The FDA has completed its evaluation of a report of a patient who died after the first dose of a multiple sclerosis drug, fingolimod (Gilenya, Novartis), and determined that the drug is now contraindicated in patients with certain pre-existing or recent (within the last six months) heart conditions or stroke, or who are taking certain anti-arrhythmic medications.
The agency also has evaluated additional clinical trial and postmarket data for fingolimod, including reports of patients who died of cardiovascular events or unknown causes.
The agency said it could not definitively conclude that fingolimod was related to any of the deaths. However, based on its re-evaluation of the data, FDA "remains concerned" about the cardiovascular effects of fingolimod after the first dose. Data show that, although the maximum heart rate lowering effect of fingolimod usually occurs within six hours of the first dose, the maximum effect may occur as late as 20 hours after the first dose in some patients.
The FDA continues to recommend that all patients starting Gilenya be monitored for signs of bradycardia for at least six hours after the first dose. The agency is now recommending hourly pulse and blood pressure measurement for all patients starting fingolimod. Electrocardiogram (ECG) 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, the FDA is recommending that the time of cardiovascular monitoring be extended past six 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," the agency said.
The higher-risk patients include those:
- Who develop severe bradycardia after administration of the first dose of fingolimod;
- 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 prior to starting fingolimod, or at any time during the cardiovascular monitoring period; and
- Receiving therapy with other drugs that prolong the QT interval and that can cause Torsades de pointes.