siponimod (Rx)

Brand and Other Names:Mayzent
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 0.25mg
  • 2mg

Multiple Sclerosis

Indicated for relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease

Patients with CYP2C9 genotypes *1/*1, *1/*2, or *2/*2

  • Initiate with a 5-day titration
  • Maintenance dose (Day 6): 2 mg PO qDay
  • Use a starter pack for patients who will be titrated to the 2-mg maintenance dosage
  • Do not use starter pack for patients who will be titrated to the 1-mg maintenance dosage
  • Titration for the 2-mg/day maintenance dose
    • Day 1: 0.25 mg (1 x 0.25 mg) PO
    • Day 2: 0.25 mg (1 x 0.25 mg) PO
    • Day 3: 0.50 mg (2 x 0.25 mg) PO
    • Day 4: 0.75 mg (3 x 0.25 mg) PO
    • Day 5: 1.25 mg (5 x 0.25 mg) PO
    • Day 6 and thereafter: 2 mg (1 x 2 mg) PO qDay

Patients with CYP2C9 genotypes *1/*3 or *2/*3

  • Initiate with a 4-day titration
  • Maintenance dose (Day 5): 1 mg PO qDay
  • Do not use the starter pack for patients who will be titrated to the 1-mg maintenance dosage
  • Titration for 1-mg/day maintenance dose
    • Day 1: 0.25 mg (1 x 0.25 mg) PO
    • Day 2: 0.25 mg (1 x 0.25 mg) PO
    • Day 3 0.50 mg (2 x 0.25 mg) PO
    • Day 4: 0.75 mg (3 x 0.25 mg) PO
    • Day 5 and thereafter: 1 mg (4 x 0.25 mg) PO qDay

Reinitiation after treatment interruption

  • After completing initial titration, if maintenance treatment is interrupted for 4 or more consecutive daily doses, reinitiate treatment with Day 1 of the titration regimen
  • Also complete first-dose monitoring in patients for whom it is recommended

Dosage Modifications

Renal impairment

  • No dosage adjustment necessary
  • End-stage renal disease or patients on hemodialysis: Not studied; owing to high plasma protein binding (>99.9%) of siponimod, hemodialysis is not expected to alter the total and unbound siponimod concentration and no dose adjustments are anticipated based on these considerations

Hepatic impairment

  • No dosage adjustment necessary
  • Increased unbound siponimod AUC observed with moderate and severe hepatic impairment is not expected to be clinically significant

Dosing Considerations

Before initiating treatment

  • Test for CYP2C9 variants to determine CYP2C9 genotype; an FDA-cleared or FDA-approved test for detecting CYP2C9 variants to direct the use of siponimod is not currently available
  • Test for antibodies to varicella-zoster virus (VZV); VZV vaccination of antibody-negative patients is recommended prior to commencing treatment
  • Determine whether patients are taking drugs that could slow heart rate or atrioventricular (AV) conduction
  • If patients are taking or have a history of taking antineoplastic, immunosuppressive, or immune-modulating therapies, consider possible unintended additive immunosuppressive effects before initiating treatment
  • Ophthalmic examination, including evaluation of the fundus, including the macula
  • Electrocardiogram (ECG)
  • Recent CBC count
  • Recent (eg, within last 6 months) transaminase and bilirubin levels

First-dose monitoring in patients with certain preexisting cardiac conditions

  • Because initiating treatment results in a decrease in heart rate (HR), recommend first-dose 6-hr monitoring for patients with sinus bradycardia (HR <55 bpm), first- or second-degree (Mobitz type I) AV block, or a history of myocardial infarction or heart failure
  • If any of the following abnormalities are present after 6 hr (even in the absence of symptoms):
    • HR 6 hr postdose <45 bpm or is at the lowest value postdose
    • ECG 6 hr postdose shows new-onset second-degree or higher AV block
    • Monitor until the abnormality resolves
  • If postdose symptomatic bradycardia, bradyarrhythmia, or conduction related symptoms occur, or if ECG 6 hr postdose shows new-onset second-degree or higher AV block or QTc ≥500 msec, initiate appropriate management; monitor ECG and symptoms until resolved if no pharmacological treatment is required
  • If pharmacological treatment is required, monitor overnight and repeat 6-hr monitoring after second dose
  • Consult with a cardiologist for patients with preexisting heart and cerebrovascular conditions, a prolonged QTc interval before dosing or during the 6-hr observation, at additional risk for QT prolongation, or on concurrent therapy with QT-prolonging drugs with a known risk of torsades de pointes or drugs that slow heart rate or AV conduction

Safety and efficacy not established

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Interactions

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            Contraindicated (1)

            • lefamulin

              lefamulin will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lefamulin is contraindicated with CYP3A substrates know to prolong the QT interval.

            Serious - Use Alternative (176)

            • abametapir

              abametapir will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • adenovirus types 4 and 7 live, oral

              siponimod decreases effects of adenovirus types 4 and 7 live, oral by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • alemtuzumab

              siponimod and alemtuzumab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Because of the characteristics and duration of alemtuzumab immune suppressive effects, initiating treatment with siponimod after alemtuzumab is not recommended.

