ponesimod (Rx)

Brand and Other Names:Ponvory
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 2mg
  • 3mg
  • 4mg
  • 5mg
  • 6mg
  • 7mg
  • 8mg
  • 9mg
  • 10mg
  • 20mg

Multiple Sclerosis

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

Initiation

  • Starter pack must be used for initiating treatment
  • 2 mg PO qDay initially; increase dose as per dose titration regimen (14-day titration)
  • Dose titration regimen
    • Days 1-2: 2 mg qDay
    • Days 3-4: 3 mg qDay
    • Days 5-6: 4 mg qDay
    • Day 7: 5 mg qDay
    • Day 8: 6 mg qDay
    • Day 9: 7 mg qDay
    • Day 10: 8 mg qDay
    • Day 11: 9 mg qDay
    • Days 12-14: 10 mg qDay

Maintenance

  • Day 15 and thereafter: 20 mg qDay

Dosage Modifications

Renal impairment

  • Mild-to-severe: No dosage adjustment necessary
  • Hemodialysis: No dose adjustment necessary; owing to high plasma protein binding (ie, >99%), dialysis not expected to alter concentration

Hepatic impairment

  • Mild (Child-Pugh A): No dosage adjustment necessary
  • Moderate-to-severe (Child-Pugh B or C): Not recommended

Dosing Considerations

Monitoring parameters

  • Before first dose
    • Recent CBC count, including lymphocyte count (eg, within the last 6 months or after discontinuing previous MS therapy)
    • ECG
    • Review medication history for drugs that may slow HR or AV conduction, antineoplastic agents, immunosuppressives, or immune-modulating therapies
    • Recent (eg, within last 6 months) AST/ALT and bilirubin levels
    • Evaluate fundus, including macula
    • Test for antibodies to varicella zoster virus (VZV); VZV vaccination for antibody-negative patients recommended; if vaccination required, administer at least 1 month before initiating ponesimod
  • First dose monitoring
    • Recommended for the following: Patients with sinus bradycardia (HR <55 beats per minute [bpm]), first- or second-degree (Mobitz type I) AV block, or a history of myocardial infarction (MI) or heart failure (HF) occurring >6 months before initiating treatment and in stable condition
    • Administer in setting where bradycardia can be appropriately managed
    • Monitor HR and BP at least hourly for 4 hr after first dose for signs and symptoms of bradycardia
    • Obtain an ECG before dosing and at the end of 4-hr observation period
  • After 4-hour monitoring
    • If symptomatic bradycardia, bradyarrhythmia, or conduction-related symptoms, or if new-onset second-degree or higher AV block or QTc ≥500 msec occur, initiate appropriate management, begin continuous ECG monitoring, and continue monitoring until resolution if no pharmacological treatment is required
    • If pharmacological treatment is required, continue monitoring overnight and repeat 4-hr monitoring after second dose
  • Possible abnormalities 4 hours post dose
    • If any of these abnormalities are present after 4 hr (even in absence of symptoms), continue monitoring until resolution
    • HR <45 bpm
    • HR is at lowest value post dose, suggesting that maximum pharmacodynamic effect on the heart may not have occurred
    • ECG shows new-onset second-degree or higher AV block
  • Consult cardiologist during treatment initiation for patients with the following
    • Preexisting heart and cerebrovascular conditions
    • Prolonged QTc interval before dosing or during 4-hr observation, or at additional risk for QT prolongation
    • Coadministration with drugs that slow HR or AV conduction, or that prolong QT with a known risk of torsades de pointes

Safety and efficacy not established

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Interactions

Interaction Checker

and ponesimod

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              Serious - Use Alternative (95)

              • adenosine

                ponesimod, adenosine. 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.

              • adenovirus types 4 and 7 live, oral

                ponesimod decreases effects of adenovirus types 4 and 7 live, oral by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • alectinib

                ponesimod, alectinib. 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.

