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Drug overview for PONVORY (ponesimod):
Generic name: PONESIMOD (poe-NES-i-mod)
Drug class: Multiple Sclerosis Agents, General
Therapeutic class: Multiple Sclerosis Agents
Ponesimod, a selective sphingosine 1-phosphate (S1P) receptor modulator, has immunomodulatory and disease-modifying activity in multiple sclerosis (MS).
No enhanced Uses information available for this drug.
Generic name: PONESIMOD (poe-NES-i-mod)
Drug class: Multiple Sclerosis Agents, General
Therapeutic class: Multiple Sclerosis Agents
Ponesimod, a selective sphingosine 1-phosphate (S1P) receptor modulator, has immunomodulatory and disease-modifying activity in multiple sclerosis (MS).
No enhanced Uses information available for this drug.
DRUG IMAGES
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The following indications for PONVORY (ponesimod) have been approved by the FDA:
Indications:
Relapsing form of multiple sclerosis
Secondary progressive multiple sclerosis
Professional Synonyms:
Multiple sclerosis, relapsing form
Indications:
Relapsing form of multiple sclerosis
Secondary progressive multiple sclerosis
Professional Synonyms:
Multiple sclerosis, relapsing form
The following dosing information is available for PONVORY (ponesimod):
Initiation of ponesimod decreases heart rate and may cause transient AV conduction delays. First-dose 4-hour monitoring is recommended in patients with heart rate <55 bpm, first- or second-degree AV block, or history of MI or heart failure occurring within the previous 6 months in stable condition. Seek advice from a cardiologist to determine the most appropriate monitoring strategy (which may include overnight monitoring) in patients with preexisting heart and cerebrovascular conditions; with prolonged significant QTc before initiation of therapy or during the 4-hour first-dose monitoring period, or risk factors for QTc prolongation; receiving concomitant therapy with QTc prolonging drugs with a known risk of torsades des pointes; or receiving concomitant treatment with drugs that slow heart rate or AV conduction.
Administer the first dose of ponesimod in a setting where there are resources to manage symptomatic bradycardia. At minimum, observe patients for at least 4 hours for signs and symptoms of bradycardia with hourly pulse and blood pressure measurements. An ECG should be obtained prior to the first dose and at the end of the 4-hour observation period.
Monitoring should be extended if any of the following abnormalities are present after 4 hours (even in the absence of symptoms) until the finding resolves: heart rate <45 beats per minute; patient is experiencing their lowest heart rate during the monitoring period, which suggests that the maximum pharmacodynamic effect on the heart may not have occurred; or ECG 4 hours post-dose shows new onset second-degree or higher AV block. If post-dose symptomatic bradycardia, bradyarrhythmia, or conduction abnormalities occur, or if the ECG 4-hours post-dose shows new onset second-degree or higher AV block or QTc >=500 msec, initiate appropriate treatment and start continuous ECG monitoring. Continue monitoring until symptoms resolve if no pharmacologic treatment is required.
If pharmacologic treatment is required, continue monitoring the patient overnight and repeat first-dose monitoring after the second dose.
During titration: If fewer than 4 consecutive doses are missed, resume treatment with the first missed titration dose and resume the titration schedule at that dose and titration day. If 4 or more consecutive doses are missed, reinitiate treatment with day 1 of the titration regimen using a new starter pack. If treatment is reinitiated with day 1 of the titration regimen, perform first-dose monitoring for patients in whom this monitoring is recommended.
During maintenance therapy: If fewer than 4 consecutive doses are missed, resume treatment with the maintenance dose. If 4 or more consecutive doses are missed, reinitiate treatment with day 1 of the titration regimen using a new starter pack. If treatment is reinitiated with day 1 of the titration regimen, perform first-dose monitoring for patients in whom this monitoring is recommended.
Administer the first dose of ponesimod in a setting where there are resources to manage symptomatic bradycardia. At minimum, observe patients for at least 4 hours for signs and symptoms of bradycardia with hourly pulse and blood pressure measurements. An ECG should be obtained prior to the first dose and at the end of the 4-hour observation period.
Monitoring should be extended if any of the following abnormalities are present after 4 hours (even in the absence of symptoms) until the finding resolves: heart rate <45 beats per minute; patient is experiencing their lowest heart rate during the monitoring period, which suggests that the maximum pharmacodynamic effect on the heart may not have occurred; or ECG 4 hours post-dose shows new onset second-degree or higher AV block. If post-dose symptomatic bradycardia, bradyarrhythmia, or conduction abnormalities occur, or if the ECG 4-hours post-dose shows new onset second-degree or higher AV block or QTc >=500 msec, initiate appropriate treatment and start continuous ECG monitoring. Continue monitoring until symptoms resolve if no pharmacologic treatment is required.
