WARNING: POTENTIAL LIVER INJURY
LETAIRIS (ambrisentan) can cause elevation of liver aminotransferases (ALT and AST) to at least 3 times the upper limit of normal (ULN). LETAIRIS treatment was associated with aminotransferase elevations >3 x ULN in 0.8% of patients in 12-week trials and 2.8% of patients including long-term open-label trials out to one year. One case of aminotransferase elevations >3 x ULN has been accompanied by bilirubin elevations >2 x ULN. Because these changes are a marker for potentially serious liver injury, serum aminotransferase levels (and bilirubin if aminotransferase levels are elevated) must be measured prior to initiation of treatment and then monthly.
In the post-marketing period with another endothelin receptor antagonist (ERA), bosentan, rare cases of unexplained hepatic cirrhosis were reported after prolonged (>12 months) therapy. In at least one case with bosentan, a late presentation (after >20 months of treatment) included pronounced elevations in aminotransferases and bilirubin levels accompanied by non-specific symptoms, all of which resolved slowly over time after discontinuation of the suspect drug. This case reinforces the importance of strict adherence to the monthly monitoring schedule for the duration of treatment.
Elevations in aminotransferases require close attention. LETAIRIS should generally be avoided in patients with elevated aminotransferases (>3 x ULN) at baseline because monitoring liver injury may be more difficult. If liver aminotransferase elevations are accompanied by clinical symptoms of liver injury (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin >2 x ULN, treatment should be stopped. There is no experience with the re-introduction of LETAIRIS in these circumstances.
CONTRAINDICATION: PREGNANCY
LETAIRIS is very likely to produce serious birth defects if used by pregnant women, as this effect has been seen consistently when it is administered to animals [see Contraindications (4.1)]. Pregnancy must therefore be excluded before the initiation of treatment with LETAIRIS and prevented thereafter by the use of at least two reliable methods of contraception unless the patient has had a tubal sterilization or Copper T 380A IUD or LNg 20 IUD inserted, in which case no other contraception is needed. Obtain monthly pregnancy tests.
Because of the risks of liver injury and birth defects, LETAIRIS is available only through a special restricted distribution program called the LETAIRIS Education and Access Program (LEAP), by calling 1-866-664-LEAP (5327). Only prescribers and pharmacies registered with LEAP may prescribe and distribute LETAIRIS. In addition, LETAIRIS may be dispensed only to patients who are enrolled in and meet all conditions of LEAP [see WARNINGS, Prescribing and Distribution Program for LETAIRIS ].
|
| |
LETAIRIS SUMMARY
LETAIRIS (ambrisentan) tablets for oral use
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.
|
NEWS HIGHLIGHTSMedia Articles Related to Letairis (Ambrisentan)
ED Drug Improves Heart's Pumping Action In Young Patients With Single-Ventricle Disease
Source: Cardiovascular / Cardiology News From Medical News Today [2009.11.19]
Heart function significantly improved in children and young adults with single-ventricle congenital heart disease who have had the Fontan operation following treatment with sildenafil, a drug used to treat erectile dysfunction and pulmonary hypertension, say researchers from The Children's Hospital of Philadelphia. Single-ventricle defects are a collection of cardiac malformations that impair the heart's ability to pump blood.
Published Studies Related to Letairis (Ambrisentan)
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...
Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. [2008.06.10]
CONCLUSIONS: Ambrisentan improves exercise capacity in patients with pulmonary arterial hypertension. Improvements were observed for several secondary end points in each of the studies, although statistical significance was more variable. Ambrisentan is well tolerated and is associated with a low risk of aminotransferase abnormalities.
Ambrisentan therapy for pulmonary arterial hypertension. [2005.08.02]
OBJECTIVES: The purpose of this study was to examine the efficacy and safety of four doses of ambrisentan, an oral endothelin type A receptor-selective antagonist, in patients with pulmonary arterial hypertension (PAH). BACKGROUND: Pulmonary arterial hypertension is a life-threatening and progressive disease with limited treatment options. Endothelin is a vasoconstrictor and smooth muscle cell mitogen that plays a critical role in the pathogenesis and progression of PAH... CONCLUSIONS: Ambrisentan appears to improve exercise capacity, symptoms, and hemodynamics in patients with PAH. The incidence and severity of liver enzyme abnormalities appear to be low.
