ambrisentan (Rx)

Brand and Other Names:Letairis
  • Print

Dosing & Uses


Dosage Forms & Strengths


  • 5mg
  • 10mg

Pulmonary Arterial Hypertension

Indicated for treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability and delay clinical worsening or in combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability

Initiate treatment at 5 mg PO qDay, with or without tadalafil 20 mg PO qDay

At 4-week intervals, either ambrisentan or tadalafil dose can be increased, as needed and tolerated, not to exceed ambrisentan 10 mg/day or tadalafil 40 mg/day

Dosage Modifications

Coadministration with cyclosporine: Limit ambrisentan to 5 mg/day

Renal impairment

  • Mild-to-moderate: No dosage adjustment required
  • Severe: Not studied
  • Hemodialysis: Not studied

Hepatic impairment

  • Pre-existing
    • Mild: No information available
    • Moderate-to-severe: Not recommended
  • Elevated LFTs after initiating
    • LFTs >5x ULN: Discontinue
    • LFTs increased and accompanied by bilirubin >2x ULN (or signs/symptoms of liver dysfunction): Discontinue

Dosing Considerations

Studies establishing effectiveness included predominantly patients with WHO functional Class II–III symptoms and etiologies of idiopathic or heritable PAH (60%) or PAH associated with connective tissue diseases (34%)

Initiate treatment with ambrisentan in females of reproductive potential only after a negative pregnancy test; obtain monthly pregnancy tests during treatment

Safety and efficacy not established



Interaction Checker

and ambrisentan

No Results

     activity indicator 
    No Interactions Found
    Interactions Found


      Serious - Use Alternative

        Significant - Monitor Closely


            All Interactions Sort By:
             activity indicator 

            Adverse Effects


            Peripheral edema (17%)

            Headache (15%)


            Nasal congestion (6%)

            Palpitations (5%)

            Constipation (4%)

            Dyspnea (4%)

            Flushing (4%)

            Abdominal pain (3%)

            Nasopharyngitis (3%)

            Sinusitis (3%)

            Postmarketing Reports




            Fluid retention

            Heart failure (associated with fluid retention)



            Increased liver aminotransferases (ALT, AST)

            Hypersensitivity (eg, angioedema, rash)

            Symptomatic hypotension


            Liver failure



            Black Box Warnings

            Embryo-fetal toxicity

            • Do not administer ambrisentan to a pregnant female because it may cause fetal harm
            • Females of reproductive potential: Exclude pregnancy before starting treatment, monthly during treatment, and 1 month after stopping treatment
            • Prevent pregnancy during treatment and for 1 month after stopping treatment by using acceptable methods of contraception
            • For all female patients, Letairis is available only through a restricted program called the Letairis Risk Evaluation and Mitigation Strategy (REMS)



            Idiopathic pulmonary fibrosis


            Fetal harm when administered during pregnancy and is contraindicated for use in females who are pregnant (see Pregnancy and Black Box Warnings)

            Caution with hepatic impairment; may be associated with rare cases of hepatic cirrhosis with prolonged use; not recommended in patients with moderate-to-severe hepatic impairment

            Discontinue in patients with elevated aminotransferases >5x ULN, or if elevations are accompanied by bilirubin >2X ULN, or signs/symptoms of liver dysfunction

            Reports of decreased hemoglobin concentrations from baseline that persisted for up to 4 yr of treatment

            Coadministration with cyclosporine or CYP3A4 or CYP2C19 inhibitors

            Peripheral edema is known class effect of endothelin receptor antagonists, and also a clinical consequence of pulmonary arterial hypertension (PAH) and worsening PAH; fluid retention in patients with pulmonary hypertension, occurring within weeks of initiating therapy reported; if clinically significant fluid retention develops, with or without associated weight gain, further evaluate to determine cause, such as ambrisentan or underlying heart failure, possible need for specific treatment or discontinuation of therapy

            Risk of fluid retention and peripheral edema; more common in combination with tadalafil, than with ambrisentan or tadalafil alone

            Decreased sperm counts observed in human and animal studies with another endothelin receptor antagonist and in animal fertility studies with ambrisentan

            Development of acute pulmonary edema during therapy initiation may be associated with pulmonary veno-occlusive disease

            Restricted Distribution Program

            • Because of risk of birth defects, available only through restricted distribution program called the Ambrisentan REMS, by calling 1-888-417-3172; only prescribers and pharmacies certified with Ambrisentan REMS may prescribe and distribute ambrisentan or the brand Letairis
            • Requirements of the REMS program include the following:
              • Prescribers must be certified with the program by enrolling and completing training
              • All females, regardless of reproductive potential, must enroll in the Ambrisentan REMS program prior to initiating treatment
              • Male patients are not enrolled in the REMS
              • Females of reproductive potential must comply with the pregnancy testing and contraception requirements
              • Pharmacies that dispense ambrisentan must be certified with the program and must dispense to female patients who are authorized to receive ambrisentan

            Pregnancy & Lactation


            Based on data from animal reproduction studies, fetal harm may occur when administered to a pregnant woman and is contraindicated during pregnancy

            There are limited data on use in pregnant women

            Advise patient of the potential hazard to a fetus

            Animal data

            • In animal reproduction studies, ambrisentan was teratogenic in rats and rabbits at doses which resulted in exposures of 3.5 and 1.7 times, respectively, the human dose of 10 mg/day


            • Female patients of reproductive potential must use acceptable methods of contraception during treatment and for 1 month after stopping treatment
            • Patients should choose one highly effective form of contraception (intrauterine device [IUD], contraceptive implant, or tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods)
            • If a partner’s vasectomy is one method of contraception, a hormone or barrier method must be used along with this method
            • Counsel patients on pregnancy planning and prevention, including emergency contraception, or designate counseling by another healthcare provider trained in contraceptive counseling


            • Males: Based on findings and preclinical data, endothelin receptor antagonists have an adverse effect on spermatogenesis; counsel patients about the potential effects on fertility


            Unknown whether present in human milk

            Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.



            Mechanism of Action

            High affinity endothelin (ETa) receptor subtype antagonist, resulting in inhibition of vasoconstriction

            Two receptor subtypes, ETA and ETB, mediate the effects of ET-1 in the vascular smooth muscle and endothelium

            Primary actions of ETA are vasoconstriction and cell proliferation, while the predominant actions of ETB are vasodilation, antiproliferation, and ET-1 clearance


            Peak Plasma Time: 2 hr


            Protein Bound: 99%


            Substrate of hepatic CYP3A4, CYP2C19, UGTs (1A9S, 2B7S, and 1A3S)


            Half-life: 15 hr

            Excretion: Predominantly nonrenal



            Oral Administration

            Administer with or without food

            Swallow whole, do not split, crush, or chew tablets


            Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F)





            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient



            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient



            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.