The Tracleer® (bosentan) REMS (Risk Evaluation
and Mitigation Strategy) Program

A Risk Evaluation and Mitigation Strategy (REMS) is a program required by the Food and Drug Administration (FDA) to manage serious risks associated with a drug product.

Because of the risks of hepatotoxicity and teratogenicity, Tracleer is available only through a restricted program called the Tracleer REMS Program. Under the Tracleer REMS, prescribers, patients, pharmacies, and hospitals must enroll in the program. In order to receive Tracleer, hospitals, prescribers, and patients must agree to comply with the requirements of the program. In addition, Tracleer is dispensed only through specialty pharmacies.

The goals of the Tracleer REMS Program are:

  • To inform prescribers, patients, and pharmacists about the risks of Tracleer
  • To minimize the risk of hepatotoxicity in patients who are exposed to Tracleer
  • To minimize the risk of fetal exposures in female patients who are exposed to Tracleer
  • To educate prescribers, patients, and pharmacies on the safe-use conditions for Tracleer

Indication

Tracleer is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%).

Considerations for use: Patients with WHO class II symptoms showed reduction in the rate of clinical deterioration and a trend for improvement in walk distance. Physicians should consider whether these benefits are sufficient to offset the risk of hepatotoxicity in WHO class II patients, which may preclude future use as their disease progresses.

Tracleer REMS Program Overview

  • All healthcare providers must enroll in the Tracleer REMS Program and comply with the REMS Program requirements in order to prescribe Tracleer
  • All patients must enroll in the Tracleer REMS Program and comply with the REMS Program requirements in order to receive Tracleer
    • All patients must agree to be counseled on the Tracleer REMS Program and the risks of treatment with Tracleer
    • All patients must agree to be contacted about completing required monthly testing
  • Prescribers must counsel all patients on the risks of Tracleer, including the risk of hepatotoxicity
  • Prescribers must order and review liver function tests prior to initiation of treatment and monthly thereafter for all patients
  • Prescribers must closely monitor transaminase levels and adjust monitoring and treatment with Tracleer if increases are reported
  • Prescribers must discontinue Tracleer if liver aminotransferase elevations are accompanied by clinical symptoms of hepatoxicity or increases in bilirubin ≥2 ULN
  • Prescribers must determine the reproductive status of female patients
  • Prescribers must counsel Females of Reproductive Potential and Pre-pubertal Females, once they become Females of Reproductive Potential about the risks of Tracleer, including the risk of teratogenicity
  • Prescribers must order and review pregnancy testing for Females of Reproductive Potential prior to initiation of treatment, monthly during treatment, and for one month after stopping treatment
  • Prescribers must report any change or misclassification in a female’s reproductive potential status to the Tracleer REMS Program
  • Definitions of Reproductive Potential Status
    • Females of Reproductive Potential
      • Females of reproductive potential include girls who have entered puberty and all females who have a uterus and have not passed through menopause (as defined below)
      • For the purposes of this REMS, puberty includes those girls who are at least Tanner Stage 3 and have not yet had a menses (premenarchal)
    • Females of Non-Reproductive Potential
      • Pre-pubertal Females: Females who are at Tanner Stages 1 and 2 are not considered to be of reproductive potential
      • Post-menopausal Females: Females who have passed through menopause. Menopause is defined as 12 months of spontaneous amenorrhea (not amenorrhea induced by a medical condition or medical therapy) or post-surgical form bilateral oophorectomy
      • Females with other medical reasons for permanent, irreversible infertility
  • For Females of Reproductive Potential:
    • Pregnancy must be ruled out prior to drug initiation, monthly during treatment, and for one month after stopping treatment
    • She must agree to be contacted by Actelion if she becomes pregnant either while on Tracleer or within one month of treatment discontinuation
  • Only pharmacies certified in the Tracleer REMS Program can dispense Tracleer to outpatients
  • Only inpatient pharmacies that are certified in the Tracleer REMS Program will stock Tracleer for inpatient use

Changes to the Tracleer REMS Program [May, 2016]