macitentan: clinical use

Prescribing considerations

• Initiation and monitoring should be led by a physician experienced in pulmonary arterial hypertension.
• Establish pregnancy status and reliable contraception where relevant before initiation.
• Do not initiate in severe anaemia; use caution in severe renal impairment and avoid use during dialysis.
• Consider pulmonary veno-occlusive disease if pulmonary oedema develops after treatment starts.

Contraindications and cautions

• Pregnancy or absence of reliable contraception in a person who could become pregnant
• Breastfeeding
• Severe hepatic impairment or baseline AST or ALT above three times the upper limit of normal
• Hypersensitivity to macitentan or formulation excipients; the film-coated tablet is contraindicated with soya hypersensitivity

Monitoring

• Obtain liver enzymes before initiation and monitor ALT and AST monthly; investigate symptoms of hepatic injury.
• Measure haemoglobin before initiation and repeat when clinically indicated.
• Consider blood-pressure and haemoglobin monitoring more closely in renal impairment.
• Verify absence of pregnancy before initiation; monthly pregnancy testing is recommended during treatment.

Clinical pharmacology

Macitentan is an orally active dual ETA/ETB receptor antagonist with greater in-vitro selectivity for ETA. CYP3A4 is the main route forming its active metabolite, aprocitentan; both parent and metabolite are highly protein-bound.

Formulation and product differences

• The film-coated tablet must be swallowed whole and contains lactose and soya bean lecithin.
• The dispersible tablet contains isomalt and must be dispersed before administration; it is unsuitable in hereditary fructose intolerance.
• Administration of the dispersible suspension through enteral tubes has not been tested.

Dispersible tablet

Route: Oral

Strengths: 2.5 mg

Tablet

Route: Oral

Strengths: 10 mg