Indications for: MAYZENT
Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
Determine CYP2C9 genotype before initiation. CYP2C9 genotypes (*1/*1, *1/*2, or *2/*2): initially 0.25mg once daily on Day 1 and Day 2; 0.50mg once daily on Day 3; 0.75mg once daily on Day 4; then 1.25mg once daily on Day 5. Maintenance: 2mg once daily starting on Day 6. CYP2C9 genotypes (*1/*3 or *2/*3): initially 0.25mg once daily on Day 1 and Day 2; 0.50mg once daily on Day 3; then 0.75mg once daily on Day 4. Maintenance: 1mg once daily starting on Day 5. First dose 6hr monitoring for bradycardia, other abnormalities: see full labeling. Re-initiation of therapy after interruption for ≥4 days: start with Day 1 of titration regimen.
CYP2C9 *3/*3 genotype. Recent (within the last 6 months) occurrence of: MI, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, Class III/IV heart failure. Presence of Mobitz Type II 2nd degree or 3rd degree AV block or sick sinus syndrome, unless paced.
Increased risk of infections (may be fatal). Obtain recent CBC prior to initiation. Consider suspending therapy if serious infection develops. Active infection: do not start until infection resolved. Test for antibodies to varicella zoster virus; if negative, consider immunization before starting siponimod. Immunosuppressed. Withhold and evaluate if progressive multifocal leukoencephalopathy (PML) suspected. Risk of bradyarrhythmia, AV conduction delays: titration is required for treatment initiation. Obtain ECG prior to initiation to determine if preexisting conduction abnormalities are present. History of cardiac arrest, cerebrovascular disease, uncontrolled hypertension, severe untreated sleep apnea: not recommended; refer to cardiologist if treatment is considered. History of recurrent syncope or symptomatic bradycardia: do benefit/risk assessment; refer to cardiologist if treatment is considered. Monitor BP during treatment. Obtain recent LFTs (within 6 months) prior to initiation. Monitor for hepatic dysfunction; discontinue if significant liver injury is confirmed. History of severe liver disease. Respiratory function: perform spirometric evaluation as needed. Diabetes, history of uveitis: increased risk of macular edema. Increased risk of cutaneous malignancies (basal cell carcinoma, squamous cell carcinoma, melanoma). Perform baseline skin exam prior to or after initiation and periodically thereafter (esp. with risk factors); monitor for suspicious skin lesions and evaluate if observed. Limit exposure to sun and UV light. Do ophthalmic exam at baseline, and if any change in vision during therapy. Monitor for severe increase in disability after treatment discontinuation. Elderly. Pregnancy. Advise females of reproductive potential to use effective contraception during and for 10 days after discontinuation. Nursing mothers.
Sphingosine 1-phosphate receptor modulator.
Concomitant QT prolonging drugs (eg, quinidine, procainamide, amiodarone, sotalol): risk of torsades de pointes. Concomitant β-blockers, digoxin, ivabradine, diltiazem, verapamil during initiation may be associated with severe bradycardia or heart block. Avoid live attenuated vaccines during and for 4 weeks after discontinuing therapy; may have suboptimal response. Concomitant antineoplastic, immunosuppressant or immune-modulating therapies may increase risk of immunosuppression; use caution when switching from long-acting immunotherapies; caution for 3–4 weeks after discontinuing siponimod. Initiation after treatment with alemtuzumab: not recommended. Concomitant moderate CYP2C9 and moderate or strong CYP3A4 inhibitors: not recommended; caution with concomitant moderate CYP2C9 inhibitors. Concomitant moderate CYP2C9 and strong CYP3A4 inducers: not recommended; caution with moderate CYP2C9 inducers. For CYP2C9 *1/*3 and *2/*3 genotypes: concomitant moderate (eg, modafinil, efavirenz) or strong CYP3A4 inducers: not recommended. Concomitant phototherapy with UV-B radiation or PUVA-photochemotherapy: not recommended.
Headache, hypertension, transaminase increased, falls, edema peripheral, nausea, dizziness, diarrhea, bradycardia, pain in extremity; macular edema, decreased pulmonary function; rare: posterior reversible encephalopathy syndrome (discontinue if suspected).
Generic Drug Availability:
Starter Packs (0.25mg)—7, 12; Tabs (0.25mg)—28; (1mg, 2mg)—30