            • amiodarone

              siponimod, amiodarone. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

              amiodarone will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

              amiodarone will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • amobarbital

              amobarbital will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • anthrax vaccine adsorbed

              siponimod decreases effects of anthrax vaccine adsorbed by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • apalutamide

              apalutamide will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • aprepitant

              aprepitant will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • armodafinil

              armodafinil will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • atazanavir

              atazanavir will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • BCG vaccine live

              siponimod decreases effects of BCG vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • bexarotene

              bexarotene will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • bicalutamide

              bicalutamide will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • bosentan

              bosentan will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • brigatinib

              brigatinib will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • butabarbital

              butabarbital will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • butalbital

              butalbital will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • capecitabine

              capecitabine will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • carbamazepine

              carbamazepine will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • ceritinib

              ceritinib will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

              ceritinib will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • chloramphenicol

              chloramphenicol will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • cholera vaccine

              siponimod decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • clarithromycin

              clarithromycin will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • clobazam

              clobazam will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • clozapine

              clozapine will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • cobicistat

              cobicistat will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • crizotinib

              crizotinib will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • cyclosporine

              cyclosporine will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • dabrafenib

              dabrafenib will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • darunavir

              darunavir will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • desipramine

              desipramine will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • digoxin

              siponimod, digoxin. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

            • diltiazem

              siponimod, diltiazem. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

              diltiazem will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • diphtheria & tetanus toxoids/ acellular pertussis vaccine

              siponimod decreases effects of diphtheria & tetanus toxoids/ acellular pertussis vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccine

              siponimod decreases effects of diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • disopyramide

              siponimod, disopyramide. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

            • dofetilide

              siponimod, dofetilide. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

            • doxycycline

              doxycycline will increase the level or effect of siponimod by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • dronedarone

              siponimod, dronedarone. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

              dronedarone will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • efavirenz

              efavirenz will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

              efavirenz will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • encorafenib

              encorafenib will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • enzalutamide

              enzalutamide will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • erythromycin base

              erythromycin base will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • etravirine

              etravirine will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

              etravirine will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • fexinidazole

              fexinidazole and siponimod both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

            • fluconazole

              fluconazole will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

              fluconazole will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • fluorouracil

              fluorouracil will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • flurbiprofen

              flurbiprofen will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • fluvastatin

              fluvastatin will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • fluvoxamine

              fluvoxamine will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor not recommended

            • fosamprenavir

              fosamprenavir will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • fostamatinib

              fostamatinib will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • gemfibrozil

              gemfibrozil will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • grapefruit

              grapefruit will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • haemophilus influenzae type b vaccine

              siponimod decreases effects of haemophilus influenzae type b vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • haloperidol

              haloperidol will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • hepatitis A vaccine inactivated

              siponimod decreases effects of hepatitis A vaccine inactivated by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • hepatitis a/b vaccine

              siponimod decreases effects of hepatitis a/b vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • hepatitis b vaccine

              siponimod decreases effects of hepatitis b vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • HIV vaccine

              siponimod decreases effects of HIV vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • human papillomavirus vaccine, nonavalent

              siponimod decreases effects of human papillomavirus vaccine, nonavalent by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • human papillomavirus vaccine, quadrivalent

              siponimod decreases effects of human papillomavirus vaccine, quadrivalent by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • ibuprofen

              ibuprofen will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • ibutilide

              siponimod, ibutilide. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

            • idelalisib

              idelalisib will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • iloperidone

              iloperidone will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • imatinib

              imatinib will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • indinavir

              indinavir will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • indomethacin

              indomethacin will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • influenza A (H5N1) vaccine

              siponimod decreases effects of influenza A (H5N1) vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • influenza virus vaccine (H5N1), adjuvanted

              siponimod decreases effects of influenza virus vaccine (H5N1), adjuvanted by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • influenza virus vaccine quadrivalent

              siponimod decreases effects of influenza virus vaccine quadrivalent by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • influenza virus vaccine quadrivalent, adjuvanted

              siponimod decreases effects of influenza virus vaccine quadrivalent, adjuvanted by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • influenza virus vaccine quadrivalent, cell-cultured

              siponimod decreases effects of influenza virus vaccine quadrivalent, cell-cultured by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • influenza virus vaccine quadrivalent, intranasal

              siponimod decreases effects of influenza virus vaccine quadrivalent, intranasal by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • influenza virus vaccine quadrivalent, recombinant

              siponimod decreases effects of influenza virus vaccine quadrivalent, recombinant by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • influenza virus vaccine trivalent

              siponimod decreases effects of influenza virus vaccine trivalent by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • influenza virus vaccine trivalent, adjuvanted

              siponimod decreases effects of influenza virus vaccine trivalent, adjuvanted by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • influenza virus vaccine trivalent, recombinant

              siponimod decreases effects of influenza virus vaccine trivalent, recombinant by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • irbesartan

              irbesartan will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • isoniazid

              isoniazid will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • itraconazole

              itraconazole will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • ivabradine

              siponimod, ivabradine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

            • ivacaftor

              ivacaftor will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • ivosidenib

              ivosidenib will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • Japanese encephalitis virus vaccine

