WARNING: EMBRYO-FETAL TOXICITY
Do not administer Letairis to a pregnant female because it may cause fetal harm. Letairis is very likely to produce serious birth defects if used by pregnant females, as this effect has been seen consistently when it is administered to animals [see Contraindications, Warnings and Precautions, and Use in Specific Populations].
Exclude pregnancy before the initiation of treatment with Letairis. Females of reproductive potential must use acceptable methods of contraception during treatment with Letairis and for one month after treatment. Obtain monthly pregnancy tests during treatment and 1 month after discontinuation of treatment [see Dosage and Administration and Use in Specific Populations].
Because of the risk of embryo-fetal toxicity, females can only receive Letairis through a restricted program called the Letairis REMS program [see Warnings and Precautions].
LETAIRIS is the brand name for ambrisentan, an endothelin receptor antagonist that is selective for the endothelin type-A (ETA) receptor.
LETAIRIS is indicated for the treatment of pulmonary arterial hypertension (WHO Group 1) in patients with WHO class II or III symptoms to improve exercise capacity and delay clinical worsening.
Published Studies Related to Letairis (Ambrisentan)
Long-term outcomes with ambrisentan monotherapy in pulmonary arterial hypertension. [2010.02]
CONCLUSIONS: Ambrisentan monotherapy led to improvements in catheterization, 6MWD, and RV ejection fraction, and shows promise as a long-term treatment for pulmonary arterial hypertension. Copyright 2010 Elsevier Inc. All rights reserved.
Long-term outcomes with ambrisentan monotherapy in pulmonary arterial
CONCLUSIONS: Ambrisentan monotherapy led to improvements in catheterization,
No clinically relevant pharmacokinetic and safety interactions of ambrisentan in combination with tadalafil in healthy volunteers. [2009.12]
Ambrisentan is a nonsulfonamide, ET(A)-selective endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH), and tadalafil is a phosphodiesterase type 5 (PDE-5) inhibitor under investigation for treatment of PAH...
Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension. [2009.11.17]
OBJECTIVES: This study evaluated the safety and efficacy of ambrisentan for a period of 2 years in patients with pulmonary arterial hypertension (PAH). BACKGROUND: Ambrisentan is an oral, once-daily endothelin receptor antagonist that is selective for the endothelin type A receptor. The ARIES-1 (Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies) and ARIES-2 trials were the pivotal 12-week, placebo-controlled studies that led to the regulatory approval of ambrisentan (5 and 10 mg) for the treatment of PAH... CONCLUSIONS: Two years of ambrisentan treatment was associated with sustained improvements in exercise capacity and a low risk of clinical worsening and death in patients with PAH. Ambrisentan was generally well tolerated and had a low risk of aminotransferase abnormalities over the 2-year study period. (A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 or AMB-321; NCT00578786).
Pharmacokinetics and safety of ambrisentan in combination with sildenafil in healthy volunteers. [2008.12]
The pharmacokinetic interaction between sildenafil, a phosphodiesterase type 5 (PDE-5) inhibitor, and ambrisentan, an ET(A)-selective, propanoic acid-based endothelin receptor antagonist (ERA), was studied in a 2-period crossover study in 19 healthy volunteers, with ambrisentan exposure (AUC(0-infinity)) and maximum plasma concentration (C(max)) determined over 24 hours for a 10-mg dose of ambrisentan alone and again after 7 days of sildenafil 20 mg 3 times daily...
Clinical Trials Related to Letairis (Ambrisentan)
A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis [Active, not recruiting]
This will be a 36-week, randomized, double-blind, parallel group study comparing the effects
of tadalafil monotherapy, ambrisentan monotherapy and combination therapy with tadalafil
and ambrisentan in patients with PAH-SSc. Standard outcome measures such as six-minute walk
distance (6MWD), NYHA classification, and hemodynamic measurements will be assessed, as well
as novel functional measures of RV-PV function including the transthoracic echocardiogram
parameter tricuspid annular plane systolic ejection (TAPSE), contrast-enhanced cardiac MRI
and heart rate variability assessed by Holter monitoring. This design (excluding a
placebo-placebo arm) was selected for ethical concerns and to provide optimal efficiency and
active therapy to all study subjects. It also allows for comparisons between the two
monotherapies and with combination therapy.
The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study [Not yet recruiting]
The purpose of this study is to find out if spironolactone added to ambrisentan for
Pulmonary Arterial Hypertension (PAH) will increase exercise capacity. We also want to find
out if spironolactone and ambrisentan effect the cardiac output (amount of blood the heart
pumps every minute), right ventricle function and quality of life.
Ambrisentan in Patients With Porto-pulmonary Hypertension A Multicenter Open Label Trial [Recruiting]
This is an Open Label, Multicenter, pilot clinical trial to assess the efficacy and safety
of an oral selective Endothelin Receptor Antagonist (ambrisentan) in patients with
Preliminary evidence suggests that ambrisentan is safe and effective in patients with
portopulmonary hypertension. The goal of therapy for these patients is to improve symptoms
of dyspnea and to improve pulmonary hemodynamics to a mean pulmonary artery pressure <35 mm
Hg in order to make patients eligible for liver transplantation. Therefore, the primary
endpoints for this study will include 6 minute walk distance (6MWD) and pulmonary vascular
Eligible subjects will receive 5 mg ambrisentan once-daily for the first 4 weeks. After the
initial 4-week period, investigators will increase study drug dose to 10 mg once daily (both
5 mg and 10 mg doses are FDA approved). If 10 mg is not tolerated in the opinion of
investigator, then the investigator may decrease the dose back to 5 mg once daily. Primary
outcome is a change in both the 6MWD and in PVR from baseline to Week 24. Subjects will be
monitored with liver function tests (LFT) every 2 weeks for the first 8 weeks, then every 4
weeks thereafter. These safety laboratory tests may be performed at a local phlebotomy
laboratory or at the Investigator clinic. In addition, the Investigator will assess each
subject for safety and efficacy at Week 4, Week 12, and Week 24. Following Week 24, subjects
will be assessed for safety and efficacy every 12 weeks. Patients will be followed for a
total of 1 year. After 1 year, if the Investigator feels that continuing the treatment will
be beneficial to the patients, they will be provided with ambrisentan by Gilead
Pharmaceuticals, free of charge.
Efficacy of Ambrisentan in Limited Scleroderma Patients in Improving Blood Flow to Hands or Feet [Completed]
The purpose of this study is to investigate the effectiveness of a drug called ambrisentan,
approved by the FDA for use in pulmonary hypertension (a condition where there is increased
pressure in the right side of the heart) in scleroderma patients, to see if this medicine
may be beneficial in relieving and/or preventing Raynaud's flares in you and other patients
like you. This medicine may have some short-term and long-term benefits in persons with
The Safety Evaluation of Aminophylline and Ambrisentan When Administered Orally Alone and in Combination to Healthy Volunteers [Completed]
This is a Phase I, three period, two sequence, open-label, randomized, crossover study, with
the primary objective of testing the safety and tolerability of combined oral doses of
aminophylline and ambrisentan in healthy human subjects. The secondary objective is to
assess the pharmacokinetic profiles of theophylline (aminophylline) and ambrisentan when
administered alone or in combination. It is hypothesized that the combination of these drugs
is generally safe, and that no drug interaction can be observed.
Reports of Suspected Letairis (Ambrisentan) Side Effects
Unevaluable Event (248),
Fluid Retention (184),
Cardiac Failure Congestive (182),
Pulmonary Arterial Hypertension (181),
Chest Pain (150),
Fall (135), more >>
Page last updated: 2013-02-10