              • alfuzosin

                alfuzosin and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • apalutamide

                apalutamide will decrease the level or effect of ponesimod by Other (see comment). Avoid or Use Alternate Drug. Not recommended. Based on limited data, coadministration of strong CYP3A4 and UGT1A1 inducers (eg, rifampin, phenytoin, carbamazepine) may decrease systemic exposure of ponesimod. The clinical relevance is unclear.

              • apomorphine

                apomorphine and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • aripiprazole

                aripiprazole and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • arsenic trioxide

                ponesimod, arsenic trioxide. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • artemether

                artemether and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • artemether/lumefantrine

                artemether/lumefantrine and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • atomoxetine

                atomoxetine and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • bedaquiline

                ponesimod, bedaquiline. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

                bedaquiline and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • brigatinib

                ponesimod, brigatinib. 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.

              • bupivacaine

                ponesimod, bupivacaine. 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.

              • carbamazepine

                carbamazepine will decrease the level or effect of ponesimod by Other (see comment). Avoid or Use Alternate Drug. Not recommended. Based on limited data, coadministration of strong CYP3A4 and UGT1A1 inducers (eg, rifampin, phenytoin, carbamazepine) may decrease systemic exposure of ponesimod. The clinical relevance is unclear.

              • ceritinib

                ponesimod, ceritinib. 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.

                ceritinib and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • chloroquine

                chloroquine and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • chlorpromazine

                ponesimod, chlorpromazine. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • cisapride

                ponesimod, cisapride. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • citalopram

                citalopram and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • clarithromycin

                clarithromycin and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • clonidine

                ponesimod, clonidine. 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.

              • clozapine

                clozapine and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • crizotinib

                ponesimod, crizotinib. 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.

                crizotinib and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • dasatinib

                dasatinib and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • degarelix

                degarelix and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • dengue vaccine

                ponesimod decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • desflurane

                desflurane and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • deutetrabenazine

                deutetrabenazine and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • dexmedetomidine

                ponesimod, dexmedetomidine. 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.

              • digoxin

                ponesimod, digoxin. 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.

              • diltiazem

                ponesimod, diltiazem. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • dobutamine

                ponesimod, dobutamine. 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.

              • dolasetron

                dolasetron and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • donepezil

                ponesimod, donepezil. 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.

                donepezil and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • dopamine

                ponesimod, dopamine. 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.

              • doxepin

                doxepin and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • dronedarone

                ponesimod, dronedarone. 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.

              • Ebola Zaire vaccine

                ponesimod decreases effects of Ebola Zaire vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • efavirenz

                efavirenz and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • encorafenib

                encorafenib and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • entrectinib

                entrectinib and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

              • fentanyl

                ponesimod, fentanyl. 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.

              • fexinidazole

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

              • fingolimod

                ponesimod, fingolimod. 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.

              • flecainide

                ponesimod, flecainide. 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.

              • galantamine

                ponesimod, galantamine. 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.

              • guanfacine

                ponesimod, guanfacine. 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.

              • ibrutinib

                ponesimod, ibrutinib. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • inamrinone

                ponesimod, inamrinone. 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.

              • influenza virus vaccine quadrivalent, intranasal

                ponesimod decreases effects of influenza virus vaccine quadrivalent, intranasal by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • ivosidenib

                ponesimod, ivosidenib. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • lanreotide

                ponesimod, lanreotide. 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.

              • lasmiditan

                ponesimod, lasmiditan. 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.

              • lenvatinib

                ponesimod, lenvatinib. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • lofexidine

                ponesimod, lofexidine. 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.

              • lorlatinib

                ponesimod, lorlatinib. 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.

              • measles (rubeola) vaccine

                ponesimod decreases effects of measles (rubeola) vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • measles mumps and rubella vaccine, live

                ponesimod decreases effects of measles mumps and rubella vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • measles, mumps, rubella and varicella vaccine, live

                ponesimod decreases effects of measles, mumps, rubella and varicella vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • methadone

                ponesimod, methadone. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • milrinone

                ponesimod, milrinone. 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.

              • mobocertinib

                mobocertinib and ponesimod both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

              • neostigmine

                ponesimod, neostigmine. 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.

