The FDA (Food and Drug Administration) has lifted a boxed warning on the labels of prescription drug Letairis (ambrisentan 5 mg and 10 mg tablets) aimed at patients with worsening pulmonary arterial hypertension to improve exercise ability and slow down worsening symptoms. The Boxed Warning referred to a possible risk of liver injury. Now, those on Letairis no longer have to undergo regular monthly liver function tests, makers Gilead Sciences announced.

The FDA says it has lifted the Boxed Warning requirement after examining post-marketing data over 7,800 patient years. The data was gathered through LEAP (Letairis Education and Access Program). LEAP findings were consistent with the clinical trial data used when Letairis was initially submitted for approval. In those 12-week controlled clinical trials, there was a 0% incidence of liver function problems among Letairis patients compared to 2.3% among the control group (those on a placebo).

Mary Ross Southworth, Pharm.D., deputy director for safety in the Division of Cardiovascular and Renal Products at the FDA’s Center for Drug Evaluation and Research, said:

“We have concluded that monthly liver enzyme testing for patients taking Letairis, as previously noted in the boxed warning, is not necessary. Health care professionals should still continue to order liver enzyme tests when they consider it clinically indicated.”

Ronald J. Oudiz, MD, Professorof Medicine, David Geffen School of Medicine at UCLA and Director, Liu Center for Pulmonary Hypertension, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, said:

“I am encouraged by these post-marketing data, which reflect the use of ambrisentan since its approval in 2007. These data are consistent with the results we have observed in controlled studies. This change will be tremendously helpful to both patients and the staff of specialist centers who diligently support them. Pulmonary arterial hypertension is a very complex disease at the best of times, so any steps to simplify care will be warmly welcomed.”

Gilead says the full services of LabSync will continue being offered. LabSync manages the administrative requirements for laboratory testing for LEAP patients.

Pregnant women should not take Letairia because of a higher risk of birth defects. The drug continues to have such a Boxed Warning and can only be prescribed and dispensed through LEAP. Prescribers and pharmacies registered with LEAP are the only ones who can prescribe, and the patient must meet all the LEAP conditions.

Trial data showed that 29% patients aged at least 65 years experienced peripheral edema when on Letairis, compared to 4% among the control group.

Letairis is an endothelin receptor antagonist, and as such can cause sperm counts to drop among some patients. During the first few weeks of treatment, some may experience a drop in hemoglobin.

If the patient develops pulmonary veno-occlusive disease during the initiation of therapy, Letairis should be discontinued.

Full Letairis prescription information (PDF)

Pulmonary Arterial Hypertension, also known as PAH occurs when the blood vessels in the lungs constrict, resulting in pulmonary arterial pressures. It is a debilitating disease. It becomes harder for the heart to pump blood through the lungs to be oxygenated. Patients experience shortness of breath. There is a significant risk of eventually dying of heart failure. PAH may have no underlying cause, or it may occur secondary to congenital heart defects, HIV infection, cirrhosis of the liver, and connective tissue disease.

According to Gilead Sciences, about 200,000 people globally are afflicted by PAH.

In a communiqué, the FDA wrote:

“People who take Letairis should not stop taking it without talking to their health care professional. Health care professionals should order and review tests for liver function as necessary based on the patient’s condition and history. Adverse events involving Letairis should be reported to the FDA MedWatch program“.

Sources: Gilead Sciences, FDA

Written by Christian Nordqvist