Pulmonary Arterial Hypertension Pregnancy: Contraindicated during pregnancy and in women of childbearing potential who are not using reliable contraception; also contraindicated during breastfeeding. There are no data in pregnant women and animal studies have shown reproductive toxicity. Absence of pregnancy must be verified before initiation, monthly pregnancy tests are recommended, and women should not become pregnant for 1 month after discontinuation. May adversely affect spermatogenesis in men.

Macitentan

Brand names: Opsumit

Macitentan is an orally active, dual endothelin receptor antagonist used for the long-term treatment of pulmonary arterial hypertension to slow disease progression.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 10 mg once daily

Route: Oral (film-coated tablets are not breakable and are to be swallowed whole with water; may be taken with or without food)

Frequency: Once daily, at about the same time every day

Treatment should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension. The 10 mg dose applies to adults and to paediatric patients aged under 18 years weighing at least 40 kg. If a dose is missed the patient should take it as soon as possible and then take the next dose at the regularly scheduled time; two doses must not be taken at the same time. Elderly: no dose adjustment is required over the age of 65 years. Hepatic impairment: on PK data no dose adjustment is required in mild, moderate or severe hepatic impairment, but there is no clinical experience in PAH patients with moderate or severe hepatic impairment; must not be initiated in severe hepatic impairment or with clinically significant elevated hepatic aminotransferases (source text: 'greater than 3 times the upper limit of normal (3 x ULN)'). Liver enzyme tests should be obtained before initiation, with monthly ALT/AST monitoring recommended. Haemoglobin should be measured before initiation and during treatment as clinically indicated; initiation is not recommended in severe anaemia. Monthly pregnancy tests are recommended in women of childbearing potential, who must use reliable contraception and must not become pregnant for 1 month after discontinuation. PAEDIATRIC: the 10 mg film-coated tablets are only recommended in paediatric patients weighing at least 40 kg; for paediatric patients weighing less than 40 kg a lower strength of 2.5 mg dispersible tablets is available and the dispersible tablet SPC must be consulted. Dosing and efficacy below 2 years of age have not been established and no posology recommendation can be made. No per-kg paediatric dose is stated, so no structured paediatric dose is recorded; verify paediatric prescribing against a children's formulary and the dispersible tablet SPC. US labelling (openFDA, OPSUMIT) states doses higher than 10 mg once daily have not been studied in patients with PAH and are not recommended. EXTRACTION NOTE: some inequality symbols were lost when the SPC text was extracted (aminotransferase thresholds shown as '3 x ULN' should read greater than 3 x ULN) — verify against the SPC.

Dose adjustments

Renal

Based on PK data no dose adjustment is required in patients with renal impairment. There is no clinical experience in PAH patients with severe renal impairment, and use is not recommended in patients undergoing dialysis.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance, to soya, or to any of the excipients
Pregnancy
Women of childbearing potential who are not using reliable contraception
Breastfeeding
Severe hepatic impairment (with or without cirrhosis)
Baseline values of hepatic aminotransferases (AST and/or ALT) above 3 x ULN (source text renders the threshold as '3 x ULN')

Side effects

Nasopharyngitis (14%) and bronchitis (very common)
Anaemia / haemoglobin decrease (13.2%, very common)
Headache (13.6%, very common)
Oedema and fluid retention (very common)
Hypotension and flushing (common)
Aminotransferase elevations (common)

Interactions

Strong CYP3A4 inducers (e.g. rifampicin, St John's wort, carbamazepine) — reduced efficacy of macitentan may occur; avoid co-administration
Strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir) — approximately double macitentan exposure; avoid co-administration (US labelling)
Moderate dual or combined CYP3A4 and CYP2C9 inhibitors (e.g. fluconazole, amiodarone) — may increase macitentan exposure approximately 4-fold; avoid co-administration (US labelling)

Clinical monograph

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.

Reference: SERAPHIN trial NEJM 2013; 369(9):809-818; NICE TA349; MHRA SPC; ESC/ERS PAH Guidelines 2022; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

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