If pharmacologic treatment is required, continue monitoring the patient overnight and repeat first-dose monitoring after the second dose.
During titration: If fewer than 4 consecutive doses are missed, resume treatment with the first missed titration dose and resume the titration schedule at that dose and titration day. If 4 or more consecutive doses are missed, reinitiate treatment with day 1 of the titration regimen using a new starter pack. If treatment is reinitiated with day 1 of the titration regimen, perform first-dose monitoring for patients in whom this monitoring is recommended.
During maintenance therapy: If fewer than 4 consecutive doses are missed, resume treatment with the maintenance dose. If 4 or more consecutive doses are missed, reinitiate treatment with day 1 of the titration regimen using a new starter pack. If treatment is reinitiated with day 1 of the titration regimen, perform first-dose monitoring for patients in whom this monitoring is recommended.
Administer orally once daily without regard to food. Swallow tablets whole; do not chew or crush. Store ponesimod tablets in their original package at temperatures of 20-25degreesC (excursions permitted to 15-30degreesC).
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| PONVORY 14-DAY STARTER PACK | Maintenance | Adults take by oral route once daily per package directions |
| PONVORY 20 MG TABLET | Maintenance | Adults take 1 tablet (20 mg) by oral route once daily |
No generic dosing information available.
The following drug interaction information is available for PONVORY (ponesimod):
There are 4 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Efalizumab; Natalizumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Natalizumab,(1-3) efalizumab,(4) immunosuppressives, and immunomodulators all suppress the immune system. CLINICAL EFFECTS: Concurrent use of natalizumab(1-3) or efalizumab(4) with immunosuppressives or immunomodulators may result in an increased risk of infections, including progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV). PREDISPOSING FACTORS: Previous JCV infection, longer duration of natalizumab treatment - especially if greater than 2 years, and prior or concomitant treatment with immunosuppressant medication are all independent risk factors which increase the risk for PML.(1,5) The FDA has estimated PML incidence stratified by risk factors: If anti-JCV antibody positive, no prior immunosuppressant use and natalizumab treatment less than 25 months, incidence <1/1,000. If anti-JCV antibody positive, history of prior immunosuppressant use and natalizumab treatment less than 25 months, incidence 2/1,000 If anti-JCV antibody positive, no prior immunosuppressant use and natalizumab treatment 25-48 months, incidence 4/1,000 If anti-JCV antibody positive, history of prior immunosuppressant use and natalizumab treatment 25-48 months, incidence 11/1,000. PATIENT MANAGEMENT: The US manufacturer of natalizumab states patients with Crohn's disease should not receive concurrent immunosuppressants, with the exception of limited overlap of corticosteroids, due to the increased risk for PML. For new natalizumab patients currently receiving chronic oral corticosteroids for Crohn's Disease, begin corticosteroid taper when therapeutic response to natalizumab has occurred. If corticosteroids cannot be discontinued within six months of starting natalizumab, discontinue natalizumab.(3) The US manufacturer of natalizumab states that natalizumab should not ordinarily be used in multiple sclerosis patients receiving immunosuppressants or immunomodulators due to the increased risk for PML. Immunosuppressives include, but are not limited to azathioprine, cyclophosphamide, cyclosporine, mercaptopurine, methotrexate, mitoxantrone, mycophenolate, and corticosteroids.(3,6) The UK manufacturer of natalizumab states that concurrent use with immunosuppressives or antineoplastic agents is contraindicated.(1) The Canadian manufacturer of natalizumab states that natalizumab should not be used with immunosuppressive or immunomodulatory agents.(2) The US manufacturer of certolizumab states that concurrent therapy with natalizumab is not recommended.(7) DISCUSSION: Progressive multifocal leukoencephalopathy has been reported in patients receiving concurrent natalizumab were recently or concomitantly taking immunomodulators or immunosuppressants.(1-5,8,9) In a retrospective cohort study of multiple sclerosis patients newly initiated on a disease-modifying therapy, use of high-efficacy agents (alemtuzumab, natalizumab, or ocrelizumab) resulted in the same risk of overall infections as moderate-efficacy agents, but there was an elevated risk of serious infections (adjusted hazard ratio [aHR] = 1.24, 95% confidence interval (CI) = 1.06-1.44) and UTIs (aHR = 1.21, 95% CI = 1.14-1.30).(10) |
TYRUKO, TYSABRI |