              siponimod decreases effects of Japanese encephalitis virus vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • ketoconazole

              ketoconazole will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

              ketoconazole will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • lapatinib

              lapatinib will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • larotrectinib

              larotrectinib will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • letermovir

              letermovir will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • lonafarnib

              lonafarnib will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

            • lopinavir

              lopinavir will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • lorlatinib

              lorlatinib will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • losartan

              losartan will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • measles (rubeola) vaccine

              siponimod decreases effects of measles (rubeola) vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • measles mumps and rubella vaccine, live

              siponimod decreases effects of measles mumps and rubella vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • measles, mumps, rubella and varicella vaccine, live

              siponimod decreases effects of measles, mumps, rubella and varicella vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • mefenamic acid

              mefenamic acid will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • meningococcal A C Y and W-135 diphtheria conjugate vaccine

              siponimod decreases effects of meningococcal A C Y and W-135 diphtheria conjugate vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • meningococcal A C Y and W-135 polysaccharide vaccine combined

              siponimod decreases effects of meningococcal A C Y and W-135 polysaccharide vaccine combined by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • meningococcal group B vaccine

              siponimod decreases effects of meningococcal group B vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • metronidazole

              metronidazole will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • mifepristone

              mifepristone will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • mitotane

              mitotane will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • modafinil

              modafinil will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • nafcillin

              nafcillin will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • nefazodone

              nefazodone will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • nelfinavir

              nelfinavir will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • netupitant/palonosetron

              netupitant/palonosetron will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • nicardipine

              nicardipine will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • nitisinone

              nitisinone will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • olanzapine

              olanzapine will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • omeprazole

              omeprazole will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • pentobarbital

              pentobarbital will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • phenobarbital

              phenobarbital will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • phenytoin

              phenytoin will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • piroxicam

              piroxicam will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • pneumococcal vaccine 13-valent

              siponimod decreases effects of pneumococcal vaccine 13-valent by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • pneumococcal vaccine heptavalent

              siponimod decreases effects of pneumococcal vaccine heptavalent by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • pneumococcal vaccine polyvalent

              siponimod decreases effects of pneumococcal vaccine polyvalent by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • poliovirus vaccine inactivated

              siponimod decreases effects of poliovirus vaccine inactivated by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • ponesimod

              ponesimod, siponimod. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Coadministration of ponesimod with drugs that decrease HR may have additive effects on decreasing HR and should generally not be initiated in these patients.

            • posaconazole

              posaconazole will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • primidone

              primidone will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • procainamide

              siponimod, procainamide. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

            • pyrimethamine

              pyrimethamine will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • quinidine

              siponimod, quinidine. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

            • quinine

              quinine will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • rabies vaccine

              siponimod decreases effects of rabies vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • rabies vaccine chick embryo cell derived

              siponimod decreases effects of rabies vaccine chick embryo cell derived by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • ribociclib

              ribociclib will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • rifabutin

              rifabutin will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • rifampin

              rifampin will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • rifapentine

              rifapentine will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • ritonavir

              ritonavir will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • rotavirus oral vaccine, live

              siponimod decreases effects of rotavirus oral vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • rubella vaccine

              siponimod decreases effects of rubella vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • saquinavir

              saquinavir will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • schisandra

              schisandra will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • secobarbital

              secobarbital will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • sertraline

              sertraline will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • smallpox (vaccinia) and monkeypox vaccine, live, nonreplicating

              siponimod decreases effects of smallpox (vaccinia) vaccine, attenuated by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • smallpox (vaccinia) vaccine, attenuated

              siponimod decreases effects of smallpox (vaccinia) vaccine, attenuated by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • smallpox (vaccinia) vaccine, live

              siponimod decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • sorafenib

              sorafenib will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • sotalol

              siponimod, sotalol. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

            • St John's Wort

              St John's Wort will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • sulfadiazine

              sulfadiazine will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • sulfamethoxazole

              sulfamethoxazole will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • telotristat ethyl

              telotristat ethyl will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

            • tetanus & reduced diphtheria toxoids/ acellular pertussis vaccine

              siponimod decreases effects of tetanus & reduced diphtheria toxoids/ acellular pertussis vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • tetanus toxoid adsorbed or fluid

              siponimod decreases effects of tetanus toxoid adsorbed or fluid by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • tetracycline

              tetracycline will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • tipranavir

              tipranavir will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • tolbutamide

              tolbutamide will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • trimethoprim

              trimethoprim will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • tucatinib

              tucatinib will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • typhoid polysaccharide vaccine

              siponimod decreases effects of typhoid polysaccharide vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • typhoid vaccine live

              siponimod decreases effects of typhoid vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • varicella virus vaccine live

              siponimod decreases effects of varicella virus vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • verapamil

              siponimod, verapamil. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

              verapamil will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • voriconazole

              voriconazole will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

              voriconazole will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • voxelotor

              voxelotor will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            • warfarin

              warfarin will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • yellow fever vaccine

              siponimod decreases effects of yellow fever vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • zafirlukast

              zafirlukast will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • zoster vaccine live

              siponimod decreases effects of zoster vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            • zoster vaccine recombinant

              siponimod decreases effects of zoster vaccine recombinant by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.