Ambrisentan, an endothelin receptor type A-selective endothelin receptor antagonist, for the treatment of pulmonary arterial hypertension. [2009.08]
Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature characterized by vasoconstriction and vascular proliferation, which leads to right heart failure and death... As with other ERAs, monthly pregnancy testing is required in all women of child bearing potential.
Effect of ketoconazole on the pharmacokinetic profile of ambrisentan. [2009.06]
Ambrisentan is an endothelin type A (ET(A))-selective receptor antagonist that is metabolized primarily by glucuronidation but also undergoes oxidative metabolism by CYP3A4. The potential for ketoconazole, the archetypal strong inhibitor of CYP3A4, to alter the pharmacokinetic profile of ambrisentan and its oxidative metabolite, 4-hydroxymethyl ambrisentan, was assessed in an open-label, nonrandomized, 2-period, single-sequence study in 16 healthy men...
Clinical Trials Related to Letairis (Ambrisentan)
Ambrisentan (Letairis) for Sarcoidosis Associated Pulmonary Hypertension [Recruiting]
Hypothesis: Ambrisentan (Letairis ®) is safe and effective in treating pulmonary
hypertension in patients with Sarcoidosis
Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan [Recruiting]
This is a randomized study of ambrisentan that will last 16 weeks. The study will include
patients with diastolic heart failure and pulmonary hypertension. Patients will be
randomized (1: 1) to ambrisentan or placebo. The ambrisentan or matching placebo will be
started at 2. 5 mg by mouth daily and increased to 5mg and then 10mg daily, if tolerated.
Patients will be seen at least monthly for 16 weeks. Adverse reactions will be reviewed and
the required monthly laboratory tests (liver function testing and pregnancy testing, if
applicable), will be performed. Patients will also complete an exercise test (six minute
walk distance) and a quality of life survey at the baseline, week 4 and week 16 visit. An
echocardiogram and a right heart catheterization and left ventricular end diastolic pressure
measurement will be performed at the 16 week visit. The primary end-point is safety, and
secondary end-points include the catheterization results, echocardiogram results, the walk
distance and the quality of life survey. The expected completion of the study is 18 months
from initiation. Ambrisentan is an FDA approved drug for PAH, but not for CHF.
ARTEMIS-PH - Study of Ambrisentan in Subjects With Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis [Recruiting]
This Phase 3, randomized, double-blind, placebo-controlled, multicenter study will compare
the efficacy and safety of ambrisentan to placebo in subjects with pulmonary hypertension
associated with idiopathic pulmonary fibrosis.
Study of Ambrisentan and Phosphodiesterase Type-5 Inhibitor (PDE-5i) to Treat Pulmonary Arterial Hypertension [Recruiting]
To evaluate the change from baseline in pulmonary vascular resistance (PVR), and other
hemodynamic parameters, following the addition of ambrisentan to background
phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial
hypertension (PAH) who have demonstrated a sub-optimal response to PDE-5i monotherapy.
(ARTEMIS-IPF)Randomized, Placebo-Controlled Study to Evaluate Safety and Effectiveness of Ambrisentan in IPF [Recruiting]
The ARTEMIS-IPF study is for people who have been diagnosed with IPF and are between 40-80
years of age. People who have been diagnosed early in the disease may be more responsive to
treatment. This is a randomized study (which means the participants will be selected by
chance (like flipping a coin) to receive one of two treatments (ambrisentan or placebo).
This is a double-blind study which means participants and their study doctor won't know what
treatment they are assigned to receive. Participants will have 2 out of 3 chances to receive
ambrisentan, or 1 out of 3 chances to receive placebo (which is a tablet that looks like the
active medicine but contains no active medicine)Taking part in the study could be up to 3
years depending on how long it takes to enroll and observe study events. After
randomization, visits take place every 3 months. Laboratory visits occur every month.
|
|
|
|
Page last updated: 2009-11-19
|
