Letairis Side Effects Center

Last updated on RxList: 6/21/2021
Letairis Side Effects Center

What Is Letairis?

Letairis (ambrisentan) is an endothelin receptor antagonist used to treat pulmonary arterial hypertension (PAH). Letairis blocks the effects of endothelin-1, helping to decrease the blood pressure in the lungs, slow the worsening of symptoms, and improve your ability to exercise.

What Are Side Effects of Letairis?

Common side effects of Letairis include:

Tell your doctor if you have unlikely but serious side effects of Letairis including:

  • fast heartbeat,
  • extreme tiredness,
  • swelling ankles or feet,
  • sudden or unexplained weight gain, or
  • trouble breathing.

Dosage for Letairis

The adult starting dose of Letairis is 5 mg once daily, and may be increased to 10 mg once daily if 5 mg is tolerated.

What Drugs, Substances, or Supplements Interact with Letairis?

Letairis may interact with cyclosporine, omeprazole, rifampin, antibiotics, or HIV medicines. Tell your doctor all medications you use.

Letairis During Pregnancy and Breastfeeding

Letairis must not be used during pregnancy. It may harm a fetus. Women must have a negative pregnancy test before starting this medication and once a month while taking it. Consult your doctor for details and to discuss birth control. Use at least 2 forms of birth control (e.g., birth control pills, condoms) while taking this medication and for 1 month after stopping it. It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breastfeeding while using this medication is not recommended.

Additional Information

Our Letairis (ambrisentan) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.


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Letairis Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • severe shortness of breath, wheezing, cough with foamy mucus, chest pain;
  • swelling, tiredness, rapid weight gain;
  • low red blood cells (anemia)--pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet; or
  • liver problems--loss of appetite, stomach pain (upper right side), nausea, vomiting, fever, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

  • swelling in your hands, legs, ankles, or feet;
  • stuffy nose, sinus pain; or
  • hot flashes, redness in your face.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Letairis (Ambrisentan Tablets)


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Letairis Professional Information


Clinically significant adverse reactions that appear in other sections of the labeling include:

  • Embryo-fetal Toxicity [see WARNINGS AND PRECAUTIONS, Use In Specific Populations]
  • Fluid Retention [see WARNINGS AND PRECAUTIONS]
  • Pulmonary Edema with PVOD [see WARNINGS AND PRECAUTIONS]
  • Decreased Sperm Count [see WARNINGS AND PRECAUTIONS]
  • Hematologic Changes [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Safety data for Letairis are presented from two 12-week, placebo-controlled studies (ARIES-1 and ARIES-2) in patients with pulmonary arterial hypertension (PAH), and one randomized, double-blind, active-controlled trial in 605 patients with PAH (AMBITION) comparing Letairis plus tadalafil to Letairis or tadalafil alone. The exposure to Letairis in these studies ranged from 1 day to 4 years (N=357 for at least 6 months and N=279 for at least 1 year).

In ARIES-1 and ARIES-2, a total of 261 patients received Letairis at doses of 2.5, 5, or 10 mg once daily and 132 patients received placebo. The adverse reactions that occurred in >3% more patients receiving Letairis than receiving placebo are shown in Table 1.

Table 1 : Adverse Reactions with Placebo-Adjusted Rates >3% in ARIES- 1 and ARIES-2

Adverse Reaction Placebo
n (%) n (%) Placebo-adjusted (%)
Peripheral edema 14 (11) 45 (17) 6
Nasal congestion 2 (2) 15 (6) 4
Sinusitis 0 (0) 8 (3) 3
Flushing 1 (1) 10 (4) 3

Most adverse drug reactions were mild to moderate and only nasal congestion was dose-dependent.

Few notable differences in the incidence of adverse reactions were observed for patients by age or sex. Peripheral edema was similar in younger patients (<65 years) receiving Letairis (14%; 29/205) or placebo (13%; 13/104), and was greater in elderly patients (≥65 years) receiving Letairis (29%; 16/56) compared to placebo (4%; 1/28). The results of such subgroup analyses must be interpreted cautiously.

The incidence of treatment discontinuations due to adverse events other than those related to PAH during the clinical trials in patients with PAH was similar for Letairis (2%; 5/261 patients) and placebo (2%; 3/132 patients). The incidence of patients with serious adverse events other than those related to PAH during the clinical trials in patients with PAH was similar for placebo (7%; 9/132 patients) and for Letairis (5%; 13/261 patients).