              • octreotide

                ponesimod, octreotide. 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.

              • ozanimod

                ponesimod, ozanimod. 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.

              • pasireotide

                ponesimod, pasireotide. 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.

              • phenytoin

                phenytoin will decrease the level or effect of ponesimod by Other (see comment). Avoid or Use Alternate Drug. Not recommended. Based on limited data, coadministration of strong CYP3A4 and UGT1A1 inducers (eg, rifampin, phenytoin, carbamazepine) may decrease systemic exposure of ponesimod. The clinical relevance is unclear.

              • poliovirus vaccine live oral trivalent

                ponesimod decreases effects of poliovirus vaccine live oral trivalent by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • poractant alfa

                ponesimod, poractant alfa. 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.

              • propafenone

                ponesimod, propafenone. 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.

              • propofol

                ponesimod, propofol. 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.

              • pyridostigmine

                ponesimod, pyridostigmine. 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.

              • quinidine

                ponesimod, quinidine. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • quinine

                ponesimod, quinine. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • remifentanil

                ponesimod, remifentanil. 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.

              • rifampin

                rifampin will decrease the level or effect of ponesimod by Other (see comment). Avoid or Use Alternate Drug. Not recommended. Based on limited data, coadministration of strong CYP3A4 and UGT1A1 inducers (eg, rifampin, phenytoin, carbamazepine) may decrease systemic exposure of ponesimod. The clinical relevance is unclear.

              • rivastigmine

                ponesimod, rivastigmine. 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.

              • rotavirus oral vaccine, live

                ponesimod decreases effects of rotavirus oral vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • rubella vaccine

                ponesimod decreases effects of rubella vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • selpercatinib

                ponesimod, selpercatinib. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • siponimod

                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.

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

                ponesimod decreases effects of smallpox (vaccinia) vaccine, attenuated by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • smallpox (vaccinia) vaccine, attenuated

                ponesimod decreases effects of smallpox (vaccinia) vaccine, attenuated by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • smallpox (vaccinia) vaccine, live

                ponesimod decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • sufentanil

                ponesimod, sufentanil. 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.

              • terfenadine

                ponesimod, terfenadine. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • thalidomide

                ponesimod, thalidomide. 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.

              • tizanidine

                ponesimod, tizanidine. 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.

              • vandetanib

                ponesimod, vandetanib. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • varicella virus vaccine live

                ponesimod decreases effects of varicella virus vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • verapamil

                ponesimod, verapamil. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • yellow fever vaccine

                ponesimod decreases effects of yellow fever vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              • ziprasidone

                ponesimod, ziprasidone. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

              • zoster vaccine live

                ponesimod decreases effects of zoster vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment. Coadministration with live attenuated vaccines may increase infection risk.

              Monitor Closely (153)

              • abatacept

                ponesimod 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.

              • acebutolol

                ponesimod and acebutolol both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • ado-trastuzumab emtansine

                ponesimod 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.

              • albuterol

                albuterol and ponesimod both increase QTc interval. Use Caution/Monitor.

              • aldesleukin

                ponesimod 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.

              • alemtuzumab

                ponesimod and alemtuzumab 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.

              • amiodarone

                ponesimod, amiodarone. Either increases effects of the other by QTc interval. Use Caution/Monitor. Consult cardiologist if considering treatment. Class III (eg, amiodarone, dofetilide, sotalol) anti-arrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.

              • antithymocyte globulin equine

                ponesimod 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

                ponesimod 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

                ponesimod 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.

              • arformoterol

                arformoterol and ponesimod both increase QTc interval. Use Caution/Monitor.

              • arsenic trioxide

                ponesimod 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.

              • atenolol

                ponesimod and atenolol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • atezolizumab

                ponesimod 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

                ponesimod 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.

              • azathioprine

                ponesimod 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

                ponesimod 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

                ponesimod 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.

              • BCG vaccine live

                ponesimod decreases effects of BCG vaccine live by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • belatacept

                ponesimod 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

                ponesimod 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

                ponesimod 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.

