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Pulmonary Arterial Hypertension Pregnancy: Absolutely contraindicated — teratogenic; Category X equivalent; mandatory Pregnancy Prevention Programme

Macitentan

Brand names: Opsumit

Adult dose

Dose: 10 mg once daily
Route: Oral
Frequency: Once daily
Max: 10 mg/day
Can be taken with or without food. No dose titration required. Available only as 10 mg tablets.

Paediatric dose

Dose: Seek specialist opinion N/A/kg
Route: Oral
Frequency: N/A
Max: N/A
Not established in paediatrics; seek specialist paediatric pulmonary hypertension opinion

Dose adjustments

Renal

No dose adjustment required — not significantly renally excreted

Hepatic

Avoid in moderate-severe hepatic impairment (Child-Pugh B or C) — hepatotoxicity risk; baseline LFTs mandatory

Paediatric weight-based calculator

Not established in paediatrics; seek specialist paediatric pulmonary hypertension opinion

Clinical pearls

  • Mechanism: dual endothelin receptor antagonist (ERA) — blocks both ETA and ETB receptors; endothelin-1 (ET-1) is a potent vasoconstrictor and mitogen in pulmonary vasculature; blocking ET-1 signalling reduces pulmonary vascular resistance and inhibits vascular remodelling
  • SERAPHIN trial (NEJM 2013): macitentan vs placebo in PAH — significant 45% relative risk reduction in composite of death, worsening PAH, atrial septostomy, lung transplantation; major trial with long follow-up (median 115 weeks); event-driven trial
  • Advantages over bosentan: once-daily dosing (bosentan twice daily); significantly less hepatotoxicity than bosentan; can be used with PDE5 inhibitors without pharmacokinetic interaction; superior trial data (event-driven vs short-term)
  • MHRA — MANDATORY PREGNANCY PREVENTION: macitentan is teratogenic; women of childbearing potential must: (1) have monthly pregnancy tests, (2) use 2 effective contraception methods, (3) be registered in the ERA Pregnancy Prevention Programme
  • Anaemia monitoring: haemoglobin falls significantly — check at baseline, 1 month, and then every 3 months; transfusion rarely required; mechanism is reduction in ET-1-stimulated erythropoiesis
  • NICE TA349: recommended for PAH in adults; prescribing restricted to specialist PAH centres

Contraindications

  • Pregnancy — teratogenicity (Category X equivalent) — MANDATORY: enrol in Pregnancy Prevention Programme (PPP)
  • Severe hepatic impairment
  • Cyclosporin co-administration (strong CYP3A4 inhibitor — increases macitentan exposure)

Side effects

  • Anaemia (most common — 13% vs 3% placebo — endothelin receptor blockade affects erythropoiesis)
  • Nasopharyngitis
  • Headache
  • Fluid retention and peripheral oedema
  • Hepatotoxicity (less common than bosentan but still requires monitoring)

Interactions

  • Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, cyclosporin) — increase macitentan exposure 2–9 fold; avoid combination
  • Strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin) — reduce efficacy
  • Sildenafil (additive vasodilation — monitor BP)

Monitoring

  • Liver function tests (monthly for 1st 3 months, then quarterly — hepatotoxicity)
  • Haemoglobin and haematocrit (monthly initially — anaemia)
  • Monthly pregnancy test (mandatory PPP)
  • Blood pressure
  • 6-minute walk test and WHO functional class (efficacy monitoring)

Reference: BNFc; BNF 90; SERAPHIN trial NEJM 2013;369(9):809-818; NICE TA349; MHRA SPC; ESC/ERS PAH Guidelines 2022. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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