e in disability upon MAYZENT discontinuation and appropriate treatmentshould be instituted, as required.
5.11 Immune System Effects After Stopping MAYZENT
After stopping MAYZENT therapy, siponimod remains in the blood for up to 10 days. Starting other therapies during thisinterval will result in concomitant exposure to siponimod.
Lymphocyte counts returned to the normal range in 90% of patients within 10 days of stopping therapy [see ClinicalPharmacology (12.2)].
However, residual pharmacodynamics effects, such as lowering effects on peripheral lymphocytecount, may persist for up to 3-4 weeks after the last dose. Use of immunosuppressants within this period may lead to anadditive effect on the immune system, and therefore caution should be applied 3-4 weeks after the last dose of
MAYZENT [see Drug Interactions (7.1)].
6 ADVERSE REACTIONS
The following serious adverse reactions are described elsewhere in labeling:
Infections [see Warnings and Precautions (5.1)]
Macular Edema [see Warnings and Precautions (5.2)]
Bradyarrhytmia and Atrioventricular (AV) Conduction Delays [see Warnings and Precautions (5.3)]
Respiratory Effects [see Warnings and Precautions (5.4)]
Liver Injury [see Warnings and Precautions (5.5)]
Increased Blood Pressure [see Warnings and Precautions (5.6)]
Fetal Risk [see Warnings and Precautions (5.7)]
Posterior Reversible Encephalopathy Syndrome [see Warnings and Precautions (5.8)]
Unintended Additive Immunosuppressive Effects From Prior Treatment With Immunosuppressive or ImmuneModulatingTherapies [see Warnings and Precautions (5.9)]
Severe Increase in Disability After Stopping MAYZENT [see Warnings and Precautions (5.10)]
Immune System Effects After Stopping MAYZENT [see Warnings and Precautions (5.11)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinicaltrials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the ratesobserved in practice.
A total of 1737 MS patients have received MAYZENT at doses of at least 2 mg daily. These patients were included inStudy 1 [see Clinical Studies (14)] and in a Phase 2 placebo-controlled study in patients with MS. In Study 1, 67% ofMAYZENT-treated patients completed the double-blind part of the study, compared to 59.0% of patients receivingplacebo. Adverse events led to discontinuation of treatment in 8.5% of MAYZENT-treated patients, compared to 5.1% ofpatients receiving placebo. The most common adverse reactions (incidence at least 10%) in MAYZENT-treated patientsin Study 1 were headache, hypertension, and transaminase increases.
Table 3 lists adverse reactions that occurred in at least 5% of MAYZENT-treated patients and at a rate at least 1% higher
than in patients receiving placebo.
Table 3 Adverse Reactions Reported in Study 1 (Occurring in at Least 5% of MAYZENT-Treated Patients
and at a Rate at Least 1% Higher Than in Patients Receiving Placebo)
Adverse Reaction
MAYZENT 2 mg
(N = 1099)
%
Placebo
(N = 546)
%
Headachea 15 14
Hypertensionb 13 9
Transaminase increasedc 11 3
Falls 11 10
Edema peripherald 8 4
Nausea 7 4
Dizziness 7 5
Diarrhea 6 4
Bradycardiae 6 3
Pain in extremityf 6 4
Terms were co |