            Monitor Closely (282)

            • abatacept

              siponimod and abatacept both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • abemaciclib

              siponimod and abemaciclib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • abiraterone

              siponimod and abiraterone both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • acalabrutinib

              siponimod and acalabrutinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • acebutolol

              siponimod, acebutolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • ado-trastuzumab emtansine

              siponimod and ado-trastuzumab emtansine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • afatinib

              siponimod and afatinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • aldesleukin

              siponimod and aldesleukin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • alectinib

              siponimod and alectinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • alitretinoin topical

              siponimod and alitretinoin topical both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • alpelisib

              alpelisib will decrease the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

            • anakinra

              siponimod and anakinra both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • anastrozole

              siponimod and anastrozole both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • antithymocyte globulin equine

              siponimod and antithymocyte globulin equine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • antithymocyte globulin rabbit

              siponimod and antithymocyte globulin rabbit both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • apalutamide

              siponimod and apalutamide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • apaziquone

              siponimod and apaziquone both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • arsenic trioxide

              siponimod and arsenic trioxide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • asparaginase Erwinia chrysanthemi

              siponimod and asparaginase Erwinia chrysanthemi both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • atenolol

              siponimod, atenolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • atezolizumab

              siponimod and atezolizumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • avelumab

              siponimod and avelumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • axitinib

              siponimod and axitinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • azacitidine

              siponimod and azacitidine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • azathioprine

              siponimod and azathioprine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • basiliximab

              siponimod and basiliximab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • BCG intravesical live

              siponimod and BCG intravesical live both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • belatacept

              siponimod and belatacept both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • belinostat

              siponimod and belinostat both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • bendamustine

              siponimod and bendamustine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • betaxolol

              siponimod, betaxolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • bevacizumab

              siponimod and bevacizumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • bexarotene

              siponimod and bexarotene both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • bicalutamide

              siponimod and bicalutamide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • binimetinib

              siponimod and binimetinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • bisoprolol

              siponimod, bisoprolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • bleomycin

              siponimod and bleomycin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • blinatumomab

              siponimod and blinatumomab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • bortezomib

              siponimod and bortezomib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • bosutinib

              siponimod and bosutinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • brentuximab vedotin

              siponimod and brentuximab vedotin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • brigatinib

              siponimod and brigatinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • busulfan

              siponimod and busulfan both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • C1 esterase inhibitor recombinant

              siponimod and C1 esterase inhibitor recombinant both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • C1 inhibitor human

              siponimod and C1 inhibitor human both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • cabazitaxel

              siponimod and cabazitaxel both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • cabozantinib

              siponimod and cabozantinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • capecitabine

              siponimod and capecitabine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • carboplatin

              siponimod and carboplatin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • carfilzomib

              siponimod and carfilzomib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • carmustine

              siponimod and carmustine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • carvedilol

              siponimod, carvedilol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • celiprolol

              siponimod, celiprolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • cemiplimab

              siponimod and cemiplimab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • cenobamate

              cenobamate will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • ceritinib

              siponimod and ceritinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • certolizumab pegol

              siponimod and certolizumab pegol both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • cetuximab

              siponimod and cetuximab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • chlorambucil

              siponimod and chlorambucil both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • cisplatin

              siponimod and cisplatin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • cladribine

              siponimod and cladribine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • clofarabine

              siponimod and clofarabine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • cobimetinib

              siponimod and cobimetinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • conivaptan

              conivaptan will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a moderate of strong CYP3A4 inhibitor plus a moderate or strong CYP2C9 inhibitor not recommended

            • copanlisib

              siponimod and copanlisib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • crizotinib

              siponimod and crizotinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • custirsen

              siponimod and custirsen both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • cyclophosphamide

              siponimod and cyclophosphamide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • cyclosporine

              siponimod, cyclosporine. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • cytarabine

              siponimod and cytarabine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • dabrafenib

              siponimod and dabrafenib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • dacarbazine

              siponimod and dacarbazine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • dacomitinib

              siponimod and dacomitinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • dactinomycin

              siponimod and dactinomycin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • daratumumab

              siponimod and daratumumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • dasatinib

              siponimod and dasatinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • daunorubicin

              siponimod and daunorubicin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • decitabine

              siponimod and decitabine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • degarelix

              siponimod and degarelix both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • denosumab

              siponimod and denosumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • dimethyl fumarate

              siponimod and dimethyl fumarate both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • dinutuximab

              siponimod and dinutuximab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • diroximel fumarate

              siponimod and diroximel fumarate both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • docetaxel

              siponimod and docetaxel both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • doxorubicin

              siponimod and doxorubicin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • doxorubicin liposomal

              siponimod and doxorubicin liposomal both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • durvalumab

              siponimod and durvalumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • duvelisib

              siponimod and duvelisib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • elagolix

              elagolix decreases levels of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • elotuzumab

              siponimod and elotuzumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • emapalumab

              siponimod and emapalumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • encorafenib

              siponimod and encorafenib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • entrectinib

              siponimod and entrectinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • enzalutamide

              siponimod and enzalutamide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • epirubicin

