Comprehensive medication guide to Ambrisentan including estimated pricing, availability information, side effects, and how to find it in stock at your local pharmacy.
Estimated Insurance Pricing
With commercial insurance and manufacturer copay programs, eligible patients may pay as little as $5/month for brand Letairis or $0/month for generic ambrisentan. Medicare Part D covers ambrisentan on specialty tier; cost-sharing varies by plan and benefit phase. Prior authorization is typically required.
Estimated Cash Pricing
Generic ambrisentan costs approximately $2,000–$2,100 per month for 30 tablets at retail; brand Letairis costs approximately $13,000–$14,200 per month. With manufacturer copay programs (LEAP for brand; Zydus copay savings for generic), commercially insured patients may pay as little as $0–$5 per month.
Medfinder Findability Score
72/100
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Ambrisentan, sold under the brand name Letairis by Gilead Sciences, is an FDA-approved medication for adults with pulmonary arterial hypertension (PAH, WHO Group 1). It belongs to a class of drugs called endothelin receptor antagonists (ERAs) and was first approved by the FDA in June 2007. Generic ambrisentan became available beginning in 2019 from multiple manufacturers including Apotex, Cipla USA, Mylan, Sun Pharma, Teva, and Zydus.
Ambrisentan is indicated to improve exercise ability and delay clinical worsening in adult PAH patients. It is also approved in combination with tadalafil to reduce the risk of disease progression and hospitalization for worsening PAH, based on the landmark AMBITION clinical trial which demonstrated a 50% reduction in clinical failure events with the combination versus monotherapy.
PAH is a rare, serious, and progressive disease characterized by high blood pressure in the arteries of the lungs, which overworks the right side of the heart. Ambrisentan does not cure PAH but significantly improves quality of life and slows disease progression. It is available as 5 mg and 10 mg film-coated tablets taken once daily.
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Ambrisentan works by selectively blocking the endothelin type A (ETA) receptor in the pulmonary vasculature. Endothelin-1 (ET-1) is one of the most potent vasoconstrictors known — a substance that causes blood vessels to tighten. In PAH, ET-1 levels are elevated, driving abnormal narrowing and thickening of the pulmonary arteries. By blocking the ETA receptor with extremely high affinity (Ki = 0.011 nM) and more than 4,000-fold selectivity over the ETB receptor, ambrisentan prevents ET-1 from causing vasoconstriction and abnormal cell proliferation in vessel walls.
This leads to relaxation and widening of the pulmonary arteries, reduced pulmonary vascular resistance, and less strain on the right ventricle. The ETA selectivity of ambrisentan also preserves the beneficial ETB receptor function — including vasodilation and ET-1 clearance from the circulation — which distinguishes it from dual-blocking ERAs like bosentan.
When combined with tadalafil (a PDE5 inhibitor targeting the nitric oxide pathway), ambrisentan addresses two distinct disease pathways simultaneously. The AMBITION trial demonstrated that this combination reduces the risk of clinical failure events — including PAH worsening, hospitalization, and death — by 50% compared to either drug alone, making it one of the most impactful pharmacological combinations in PAH treatment.
5 mg — tablet
Starting dose; pale pink, square, film-coated tablet; once daily with or without food
10 mg — tablet
Maintenance dose (may increase from 5 mg after 4 weeks if tolerated); deep pink, oval, film-coated tablet; once daily; maximum dose
Ambrisentan has a findability score of 72 out of 100 — meaning it is generally available from multiple manufacturers and at multiple pharmacy types, but patients may still encounter localized stock gaps. In May 2024, ASHP published a shortage bulletin for ambrisentan tablets from Zydus Pharmaceuticals. This was updated in December 2024 as supply returned. As of early 2026, six generic manufacturers (Apotex, Cipla USA, Mylan, Sun Pharma, Teva, Zydus) and brand Letairis from Gilead have product available in both 5 mg and 10 mg strengths.
Generic ambrisentan is available at retail pharmacies including Walgreens, CVS, Kroger, and Walmart, in addition to specialty pharmacies. Brand Letairis is only dispensed through REMS-certified specialty pharmacies. Because PAH is a rare disease, some retail pharmacies may not stock ambrisentan routinely and may need to order it (typically 1 to 2 business days). Patients who take ambrisentan should refill early — at least 10 to 14 days before running out — and identify backup pharmacies in advance.
If you are struggling to find ambrisentan at your pharmacy, medfinder can help. Simply provide your medication, dosage, and location, and medfinder contacts pharmacies near you to identify which ones can fill your prescription. Results are texted directly to you.
Ambrisentan is not a DEA scheduled substance, so there are no DEA-mandated prescribing restrictions. However, due to the REMS program, prescribers who prescribe ambrisentan to females of reproductive potential must be certified in the Ambrisentan REMS program. This requires completing REMS enrollment and agreeing to ensure monthly pregnancy testing and contraception counseling for eligible female patients. Certifying pharmacies must also be enrolled.
In practice, ambrisentan is almost exclusively prescribed by physicians and advanced practice providers with PAH expertise. Typical prescribers include:
Pulmonary hypertension specialists at PHA-accredited care centers
Pulmonologists — especially those with a focus on PAH or interstitial lung disease
Cardiologists — particularly those at centers with dedicated PAH programs
Rheumatologists — for connective tissue disease-associated PAH (e.g., scleroderma)
Nurse Practitioners (NPs) and Physician Assistants (PAs) — in PAH specialty practices
Telehealth is available for follow-up management of established PAH patients in many states, but initial diagnosis requires in-person evaluation including right heart catheterization. Patients should contact a PHA-accredited center or their insurance provider directory to locate a PAH specialist near them.
