Letairis

Important Safety Information

BOXED WARNING: CONTRAINDICATED IN PREGNANCY

See full prescribing information for complete 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. Because of this risk:

  • Exclude pregnancy before the start of treatment and monthly thereafter
  • Prevent pregnancy 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
  • Educate and counsel women of childbearing potential on the use of emergency contraception in the event of unprotected sex or known or suspected contraceptive failure
  • LETAIRIS is available only through a restricted program called the LETAIRIS Education and Access Program (LEAP). Prescribers, patients, and pharmacies must enroll in the program. Further information is available at www.letairisrems.com or 1-866-664-LEAP (5327)

Contraindication

  • Do not administer LETAIRIS to a pregnant woman because it can cause fetal harm

Warnings and precautions

  • Mild to moderate peripheral edema. Peripheral edema occurred more frequently in elderly patients (age ≥65 years) receiving LETAIRIS (29%; 16/56) compared to placebo (4%; 1/28). Peripheral edema is a known class effect of endothelin receptor antagonists. In addition, there have been postmarketing reports of fluid retention occurring within weeks after starting LETAIRIS that required intervention with a diuretic, fluid management, or, in some cases, hospitalization for decompensating heart failure
  • If patients develop acute pulmonary edema during initiation of therapy with vasodilating agents such as LETAIRIS, pulmonary veno-occlusive disease should be considered, and if confirmed, LETAIRIS should be discontinued
  • Decreases in sperm count have been observed in patients taking endothelin receptor antagonists
  • Decreases in hemoglobin have been observed within the first few weeks of treatment with LETAIRIS, and may persist during treatment. There have been postmarketing reports of anemia requiring transfusion. Measure hemoglobin prior to initiation, at 1 month, and periodically thereafter. Initiation of LETAIRIS therapy is not recommended for patients with clinically significant anemia

Adverse reactions

Adverse Reaction Table

  • During 12-week controlled clinical trials, the incidence of liver aminotransferase (AST, ALT) elevations >3× ULN was 0% for LETAIRIS and 2.3% for placebo
  • In postmarketing experience, elevations of aminotransferases have been reported with LETAIRIS use; in most cases alternative causes of liver injury could be identified (heart failure, hepatic congestion, hepatitis, alcohol use, hepatotoxic medications). In practice, cases of hepatic injury should be carefully evaluated for cause
  • Other ERAs have been associated with aminotransferase elevations, hepatotoxicity, and cases of liver failure
  • Discontinue LETAIRIS if aminotransferase elevations are >5× ULN or if elevations are accompanied by bilirubin >2× ULN or by signs or symptoms of liver dysfunction, and other causes are excluded

Drug interactions

  • Multiple-dose coadministration of LETAIRIS and cyclosporine resulted in an approximately 2-fold increase in LETAIRIS exposure in healthy volunteers. Limit the dose of LETAIRIS to 5 mg once daily when coadministered with cyclosporine

Dosage and administration

  • Providers and patients must enroll in the restricted program called LEAP and comply with the required monitoring to ensure safe use
  • Initiate treatment at 5 mg once daily and consider increasing the dose to 10 mg once daily if 5 mg is tolerated
  • Tablets may be taken with or without food and should not be split, crushed, or chewed
  • Initiate treatment in women of childbearing potential only after a negative pregnancy test and obtain monthly pregnancy tests thereafter
  • Not recommended in patients with moderate or severe hepatic impairment. There is no information on the use of LETAIRIS in patients with mild hepatic impairment; however, exposure to LETAIRIS may be increased in these patients

Please see full prescribing information for complete details.