During 12-week controlled clinical trials, the incidence of aminotransferase elevations >3 x upper limit of normal (ULN) were 0% on Letairis and 2.3% on placebo. In practice, cases of hepatic injury should be carefully evaluated for cause.

Combination Use With Tadalafil

The mean exposure to Letairis + tadalafil in the AMBITION study was 78.7 weeks. The adverse reactions that occurred in >5% more patients receiving Letairis + tadalafil than receiving Letairis or tadalafil monotherapy in AMBITION are shown in Table 2.

Table 2 : Adverse Reactions Reported More Commonly (>5%) on Letairis + Tadalafil than on Letairis or Tadalafil Monotherapy (ITT) in AMBITION

Adverse Reactions Letairis +Tadalafil Combination Therapy
n (%)
Letairis Monotherapy
n (%)
Tadalafil Monotherapy
n (%)
Peripheral edema 135 (45%) 58 (38%) 43 (28%)
Headache 125 (41%) 51 (34%) 53 (35%)
Nasal congestion 58 (19%) 25 (16%) 17 (11%)
Cough 53 (18%) 20 (13%) 24 (16%)
Anemia 44 (15%) 11 (7%) 17 (11%)
Dyspepsia 32 (11%) 5 (3%) 18 (12%)
Bronchitis 31 (10%) 6 (4%) 13 (9%)

Peripheral edema was more frequent on combination therapy; however, there was no notable difference observed in the incidence of peripheral edema in elderly patients (≥65 years) versus younger patients (<65 years) on combination therapy (44% vs. 45%) or Letairis monotherapy (37% vs. 39%) in AMBITION.

Treatment discontinuations due to adverse events while on randomized treatment were similar across treatment groups: 16% for Letairis + tadalafil, 14% for Letairis alone, and 13% for tadalafil alone.

Use In Patients With Prior Endothelin Receptor Antagonist (ERA) Related Serum Liver Enzyme Abnormalities

In an uncontrolled, open -label study, 36 patients who had previously discontinued endothelin receptor antagonists (ERAs: bosentan, an investigational drug, or both) due to aminotransferase elevations >3 x ULN were treated with Letairis. Prior elevations were predominantly moderate, with 64% of the ALT elevations <5 x ULN, but 9 patients had elevations >8 x ULN. Eight patients had been re-challenged with bosentan and/or the investigational ERA and all eight had a recurrence of aminotransferase abnormalities that required discontinuation of ERA therapy. All patients had to have normal aminotransferase levels on entry to this study. Twenty-five of the 36 patients were also receiving prostanoid and/or phosphodiesterase type 5 (PDE5) inhibitor therapy. Two patients discontinued early (including one of the patients with a prior 8 x ULN elevation). Of the remaining 34 patients, one patient experienced a mild aminotransferase elevation at 12 weeks on Letairis 5 mg that resolved with decreasing the dosage to 2.5 mg, and that did not recur with later escalations to 10 mg. With a median follow-up of 13 months and with 50% of patients increasing the dose of Letairis to 10 mg, no patients were discontinued for aminotransferase elevations. While the uncontrolled study design does not provide information about what would have occurred with re -administration of previously used ERAs or show that Letairis led to fewer aminotransferase elevations than would have been seen with those drugs, the study indicates that Letairis may be tried in patients who have experienced asymptomatic aminotransferase elevations on other ERAs after aminotransferase levels have returned to normal.

Postmarketing Experience

The following adverse reactions were identified during post-approval use of Letairis. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to estimate reliably the frequency or to establish a causal relationship to drug exposure: anemia requiring transfusion [see WARNINGS AND PRECAUTIONS] heart failure (associated with fluid retention), symptomatic hypotension, and hypersensitivity (e.g., angioedema, rash).

Elevations of liver aminotransferases (ALT, AST) have been reported with Letairis use; in most cases alternative causes of the liver injury could be identified (heart failure, hepatic congestion, hepatitis, alcohol use, hepatotoxic medications). Other endothelin receptor antagonists have been associated with elevations of aminotransferases, hepatotoxicity, and cases of liver failure [see ADVERSE REACTIONS].


Multiple dose coadministration of ambrisentan and cyclosporine resulted in an approximately 2-fold increase in ambrisentan exposure in healthy volunteers; therefore, limit the dose of ambrisentan to 5 mg once daily when coadministered with cyclosporine [see CLINICAL PHARMACOLOGY].

Read the entire FDA prescribing information for Letairis (Ambrisentan Tablets)

© Letairis Patient Information is supplied by Cerner Multum, Inc. and Letairis Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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