              siponimod and epirubicin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • erdafitinib

              siponimod and erdafitinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • eribulin

              siponimod and eribulin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • erlotinib

              siponimod and erlotinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • esmolol

              siponimod, esmolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • estramustine

              siponimod and estramustine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • estrogens esterified

              siponimod and estrogens esterified both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • etanercept

              siponimod and etanercept both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • etoposide

              siponimod and etoposide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • everolimus

              siponimod and everolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • exemestane

              siponimod and exemestane both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • fedratinib

              siponimod and fedratinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

              fedratinib will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fingolimod

              siponimod and fingolimod both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • floxuridine

              siponimod and floxuridine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • fludarabine

              siponimod and fludarabine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • fluorouracil

              siponimod and fluorouracil both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • flutamide

              siponimod and flutamide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • fostamatinib

              siponimod and fostamatinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • fostemsavir

              siponimod and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

            • fulvestrant

              siponimod and fulvestrant both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • gefitinib

              siponimod and gefitinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • gemcitabine

              siponimod and gemcitabine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • gemtuzumab

              siponimod and gemtuzumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • gilteritinib

              siponimod and gilteritinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • glasdegib

              siponimod and glasdegib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • glatiramer

              siponimod and glatiramer both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immune effects during such therapy and in the weeks following administration. Siponimod can generally be started immediately after discontinuation of glatiramer.

            • goserelin

              siponimod and goserelin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • histrelin

              siponimod and histrelin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • hydroxychloroquine sulfate

              siponimod and hydroxychloroquine sulfate both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • hydroxyurea

              siponimod and hydroxyurea both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • ibritumomab tiuxetan

              siponimod and ibritumomab tiuxetan both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • ibrutinib

              siponimod and ibrutinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • icatibant

              siponimod and icatibant both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • idarubicin

              siponimod and idarubicin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • idelalisib

              siponimod and idelalisib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • ifosfamide

              siponimod and ifosfamide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • imatinib

              siponimod and imatinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • infliximab

              siponimod and infliximab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • inotuzumab

              siponimod and inotuzumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • interferon alfa 2b

              siponimod and interferon alfa 2b both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • interferon alfa n3

              siponimod and interferon alfa n3 both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • interferon beta 1a

              siponimod and interferon beta 1a both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immune effects during such therapy and in the weeks following administration. Siponimod can generally be started immediately after discontinuation of beta interferon.

            • interferon beta 1b

              siponimod and interferon beta 1b both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immune effects during such therapy and in the weeks following administration. Siponimod can generally be started immediately after discontinuation of beta interferon.

            • interferon gamma 1b

              siponimod and interferon gamma 1b both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • iobenguane I 131

              siponimod and iobenguane I 131 both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • ipilimumab

              siponimod and ipilimumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • irinotecan

              siponimod and irinotecan both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • irinotecan liposomal

              siponimod and irinotecan liposomal both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • istradefylline

              istradefylline will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • ivosidenib

              siponimod and ivosidenib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • ixabepilone

              siponimod and ixabepilone both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • ixazomib

              siponimod and ixazomib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • labetalol

              siponimod, labetalol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • lapatinib

              siponimod and lapatinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • larotrectinib

              siponimod and larotrectinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • leflunomide

              siponimod and leflunomide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • lenalidomide

              siponimod and lenalidomide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • lenvatinib

              siponimod and lenvatinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • letrozole

              siponimod and letrozole both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • leuprolide

              siponimod and leuprolide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • lomustine

              siponimod and lomustine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • lorlatinib

              siponimod and lorlatinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • lutetium Lu 177-dota-tate

              siponimod and lutetium Lu 177-dota-tate both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • mechlorethamine

              siponimod and mechlorethamine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • mechlorethamine topical

              siponimod and mechlorethamine topical both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • medroxyprogesterone

              siponimod and medroxyprogesterone both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • megestrol

              siponimod and megestrol both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • melphalan

              siponimod and melphalan both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • mercaptopurine

              siponimod and mercaptopurine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • methotrexate

              siponimod and methotrexate both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • methyltestosterone

              siponimod and methyltestosterone both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • metoprolol

              siponimod, metoprolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • midostaurin

              siponimod and midostaurin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • mitomycin

              siponimod and mitomycin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • mitotane

              siponimod and mitotane both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • mitoxantrone

              siponimod and mitoxantrone both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • mogamulizumab

              siponimod and mogamulizumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • moxetumomab pasudotox

              siponimod and moxetumomab pasudotox both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • muromonab CD3

              siponimod and muromonab CD3 both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • mycophenolate

              siponimod and mycophenolate both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • nadolol

              siponimod, nadolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • nebivolol

              siponimod, nebivolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • necitumumab

              siponimod and necitumumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • nelarabine

              siponimod and nelarabine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • neratinib

              siponimod and neratinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • nilotinib

              siponimod and nilotinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • nilutamide

              siponimod and nilutamide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • niraparib

              siponimod and niraparib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • nivolumab

              siponimod and nivolumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • obinutuzumab

              siponimod and obinutuzumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • ofatumumab

              siponimod and ofatumumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • ofatumumab SC

              ofatumumab SC, siponimod. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.

