The U.S. Food and Drug Administration (FDA) approved MAYZENT (siponimod) for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Before initiation of treatment with MAYZENT, determine CYP2C9 genotype, review results of a recent complete blood count, obtain ophthalmic and cardiac evaluations, test for antibodies to varicella zoster virus, and obtain recent transaminase and bilirubin levels. If patients are taking antineoplastic, immunosuppressive, or immune-modulating therapies, or if there is a history of prior use of these drugs, consider possible unintended additive immunosuppressive effects before initiating treatment with MAYZENT (see drug interactions below).
The approved recommended dosage of MAYZENT is based on CYP2C9 genotype:
- CYP2C9 Genotypes *1/*1, *1/*2, or *2/*2: Initiate MAYZENT with a 5-day titration (Day 1: 0.25 mg, Day 2: 0.25 mg, Day 3: 0.50 mg, Day 4: 0.75 mg, and Day 5: 1.25 mg). If one titration dose is missed for more than 24 hours, reinitiate treatment with Day 1 of the titration regimen. After treatment titration, the recommended maintenance dosage of MAYZENT is 2 mg taken orally once daily starting on Day 6.
- CYP2C9 Genotypes *1/*3 or *2/*3: Initiate MAYZENT with a 4-day titration (Day 1: 0.25 mg, Day 2: 0.25 mg, Day 3: 0.50 mg, and Day 4: 0.75 mg). If one titration dose is missed for more than 24 hours, reinitiate treatment with Day 1 of the titration regimen. After treatment titration, the recommended maintenance dosage of MAYZENT is 1 mg taken orally once daily starting on Day 5.
Because initiation of MAYZENT treatment results in a decrease in heart rate (HR), first-dose 6 hour monitoring is recommended for patients with sinus bradycardia [HR less than 55 beats per minute (bpm)], first- or second-degree [Mobitz type I] AV block, or a history of myocardial infarction or heart failure.
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MAYZENT is contraindicated in patients who have: a CYP2C9*3/*3 genotype; in the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III or IV heart failure; or presence of Mobitz type II second-degree, third-degree AV block, or sick sinus syndrome, unless patient has a functioning pacemaker.
Additional information regarding dosage and administration and important warnings and precautions, such as risk of infection, macular edema, bradyarrhythmia and atrioventricular conduction delays, respiratory effects, liver injury, increased blood pressure, and fetal risk can be found in the full prescribing information linked below.
Siponimod is a sphingosine-1-phosphate (S1P) receptor modulator. The mechanism by which siponimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system.
Siponimod mean Cmax was 30.4 ng/mL and mean AUCtau was 558 h*ng/mL on day 10 after administration of siponimod 2 mg once-daily over 10 days. Siponimod concentration increases in an apparent dose-proportional manner after multiple once-daily doses of siponimod 0.3 mg to 20 mg. Steady-state plasma concentrations are reached after approximately 6 days of once-daily dosing, and steady-state levels are approximately 2-3-fold greater than the initial dose.