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INITIATING TREATMENT WITH MAYZENT®—A ONCE-DAILY ORAL1

INITIATING TREATMENT WITH MAYZENT®—A ONCE-DAILY ORAL1

Assessments recommended for all patients

Blood Test

BLOOD TESTS

  • CBC

  • CYP2C9 genotype testing*

  • VZV antibody serology

  • LFT (transaminase & bilirubin)

Ophthalmic Evaluation

AN OPHTHALMIC EVALUATION

  • Evaluation of the fundus, including the macula

  • If there is any change in vision during treatment, a follow-up evaluation is recommended

ECG Test

AN ECG TEST

  • ECG to determine whether an FDO is recommended

*Genotype testing is required to determine the appropriate maintenance dose.

Assessments recommended for all patients

Blood Test

BLOOD TESTS

  • CBC

  • CYP2C9 genotype testing*

  • VZV antibody serology

  • LFT (transaminase & bilirubin)

Ophthalmic Evaluation

AN OPHTHALMIC EVALUATION

  • Evaluation of the fundus, including the macula

  • If there is any change in vision during treatment, a follow-up evaluation is recommended

ECG Test

AN ECG TEST

  • ECG to determine whether an FDO is recommended

*Genotype testing is required to determine the appropriate maintenance dose.

First-dose observation for patients with preexisting
cardiac conditions

An FDO of 6 hours is needed for patients with:

  • Sinus bradycardia (HR <55 BPM)

  • First- or second-degree Mobitz type I AV block

  • A history of myocardial infarction or heart failure

  • Monitoring should continue for 6 hours after the first dose to evaluate for signs and symptoms of bradycardia

  • An ECG should be conducted at the end of the observation period

First-dose observation for patients with preexisting
cardiac conditions

An FDO of 6 hours is needed for patients with:

  • Sinus bradycardia (HR <55 BPM)

  • First- or second-degree Mobitz type I AV block

  • A history of myocardial infarction or heart failure

  • Monitoring should continue for 6 hours after the first dose to evaluate for signs and symptoms of bradycardia

  • An ECG should be conducted at the end of the observation period

MOST PATIENTS WILL NOT REQUIRE AN FDO1

MOST PATIENTS WILL NOT
REQUIRE AN FDO1

Regular ophthalmic follow-ups for patients with a history
of diabetes or uveitis1

Regular follow-up ophthalmic
evaluations are recommended

Regular ophthalmic follow-ups for patients with a history
of diabetes or uveitis1

Regular follow-up ophthalmic
evaluations are recommended

A 4- OR 5-DAY TITRATION REGIMEN HELPS PATIENTS REACH THEIR MAINTENANCE DOSE

MAYZENT is a once-daily treatment with a recommended dosage of 1 mg or 2 mg,
based on the results of genotype testing

Chart shows 4-or 5- day titration regimen to help patients reach their maintenance dosage Chart shows 4-or 5- day titration regimen to help patients reach their maintenance dosage

Before opening, MAYZENT 0.25-mg and 2-mg tablets should be stored in a refrigerator between 36°F to 46°F (2°C to 8°C).

Dosing and Administration Guide

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Interruption during
titration regimen1
Interruption During MAYZENT Titration
Interruption During MAYZENT Titration

If 1 titration dose is missed for more than 24 hours, treatment needs to be reinitiated with Day 1 of the titration regimen

Interruption during
maintenance dose1
Interruption During MAYZENT Maintenance Dosage
Interruption During MAYZENT Maintenance Dosage

If treatment is interrupted for 4 or more consecutive days, MAYZENT must be reinitiated with Day 1 of the titration regimen. Treatment interruptions for up to 3 consecutive days do not require retitration, and treatment can be continued safely at the prescribed maintenance dose level

Additional considerations1

  • If treatment reinitiation is required, repeat assessments and FDO as needed

  • For patients who are taking antineoplastic, immunosuppressive, or immune-modulating therapies, or who have previously used these types of medications, consider the potential unintended additive immunosuppressive effects before initiating treatment with MAYZENT

  • Determine whether patients are taking drugs that could slow heart rate or AV conduction

  • Avoid the administration of live attenuated vaccines during treatment, and for 4 weeks after stopping treatment

  • For patients with a CYP2C9*1/*3 or *2/*3 genotype, the recommended maintenance dosage is 1 mg daily starting on Day 5. MAYZENT should not be used in patients with a CYP2C9*3/*3 genotype

MOD/MOA

AV=atrioventricular; BPM=beats per minute; CBC=complete blood count; ECG=electrocardiogram; FDO=first-dose observation; HR=heart rate; LFT=liver function test; VZV=varicella zoster virus.

Reference: 1. Mayzent [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; March 2019.

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Indication and Important Safety Information

INDICATION

MAYZENT® (siponimod) 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.