            • olaparib

              siponimod and olaparib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • olaratumab

              siponimod and olaratumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • omacetaxine

              siponimod and omacetaxine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • osilodrostat

              osilodrostat and siponimod both increase QTc interval. Use Caution/Monitor.

            • osimertinib

              siponimod and osimertinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • oxaliplatin

              siponimod and oxaliplatin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • ozanimod

              ozanimod, siponimod. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Coadministration with immunosuppressive therapies may increase the risk of additive immune effects during therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs in order to avoid unintended additive immunosuppressive effects.

            • paclitaxel

              siponimod and paclitaxel both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • paclitaxel protein bound

              siponimod and paclitaxel protein bound both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • pacritinib

              siponimod and pacritinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • palbociclib

              siponimod and palbociclib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • palifermin

              siponimod and palifermin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • panitumumab

              siponimod and panitumumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • panobinostat

              siponimod and panobinostat both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • pazopanib

              siponimod and pazopanib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • pegaspargase

              siponimod and pegaspargase both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • peginterferon beta-1a

              siponimod and peginterferon beta-1a both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immune effects during such therapy and in the weeks following administration. Siponimod can generally be started immediately after discontinuation of beta interferon.

            • pegloticase

              siponimod and pegloticase both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • pembrolizumab

              siponimod and pembrolizumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • pemetrexed

              siponimod and pemetrexed both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • penbutolol

              siponimod, penbutolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • pentostatin

              siponimod and pentostatin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • pertuzumab

              siponimod and pertuzumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • pexidartinib

              siponimod and pexidartinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • pindolol

              siponimod, pindolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • polatuzumab vedotin

              siponimod and polatuzumab vedotin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • pomalidomide

              siponimod and pomalidomide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • ponatinib

              siponimod and ponatinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • porfimer

              siponimod and porfimer both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • pralatrexate

              siponimod and pralatrexate both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • procarbazine

              siponimod and procarbazine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • propranolol

              siponimod, propranolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • quizartinib

              siponimod and quizartinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • radium-223 dichloride

              siponimod and radium-223 dichloride both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • ramucirumab

              siponimod and ramucirumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • rasburicase

              siponimod and rasburicase both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • regorafenib

              siponimod and regorafenib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • ribociclib

              siponimod and ribociclib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • rilonacept

              siponimod and rilonacept both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • rituximab

              siponimod and rituximab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • rituximab-hyaluronidase

              siponimod and rituximab-hyaluronidase both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • romidepsin

              siponimod and romidepsin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • rucaparib

              siponimod and rucaparib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • ruxolitinib

              siponimod and ruxolitinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • sacituzumab govitecan

              siponimod and sacituzumab govitecan both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • samarium sm 153 lexidronam

              siponimod and samarium sm 153 lexidronam both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • siltuximab

              siponimod and siltuximab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • sipuleucel-T

              siponimod decreases effects of sipuleucel-T by pharmacodynamic antagonism. Modify Therapy/Monitor Closely.

            • sirolimus

              siponimod and sirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • sirolimus intravitreal

              siponimod and sirolimus intravitreal both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • sirukumab

              siponimod and sirukumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • sodium iodide I-131

              siponimod and sodium iodide I-131 both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • sonidegib

              siponimod and sonidegib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • sorafenib

              siponimod and sorafenib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • sotalol

              siponimod, sotalol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • streptozocin

              siponimod and streptozocin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • strontium 89 chloride

              siponimod and strontium 89 chloride both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • sunitinib

              siponimod and sunitinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • tacrolimus

              siponimod and tacrolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • tagraxofusp

              siponimod and tagraxofusp both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • talazoparib

              siponimod and talazoparib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • tamoxifen

              siponimod and tamoxifen both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • tazemetostat

              siponimod and tazemetostat both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

              tazemetostat will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • technetium Tc 99m tilmanocept

              siponimod and technetium Tc 99m tilmanocept both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • temozolomide

              siponimod and temozolomide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • temsirolimus

              siponimod and temsirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • teniposide

              siponimod and teniposide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • thalidomide

              siponimod and thalidomide both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • thioguanine

              siponimod and thioguanine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • thiotepa

              siponimod and thiotepa both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • timolol

              siponimod, timolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • tivozanib

              siponimod and tivozanib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • tocilizumab

              siponimod and tocilizumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • tofacitinib

              siponimod and tofacitinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • topotecan

              siponimod and topotecan both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • toremifene

              siponimod and toremifene both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • tositumomab

              siponimod and tositumomab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • trabectedin

              siponimod and trabectedin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • trametinib

              siponimod and trametinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • trastuzumab

              siponimod and trastuzumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • trastuzumab deruxtecan

              siponimod and trastuzumab deruxtecan both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • tretinoin

              siponimod and tretinoin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • trifluridine/tipiracil

              siponimod and trifluridine/tipiracil both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • triptorelin

              siponimod and triptorelin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • tumor necrosis factor-alpha (TNF-alpha) adenovector

              siponimod and tumor necrosis factor-alpha (TNF-alpha) adenovector both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • valrubicin

              siponimod and valrubicin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • vandetanib

              siponimod and vandetanib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • vemurafenib

              siponimod and vemurafenib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • venetoclax

              siponimod and venetoclax both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • vinblastine

              siponimod and vinblastine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • vincristine

              siponimod and vincristine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • vincristine liposomal

              siponimod and vincristine liposomal both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • vinorelbine

              siponimod and vinorelbine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • vismodegib

              siponimod and vismodegib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • vorinostat

              siponimod and vorinostat both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • ziv-aflibercept

              siponimod and ziv-aflibercept both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            Minor (0)

