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From a preplanned interim analysis of an open-label extension study.2 |
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| INDICATION |
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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.
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| IMPORTANT SAFETY INFORMATION |
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| Contraindications |
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Patients with a CYP2C9*3/*3 genotype |
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In the last 6 months, experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III/IV heart failure |
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Presence of Mobitz type II second-degree, third-degree atrioventricular block, or sick sinus syndrome, unless patient has a functioning pacemaker |
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| Infections: MAYZENT may increase risk of infections with some that are serious in nature. Life-threatening and rare fatal infections have occurred. |
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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. |
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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. |
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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. |
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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. |
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Use of live vaccines should be avoided while taking
MAYZENT and for 4 weeks after stopping treatment. |
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Caution should be used when combining treatment (ie,
anti-neoplastic,
immune-modulating, or immunosuppressive therapies) due to additive immune system effects. |
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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. |
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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. |
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| MAYZENT was not studied in patients who had: |
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In the last 6 months, experienced myocardial infarction, unstable angina, stroke, TIA, or
decompensated heart failure requiring hospitalization |
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New York Heart Association
Class II-IV heart failure |
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Cardiac conduction or rhythm disorders, including complete
left bundle branch block, sinus arrest or sino-atrial block, symptomatic bradycardia, sick sinus syndrome, Mobitz type II second-degree
AV-block or higher-grade
AV-block (either history or observed at screening), unless patient has a functioning pacemaker |
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Significant QT prolongation
(QTc greater than 500 msec) |
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Arrhythmias requiring treatment with Class Ia or Class III
anti-arrhythmic drugs |
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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. |
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Respiratory Effects: MAYZENT may cause a decline in
pulmonary function. Spirometric evaluation of respiratory
function should be performed during therapy if clinically warranted. |
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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. |
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Cutaneous Malignancies:
Long-term use of S1P
modulators, including MAYZENT, have been associated with an increased risk of basal cell carcinoma (BCC). Cases of other cutaneous malignancies,
including melanoma and squamous cell carcinoma, have also been reported in patients treated with MAYZENT and in patients treated with another S1P modulator. |
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Periodic skin examination is recommended. Monitor for suspicious skin lesions and promptly evaluate any that are observed. Exposure to sunlight and ultraviolet light should be limited by wearing protective clothing and using a sunscreen with high protection factor. Concomitant phototherapy with
UV-B radiation or
PUVA-photochemotherapy is not recommended. |
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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. |
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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. |
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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. |
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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. |
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Initiating treatment with
MAYZENT after treatment with
alemtuzumab is not
recommended. |
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| 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. |
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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. |
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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. |
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Most Common Adverse Reactions: Most common
adverse reactions (>10%) are headache, hypertension, and transaminase increases. |
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Please click here for full Prescribing Information,
including Medication Guide. |
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Trial design: EXPAND was a randomized, double-blind,
parallel-group, placebo-controlled, time-to-event study in 1651
patients with SPMS who had evidence of disability
progression in the prior 2 years, no evidence of relapse in 3 months prior to study enrollment, and an EDSS score of
3.0-6.5 at study entry. The primary end point of the
study was the time to 3-month
CDP, defined as at least a 1-point
increase from baseline in EDSS (0.5-point increase for
patients
with baseline EDSS of 5.5 or higher) sustained for 3 months.
Key secondary end points were time to 3-month confirmed worsening by ≥20% from baseline on the T25-FW test, and the change from baseline in T2 lesion volume.1 |
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References: 1. Mayzent [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021.
2. Kappos L, Bar-Or A, Cree BAC,
et al; for the EXPAND Clinical Investigators. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018;391(10127):
1263-1273. 3. Data on file. US National Library of Medicine. ClinicalTrials.gov. SPMS Clinical Trial Search Results. Accessed December 19, 2020. 4. Data on file. Long-term Efficacy and Safety of Siponimod in Patients with SPMS: EXPAND Extension Analysis up to
5 Years. Novartis Pharmaceuticals Corp; May 2020. |
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| MAYZENT and the MAYZENT logo are registered trademarks of Novartis AG. |
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| CoverMyMeds is a registered trademark of CoverMyMeds, LLC. |
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Novartis Pharmaceuticals
Corporation |
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