New Direct Thrombin Inhibitor Becomes Available

Cheryl A. Thompson

BETHESDA, MD 04 March 2010—Desirudin, the direct thrombin inhibitor that was approved for the U.S. market in 2003 but not immediately launched, is now available, Canyon Pharmaceuticals announced earlier this week.

Similar in structure to the anticoagulant secreted by the medicinal leech, desirudin selectively inhibits free circulating and clot-bound thrombin.

The FDA-approved labeling (PDF) states that desirudin, or Iprivask, is for use in preventing deep vein thrombosis, which may lead to pulmonary embolism, in patients undergoing elective hip-replacement surgery.

Patients with active bleeding or an irreversible coagulation disorder must not receive desirudin. In addition, the labeling urges caution in using the drug in patients with renal impairment, particularly if moderate or severe.

The labeling recommends a dosage of 15 mg every 12 hours by deep s.c. injection, with the first dose given up to 15 minutes before surgery but after the induction of regional anesthesia. There is no recommended duration of therapy, although the labeling states that the drug was well tolerated for up to 12 days in the controlled clinical trials. Some patients in the trials received the drug for as few as 8 days.

Patients with a moderate degree of renal insufficiency should receive an initial desirudin dosage of 5 mg every 12 hours. Those with severe renal insufficiency should start with a dosage of 1.7 mg every 12 hours. Patients' activated partial thromboplastin time and serum creatinine should be monitored at least daily and used as the basis for dosage adjustments.

Among the patients in the clinical trials who received desirudin 15 mg every 12 hours because of hip-replacement surgery, 30% had some degree of hemorrhage, such as a hematoma, and 3% had a serious hemorrhage. The labeling also states that rare reports of major hemorrhages, some of them fatal, and anaphylactic or anaphylactoid reactions have been received by the company since approval of the drug.

A boxed warning in the labeling states that recipients of selected thrombin inhibitors may be at risk of developing an epidural or spinal hematoma and resultant paralysis if epidural or spinal anesthesia is administered or a spinal puncture is made.

The most frequent adverse events other than hemorrhage during the clinical trials were injection-site mass, wound secretion, anemia, deep thrombophlebitis, and nausea. None of these events occurred in more than 4% of the patients.

Canyon is distributing Iprivask in 10-dose cartons, with the components of each dose on a separate tray. Each tray has one 15.75-mg single-dose vial of desirudin lyophilized powder, one syringe with 0.6 mL of diluent, one vial adapter for adding the diluent to the drug powder, and one BD Eclipse needle for administration of the dose.

Iprivask's labeling states that the unopened vials and diluent-containing syringes are to be stored at controlled room temperature. Once the diluent is added to the drug, the solution must be used within 24 hours. If the dose is 15 mg, all 0.5 mL of the solution is to be withdrawn into the syringe.

Canyon acquired the rights to desirudin immediately after FDA approved the new drug application that had been submitted by Aventis Pharmaceuticals Inc. in 2000.