Endothelin receptor antagonist

Letairis (ambrisentan)

An approved treatment for Pulmonary Arterial Hypertension.

FDA Approved (2007)by Gilead Sciences
Preclinical
Phase 1
Phase 2
Phase 3
Approved
2007
Drug facts

The same compound appears under different names depending on the context. Here is how to identify Ambrisentan wherever you encounter it, plus the key facts at a glance.

Generic name
Ambrisentan
Brand name
Letairis
Development code
BSF-208075
Drug class
Endothelin receptor antagonist
Manufacturer
Gilead Sciences
How it's taken
Taken as a single oral tablet once daily, either 5 mg or 10 mg.

A selective endothelin type A receptor blocker for adults with PAH (WHO Group 1). Its safety and effectiveness in children have not been established. By specifically blocking the ETA receptor while largely sparing ETB, it reduces vessel constriction while potentially preserving some beneficial ETB-mediated effects like nitric oxide release.

Where Ambrisentan fits

Selective endothelin A receptor antagonist for PAH, part of the standard combination therapy approach. Notable for the AMBITION trial demonstrating benefit of upfront combination therapy.

How Ambrisentan works

Ambrisentan preferentially blocks the ETA receptor, which mediates the vasoconstriction and cell proliferation effects of endothelin-1 in pulmonary arteries. By being selective for ETA over ETB, it may preserve ETB-mediated clearance of endothelin and production of vasodilators like nitric oxide and prostacyclin.

Mechanism: Selective ETA endothelin receptor antagonist that blocks vessel constriction

Side effects and safety

What patients report

Peripheral edema, nasal congestion, sinusitis, and flushing are common. It can lower hemoglobin (anemia), sometimes enough to need a blood transfusion, so hemoglobin is checked before starting, at 1 month, and from time to time after that. The label also warns about fluid buildup that sometimes needs hospital care, sudden fluid in the lungs in people with a rare condition called pulmonary veno-occlusive disease, and lower sperm counts. It has a boxed warning: it must not be used in pregnancy because it may cause serious birth defects. Pregnancy must be ruled out before starting, and people who can become pregnant must use effective birth control during treatment and for 1 month after stopping. It should not be used by people with idiopathic pulmonary fibrosis. Since April 2025 it is no longer limited to a REMS program, and the label no longer requires monthly pregnancy tests.

This is not a complete list of side effects. Talk to your doctor or pharmacist about what to expect and when to seek medical attention.

Taking Ambrisentan

Taken as a single oral tablet once daily, either 5 mg or 10 mg. No food restrictions. It is usually started at 5 mg, alone or with tadalafil, and can be raised to 10 mg at 4-week intervals. Do not split, crush, or chew the tablets. The REMS program that required prescriber and pharmacy certification was removed in April 2025.

Availability and cost

Generic available

Generic versions may be available at a lower cost. Ask your pharmacist.

Why it costs what it costs

Selective endothelin A receptor antagonist for PAH. Generic ambrisentan is available from several manufacturers, and brand Letairis is still sold by Gilead.

Help paying for Letairis

Pick your insurance to see which help fits. Drugmaker copay cards can't be used with Medicare, Medicaid or TRICARE; charity funds are the usual route there.

Your insurance
From the drugmaker
Letairis (Ambrisentan)
LEAP (Letairis Education and Access Program)
  • Copay help

    Eligible commercially insured patients pay no more than $5 per fill; up to $20,000 per year.

    For: private insurance · source
  • Free medicine program

    LEAP checks whether uninsured patients qualify for free Letairis through the Letairis Patient Assistance Program.

    For: no insurance · source
  • Insurance and case manager help

    LEAP case specialists explain insurance benefits, estimate Medicare Part D costs, and point to outside help for underinsured patients.

    For: private insurance, Medicare, no insurance, underinsured · source

Good to know: Sponsor: Gilead. Programs cover brand Letairis only; generic ambrisentan is also available. Copay excludes Medicare, Part D, Medicaid, TRICARE, VA, DoD and other government coverage.

Checked on the drugmaker's official pages on September 24, 2026. Programs change; confirm with the program before you rely on it.
Charity funds for Pulmonary Arterial Hypertension
  • From a charity · HealthWell Foundation
    Pulmonary Hypertension (Medicare Access) fund
    Open

    Pays for: Copays, premiums or other treatment costs. Medicare patients only.

  • From a charity · TotalAssist (formerly PAN Foundation)
    Pulmonary Hypertension fund
    Open

    Pays for: Out-of-pocket costs for approved medications, up to $9,500 per year. Requires health insurance (any kind).