              • betamethasone

                ponesimod and betamethasone 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

                ponesimod and betaxolol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • bevacizumab

                ponesimod 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

                ponesimod 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

                ponesimod 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

                ponesimod 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

                ponesimod and bisoprolol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • bortezomib

                ponesimod 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

                ponesimod 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.

              • bretylium

                ponesimod, bretylium. Either increases effects of the other by QTc interval. Use Caution/Monitor. Consult cardiologist if considering treatment. Class III (eg, amiodarone, dofetilide, sotalol) anti-arrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.

              • carfilzomib

                ponesimod 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.

              • carvedilol

                ponesimod and carvedilol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • celiprolol

                ponesimod and celiprolol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • cemiplimab

                ponesimod 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.

              • certolizumab pegol

                ponesimod 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

                ponesimod 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.

              • cholera vaccine

                ponesimod decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • cobimetinib

                ponesimod 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.

              • corticotropin

                ponesimod and corticotropin 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.

              • cortisone

                ponesimod and cortisone 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.

              • COVID-19 vaccine, mRNA-Pfizer

                ponesimod decreases effects of COVID-19 vaccine, mRNA-Pfizer by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • COVID-19 vaccine, subunit-Novavax

                ponesimod decreases effects of COVID-19 vaccine, subunit-Novavax by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • COVID-19 vaccine, viral vector-Janssen

                ponesimod decreases effects of COVID-19 vaccine, viral vector-Janssen by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • cyclosporine

                ponesimod and cyclosporine 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

                ponesimod 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.

              • decitabine

                ponesimod 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.

              • deflazacort

                ponesimod and deflazacort 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

                ponesimod 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.

              • dexamethasone

                ponesimod and dexamethasone 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

                ponesimod 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

                ponesimod 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.

              • disopyramide

                ponesimod, disopyramide. Either increases effects of the other by QTc interval. Use Caution/Monitor. Consult cardiologist if considering treatment. Class Ia (eg, quinidine, procainamide) anti-arrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.

              • dofetilide

                ponesimod, dofetilide. Either increases effects of the other by QTc interval. Use Caution/Monitor. Consult cardiologist if considering treatment. Class III (eg, amiodarone, dofetilide, sotalol) anti-arrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.

              • dronedarone

                ponesimod, dronedarone. Either increases effects of the other by QTc interval. Use Caution/Monitor. Consult cardiologist if considering treatment. Class III (eg, amiodarone, dofetilide, sotalol) anti-arrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.

              • durvalumab

                ponesimod 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

                ponesimod 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.

              • elotuzumab

                ponesimod 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

                ponesimod 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.

              • entrectinib

                ponesimod 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.

              • eribulin

                ponesimod 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.

              • esmolol

                ponesimod and esmolol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • etanercept

                ponesimod 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.

              • fingolimod

                ponesimod 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.

              • fludrocortisone

                ponesimod and fludrocortisone 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

                ponesimod 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.

              • hepatitis A vaccine inactivated

                ponesimod decreases effects of hepatitis A vaccine inactivated by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • hepatitis a/b vaccine

                ponesimod decreases effects of hepatitis a/b vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • hepatitis b vaccine

                ponesimod decreases effects of hepatitis b vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • HIV vaccine

                ponesimod decreases effects of HIV vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • human papillomavirus vaccine, bivalent

                ponesimod decreases effects of human papillomavirus vaccine, bivalent by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • human papillomavirus vaccine, nonavalent

                ponesimod decreases effects of human papillomavirus vaccine, nonavalent by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • human papillomavirus vaccine, quadrivalent

                ponesimod decreases effects of human papillomavirus vaccine, quadrivalent by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • hydrocortisone

                ponesimod and hydrocortisone 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

                ponesimod 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.

              • ibritumomab tiuxetan

                ponesimod 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.

              • ibutilide

                ponesimod, ibutilide. Either increases effects of the other by QTc interval. Use Caution/Monitor. Consult cardiologist if considering treatment. Class III (eg, amiodarone, dofetilide, sotalol) anti-arrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.

              • infliximab

                ponesimod 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.

