Label Changes for:

Letairis (ambrisentan) tablets

October 2010

Changes have been made to the BOXED WARNING, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS sections of the safety label.

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

 

March 2011

WARNINGS AND PRECAUTIONS

  • LETAIRIS is available only through a special restricted distribution program
  • If patients develop acute pulmonary edema during initiation of therapy with LETAIRIS, consider the possibility of underlying pulmonary veno-occlusive disease and discontinue treatment if necessary

ADVERSE REACTIONS

Clinical Trials Experience
  • 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.
  • Use in Patients with Prior Endothelin Receptor Antagonist (ERA) Related Liver Function 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...
Postmarketing Experience
  • 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. Discontinue Letairis if >5x ULN or if elevations are accompanied by bilirubin >2x ULN, or by signs or symptoms of liver dysfunction and other causes are excluded.

PATIENT COUNSELING INFORMATION

  • Educate and counsel women of childbearing potential on use of emergency contraception for patients whom have had unprotected sex or known or suspected contraceptive failure.
Hepatic Effects
  • Some members of this pharmacological class are hepatotoxic. Patients should be educated on the symptoms of potential liver injury (such as anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant abdominal discomfort, jaundice, dark urine or itching) and instructed to report any of these symptoms to their physician.

 

 

October 2010

 

BOXED WARNING

  • Letairis can be prescribed and dispensed only through a restricted distribution program (Letairis Education and Access Program [LEAP]) because of these risks…

WARNINGS AND PRECAUTIONS

Pulmonary Veno-occlusive Disease
  • If patients develop acute pulmonary edema during initiation of therapy with vasodilating agents such as Letairis, the possibility of pulmonary venoocclusive disease should be considered, and if confirmed Letairis should be discontinued.

ADVERSE REACTIONS

Postmarketing Experience
  • Fluid retention nausea and vomiting

DRUG INTERACTIONS

  • Multiple dose co-administration 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 co-administered with cyclosporine.

MEDICATION GUIDE

Who should not take Letairis?
  • Especially tell your doctor if you take the medicine cyclosporine (Gengraf, Neoral, Sandimmune). Your doctor may need to change your dose of Letairis. You should not take more than 5 mg of Letairis each day if you also take cyclosporine.
What are the possible side effects of Letairis?
  • Serious side effects of Letairis include: Low red blood cell levels (anemia) can happen during the first weeks after starting Letairis. Your doctor will do blood tests to check your red blood cells before starting Letairis . Your doctor may also do these tests during treatment with Letairis.
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