IMPORTANT SAFETY INFORMATION

Contraindications

  • Patients with 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/IV heart failure

  • Presence of Mobitz type II second-degree, third-degree atrioventricular block, or sick sinus syndrome, unless patient has a functioning pacemaker

INDICATION

MAYZENT® (siponimod) 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.

Infections: MAYZENT may increase risk of infections with some that are serious in nature. Life-threatening and rare fatal infections have occurred.

Before starting MAYZENT, review a recent complete blood count (CBC) (ie, within 6 months or after discontinuation of prior therapy). Delay initiation of treatment in patients with severe active infections until resolved. Employ effective treatments and monitor patients with symptoms of infection while on therapy. Consider discontinuing treatment if patient develops a serious infection.

Cases of fatal cryptococcal meningitis (CM) were reported in patients treated with another sphingosine 1-phosphate (S1P) receptor modulator. Rare cases of CM have occurred with MAYZENT. If CM is suspected, MAYZENT should be suspended until cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated.

No cases of progressive multifocal leukoencephalopathy (PML) were reported in MAYZENT clinical trials; however, they have been observed in patients treated with another sphingosine 1-phosphate (S1P) receptor modulator and other multiple sclerosis (MS) therapies. If PML is suspected, MAYZENT should be discontinued.

Cases of herpes viral infection, including one case of reactivation of varicella zoster virus leading to varicella zoster meningitis, have been reported. Patients without a confirmed history of varicella zoster virus (VZV) or without vaccination should be tested for antibodies before starting MAYZENT. If VZV antibodies are not present or detected, then VZV immunization is recommended and MAYZENT should be initiated 4 weeks after vaccination.

Use of live vaccines should be avoided while taking MAYZENT and for 4 weeks after stopping treatment.

Caution should be used when combining treatment (ie, anti-neoplastic, immune-modulating, or immunosuppressive therapies) due to additive immune system effects.

Macular Edema: In most cases, macular edema occurred within 4 months of therapy. Patients with history of uveitis or diabetes are at an increased risk. Before starting treatment, an ophthalmic evaluation of the fundus, including the macula, is recommended and at any time if there is a change in vision. The use of MAYZENT in patients with macular edema has not been evaluated; the potential risks and benefits to the individual patient should be considered.

Bradyarrhythmia and Atrioventricular Conduction Delays: Prior to initiation of MAYZENT, an ECG should be obtained to determine if preexisting cardiac conduction abnormalities are present. In all patients, a dose titration is recommended for initiation of MAYZENT treatment to help reduce cardiac effects.

MAYZENT was not studied in patients who had:

Reinitiation of treatment (initial dose titration, monitoring effects on heart rate and AV conduction [ie, ECG]) should apply if ≥4 consecutive daily doses are missed.

Respiratory Effects: MAYZENT may cause a decline in pulmonary function. Spirometric evaluation of respiratory function should be performed during therapy if clinically warranted.

Liver Injury: Elevation of transaminases may occur in patients taking MAYZENT. Before starting treatment, obtain liver transaminase and bilirubin levels. Closely monitor patients with severe hepatic impairment. Patients who develop symptoms suggestive of hepatic dysfunction should have liver enzymes checked, and MAYZENT should be discontinued if significant liver injury is confirmed.

Increased Blood Pressure: Increase in systolic and diastolic pressure was observed about 1 month after initiation of treatment and persisted with continued treatment. During therapy, blood pressure should be monitored and managed appropriately.

Fetal Risk: Based on animal studies, MAYZENT may cause fetal harm. Women of childbearing potential should use effective contraception to avoid pregnancy during and for 10 days after stopping MAYZENT therapy.

Posterior Reversible Encephalopathy Syndrome (PRES): Rare cases of PRES have been reported in patients receiving a sphingosine 1-phosphate (S1P) receptor modulator. Such events have not been reported for patients treated with MAYZENT in clinical trials. If patients develop any unexpected neurological or psychiatric symptoms, a prompt evaluation should be considered. If PRES is suspected, MAYZENT should be discontinued.

Unintended Additive Immunosuppressive Effects From Prior Treatment or After Stopping MAYZENT: When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects.

Initiating treatment with MAYZENT after treatment with alemtuzumab is not recommended.

After stopping MAYZENT therapy, siponimod remains in the blood for up to 10 days. Starting other therapies during this interval will result in concomitant exposure to siponimod.

Lymphocyte counts returned to the normal range in 90% of patients within 10 days of stopping therapy. However, residual pharmacodynamic effects, such as lowering effects on peripheral lymphocyte count, may persist for up to 3-4 weeks after the last dose. Use of immunosuppressants within this period may lead to an additive effect on the immune system, and therefore, caution should be applied 3-4 weeks after the last dose of MAYZENT.

Severe Increase in Disability After Stopping MAYZENT: Severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of an S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping MAYZENT treatment, thus patients should be monitored upon discontinuation.

Most Common Adverse Reactions: Most common adverse reactions (>10%) are headache, hypertension, and transaminase increases.

Please click here for full Prescribing Information, including Medication Guide.