              • influenza A (H5N1) vaccine

                ponesimod decreases effects of influenza A (H5N1) vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • influenza virus vaccine (H5N1), adjuvanted

                ponesimod decreases effects of influenza virus vaccine (H5N1), adjuvanted by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • influenza virus vaccine quadrivalent

                ponesimod decreases effects of influenza virus vaccine quadrivalent by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • influenza virus vaccine quadrivalent, adjuvanted

                ponesimod decreases effects of influenza virus vaccine quadrivalent, adjuvanted by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • influenza virus vaccine quadrivalent, cell-cultured

                ponesimod decreases effects of influenza virus vaccine quadrivalent, cell-cultured by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • influenza virus vaccine quadrivalent, recombinant

                ponesimod decreases effects of influenza virus vaccine quadrivalent, recombinant by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • influenza virus vaccine trivalent

                ponesimod decreases effects of influenza virus vaccine trivalent by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • influenza virus vaccine trivalent, adjuvanted

                ponesimod decreases effects of influenza virus vaccine trivalent, adjuvanted by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • influenza virus vaccine trivalent, recombinant

                ponesimod decreases effects of influenza virus vaccine trivalent, recombinant by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • inotuzumab

                ponesimod 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

                ponesimod 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 gamma 1b

                ponesimod 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.

              • ipilimumab

                ponesimod 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.

              • ixabepilone

                ponesimod 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.

              • Japanese encephalitis virus vaccine

                ponesimod decreases effects of Japanese encephalitis virus vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • labetalol

                ponesimod and labetalol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • leflunomide

                ponesimod 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

                ponesimod 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.

              • methotrexate

                ponesimod 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.

              • methylprednisolone

                ponesimod and methylprednisolone 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

                ponesimod and metoprolol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • midostaurin

                ponesimod 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.

              • mogamulizumab

                ponesimod 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.

              • mometasone sinus implant

                ponesimod and mometasone sinus implant 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

                ponesimod 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

                ponesimod 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

                ponesimod 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

                ponesimod and nadolol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • natalizumab

                ponesimod and natalizumab 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.

              • nebivolol

                ponesimod and nebivolol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • nivolumab

                ponesimod 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.

              • olaratumab

                ponesimod 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

                ponesimod 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.

              • oportuzumab monatox

                ponesimod and oportuzumab monatox 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

                ponesimod 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

                ponesimod and ozanimod 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

                ponesimod 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.

              • pembrolizumab

                ponesimod 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.

              • penbutolol

                ponesimod and penbutolol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • pindolol

                ponesimod and pindolol both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • polatuzumab vedotin

                ponesimod 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.

              • poliovirus vaccine inactivated

                ponesimod decreases effects of poliovirus vaccine inactivated by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • ponatinib

                ponesimod 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.

              • prednisolone

                ponesimod and prednisolone 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.

              • prednisone

                ponesimod and prednisone 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.

              • procainamide

                ponesimod, procainamide. Either increases effects of the other by QTc interval. Use Caution/Monitor. Consult cardiologist if considering treatment. Class Ia (eg, quinidine, procainamide) anti-arrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.

              • propranolol

                ponesimod and propranolol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • rabies vaccine

                ponesimod decreases effects of rabies vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • rabies vaccine chick embryo cell derived

                ponesimod decreases effects of rabies vaccine chick embryo cell derived by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • rituximab

                ponesimod 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

                ponesimod 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.

              • SARS-CoV-2 vaccine, inactivated

                ponesimod decreases effects of SARS-CoV-2 vaccine, inactivated by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • selumetinib

                ponesimod and selumetinib 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

                ponesimod 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.

              • sirolimus

                ponesimod 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

                ponesimod 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.

              • sotalol

                ponesimod and sotalol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

                ponesimod, sotalol. Either increases effects of the other by QTc interval. Use Caution/Monitor. Consult cardiologist if considering treatment. Class III (eg, amiodarone, dofetilide, sotalol) anti-arrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.

              • tacrolimus

                ponesimod 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.

              • temozolomide

                ponesimod 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.

