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U.S. Department of Health and Human Services

Safety

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Letairis (ambrisentan) tablets

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

 

January 2014

Summary View

MEDICATION GUIDE

What is the most important information I should know about Letairis?

  • Serious birth defects ... See extensive changes in this section in PI/Medication Guide

 

October 2012

Summary View

 

CONTRAINDICATIONS

Idiopathic Pulmonary Fibrosis
  • Letairis is contraindicated in patients with Idiopathic Pulmonary Fibrosis (IPF) including IPF patients with pulmonary hypertension (WHO Group 3).

 

ADVERSE REACTIONS

Postmarketing Experience
  • asthenia, dizziness, and fatigue

 

MEDICATION GUIDE

Who should not take Letairis?
  • you have a condition called Idiopathic Pulmonary Fibrosis (IPF)

 

February 2012

Summary View

 

BOXED WARNING

  • Do not administer Letairis to a pregnant woman because it may cause fetal harm. 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.
  • Pregnancy must therefore be excluded before the initiation of treatment with Letairis and prevented during treatment and for one month after stopping treatment by the use of two acceptable methods of contraception unless the patient has had a tubal sterilization or chooses to use a Copper T 380A IUD or LNg 20 IUS, in which case no additional contraception is needed. Obtain monthly pregnancy tests.
  • Because of the risk of birth defects, Letairis is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Letairis Education and Access Program (LEAP). As a component of the Letairis REMS, prescribers, patients, and pharmacies must enroll in the program.
 

CONTRAINDICATIONS

  • Pregnancy
  • Pregnancy must be excluded before the initiation of treatment with Letairis and prevented during treatment and for one month after stopping treatment.
 

WARNINGS AND PRECAUTIONS

Letairis Education and Access Program (LEAP)
  • Because of the risk of birth defects, Letairis is available only through a restricted program called the Letairis Education and Access Program (LEAP). Required components of LEAP:
  • Healthcare professionals who prescribe Letairis must complete the LEAP Prescriber Enrollment and Agreement Form, enroll in the program, and comply with the REMS requirements.
  • To receive Letairis, all patients must complete a patient enrollment form and be re-enrolled annually by their prescriber. For women of childbearing potential, (1) a pregnancy test must be ordered and reviewed by the prescriber prior to initiation of Letairis treatment and monthly during treatment, (2) she must agree to be contacted prior to each shipment to confirm that a pregnancy test was completed, (3) she must agree to be counseled on the requirements of the REMS program and the risks of Letairis, and (4) she must agree to be contacted by Gilead if she becomes pregnant while on Letairis or within 30 days of treatment discontinuation.
  • Pharmacies that dispense LETAIRIS must enroll in the program and agree to comply with the REMS requirements.
  • Further information is available at www.letairisrems.com or 1-866-664-LEAP (5327).
 
Hematological Changes
  • In the long-term open-label extension of the two pivotal clinical studies, mean decreases from baseline (ranging from 0.9 to 1.2 g/dL) in hemoglobin concentrations persisted for up to 4 years of treatment.
  • There have been postmarketing reports of decreases in hemoglobin concentration and hematocrit that have resulted in anemia requiring transfusion.
 

ADVERSE REACTIONS

  • Most common adverse reactions (>3% compared to placebo) are peripheral edema, nasal congestion, sinusitis, and flushing.
Clinical Trials Experience
  • Adverse Reactions with Placebo-Adjusted Rates >3%
 

USE IN SPECIFIC POPULATIONS

  • Breastfeeding: Choose Letairis or breastfeeding
  • Not recommended in patients with moderate or severe hepatic impairment.
Pregnancy
  • Pregnancy Category X. Treat women of childbearing potential only after a negative pregnancy test and treat only women who are using acceptable methods of contraception. Pregnancy tests should be obtained monthly in women of childbearing potential taking Letairis.
Hepatic Impairment
  • Elevation of Liver Transaminases: Other endothelin receptor antagonists (ERAs) have been associated with aminotransferase (AST, ALT) elevations, hepatotoxicity, and cases of liver failure. In patients who develop hepatic impairment after Letairis initiation, the cause of liver injury should be fully investigated. Discontinue Letairis if aminotransferase elevations >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

Letairis Education and Access Program (LEAP)
  • Advise the patient that Letairis is available only through a restricted program called LEAP.
  • As a component of LEAP, prescribers must review the contents of the Letairis Medication Guide and the Letairis Patient Enrollment Guide before initiating treatment with Letairis.
  • Inform the patient that Letairis is available only from Certified Specialty Pharmacies enrolled in LEAP. Provide patients with a list of Certified Specialty Pharmacies. As a component of LEAP, Certified Specialty Pharmacies must provide a copy of the Medication Guide to patients or caregivers each time Letairis is dispensed…
Pregnancy
  • Instruct patients that the risks associated with Letairis include serious birth defects if used by pregnant women:
  • Educate and counsel women of childbearing potential to use highly reliable contraception during LETAIRIS treatment and for one month after stopping treatment. If the patient has had a tubal sterilization or chooses to use a Copper T 380A IUD or LNg 20 IUS for pregnancy prevention, no additional contraception is needed. Women who do not choose one of these methods should always use two acceptable forms of contraception: one hormone method and one barrier method, or two barrier methods where one method is the male condom...
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.
Hematological Change
  • Patients should be advised of the importance of hemoglobin testing.
Other Risks Associated with Letairis
  • Instruct patients that the risks associated with Letairis also include the following:
  • Decreases in hemoglobin and hematocrit
  • Decreases in sperm count
  • Fluid overload
Administration
  • Patients should be advised not to split, crush, or chew tablets.
 

MEDICATION GUIDE

What is the most important information I should know about Letairis?
  • Your doctor may tell you to use emergency birth control.
What are the possible side effects of Letairis?
Low red blood cell levels
  • If this happens, you may need a blood transfusion.

 

March 2011

Summary View

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

Summary View

 

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.