U.S. health regulators have issued new restrictions for Gilenya, Novartis AG’s’ pill for treating multiple sclerosis. According to a Drug Safety Communication issued by the Food & Drug Administration (FDA) yesterday, 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. The agency also said Gilenya should not be prescribed to patients who are taking certain antiarrhythmic medications.
The FDA launched a Gilenya safety review late last year, after a patient died within 24 hours of taking their first dose of the drug. As part of its review, the agency also analyzed postmarket data reported for Gilenya, including other deaths from apparent cardiovascular origin or of unknown origin. While it couldn’t definitively conclude that Gilenya was related to any of the deaths, the FDA said it has concerns about the cardiovascular effects of the drug after the first dose.
According to the FDA analysis, the heart rate lowering affects of Gilenya can occur within six hours of taking the first dose, and as late as 20 hours after the first dose. As such, the agency is continuing 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. The agency is also 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, the FDA said.
Finally, the FDA is also recommending that cardiovascular monitoring be extended past 6 hours in patients who are at higher risk for or who may not tolerate bradycardia. These patients include:
- Patients who develop severe bradycardia after administration of the first dose of Gilenya
- Patients with certain pre-existing conditions in whom bradycardia may be poorly tolerated
- Patients receiving therapy with other drugs that slow the heart rate or atrioventricular conduction
- Patients with QT interval prolongation (a type of heart rhythm abnormality) prior to starting Gilenya, or at any time during the cardiovascular monitoring period
- Patients 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
Gilenya was approved for the treatment of relapsing-remitting multiple sclerosis in 2010. It was the first multiple sclerosis drug approved in pill form, and is used to reduce the frequency of multiple sclerosis flare-ups and delay physical disability. Since its approval, more than 30,000 people worldwide have taken Gilenya, according to the FDA.
One of the known side effects of Gilenya is bradycardia, or a slow heart rate. However, according to the FDA, heart rate usually returns to normal within 1 month after patients start taking the drug.
In yesterday’s Drug Safety Communication, the FDA did not specify the number or nature of the deaths reported among Gilenya patients in recent clinical and postmarket studies. However, European regulators began a safety review of Gilenya in January, after receiving reports of 10 additional deaths among Gilenya patients. According to Novartis, six of those deaths were unexplained, three resulted from heart attacks and one was due to disruption of heart rhythm.