              • tick-borne encephalitis vaccine

                ponesimod decreases effects of tick-borne encephalitis vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • timolol

                ponesimod and timolol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

              • tivozanib

                ponesimod 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.

              • tositumomab

                ponesimod 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.

              • trametinib

                ponesimod 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

                ponesimod 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

                ponesimod 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.

              • triamcinolone acetonide extended-release injectable suspension

                ponesimod and triamcinolone acetonide extended-release injectable suspension 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.

              • triamcinolone acetonide injectable suspension

                ponesimod and triamcinolone acetonide injectable suspension 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.

              • typhoid polysaccharide vaccine

                ponesimod decreases effects of typhoid polysaccharide vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • typhoid vaccine live

                ponesimod decreases effects of typhoid vaccine live by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              • vedolizumab

                ponesimod and vedolizumab 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

                ponesimod 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.

              • vernakalant

                ponesimod, vernakalant. Either increases effects of the other by QTc interval. Use Caution/Monitor. Consult cardiologist if considering treatment. Class III (eg, amiodarone, dofetilide, sotalol) anti-arrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.

              • zoster vaccine recombinant

                ponesimod decreases effects of zoster vaccine recombinant by immunosuppressive effects; risk of infection. Use Caution/Monitor. If possible, complete all age-appropriate vaccinations at least 4 weeks before initiating ponesimod.

              Minor (0)

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                Adverse Effects

                >10%

                Upper respiratory tract infection (37%)

                Elevated hepatic transaminases (23%)

                1-10%

                Hypertension (10%)

                Urinary tract infection (6%)

                Dyspnea (5%)

                Dizziness (5%)

                Cough (4%)

                Pain in extremity (4%)

                Somnolence (3%)

                Pyrexia (2%)

                C-reactive protein increased (2%)

                Hypercholesterolemia (2%)

                Vertigo (2%)

                Seizures (1.4%)

                <1%

                Basal cell carcinoma (0.4%)

                Frequency Not Defined

                Dose-dependent reductions in FEV1

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                Warnings

                Contraindications

                In the past 6 months, experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure (HF) requiring hospitalization, or Class III/IV HF

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

                Cautions

                Elevated transaminases may occur; if symptoms (eg, unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, rash with eosinophilia, jaundice, dark urine) occur during therapy, check hepatic enzymes; if significant liver injury confirmed, discontinue therapy

                Hypertensive events reported; first detected ~1 month of treatment initiation and persisted with continued treatment; monitor BP and manage appropriately

                Based on animal studies, fetal harm may occur

                Consider possibility of severe exacerbation of disease after discontinuing therapy; monitor for severe increase in disability upon discontinuation and appropriately treat

                Risk of infections

                • May cause dose-dependent reduction in peripheral lymphocyte count to 30-40% of baseline; potentially increases susceptibility to infections
                • Life-threatening and rare fatal infections (herpes simplex encephalitis, varicella zoster meningitis, cryptococcal meningitis [CM], disseminated cryptococcal infections) reported with other sphingosine 1-phosphate (S1P) receptor modulators
                • Cases of herpes viral infection reported; confirm history of varicella (chicken pox) or full course of vaccination against VZV; if no proper documentation, test for antibodies against VZV
                • Monitor for clinical signs and symptoms of CM; if CM suspected, suspend therapy until CM is ruled out and undergo prompt diagnostic evaluation and treatment; if CM diagnosed, initiate appropriate treatment
                • Progressive multifocal leukoencephalopathy (PML) reported in patients treated with S1P receptor modulators and other MS therapies and is associated with some risk factors (eg, immunocompromised patients, polytherapy with immunosuppressants); monitor for clinical symptoms or MRI findings; if PML suspected, suspend treatment; if PML confirmed, discontinue treatment
                • Delay initiating treatment in patients with active infection until resolution
                • After discontinuation, lowering effect on peripheral lymphocyte count may persist for 1-2 weeks; continue vigilance for infection during these 1-2 weeks

