Macitentan
Pulmonary arterial hypertension drugs (endothelin receptor antagonists and prostacyclins)
Pulmonary arterial hypertension drugs (endothelin receptor antagonists and prostacyclins)Pregnancy: contraindicated
Contraindicated: it may cause serious birth defects. Pregnancy is excluded before treatment and contraception continues until one month after stopping.
An oral dual endothelin receptor blocker for pulmonary arterial hypertension; it can harm the fetus, so pregnancy is excluded and prevented.
Quick facts
- Group
- Pulmonary arterial hypertension drugs (endothelin receptor antagonists and prostacyclins)
- Target
- Endothelin receptors type A and type B
- Used for
- Pulmonary arterial hypertension
- Key effects
- Anaemia · Nasopharyngitis · Headache and influenza
- Monitor
- Pregnancy test before starting
- ATC
- C02KX04
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows macitentan bound to the human endothelin receptor type A (cryo-EM); macitentan also blocks type B receptors.
Endothelin 1 is raised in the lungs of patients with pulmonary arterial hypertension; through the ETA and ETB receptors it constricts pulmonary arteries and makes their smooth muscle grow. Macitentan is an oral, competitive antagonist of both receptors. Its active metabolite also blocks them and adds to the effect. Pulmonary vascular resistance falls and the disease progresses more slowly.
- In PAH, endothelin 1 is produced in excess in the lung
- Macitentan blocks ETA and ETB receptors on pulmonary vessels
- Arteries constrict and proliferate less
- Disease progression and PAH hospitalisation are reduced
Indications
- Pulmonary arterial hypertension (WHO group 1) in adults, to reduce disease progression and hospitalisation Pulmonary hypertension and cor pulmonale →
Adverse effects
Common
- Anaemia (fall in haemoglobin)
- Nasopharyngitis, pharyngitis and bronchitis
- Headache and influenza
- Urinary tract infection
Contraindications
- Pregnancy
- Hypersensitivity to macitentan
- Starting treatment in severe anaemia is not recommended
Key interactions
- Strong CYP3A4 inducers (rifampicin, St John's wort)
- Lower macitentan exposure; avoided
- Strong CYP3A4 inhibitors (ketoconazole, ritonavir)
- Higher macitentan exposure; avoided
- Moderate dual CYP3A4 and CYP2C9 inhibitors (fluconazole, amiodarone)
- Higher macitentan exposure; avoided
What is monitored
- Pregnancy test before starting in women who can become pregnant
- Liver enzymes before starting and as clinically indicated
- Haemoglobin before starting and during treatment
- Weight gain and leg swelling (fluid retention)
Administration and safety
- Oral tablet once a day, with or without food, at about the same time
- Effective contraception during treatment and for one month after the last dose
Pregnancy and breastfeeding
Contraindicated: it may cause serious birth defects. Pregnancy is excluded before treatment and contraception continues until one month after stopping.
Nursing care
- Confirm a negative pregnancy test and contraception counselling
- Teach the signs of liver injury: jaundice, dark urine, nausea, right upper abdominal pain
- Weigh the patient and look for oedema and worsening breathlessness
- Review the medicine list for rifampicin, ketoconazole, ritonavir, fluconazole and amiodarone
- Breastfeeding is avoided
Pharmacokinetics
- Absorption
- Oral, once daily; food does not change exposure; peak at about eight hours
- Distribution
- Very highly bound to plasma proteins (more than 99%), mainly albumin
- Metabolism
- Liver, mainly CYP3A4, to an active metabolite with a longer half-life
- Elimination
- Urine and faeces as metabolites
- Half-life
- About 16 hours (active metabolite about 48 hours)
Test yourself
Think of the answer, then tap the question to see it.
Which receptors does macitentan block?
Both endothelin ETA and ETB receptors.
What is the boxed warning for macitentan?
Embryo-fetal toxicity: pregnancy must be excluded before and prevented during treatment and for one month after.
Which blood test, besides liver enzymes, is checked during macitentan treatment?
Haemoglobin, because macitentan can cause anaemia.
Connections
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - MACITENTAN tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); Macitentan: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); RCSB PDB - 8XVJ: Cryo-EM structure of ETAR bound with Macitentan (RCSB Protein Data Bank, 2024); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.