Siponimod

MAYZENT is indicated 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. MAYZENT is a sphingosine 1-phosphate (S1P) receptor modulator indicated 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.

Siponimod is an S1P receptor modulator. Siponimod binds with high affinity to S1P receptors 1 and 5. Siponimod blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. 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.

Assessments are required prior to initiating MAYZENT. Titration is required for treatment initiation. The recommended maintenance dosage is 2 mg. The recommended maintenance dosage in patients with a CYP2C9*1/*3 or *2/*3 genotype is 1 mg. Administer tablets whole, do not split, crush, or chew. First-dose monitoring is recommended for patients with sinus bradycardia, first- or second-degree [Mobitz type I] atrioventricular (AV) block, or a history of myocardial infarction or heart failure.

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 Presence of Mobitz type II second-degree, third-degree AV block, or sick sinus syndrome, unless patient has a functioning pacemaker Known hypersensitivity to siponimod, or to any of the inactive ingredients in MAYZENT. Observed reactions include angioedema. Patients with a CYP2C9*3/*3 genotype.

Infections: MAYZENT may increase the risk. Obtain a complete blood count (CBC) before initiating treatment. Monitor for infection during treatment. Do not start in patients with active infection. Progressive Multifocal Leukoencephalopathy (PML): Withhold MAYZENT at the first sign or symptom of PML. Macular Edema: Increases the risk of macular edema. Obtain a baseline evaluation of the fundus, including the macula, near the start of treatment with MAYZENT. Conduct an evaluation of the fundus, including the macula, periodically while on therapy and any time there is a change in vision. Consider discontinuing MAYZENT if macular edema develops. Diabetes mellitus and uveitis increase the risk. Bradyarrhythmia and Atrioventricular Conduction Delays: MAYZENT may result in a transient decrease in heart rate, titration is required for treatment initiation.

The following serious adverse reactions are described elsewhere in the labeling: Infections Progressive Multifocal Leukoencephalopathy Macular Edema Bradyarrhythmia and Atrioventricular Conduction Delays Respiratory Effects Liver Injury Cutaneous Malignancies Hypersensitivity Increased Blood Pressure Fetal Risk Posterior Reversible Encephalopathy Syndrome Unintended Additive Immunosuppressive Effects From Prior Treatment With Immunosuppressive or Immune-Modulating Therapies Severe Increase in Disability After Stopping MAYZENT Immune System Effects After Stopping MAYZENT Most common adverse reactions (incidence greater than 10%) are headache, hypertension, and transaminase increases.

Vaccination: Avoid live-attenuated vaccines during and for up to 4 weeks after treatment with MAYZENT. CYP2C9 and Dual CYP2C9/3A4 Inhibitors: Strong CYP2C9 inhibitors increase siponimod exposure, concomitant use with MAYZENT is not recommended. Monitor for adverse reactions during concomitant use of MAYZENT with moderate CYP2C9 inhibitors or moderate CYP2C9/CYP3A4 dual inhibitors. CYP2C9 and CYP3A4 Inducers: Dual moderate CYP2C9/strong CYP3A4 inducers decrease siponimod exposure, concomitant use with MAYZENT is not recommended. Monitor for loss of efficacy with concomitant use of MAYZENT and moderate or strong CYP3A4 inducers in patients with CYP2C9*1/*3 or *2/*3 genotypes.

Unopened Containers Store MAYZENT 0.25 mg, 1 mg, and 2 mg film-coated tablets in a refrigerator between 2°C to 8°C (36°F to 46°F). After dispensed by pharmacy to patient, MAYZENT 0.25 mg, 1 mg, and 2 mg film-coated tablets may be stored at 20°C to 25°C (68°F to 77°F) for up to 3 months. Opened Containers Bottles MAYZENT 0.25 mg, 1 mg, and 2 mg film-coated tablets may be stored at 20°C to 25°C (68°F to 77°F) for up to 3 months. Starter Pack/Blister Card MAYZENT 0.25 mg film-coated tablets may be stored at 20°C to 25°C (68°F to 77°F) for up to 3 months. Do not refrigerate after opening. Store in original calendarized blister wallet container.