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              Adverse Effects

              >10%

              Headache (15%)

              Hypertension (13%)

              Transaminase increased (11%)

              Falls (11%)

              1-10%

              Peripheral edema (8%)

              Nausea (7%)

              Dizziness (7%)

              Diarrhea (6%)

              Bradycardia (6%)

              Pain in extremity (6%)

              Vascular events (eg, ischemic strokes, pulmonary embolisms, myocardial infarctions) (3%)

              Seizures (1.7%)

              Frequency Not Defined

              Malignancies (eg, melanoma in situ)

              Dose-dependent reductions in forced expiratory volume over 1 sec (FEV1)

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              Warnings

              Contraindications

              A CYP2C9*3/*3 genotype

              In the last 6 months experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III or IV heart failure

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

              Cautions

              Macular edema reported; majority of cases occurred within the first 4 months of therapy

              Dose-dependent reductions in absolute FEV1 observed as early as 3 months after treatment initiation

              Elevated transaminases may occur; exercise caution when treating patients with a history of significant liver disease

              Incidence of hypertension reported in clinical trials in patients treated with siponimod was slightly higher than those treated with placebo; monitor blood pressure during treatment and manage appropriately

              Based on animal studies, fetal harm may occur (see Pregnancy)

              Rare cases of posterior reversible encephalopathy syndrome reported in patients receiving a sphingosine 1-phosphate (S1P) receptor modulator; such events have not been reported for siponimod-treated patients in the development program

              Severe disease exacerbation, including disease rebound, rarely reported after discontinuing S1P receptor modulator

              After discontinuing, siponimod remains in the blood for up to 10 days; starting other therapies during this interval results in concomitant exposure to siponimod

              May cause a decline in pulmonary function; assess pulmonary function (eg, spirometry) if clinically indicated

              Cutaneous malignancies

              • Long-term use of S1P modulators, have been associated with an increased risk of basal cell carcinoma (BCC).
              • Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer; providers and patients are advised to monitor for suspicious skin lesions; if a suspicious skin lesion is observed, evaluate promptly
              • As usual for patients with increased risk for skin cancer, exposure to sunlight and ultraviolet light should be limited by wearing protective clothing and using a sunscreen with a high protection factor
              • Concomitant phototherapy with UV-B radiation or PUVA-photochemotherapy is not recommended in patients receiving therapy

              Bradyarrhythmia and AV conduction delays

              • Since initiation of treatment results in a transient decrease in HR and AV conduction delays, use an up-titration scheme to reach maintenance dosage
              • After first titration dose, decrease in HR starts within 1 hr, and on Day 1 declines at ~3-4 hr; with continued up-titration, further HR decreases are seen on subsequent days, with maximal decrease from Day 1-baseline reached on Day 5-6; with continued dosing, HR starts increasing after Day 6 and reaches placebo levels within 10 days after treatment initiation
              • The resting heart rate under stable dose of beta-blocker should be considered before introducing therapy
              • Not studied in patients who had:
                • In the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, or decompensated heart failure requiring hospitalization
                • New York Heart Association Class II-IV heart failure
                • Cardiac conduction or rhythm disorders (eg, complete left bundle-branch block, sinus arrest, sinoatrial 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
                • Significant QT prolongation (QTc >500 msec)
                • Arrhythmias requiring treatment with Class Ia or Class III antiarrhythmic drugs
                • If such patients are considered for treatment, consult with cardiologist

              Infections

              • Dose-dependent reduction in peripheral lymphocyte count to 20-30% of baseline values may occur because of reversible sequestration of lymphocytes in lymphoid tissues; therefore, increased risk of infections; life-threatening and rare fatal infections have occurred
              • Delay treatment initiation in patients with severe active infection until resolution
              • Infection risk may persist for up to 3-4 weeks after discontinuing because of residual pharmacodynamic effects (eg, decreased lymphocyte count); continue monitoring
              • Appropriately diagnose and treat symptomatic patients with infection while on therapy; consider suspending treatment if a patient develops a serious infection
              • Cases of fatal cryptococcal meningitis (CM) and disseminated cryptococcal infections reported with another S1P receptor modulator
              • Rare cases of CM have also occurred
              • Herpes viral infection, including 1 case of reactivation of VZV infection leading to varicella- zoster meningitis, reported in clinical trialshave
              • Progressive multifocal leukoencephalopathy is an opportunistic viral infection of the brain caused by the JC virus that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability

