MAYZENT (Siponimod) for Treatment of Relapsing Forms of Multiple Sclerosis (MS)

MAYZENT® (siponimod) tablets, for oral use
Siponimod is a sphingosine-1-phosphate (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. 


Initial U.S. Approval: 2019

INDICATIONS AND USAGE
MAYZENT is a sphingosine 1-phosphate 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.

DOSAGE AND ADMINISTRATION
  • 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 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

DOSAGE FORMS AND STRENGTHS
Tablets: 0.25 mg and 2 mg 

CONTRAINDICATIONS
  1. Patients with a CYP2C9*3/*3 genotype 
  2. In the last 6 months, experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III/IV heart failure 
  3. Presence of Mobitz type II second-degree, third-degree AV block, or sick sinus syndrome, unless patient has a functioning pacemaker 

WARNINGS AND PRECAUTIONS
  • 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.
  • Macular Edema: An ophthalmic evaluation is recommended before starting treatment and if there is any change in vision while taking MAYZENT. 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. Consider resting heart rate with concomitant betablocker use; obtain cardiologist consultation before concomitant use with other drugs that decrease heart rate 
  • Respiratory Effects: May cause a decline in pulmonary function. Assess pulmonary function (e.g., spirometry) if clinically indicated. 
  • Liver Injury: Obtain liver enzyme results before initiation. Closely monitor patients with severe hepatic impairment. Discontinue if a significant liver injury occurs. 
  • Increased Blood Pressure (BP): Monitor BP during treatment. 
  • Fetal Risk: Women of childbearing potential should use effective contraception during and for 10 days after stopping MAYZENT. 

ADVERS E REACTIONS
Most common adverse reactions (incidence greater than 10%) are headache, hypertension, and transaminase increases.

DRUG INTERACTIONS\
  • Vaccines: Avoid live attenuated vaccines during and for up to 4 weeks after treatment with MAYZENT 
  • CYP2C9 and CYP3A4 Inhibitors: Increase in siponimod exposure; concomitant use of MAYZENT with moderate CYP2C9 and moderate or strong CYP3A4 inhibitors is not recommended 
  • CYP2C9 and CYP3A4 Inducers: Decrease in siponimod exposure; concomitant use of MAYZENT with moderate CYP2C9 and strong CYP3A4 inducers is not recommended

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