June 16, 2005 — The U.S. Food and Drug Administration (FDA) has approved bivalirudin injection for use with aspirin and provisional glycoprotein inhibitors as anticoagulation therapy for patients undergoing a percutaneous coronary intervention; adjunctive use of pregabalin capsules for partial seizures in epileptic adults; and a 2-g formulation of extended-release azithromycin oral suspension for the single-dose treatment of mild to moderate acute bacterial sinusitis and community-acquired pneumonia in adults.
Bivalirudin (Angiomax) for Use in Percutaneous Coronary Interventions
On June 13, the FDA approved an expanded indication for bivalirudin injection (Angiomax, made by the Medicines Co.), allowing its use with concomitant aspirin as anticoagulation therapy in patients undergoing a percutaneous coronary intervention (PCI).
The indication includes "provisional use" of concomitant glycoprotein 2b/2a inhibitors (GPI) and is based on data from the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) study which compared the efficacy of bivalirudin (n = 2,994) and heparin (n = 3,008) anticoagulation therapy (each with provisional GPI) in patients undergoing elective or urgent PCI procedures.
Results showed that treatment with bivalirudin plus provisional GPI was associated with an increased incidence of the 30-day composite ischemic endpoint (death, myocardial infarction, or urgent revascularization), compared with heparin plus provisional GPI (7.6%; 95% confidence interval [CI], 6.7% - 8.6% vs 7.1%; 95% CI, 6.1% - 8.0%). According to the FDA, noninferiority of bivalirudin was not demonstrated in the study.
However, study investigators point out that the 30-day rate of major hemorrhage was significantly decreased (2.4% vs 4.1%; P < .001), and follow-up showed a decreased one-year mortality rate (1.9% vs 2.5%) in patients treated with bivalirudin compared with heparin.
New dosage recommendations per study guidelines have also been approved to allow use of a smaller bolus (0.75 vs 1 mg/kg) and reduced infusion rate (1.75 vs 2.5 mg/kg/hour) of bivalirudin for the duration of the procedure, rather than for a four-hour period.
According to a company news release, an indication allowing use of bivalirudin in patients with heparin-induced thrombocytopenia and thrombosis undergoing PCI is currently under evaluation by the FDA for approval.
Bivalirudin injection was previously approved for concomitant use with aspirin as an anticoagulant in patients with unstable angina undergoing percutaneous coronary angioplasty. It is approved in the European Union (marketed as Angiox by Nycomed Group and Grupo Ferrer) for use as an anticoagulant in patients undergoing PCI.
Pregabalin (Lyrica) as Adjunctive Therapy for Partial Seizures in Adults With Epilepsy
On June 10, the FDA approved a new indication for pregabalin (Lyrica capsules, made by Pfizer, Inc.), allowing its use as adjunctive therapy for partial seizures in epileptic adults.
The approval was based on the results of three double-blind controlled trials in 1,052 patients, showing that the addition of pregabalin to an ongoing one- to three-drug standard regimen decreased the incidence of partial seizures by up to 51% in patients with inadequately controlled epilepsy.
Adverse events included dizziness, somnolence, dry mouth, peripheral edema, blurred vision, weight gain, and difficulty with concentration and attention. According to a company news release, the discontinuation rate due to adverse effects was low.
Pregabalin was previously approved by the FDA on Dec. 30, 2004, for the management of neuropathic pain associated with diabetic peripheral neuropathy and by the European Commission on July 6, 2004, for the treatment of peripheral neuropathic pain and as adjunctive therapy for partial seizures in adults with epilepsy.
Single-Dose Azithromycin (Zmax) for Certain Types of Sinusitis and Pneumonia in Adults
On June 10, the FDA approved a 2-g formulation of extended-release azithromycin oral suspension (Zmax, made by Pfizer, Inc.) for the single-dose treatment of adults with mild to moderate acute bacterial sinusitis or community-acquired pneumonia due to susceptible strains of microorganisms.
The formulation uses microsphere technology to achieve azithromycin tissue levels three times greater than that of immediate-release formulations during the first 24 hours, when bacterial burden is highest.
In phase 3 studies of the 2-g formulation, mild to moderate gastrointestinal tract adverse events were most commonly reported and included diarrhea/loose stools (11.6%), nausea (3.9%), abdominal pain (2.7%), headache (1.3%), and vomiting (1.1%). The formulation was associated with an increased incidence of gastrointestinal tract adverse events (17.2% vs 9.7%) relative to pooled comparators.
Immediate-release formulations of azithromycin (Zithromax, made by Pfizer, Inc.) have been approved by the FDA since Nov. 1, 1991.
Reviewed by Gary D. Vogin, MD
Medscape Medical News В© 2005
Cite this: Yael Waknine. FDA Approvals: Angiomax, Lyrica, Zmax - Medscape - Jun 16, 2005.
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