  • From a charity · The Assistance Fund
    Pulmonary Hypertension fund
    Waitlist

    Pays for: Copays, coinsurance, deductibles and other health-related expenses.

    The foundation says: “WAITLIST — Accepting Waitlist Patients. TAF is currently accepting requests to join the enrollment waitlist for this program. Waitlists a…”
Status as each foundation showed it on September 28, 2026.

More ways to get help paying for treatment →

Clinical trial results

ARIES-1 and ARIES-2 Phase 3 trials showed improvement in exercise capacity and time to clinical worsening. AMBITION trial demonstrated superiority of initial combination therapy (ambrisentan + tadalafil) over monotherapy.

Development history

Approved by FDA in June 2007. The AMBITION trial (2015) was pivotal in establishing upfront combination therapy as standard of care in PAH. Often used in combination with tadalafil as a first-line oral regimen.

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Common questions about Ambrisentan

▸What is Ambrisentan (Letairis)?

A selective endothelin type A receptor blocker for adults with PAH (WHO Group 1). Its safety and effectiveness in children have not been established. By specifically blocking the ETA receptor while largely sparing ETB, it reduces vessel constriction while potentially preserving some beneficial ETB-mediated effects like nitric oxide release.

▸How does Ambrisentan work?

Ambrisentan preferentially blocks the ETA receptor, which mediates the vasoconstriction and cell proliferation effects of endothelin-1 in pulmonary arteries. By being selective for ETA over ETB, it may preserve ETB-mediated clearance of endothelin and production of vasodilators like nitric oxide and prostacyclin.

▸What are the side effects of Ambrisentan?

Peripheral edema, nasal congestion, sinusitis, and flushing are common. It can lower hemoglobin (anemia), sometimes enough to need a blood transfusion, so hemoglobin is checked before starting, at 1 month, and from time to time after that. The label also warns about fluid buildup that sometimes needs hospital care, sudden fluid in the lungs in people with a rare condition called pulmonary veno-occlusive disease, and lower sperm counts. It has a boxed warning: it must not be used in pregnancy because it may cause serious birth defects. Pregnancy must be ruled out before starting, and people who can become pregnant must use effective birth control during treatment and for 1 month after stopping. It should not be used by people with idiopathic pulmonary fibrosis. Since April 2025 it is no longer limited to a REMS program, and the label no longer requires monthly pregnancy tests.

▸How is Ambrisentan taken?

Taken as a single oral tablet once daily, either 5 mg or 10 mg. No food restrictions. It is usually started at 5 mg, alone or with tadalafil, and can be raised to 10 mg at 4-week intervals. Do not split, crush, or chew the tablets. The REMS program that required prescriber and pharmacy certification was removed in April 2025.

▸Is Ambrisentan FDA approved?

Yes, Ambrisentan (Letairis) is FDA approved (2007) for the treatment of Pulmonary Arterial Hypertension.

▸What is the AMBITION trial and why is it important?

The AMBITION trial was a landmark PAH study that compared initial upfront combination therapy (ambrisentan plus tadalafil together from the start) to monotherapy with either drug alone. Combination therapy reduced clinical failure events by 50% compared to monotherapy. This trial established upfront combination therapy as the standard of care for PAH, changing how newly diagnosed patients are treated worldwide.

▸How does ambrisentan differ from bosentan and macitentan?

Ambrisentan is a selective ETA receptor antagonist, while bosentan and macitentan block both ETA and ETB receptors. The clinical significance of this selectivity is debated. Practically, ambrisentan does not require the monthly liver testing that bosentan does (lower hepatotoxicity risk), is dosed once daily, and has well-established combination data with tadalafil from the AMBITION trial. Peripheral edema (leg swelling) may be more common with ambrisentan.

▸Why is ambrisentan often paired with tadalafil?

The AMBITION trial specifically tested the combination of ambrisentan and tadalafil and showed superior outcomes compared to either drug alone. This evidence-based pairing has made ambrisentan plus tadalafil one of the most commonly prescribed initial combination regimens for PAH. Other combinations are also used, but the AMBITION data provides the strongest evidence for this specific pair.

▸Is ambrisentan safe during pregnancy?

No. Ambrisentan is teratogenic and can cause serious birth defects. It is contraindicated in pregnancy, and women of reproductive potential must use reliable contraception. A pregnancy test is required before starting. Since April 2025 the label no longer requires monthly tests or the REMS program, so contact your doctor right away if a period is late or you think you might be pregnant. Ambrisentan must be stopped immediately if pregnancy is suspected.

This page is for informational purposes only and does not constitute medical advice. Drug information is sourced from public databases and peer-reviewed literature and may not reflect the most recent updates. Always discuss treatment options with your healthcare provider. Last reviewed: September 2026.

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