                Bradyarrhythmias and AV conduction delays

                • Initiating treatment may result in transient decreases in HR and AV conduction delays
                • After first dose titration, decrease in HR typically begins with an hour and reaches its nadir within 2-4 hr; less pronounced with uptitration after Day 1
                • Conduction abnormalities typically were transient, asymptomatic, resolved without intervention within 24 hr and did not require discontinuing treatment
                • Not recommended for patients with the following
                  • History of cardiac arrest
                  • Cerebrovascular disease (eg, TIA, stroke occurring >6 months before initiating therapy)
                  • Uncontrolled hypertension
                  • Severe untreated sleep apnea
                • Consult cardiologist if considering treatment for patients with the following
                  • Significant QT prolongation (QTc >500 msec)
                  • Atrial flutter/fibrillation or arrhythmia treated with Class Ia or Class III anti-arrhythmic drugs
                  • Unstable ischemic heart disease, cardiac decompensated failure occurring >6 months prior to initiation, history of cardiac arrest, cerebrovascular disease (TIA, stroke occurring >6 months prior to initiation), or uncontrolled hypertension
                  • History of Mobitz type II second-degree AV block or higher-grade AV block, sick sinus syndrome, or sinoatrial heart block

                Respiratory effects

                • Dose-dependent reductions in FEV1 and reductions in diffusion lung capacity for carbon monoxide were observed mostly occurring in the first month after initiating therapy
                • Data are insufficient on reversibility of the decrease in FEV1 or forced vital capacity after discontinuation
                • Use with caution in patients with severe respiratory disease (eg, pulmonary fibrosis, asthma, chronic obstructive pulmonary disease)
                • Perform spirometric evaluation of respiratory function during therapy if clinically indicated

                Cutaneous malignancies

                • Basal cell carcinoma and other skin malignancies reported with S1P receptor modulators, including ponesimod
                • Perform skin examination for all patients, particularly those with risk factors for skin cancer
                • Advise to monitor suspicious skin lesions; if suspicious skin observed, promptly evaluate
                • Limit exposure to sunlight and UV light and use sunscreen with high protection factor in patients with increased risk of skin cancer
                • Concomitant phototherapy with UV-B radiation or psoralen plus UV A-photochemotherapy is not recommended

                Macular edema

                • S1P receptor modulators, including ponesimod, have been associated with an increased risk of macular edema
                • Patients with a history of uveitis and patients with diabetes mellitus are at increased risk of macular edema; these patients should have regular follow-up examinations of the fundus, including the macula, during treatment
                • Continuation of therapy in patients with macular edema not evaluated; consider risks and benefits on whether to discontinue treatment

                Posterior reversible encephalopathy syndrome

                • Rare case of posterior reversible encephalopathy syndrome (PRES) reported with S1P receptor modulators
                • If unexpected neurological or psychiatric signs/symptoms develop, promptly schedule a complete physical and neurological examination and consider an MRI
                • Symptoms usually reversible, but may evolve into ischemic stroke or cerebral hemorrhage
                • Delayed diagnosis and treatment may lead to permanent neurological sequelae
                • If PRES suspected, discontinued treatment

