Mayzent

Secondary progressive multiple sclerosis w/ active disease evidenced by relapses or imaging features of inflammatory activity in adults.

Genotype for CYP2C9 to determine CYP2C9 metaboliser status before treatment initiation. Initiate w/ titration pack: Days 1 & 2: 0.25 mg once daily. Day 3: 0.5 mg once daily (2 tab of 0.25 mg). Day 4: 0.75 mg once daily (3 tab of 0.25 mg). Day 5: 1.25 mg once daily (5 tab of 0.25 mg). Maintenance dose: Day 6 onwards: 2 mg once daily (1 tab of 2 mg). Patient w/ CYP2C9*2*3 or *1*3 genotype Maintenance: 1 mg once daily (4 tab of 0.25 mg). Patient w/ other CYP2C9 genotype Maintenance: 2 mg once daily.

May be taken with or without food.

Hypersensitivity to siponimod, peanut, soya or any of the excipients. Immunodeficiency syndrome. History of progressive multifocal leukoencephalopathy (PML) or cryptococcal meningitis (CM). Active malignancies. Patients who in the previous 6 mth had MI, unstable angina pectoris, stroke/transient ischaemic attack, decompensated heart failure (requiring inpatient treatment), or New York Heart Association (NYHA) class III/IV heart failure. Patients w/ a history of 2nd degree Mobitz type II AV block, 3rd degree AV block, SA heart block or sick-sinus syndrome, if they do not wear a pacemaker. Patients homozygous for CYP2C9*3 (CYP2C9*3*3) genotype (poor metaboliser). Severe liver impairment (Child-Pugh class C). Pregnancy & women of childbearing potential not using effective contraception.

Assess complete blood count before initiating treatment & periodically during treatment. Increased risk of infection. Delay treatment initiation in patients w/ severe active infection until resolution. A full course of vaccination w/ varicella vaccine is recommended for Ab-negative patients; postpone treatment initiation for 1 mth. Avoid use of live attenuated vaccines during treatment & for 4 wk after stopping treatment. Risk of macular oedema w/ or w/o visual symptoms. Ophthalmological evaluation is recommended before, during & 3-4 mth after treatment initiation. Should not be initiated in patients w/ macular oedema until resolution. Transient decrease in heart rate & transient AV conduction delays during dose titration. Observe for 6 hr after the 1st dose for signs & symptoms of bradycardia in patients w/ sinus bradycardia (heart rate <55 bpm), history of 1st or 2nd degree [Mobitz type I] AV block, history of MI, or history of heart failure (patients w/ NYHA class I & II). Should not be used in patients w/ history of symptomatic bradycardia or recurrent syncope, uncontrolled HTN, or severe untreated sleep apnoea. Regularly monitor BP during treatment. Check liver enzymes in patients who develop symptoms suggestive of hepatic dysfunction; discontinue treatment if significant liver injury is confirmed. Risk of cutaneous neoplasms. Caution against exposure to sunlight w/o protection. Should not receive concomitant phototherapy w/ UV-B radiation or PUVA-photochemotherapy. Perform complete physical & neurological examination & MRI if patient develops any unexpected neurological or psychiatric symptoms/signs or accelerated neurological deterioration. Possibility of severe disease exacerbation after stopping treatment. Exercise caution for 3-4 wk after the last dose. Caution when concomitantly treated w/ anti-neoplastic, immune-modulating or immunosuppressive therapies. Consider t_½ & mode of action of other disease-modifying therapies when switching to Mayzent. Not recommended to initiate treatment after alemtuzumab. Interference w/ haematological testing involving use of lymphocytes. Patients w/ rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Patients w/ mild or moderate hepatic impairment; history of significant liver disease. Women of childbearing potential must use effective contraception during treatment & for at least 10 days after treatment discontinuation. Should not be used during breast-feeding. Elderly ≥65 yr. Childn & adolescents ≤18 yr.

Headache; HTN; increased liver function test. Herpes zoster; melanocytic naevus; lymphopenia; dizziness, seizure, tremor; macular oedema; bradycardia, AV block (1st & 2nd degree); nausea, diarrhoea; pain in extremity; oedema peripheral, asthenia; decreased pulmonary function test.

Risk of additive immune effects w/ antineoplastic, immune-modulating or immunosuppressive therapies. Risk of additive effects on lowering heart rate w/ class Ia (eg, quinidine, procainamide) or class III (eg, amiodarone, sotalol) anti-arrhythmic medicinal products, QT-prolonging medicinal products w/ known arrhythmogenic properties, heart-rate-lowering Ca channel blockers (eg, verapamil or diltiazem) or other substances that may decrease heart rate (eg, ivabradine or digoxin); β-blockers. Risk of infection w/ live attenuated vaccines. Vaccinations may be less effective during & for up to 4 wk after siponimod treatment. Not recommended w/ moderate CYP2C9 & moderate or strong CYP3A4 inhibitors. Consider appropriateness & possible benefit of treatment w/ strong CYP3A4/moderate CYP2C9 inducers (eg, carbamazepine) in all patients regardless of genotype; moderate CYP3A4 inducers (eg, modafinil) in patients w/ a CYP2C9*1*3 or *2*3 genotype.

Immunosuppressants

L04AE03 - siponimod ; Belongs to the class of sphingosine-1-phosphate (S1P) receptor modulators. Used as immunosuppressants.

P₁S₁S₃