FDA Modifies Boxed Warning for Letairis


March 8, 2011

March 8, 2011 – The U.S. Food and Drug Administration (FDA) announced monthly liver enzyme tests are no longer required for those taking Letairis tablets (ambrisentan), made by Gilead Sciences. Ambrisentan is used to treat pulmonary arterial hypertension (PAH).

Citing data from clinical trials and postmarket reports, the FDA said that the drug poses only a low risk of liver injury. Information related to potential serious liver injury and the need to monitor for such serious injury is being removed from the drug’s boxed warning.

In patients with PAH, Letairis slows the worsening of symptoms and improves the ability to exercise. Approved in 2007, Letairis is in a class of medications called endothelin receptor antagonists, which stop the action of endothelin, a substance that narrows blood vessels and prevents normal blood flow in those with PAH.

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

Letairis was approved with a risk minimization action plan (RiskMAP) to manage liver damage and fetal malformation. The RiskMAP called for liver enzyme testing prior to treatment and monthly during treatment for all patients. It also required monthly pregnancy testing for women of childbearing potential because the drug causes birth defects in animals. The RiskMAP was converted to a risk evaluation and mitigation strategy in 2009.

The boxed warning on the risk of serious birth defects and the contraindication for use during pregnancy will remain in the labeling. The drug will continue to be available only through a restricted distribution program called the Letairis Education and Access Program (LEAP). For women who can become pregnant, monthly pregnancy tests will still be required before it is shipped.

The liver warnings were based on experience with other drugs in the same drug class, as well as a few observed instances of increased liver enzymes in people treated with Letairis. The FDA’s further evaluation has shown that rates of liver problems in patients are consistent with rates within the general PAH population. In the controlled clinical trials, the rates of liver problems in Letairis-treated patients are similar to the rates in people receiving a placebo.

For more information: www.fda.gov