) and Class III (e.g., amiodarone, sotalol) anti-arrhythmic drugs have beenassociated with cases of Torsades de Pointes in patients with bradycardia. If treatment with MAYZENT is considered,advice from a cardiologist should be sought.
Because of the potential additive effects on heart rate, treatment with MAYZENT should generally not be initiated inpatients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties, heart ratelowering calcium channel blockers (e.g., verapamil, diltiazem), or other drugs that may decrease heart rate (e.g.,ivabradine, digoxin) [see Warnings and Precautions (5.3) and Drug Interactions (7.3)]. If treatment with MAYZENT isconsidered, advice from a cardiologist should be sought regarding the switch to non-heart-rate lowering drugs orappropriate monitoring for treatment initiation.
7.3 Beta-Blockers
Caution should be applied when MAYZENT is initiated in patients receiving treatment with a beta-blocker because of theadditive effects on lowering heart rate; temporary interruption of the beta-blocker treatment may be needed prior toinitiation of MAYZENT [see Warnings and Precautions (5.3)]. Beta-blocker treatment can be initiated in patientsreceiving stable doses of MAYZENT [see Clinical Pharmacology (12.2)].
7.4 Vaccination
During and for up to one month after discontinuation of treatment with MAYZENT, vaccinations may be less effective;therefore MAYZENT treatment should be paused 1 week prior and for 4 weeks after vaccination [see Warnings andPrecautions (5.1)].
The use of live attenuated vaccines may carry the risk of infection and should therefore be avoided during MAYZENTtreatment and for up to 4 weeks after discontinuation of treatment with MAYZENT [see Warnings and Precautions(5.1)].
7.5 CYP2C9 and CYP3A4 Inhibitors
Because of a significant increase in exposure to siponimod, concomitant use of MAYZENT and drugs that causemoderate CYP2C9 and moderate or strong CYP3A4 inhibition is not recommended. This concomitant drug regimen canconsist of a moderate CYP2C9/CYP3A4 dual inhibitor (e.g., fluconazole) or a moderate CYP2C9 inhibitor incombination with a separate - moderate or strong CYP3A4 inhibitor.
Caution should be exercised for concomitant use of MAYZENT with moderate CYP2C9 inhibitors.
7.6 CYP2C9 and CYP3A4 Inducers
Because of a significant decrease in siponimod exposure, concomitant use of MAYZENT and drugs that cause moderateCYP2C9 and strong CYP3A4 induction is not recommended for all patients. This concomitant drug regimen can consistof moderate CYP2C9/strong CYP3A4 dual inducer (e.g., rifampin or carbamazepine) or a moderate CYP2C9 inducer incombination with a separate strong CYP3A4 inducer.
Caution should be exercised for concomitant use of MAYZENT with moderate CYP2C9 inducers.
Concomitant use of MAYZENT and moderate (e.g., modafinil, efavirenz) or strong CYP3A4 inducers is notrecommended for patients with CYP2C9*1/*3 and*2/*3 genotype [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no adequate data on the developmental risk associated with the use of MAYZENT in pregnant women. Basedon animal data and its mechanism of action, MAYZENT can cause fetal harm when administered to a pregnant woman see Data). Reproductive and developmental studies in pregnant rats and rabbits have demonstrated MAYZENT-induced
embryotoxicity and fetotoxicity in ra |