              Drug interactions overview

              • When switching from drugs with prolonged immune effects, consider half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects and to minimize risk of disease reactivation when initiating treatment
              • Initiating siponimod after treatment with alemtuzumab is not recommended
              • Siponimod can generally be started immediately after discontinuation of beta-interferon or glatiramer acetate
              • Owing to the potential additive HR effects, should not be initiated in patients who are concurrently treated with QT-prolonging drugs with known arrhythmogenic properties, Class 1a or III antiarrhythmics, HR-lowering calcium channel blockers (eg, verapamil, diltiazem), or other drugs that may decrease HR (eg, ivabradine, digoxin)
              • Use caution when initiating treatment in patients concomitantly using a beta-blocker because of the additive effects on lowering HR; consider temporary interruption of the beta-blocker prior to initiation of treatment; beta-blocker treatment can be initiated in patients receiving stable doses of siponimod
              • During and for up to 1 month after discontinuation of treatment, vaccinations may be less effective; therefore, withhold treatment 1 week prior to and for 4 weeks after vaccination
              • Avoid use with live-attenuated vaccines during and for up to 4 weeks after treatment owing to the potential risk of infection
              • Because of a significant increase in exposure to siponimod, coadministration with moderate CYP2C9 plus moderate/strong CYP3A4 inhibitors is not recommended; exercise caution if concomitantly used alone with moderate CYP2C9 inhibitors
              • Because of a significant decrease in siponimod exposure, coadministration with moderate CYP2C9 plus moderate/strong CYP3A4 inducers is not recommended for all patients; exercise caution if coadministered alone with moderate CYP2C9 inducers; concurrent use of siponimod and moderate (eg, modafinil, efavirenz) or strong CYP3A4 inducers is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype
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              Pregnancy

              Pregnancy

              There are no adequate data on the developmental risk associated with the use in pregnant women

              Animal data

              • Based on animal data and its mechanism of action, fetal harm may occur when administered to a pregnant woman
              • Reproductive and developmental studies in pregnant rats and rabbits have demonstrated drug-induced embryotoxicity and fetotoxicity in rats and rabbits and teratogenicity in rats
              • Increased incidences of postimplantation loss and fetal abnormalities (external, urogenital, and skeletal) in rats and of embryofetal deaths, abortions, and fetal variations (skeletal and visceral) in rabbits observed following prenatal exposure to siponimod starting at a dose 2 times the exposure in humans at the highest recommended dose of 2 mg/day

              Contraception

              • Before initiating treatment, counsel women of childbearing potential on the potential risks to the fetus
              • Advise on effective contraception during treatment
              • Since it takes ~10 days to eliminate drug from the body after discontinuation, potential risks to the fetus may persist and women should use effective contraception during this period

              Lactation

              Unknown if distributed in human breast milk

              A study in lactating rats has shown excretion of siponimod and/or its metabolites in milk

              Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Sphingosine-1-phosphate (S1P) receptor modulator

              Binds with high affinity to S1P receptors 1 and 5; blocks lymphocyte egress from lymph nodes, reducing the number of lymphocytes in peripheral blood

              Mechanism by which siponimod exerts therapeutic effects in MS is unknown, but may involve reduction of lymphocyte migration into the central nervous system

              Absorption

              Peak plasma time: 4 hr

              Peak plasma concentration: 30.4 ng/mL (2 mg/day over 10 days)

              AUC: 558 ng·hr/mL (2mg/day over 10 days)

              Steady-state reached after ~ 6 days

              Oral bioavailability: ~84%

              Siponimod absorption is extensive (≥70%)

              Distribution

              Vd: 124 L

              Animal studies show that siponimod readily crosses the blood-brain barrier

              Protein bound: >99.9%

              Metabolism

              Extensively metabolized, mainly via CYP2C9 (79.3%), followed by CYP3A4 (18.5%)

              Pharmacological activity of the main metabolites M3 and M17 is not expected to contribute to the clinical effect and safety of siponimod in humans

              Elimination

              Clearance: 3.11 L/hr

              Half-life: ~30 hr

              Eliminated from the systemic circulation mainly due to metabolism, and subsequent biliary/fecal excretion; unchanged siponimod was not detected in urine

              Pharmacogenomics

              CYP2C9 genotype

              • Before initiating treatment, test patients to determine CYP2C9 genotype
              • Contraindicated in patients homozygous for CYP2C9*3 (eg, CYP2C9*3/*3 genotype)
              • Dosage adjustment recommended in patients with CYP2C9 *1/*3 or *2/*3 genotype because of an increase in exposure to siponimod
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              Administration

              Oral Administration

              Administer with or without food

              Missed dose

              • During titration: If 1 titration dose is missed for >24 hr, treatment needs to be reinitiated with Day 1 of the titration regimen
              • During maintenance
                • If 1 dose missed after initial dose titration, take as soon as possible
                • Dosing interrupted for ≥4 consecutive daily doses: Reinitiate treatment with Day 1 of the titration regimen

              Storage

              Unopened bottles: Refrigerate at 2-8°C (36-46°F)

              After opening

              • Starter pack: Store at room temperature (20-25°C [68-77°F]) for up to 1 week after opening
              • Bottles (0.25- or 2-mg tablets): Store at room temperature (20-25°C [68-77°F]) for up to 1 month after opening
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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.