Class Ia or Class III antiarrhythmic drugs

GILENYA has not been studied in patients with arrhythmias requiring treatment with Class Ia (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic drugs. Class Ia and Class III antiarrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia. Since initiation of GILENYA treatment results in decreased heart rate, patients on Class Ia or Class III antiarrhythmic drugs should be closely monitored [see Warnings and Precautions (5.1)].

Ketoconazole

The blood levels of fingolimod and fingolimod-phosphate are increased by 1.7-fold when coadministered with ketoconazole. Patients who use GILENYA and systemic ketoconazole concomitantly should be closely monitored, as the risk of adverse reactions is greater.

Vaccines

Vaccination may be less effective during and for up to 2 months after discontinuation of treatment with GILENYA [see Clinical Pharmacology (12.2)]. The use of live attenuated vaccines should be avoided during and for 2 months after treatment with GILENYA because of the risk of infection. 

Antineoplastic, immunosuppressive or immunomodulating therapies

Antineoplastic, immunosuppressive or immune modulating therapies are expected to increase the risk of immunosuppression. Use caution when switching patients from long-acting therapies with immune effects such as natalizumab or mitoxantrone.

Heart rate-lowering drugs (e.g., b eta blockers or diltiazem)

Experience with GILENYA in patients receiving concurrent therapy with beta blockers is limited. These patients should be carefully monitored during initiation of therapy. When GILENYA is used with atenolol, there is an additional 15% reduction of heart rate upon GILENYA initiation, an effect not seen with diltiazem [see Warnings and Precautions (5.1)].

Laboratory test interaction

Because GILENYA reduces blood lymphocyte counts via redistribution in secondary lymphoid organs, peripheral blood lymphocyte counts cannot be utilized to eva luate the lymphocyte subset status of a patient treated with GILENYA. A recent CBC should be available before initiating treatment with GILENYA.

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. In oral studies conducted in rats and rabbits, fingolimod demonstrated developmental toxicity, including teratogenicity (rats) and embryolethality, when given to pregnant animals. In rats, the highest no-effect dose was less than the recommended human dose (RHD) of 0.5 mg/day on a body surface area (mg/m) basis. The most common fetal visceral malformations in rats included persistent truncus arteriosus and ventricular septal defect. The receptor affected by fingolimod (sphingosine 1-phosphate receptor) is known to be involved in vascular formation during embryogenesis. Because it takes approximately 2 months to eliminate fingolimod from the body, potential risks to the fetus may persist after treatment ends [see Warnings and Precautions (5.7, 5.8)]. GILENYA should be used during pregnancy only if the potential benefit justifies the potential ri