Gilenya Drug Interactions

Anti-neoplastic, immunomodulatory or immunosuppressive therapies: Anti-neoplastic, immunomodulatory or immunosuppressive therapies should not be co-administered due to the risk of additive immune system effects (see Contraindications and Precautions).
Caution should also be exercised when switching patients from long-acting therapies with immune effects such as natalizumab, teriflunomide or mitoxantrone (see Precautions). In multiple sclerosis clinical studies, the concomitant treatment of relapses with a short course of corticosteroids was not associated with an increased rate of infection.
Vaccination: During and for up to two months after treatment with Gilenya, vaccination may be less effective. The use of live attenuated vaccines may carry a risk of infections and should therefore be avoided (see Precautions and Adverse Reactions).
Bradycardia-inducing substances: Fingolimod has been studied in combination with atenolol and diltiazem. When fingolimod was used with atenolol in an interaction study in healthy volunteers, there was an additional 15% reduction of heart rate at fingolimod treatment initiation, an effect not seen with diltiazem. Treatment with Gilenya should not be initiated in patients receiving beta blockers, or other substances which may decrease heart rate, such as class Ia and III antiarrhythmics, calcium channel blockers (such as verapamil or diltiazem), ivabradine, digoxin, anticholinesteratic agents or pilocarpine because of the potential additive effects on heart rate (see Precautions and Adverse Reactions). If treatment with Gilenya is considered in such patients, advice from a cardiologist should be sought regarding the switch to non-heart-rate-lowering medicinal products or appropriate monitoring for treatment initiation, at least overnight monitoring is recommended, if the heart-rate-lowering medication cannot be stopped.
Pharmacokinetic interactions of other substances on fingolimod: Fingolimod is metabolised mainly by CYP4F2. Other enzymes like CYP3A4 may also contribute to its metabolism, notably in the case of strong induction of CYP3A4. Potent inhibitors of transporter proteins are not expected to influence fingolimod disposition. Co-administration of fingolimod with ketoconazole resulted in a 1.7-fold increase in fingolimod and fingolimod phosphate exposure (AUC) by inhibition of CYP4F2. Caution should be exercised with substances that may inhibit CYP3A4 (protease inhibitors, azole antifungals, some macrolides such as clarithromycin or telithromycin).
Co-administration of carbamazepine 600 mg twice daily at steady-state and a single dose of fingolimod 2 mg reduced the AUC of fingolimod and its metabolite by approximately 40%. Other strong CYP3A4 enzyme inducers, for example rifampicin, phenobarbital, phenytoin, efavirenz and St. John's wort, may reduce the AUC of fingolimod and its metabolite at least to this extent. As this could potentially impair the efficacy, their co-administration should be used with caution. Concomitant administration with St. John's wort is however not recommended (see Precautions).
Pharmacokinetic interactions of fingolimod on other substances: Fingolimod is unlikely to interact with substances mainly cleared by the CYP450 enzymes or by substrates of the main transporter proteins.
Co-administration of fingolimod with ciclosporin did not elicit any change in the ciclosporin or fingolimod exposure. Therefore, fingolimod is not expected to alter the pharmacokinetics of medicinal products that are CYP3A4 substrates.
Co-administration of fingolimod with oral contraceptives (ethinylestradiol and levonorgestrel) did not elicit any change in oral contraceptive exposure. No interaction studies have been performed with oral contraceptives containing other progestagens, however an effect of fingolimod on their exposure is not expected.