Tuesday, May 15, 2012

FDA Drug Safety Communication: Revised recommendations for cardiovascular monitoring and use of multiple sclerosis drug Gilenya (fingolimod)

The U.S. Food and Drug Administration (FDA) has completed its evaluation of a report of a patient who died after the first dose of multiple sclerosis drug Gilenya (fingolimod).  The agency also has evaluated additional clinical trial and postmarket data for Gilenya, including reports of patients who died of cardiovascular events or unknown causes.  FDA could not definitively conclude that Gilenya was related to any of the deaths (see Data Summary, below). However, based on its reevaluation of the data, FDA remains concerned about the cardiovascular effects of Gilenya after the first dose. Data show that, although the maximum heart rate lowering effect of Gilenya usually occurs within 6 hours of the first dose, the maximum effect may occur as late as 20 hours after the first dose in some patients (See Data Summary).  
For this reason, Gilenya is now contraindicated (FDA advises against its use) in patients with certain pre-existing or recent (within last 6 months) heart conditions or stroke, or who are taking certain antiarrhythmic medications. See CONTRAINDICATION section of the drug label.
FDA continues to recommend that all patients starting Gilenya be monitored for signs of a slow heart rate (bradycardia) for at least 6 hours after the first dose.  FDA is now recommending hourly pulse and blood pressure measurement for all patients starting Gilenya.  Electrocardiogram (ECG or EKG) testing should be performed prior to dosing and at the end of the observation period.  Cardiovascular monitoring should continue until any symptoms resolve.
In addition, FDA is now also recommending that the time of cardiovascular monitoring be extended past 6 hours in patients who are at higher risk for or who may not tolerate bradycardia.   Extended monitoring should include continuous ECG monitoring that continues overnight. See DOSAGE AND ADMINISTRATION section of the drug label. These higher risk patients include those:
  • Who develop severe bradycardia after administration of the first dose of Gilenya
  • With certain pre-existing conditions in whom bradycardia may be poorly tolerated
  • Receiving therapy with other drugs that slow the heart rate or atrioventricular conduction
  • With QT interval prolongation (a type of heart rhythm abnormality) prior to starting Gilenya, or at any time during the cardiovascular monitoring period
  • Receiving therapy with other drugs that prolong the QT interval and that can cause a serious and life-threatening abnormal heart rhythm called Torsades de pointes