No. Ambrisentan (Letairis) is not a controlled substance and is not scheduled by the DEA. You do not need any special DEA-related prescribing authorization to prescribe it, and there are no DEA-mandated limits on refills based on scheduling.
However, ambrisentan does have significant prescribing restrictions through its REMS (Risk Evaluation and Mitigation Strategy) program due to its risk of fetal harm. All females of reproductive potential who are prescribed ambrisentan must be enrolled in the Ambrisentan REMS program before the medication can be dispensed to them. This requires: a negative pregnancy test before starting, monthly pregnancy testing during treatment, and use of two highly effective forms of contraception during treatment and for one month after the last dose. Prescribers must also be REMS-certified to prescribe ambrisentan to females of reproductive potential.
For male patients, the REMS enrollment requirements do not apply, though prescribers should be aware of potential effects on male fertility. These REMS requirements are distinct from DEA controlled substance scheduling and are driven by the teratogenicity risk, not abuse potential.
The following side effects are commonly reported by patients taking ambrisentan:
Peripheral edema (swelling of the ankles, legs, or arms) — most common; more frequent when combined with tadalafil
Headache — mild to moderate, typically improves over time
Nasal congestion
Flushing (feeling of warmth in the face)
Palpitations
Constipation
Anemia (decreased hemoglobin/hematocrit) — monitor for fatigue, pallor, shortness of breath
Serious side effects requiring immediate medical attention:
Fetal harm — contraindicated in pregnancy; BOXED WARNING
Liver injury — jaundice, upper right abdominal pain, dark urine, clay-colored stools
Severe fluid retention or pulmonary edema — sudden significant weight gain, difficulty breathing
Allergic reaction — hives, swelling of face/lips/tongue/throat, difficulty breathing (call 911)
Decreased male fertility (sperm count effects observed in animal studies)
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Bosentan (Tracleer)
Dual ETA/ETB endothelin receptor antagonist; generic available; twice-daily dosing; requires monthly liver function monitoring; more drug interactions than ambrisentan.
Macitentan (Opsumit)
Newer dual ERA; reduced morbidity/mortality in SERAPHIN trial; once daily; no routine liver monitoring required; also available combined with tadalafil as Opsynvi.
Tadalafil (Adcirca)
PDE5 inhibitor targeting the nitric oxide pathway; often combined with ambrisentan; once daily at 40 mg; shown to improve exercise capacity in PAH.
Riociguat (Adempas)
sGC stimulator; FDA-approved for PAH and CTEPH; different mechanism from ambrisentan; cannot be used with PDE5 inhibitors; also has REMS due to teratogenicity.
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Sparsentan (Filspari)
majorContraindicated — combined endothelin antagonism increases risk of hypotension, syncope, hyperkalemia, and acute renal failure.
Cyclosporine
majorSignificantly increases ambrisentan exposure (~2-fold) by inhibiting OATP1B1/1B3 transporters. Limit ambrisentan dose to 5 mg/day maximum when co-administered.
Apalutamide
majorStrong CYP3A4 and CYP2C19 inducer; significantly decreases ambrisentan levels. Avoid combination or evaluate for loss of therapeutic effect.
Enasidenib
majorOATP1B1/1B3 inhibitor that may significantly increase ambrisentan exposure. Avoid combination — may cause serious toxicity.
Idelalisib
majorStrong CYP3A4 inhibitor that increases ambrisentan levels. Avoid combination or use alternative drug.
Sofosbuvir/Velpatasvir (Epclusa)
moderateVelpatasvir inhibits OATP1B1/1B3 and OATP2B1 transporters, potentially increasing ambrisentan levels. Use caution and monitor closely.
Cannabidiol (CBD)
moderateCYP2C19 inhibitor that may increase ambrisentan levels. Consider reducing ambrisentan dose if clinically appropriate.
Hormonal contraceptives
moderateAmbrisentan may increase levels of hormonal contraceptives via CYP3A4 inhibition. Additionally, hormonal methods alone are insufficient for REMS contraception requirements — must be combined with a barrier method.
Ambrisentan (Letairis) is a well-established, effective treatment for pulmonary arterial hypertension with over 15 years of real-world use. Its once-daily dosing, highly selective ETA mechanism of action, and strong combination therapy evidence from the AMBITION trial make it a cornerstone of modern PAH management. The availability of multiple FDA-approved generics since 2019 has significantly improved access and affordability compared to the brand-only era.
For patients, the primary challenges are cost and navigation — ensuring insurance covers the drug, leveraging available savings programs (LEAP, Zydus Copay Savings), and finding it in stock at a pharmacy. The REMS requirements add a layer of administrative complexity, particularly for females of reproductive potential who require monthly pregnancy testing and dual contraception. Staying organized, refilling early, and maintaining open communication with your PAH specialist are the most effective ways to ensure uninterrupted therapy.
If you are ever struggling to locate ambrisentan at a pharmacy near you, medfinder is here to help. medfinder contacts pharmacies on your behalf, identifies which ones can fill your prescription, and texts you the results. No more hours on hold — just faster access to the treatment you need.
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Our medication guides are researched and written to help patients make informed decisions. All content is reviewed for accuracy and updated regularly. Learn more about our standards
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