Fingolimod (Gilenya) is a new kind of immunosuppressant drug that has found a home as a treatment for multiple sclerosis (MS) after failing in clinical trials as a drug to prevent rejection of transplanted kidneys. It provides new benefits – it's the first disease-modifying drug for MS that can be orally administered, unlike other drugs that must be injected. Unfortunately, fingolimod is also associated with substantial risks that raise the question of whether it is, in fact, safe enough for unrestricted use.
On April 5, 2012, my organization, the Institute for Safe Medication Practices (ISMP), released its most recent QuarterWatch report. This is an independent publication that seeks to improve patient safety through regular monitoring and analysis of serious adverse drug events reported to the Food and Drug Administration. In this latest edition, which looked at data from April-June 2011, we identified numerous problems of widespread toxicity with this drug.
Notable among 286 fingolimod reports overall were six patient deaths and eight indicating permanent disability. There were 60 cases of reported injuries to retina of the eye and other adverse effects on vision. As might be expected from a drug suppressing the immune response, serious and fatal infections were reported. The biggest group involved disseminated herpes infections of both types - simplex and zoster. The cases also included 68 reports of infections at various sites including the eye, skin, urinary and upper respiratory tracts.
Importantly, the drug can have adverse effects on the heart. When the drug was approved in 2010 it was known that patients may experience heart-rhythm disorders including a drop in their heart rates. Possible complications of its adverse effects seen in our analysis included blackouts or fainting (16 cases), reduced blood pressure, a heart rate that was too slow (27 cases), and swelling in the extremities (10 cases). After a patient died suddenly with the first dose last December, the FDA and regulatory agencies in Europe announced they'd perform new safety reviews. Assessments in prominent medical journals in the United States and France have questioned whether fingolimod should be available without restriction, as we did in our QuarterWatch report.
Last week, Novartis announced that as a result of the reviews they now have approval from FDA for fingolimod label changes to address heart concerns. Patients starting treatment with Gilenya need to have an electrocardiogram (ECG) prior to the first dose and after six-hours of observation. They also need to have hourly measurement of blood pressure and heart rate. The label also recommends that patients with certain pre-existing heart conditions or those taking certain medications that can slow the heart should have overnight monitoring following administration of the first dose of medication. Gilenya shouldn't be used at all in patients with history or presence of heart attack or stroke in the past six months, and other serious heart rhythm disturbances.