U.K. regulator, the Medicines and Healthcare products Regulatory Agency (MHRA), just issued a warning against Gilenya (fingolimod) use in heart patients. The MHRA also called for extended early monitoring for patients diagnosed with significant bradycardia or heart block after the first dose. Gilenya is a sphingosine-1 phosphate receptor ligand.
The MHRA announcement followed new restrictions issued by the U.S. Food & Drug Administration (FDA). In the U.S., Gilenya was approved in 2010 for the treatment of relapsing-remitting multiple sclerosis (MS). The first MS pill medication, Gilenya is used to reduce the frequency of MS flare-ups and delay physical disability; however, reports of patient deaths prompted concerns.
The MHRA noted that Gilenya is known to cause transient bradycardias and heart block following the initial dose and points out that the medication is, now, not recommended for patients at increased risks for adverse cardiovascular events. This can include patients with significant QT prolongation or history of bradycardia, ischemic heart disease, cardiac failure, cerebrovascular disease, uncontrolled hypertension, and patients being treated with anti-arrhythmic or heart-rate lowering drugs.
The MHRA, called for monitoring following the first dose and said all Gilenya patients should now be monitored prior, during, and immediately following the first six hours of treatment. Should a patient’s heart rate drop to its lowest point at the end of the initial six-hour treatment period, monitoring should be extended until the heart rate increases. Monitoring should be extended to at least overnight should significant atrioventricular block, bradycardia, or QTc prolongation occur, the U.K. agency added.
The MHRA first discussed changes to its Gilenya monitoring advice in February 2012, which followed an additional, global review of data that included reports of 15 sudden unexplained fatalities associated with Gilenya use. Similar to MHRA’s advice, the FDA recently announced that Gilenya should not be prescribed for patients diagnosed with some pre-existing conditions, recent heart conditions, or stroke and should also not be prescribed for patients taking specific drugs to correct heart rhythm issues.
Gilenya maker, Novartis, recently announced a change to the drug’s label following safety reviews in the U.S. and Europe and the FDA and the European Medicines Agency (EMA) initiated Gilenya safety reviews after reports were received concerning deaths in patients within hours of taking their first Gilenya dose.
Last December, the FDA announced a Gilenya safety review following the death of one patient in the first 24 hours of taking the first Gilenya dose. European regulators initiated their review in January, after receiving reports of 10 more deaths in Gilenya patients. Although Gilenya could not be definitively connected to the deaths, the FDA announced that it was concerned with the drug’s cardiovascular effects following the first dose. Analysis revealed that while most rate-lowering Gilenya effects typically occur within the first six hours of the first dose, the effect can occur up to 20 hours following that dose.
Also similar to MHRA advice, the FDA said that all patients starting Gilenya should be monitored for signs of a slow heart rate for a minimum of six hours following the first dose and undergo hourly pulse and blood pressure measurements. Patients should also undergo electrocardiogram testing before receiving Gilenya and after the observation period. Extended cardiovascular monitoring should continue overnight for patients with increased risk or low tolerance for bradycardia, which includes those who develop severe bradycardia following the first Gilenya dose, those with pre-existing conditions in whom bradycardia may be poorly tolerated, and patients receiving therapy with other medications that slow the heart rate or electrical impulses that regulate the heartbeat.