Aprocitentan: clinical use

Prescribing considerations

• Confirm resistant rather than pseudo-resistant hypertension and continue appropriate background antihypertensive therapy.
• Assess fluid-retention risk, particularly with renal impairment, heart failure, older age, diabetes or severe obesity.
• Use is not recommended in unstable or severe cardiac disease or following a recent major cardiovascular or cerebrovascular event.
• There is limited clinical experience in people aged 75 years or older.
• Do not initiate when aminotransferases exceed three times the upper limit of normal or in severe anaemia.
• Contains lactose; avoid in specified rare hereditary disorders of galactose metabolism or absorption.

Contraindications and cautions

• Hypersensitivity to aprocitentan or an excipient
• Pregnancy
• Breastfeeding
• Women of childbearing potential not using reliable contraception
• Severe hepatic impairment, with or without cirrhosis

Monitoring

• Check liver enzymes before initiation and during treatment; discontinue for sustained clinically relevant elevations, associated bilirubin elevation or symptoms of hepatotoxicity.
• Monitor for oedema, weight gain, breathlessness and other evidence of fluid retention or heart failure.
• Assess haemoglobin before and during treatment when clinically indicated, especially with renal impairment or older age.
• Women of childbearing potential require pregnancy testing before treatment, monthly during treatment and one month after stopping.
• Monitor renal function according to clinical context; an initial reduction in estimated filtration rate can occur.

Clinical pharmacology

Aprocitentan blocks ETA and ETB endothelin receptors. It is highly protein-bound, is mainly present unchanged in plasma and has a terminal plasma half-life of approximately 46 hours. Drug-related material is eliminated through urine and faeces.

Formulation and product differences

• The film-coated tablet is yellow-to-orange, round and marked “AN” on one side.
• The tablet is not scored and should be swallowed whole.
• The formulation contains lactose and is essentially sodium-free.
• Store in the original package and keep bottles tightly closed to protect the tablets from moisture.

Tablet

Route: Oral

Strengths: 12.5 mg, 25 mg