight or swallowing difficulty.

Tablet

Route: Oral

Strengths: 62.5 mg, 125 mg