                Drug interaction overview

                • Antineoplastic, immune-modulating, or immunosuppressive therapies
                  • Use with caution
                  • May increase risk of additive immune effects during therapy and in weeks following administration
                  • When switching from drugs with prolonged immune effects, consider half-life and mode of action of such drugs to avoid unintended additive effects
                  • Initiating ponesimod after alemtuzumab is not recommended
                  • May be started immediately after discontinuing beta interferon or glatiramer acetate
                • Vaccinations
                  • Avoid use of live attenuated vaccines at least 1 month before initiating, during, and for 1-2 weeks after treatment
                  • If tested negative for VZV antibodies, a full course of the varicella vaccine is recommended before initiating ponesimod
                  • Vaccinations may be less effective if administered during treatment
                • Antiarrhythmic drugs, QT prolonging drugs, drugs that may decrease HR
                  • Consult cardiologist if considering treatment
                  • Class Ia (eg, quinidine, procainamide) and Class III (eg, amiodarone, sotalol) anti-arrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia
                  • Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, HR-lowering calcium channel blockers (eg, verapamil, diltiazem), or other drugs that may decrease HR (eg, digoxin)
                • Beta-blockers
                  • Use with caution
                  • Beta-blockers may have additive effects on lowering HR
                  • Patients on stable dose of beta-blocker; consider resting HR before initiating ponesimod
                  • If resting HR >55 bpm under long-term beta-blocker treatment, therapy may be introduced
                  • If resting HR ≤55 bpm, interrupt beta-blocker until baseline HR >55 bpm; ponesimod can then be initiated; restart beta-blocker once ponesimod is uptitrated to maintenance dose
                • Strong CYP3A4 and UGT1A1 inducers
                  • Not recommended
                  • In vitro assessments and limited clinical data indicated that concomitant use of strong CYP3A4 and UGT1A1 inducers (eg, rifampin, phenytoin, carbamazepine) may decrease systemic exposure of ponesimod; clinical relevance is unclear
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                Pregnancy & Lactation

                Pregnancy

                There are no adequate and well-controlled studies in pregnant females

                Animal data

                • Administration during pregnancy produced adverse effects on development (eg, embryolethality, fetal malformations), in absence of maternal toxicity
                • In rats and rabbits, visceral and skeletal malformations occurred at clinically relevant maternal ponesimod exposures
                • Receptor affected by ponesimod (sphingosine-1-phosphate receptor 1) has demonstrated to have an important role in embryogenesis, including vascular and neural development

                Contraception

                Females of childbearing potential
                • Before initiating: Counsel on potential for risks to the fetus
                • During treatment: Use effective contraception
                • Discontinuation: Elimination of ponesimod from body may take ~1 week, potential risk to the fetus may persist; use effective contraception during this period

                Lactation

                No data are available on presence in human milk, effects on breastfed infants, or effects on milk production

                When orally administered to female rats during pregnancy and lactation, drug was detected in plasma of offspring, suggesting excretion in milk

                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 1 modulator that binds with high affinity to S1P receptor 1

                Blocks capacity of lymphocytes to regress from lymph nodes, reducing number of lymphocytes in peripheral blood

                Mechanism of action in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into CNS

                Absorption

                Peak plasma time: 2-4 hr

                Absolute oral bioavailability: 84% (10-mg dose)

                Steady-state achieved following 3 days on maintenance dose

                Distribution

                Vd (steady-state): 160 L

                Protein-bound: >99%

                Readily crosses blood-brain-barrier as per animal studies

                Metabolism

                Extensively metabolized before excretion in humans, although unchanged ponesimod was the main circulating component in plasma

                Inactive circulating metabolites: M12, M13

                Metabolism to M13 occurs primarily through a combination of non-CYP450 enzymatic activities

                Multiple CYP450 (CYP2J2, CYP3A4, CYP3A5, CYP4F3A, and CYP4F12) and nonCYP450 enzymes catalyze oxidation to M12

                Also undergoes direct glucuronidation (mainly UGT1A1 and UGT2B7)

                Elimination

                Half-life: ~33 hr

                Clearance: 3.8 L/hr

                Excretion: Feces (57-80% [16% unchanged]); urine (10-18%)

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                Administration

                Oral Administration

                Take with or without food

                Swallow tablets whole

                Reinitiation after interruption

                • Interruption during treatment, especially during titration, is not recommended
                • <4 consecutive doses missed
                  • During titration: Resume with first missed titration dose and resume titration schedule at that dose and titration day
                  • During maintenance: Resume maintenance dose
                • ≥4 consecutive doses missed
                  • During titration or maintenance: Reinitiate with Day 1 of titration regimen (new starter pack); complete first-dose monitoring if recommended

                Storage

                Starter pack and maintenance dose bottle

                • Store at 20-25ºC (68-77ºF); excursions permitted from 15-30ºC (59-86ºF)
                • Store in the original package
                • Do not discard desiccant; protect from moisture
                • Keep out of reach of children
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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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                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
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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.