Ambrisentan
Pulmonary arterial hypertension drugs (endothelin receptor antagonists and prostacyclins)
Pulmonary arterial hypertension drugs (endothelin receptor antagonists and prostacyclins)Pregnancy: contraindicated
Contraindicated: animal studies show birth defects and fetal death; pregnancy is excluded before treatment and effective contraception continues until a month after stopping.
An oral endothelin receptor blocker selective for ETA, used in pulmonary arterial hypertension; it must never be used in pregnancy.
Quick facts
- Group
- Pulmonary arterial hypertension drugs (endothelin receptor antagonists and prostacyclins)
- Target
- Endothelin receptor type A
- Used for
- Pulmonary arterial hypertension
- Key effects
- Peripheral oedema · Nasal congestion and sinusitis
- Monitor
- Pregnancy test before starting · Weight
- ATC
- C02KX02
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows ambrisentan bound to the human endothelin receptor type A (cryo-EM).
Ambrisentan is a high-affinity antagonist that is highly selective for the ETA receptor over ETB. ETA mediates the vasoconstriction and smooth-muscle growth caused by endothelin-1, which is raised in pulmonary arterial hypertension; ETB, which it largely spares, mediates vasodilation and endothelin clearance. Blocking ETA relaxes and remodels the pulmonary arteries, improving exercise capacity and delaying clinical worsening.
- Endothelin-1 is raised in the lungs in PAH
- Ambrisentan blocks the ETA receptor and largely spares ETB
- Pulmonary arteries constrict and proliferate less
- Exercise capacity improves and worsening is delayed
Indications
- Pulmonary arterial hypertension (WHO group 1), to improve exercise ability and delay clinical worsening Pulmonary hypertension and cor pulmonale →
Adverse effects
Common
- Peripheral oedema
- Nasal congestion and sinusitis
- Flushing
- Headache
- Falling haemoglobin
Contraindications
- Pregnancy
- Idiopathic pulmonary fibrosis
- Not recommended in moderate or severe liver impairment
Key interactions
- Ciclosporin
- Raises ambrisentan exposure; the regimen is limited
- Phosphodiesterase-5 inhibitors (tadalafil, sildenafil)
- Often combined on purpose; additive blood pressure lowering
What is monitored
- Pregnancy test before starting in females who could become pregnant, and as clinically indicated
- Haemoglobin at the start, after a month and periodically
- Weight, oedema and breathlessness
- Liver tests if symptoms of liver injury appear
Administration and safety
- Oral tablet, swallowed whole: not split, crushed or chewed
- Effective contraception before, during and for a month after treatment in females who could become pregnant
Pregnancy and breastfeeding
Contraindicated: animal studies show birth defects and fetal death; pregnancy is excluded before treatment and effective contraception continues until a month after stopping.
Nursing care
- Confirm the pregnancy test and contraception counselling
- Weigh the patient and check for ankle swelling and new breathlessness
- Watch for acute breathlessness at the start of treatment, a sign of pulmonary oedema
- Teach that breastfeeding is not recommended during treatment
Pharmacokinetics
- Absorption
- Oral; food does not change bioavailability
- Distribution
- Very highly bound to plasma proteins
- Metabolism
- Liver, by CYP3A, CYP2C19 and glucuronidation; substrate of P-glycoprotein
- Elimination
- Mainly non-renal
- Half-life
- Terminal half-life about 15 hours; effective half-life about 9 hours
- Onset and duration
- Peak levels about two hours after a dose
Test yourself
Think of the answer, then tap the question to see it.
How does ambrisentan differ from bosentan at the receptor level?
Ambrisentan is highly selective for ETA; bosentan blocks both ETA and ETB.
In which lung disease is ambrisentan contraindicated?
Idiopathic pulmonary fibrosis.
Which common side effect of ambrisentan requires checking weight and ankles?
Fluid retention with peripheral oedema.
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 - AMBRISENTAN tablet, film coated (DailyMed (U.S. National Library of Medicine), 2025); Ambrisentan: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); RCSB PDB - 8XVK: Cryo-EM structure of ETAR bound with Ambrisentan (RCSB Protein Data Bank, 2024).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.