Macitentan

How it works

It blocks endothelin-1 binding at both endothelin-A and endothelin-B receptors on vascular smooth muscle and endothelium, reducing the vasoconstriction, proliferation and fibrosis that endothelin-1 drives in the pulmonary circulation.

Prescribing in practice

• It is highly teratogenic and contraindicated in pregnancy, so it is supplied within a pregnancy prevention programme requiring reliable contraception and regular pregnancy testing in women of childbearing potential.
• Endothelin receptor antagonists can cause hepatotoxicity and clinically significant anaemia, so baseline and periodic checks are required.
• It can cause fluid retention, which may unmask or worsen heart failure and may require diuretic adjustment.

Monitoring

Check liver function and haemoglobin before starting and periodically during treatment, and perform regular pregnancy testing in women of childbearing potential.

Counselling the patient

• You must not become pregnant on this medicine; use reliable contraception and attend regular pregnancy tests.
• Report unusual tiredness, breathlessness or ankle swelling, which may indicate anaemia or fluid retention.
• Tell your doctor about yellowing of the skin or eyes, dark urine or nausea, which may signal a liver problem.

Evidence & guidelines

Macitentan reduced morbidity and mortality events in pulmonary arterial hypertension in the long-term randomised SERAPHIN trial and is recommended within specialist pulmonary hypertension pathways.