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Bosentan Enters Market With Risk Management Program

Cheryl A. Thompson

To decrease the risk of liver injury and prevent fetal damage from bosentan exposure, Actelion Pharmaceuticals US Inc. has set up the Tracleer Access Program for the company's recently approved oral treatment for pulmonary arterial hypertension. The risk management program, which requires participating dispensers to track but not monitor patients, is coordinated by a business unit of AmerisourceBergen Corp. and involves a network of specialty pharmaceutical companies.

Bosentan is indicated to improve patients' exercise ability and delay their clinical decline. The drug blocks endothelin-1, a blood vessel constrictor, from binding to receptors in endothelia and vascular smooth muscles.

Warnings about bosentan's potential to injure the liver—11% of patients in the premarketing studies had at least a threefold increase in the serum concentration of one or both liver transaminases—and almost-certain likelihood to cause serious birth defects appear in a black box in the product's labeling.

FDA, in approving the marketing of bosentan, required that the company set up a restricted distribution system to track every patient taking the drug. The patient and the prescriber must complete the enrollment form, which collects information about insurance coverage and the diagnosis and also serves as the prescription. FDA does not require the specialty pharmaceutical companies to evaluate a patient's test results before shipping each 30-day supply of the drug. Actelion must submit an annual report to FDA regarding the program's success in minimizing fetal exposure and liver toxicity.

Responsibilities of Bosentan Dispensers

The specialty pharmaceutical companies participating in the Tracleer Access Program must

  • Include with each supply of bosentan the FDA-approved medication guide and a reminder card about undergoing liver function and pregnancy testing, 
  • Send the prescriber a letter confirming the filling of the prescription, noting the need for monthly liver function and pregnancy tests, and providing the telephone numbers for the reporting of any bosentan-related adverse event, 
  • Confirm with the patient, before sending the next month's supply, that bosentan therapy is to be continued, 
  • Remind the patient, if therapy is to continue, that liver function must be tested monthly and that, if the patient is female, she should not become pregnant while taking bosentan, 
  • Ask the patient whether a blood sample was obtained in the past month for "reasons other than checking blood thinning" and, if the patient is female, whether a pregnancy test was done in the past month, 
  • Promptly contact the prescriber if the patient does not confirm that the requisite testing has been done, and 
  • Document the above actions in the tracking database.

An Actelion spokesman said that the companies are also supposed to check patients' medication profiles for concomitant drugs (glyburide and cyclosporine are contraindicated) and send the Lash Group a daily record of bosentan-related activities, including refills that should have been obtained but were not requested.

To obtain the initial supply of bosentan, a patient or prescriber contacts the Lash Group, an AmerisourceBergen firm that describes itself as primarily a reimbursement consultant. The Lash Group uses the insurance information on the enrollment form to select which of the participating specialty pharmaceutical companies—Caremark Inc., Gentiva Health Services Inc., Nova Factor Inc., or CVS ProCare—will dispense bosentan to the patient.

For patients with primary pulmonary hypertension, bosentan may be an alternative to epoprostenol, or Flolan, a prostacyclin that must be administered by continuous i.v. infusion. Manufacturer GlaxoSmithKline makes the drug available through two specialty pharmaceutical companies: Gentiva Health and AdvancePCS's TheraCom.

Treprostinil sodium, or Remodulin, another prostacyclin, is in the final stage of the approval process to carry an indication for the treatment of pulmonary arterial hypertension, according to manufacturer United Therapeutics Corp. The drug is be delivered by continuous subcutaneous infusion and distributed by Gentiva Health and Priority Healthcare Corp.