| Live Vaccines; Live BCG/Selected Immunosuppressive Agents SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: A variety of disease modifying agents suppress the immune system. Immunocompromised patients may be at increased risk for uninhibited replication after administration of live, attenuated vaccines or intravesicular BCG. Immune response to vaccines may be decreased during periods of immunocompromise.(1) CLINICAL EFFECTS: The expected serum antibody response may not be obtained and/or the vaccine may result in illness.(1) After instillation of intravesicular BCG, immunosuppression may interfere with local immune response, or increase the severity of mycobacterial infection following inadvertent systemic exposure.(2) PREDISPOSING FACTORS: Immunosuppressive diseases (e.g. hematologic malignancies, HIV disease), treatments (e.g. radiation) and drugs may all increase the magnitude of immunodeficiency. PATIENT MANAGEMENT: The Centers for Disease Control(CDC) Advisory Committee on Immunization Practices (ACIP) states that live-virus and live, attenuated vaccines should not be administered to patients who are immunocompromised. The magnitude of immunocompromise and associated risks should be determined by a physician.(1) For patients scheduled to receive chemotherapy, vaccination should ideally precede the initiation of chemotherapy by 14 days. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy.(1) Patients who receive anti-B cell therapies should not receive live vaccines for at least 6 months after such therapies due to a prolonged duration of immunosuppression. An exception is the Zoster vaccine, which can be given at least 1 month after receipt of anti-B cell therapies.(1) The US manufacturer of abatacept states live vaccines should not be given during or for up to 3 months after discontinuation of abatacept.(2) The US manufacturer of live BCG for intravesicular treatment of bladder cancer states use is contraindicated in immunosuppressed patients.(3) The US manufacturer of daclizumab states live vaccines are not recommended during and for up to 4 months after discontinuation of treatment.(4) The US manufacturer of guselkumab states that live vaccines should be avoided during treatment with guselkumab.(5) The US manufacturer of inebilizumab-cdon states that live vaccines are not recommended during treatment and after discontinuation until B-cell repletion. Administer all live vaccinations at least 4 weeks prior to initiation of inebilizumab-cdon.(6) The US manufacturer of ocrelizumab states that live vaccines are not recommended during treatment and until B-cell repletion occurs after discontinuation of therapy. Administer all live vaccines at least 4 weeks prior to initiation of ocrelizumab.(7) The US manufacturer of ozanimod states that live vaccines should be avoided during and for up to 3 months after discontinuation of ozanimod.(8) The US manufacturer of siponimod states that live vaccines are not recommended during treatment and for up to 4 weeks after discontinuation of treatment.(9) The US manufacturer of ustekinumab states BCG vaccines should not be given in the year prior to, during, or the year after ustekinumab therapy.(10) The US manufacturer of satralizumab-mwge states that live vaccines are not recommended during treatment and should be administered at least four weeks prior to initiation of satralizumab-mwge.(11) The US manufacturer of ublituximab-xiiy states that live vaccines are not recommended during treatment and until B-cell recovery. Live vaccines should be administered at least 4 weeks prior to initiation of ublituximab-xiiy.(12) The US manufacturer of etrasimod states that live vaccines should be avoided during and for 5 weeks after treatment. Live vaccines should be administered at least 4 weeks prior to initiation of etrasimod.(13) The US manufacturer of emapalumab-lzsg states that live vaccines should not be administered to patients receiving emapalumab-lzsg and for at least 4 weeks after the last dose of emapalumab-lzsg. The safety of immunization with live vaccines during or following emapalumab-lzsg therapy has not been studied.(14) The US manufacturer of sibeprenlimab-szsi states live vaccines should not be given within 30 days prior to initiation or during treatment with sibeprenlimab-szsi.(15) DISCUSSION: Killed or inactivated vaccines do not pose a danger to immunocompromised patients.(1) Patients with a history of leukemia who are in remission and have not received chemotherapy for at least 3 months are not considered to be immunocompromised.(1) |
ACAM2000 (NATIONAL STOCKPILE), ADENOVIRUS TYPE 4, ADENOVIRUS TYPE 4 AND TYPE 7, ADENOVIRUS TYPE 7, BCG (TICE STRAIN), BCG VACCINE (TICE STRAIN), DENGVAXIA, ERVEBO (NATIONAL STOCKPILE), FLUMIST 2025-2026, FLUMIST HOME 2025-2026, M-M-R II VACCINE, PRIORIX, PROQUAD, ROTARIX, ROTATEQ, STAMARIL, VARIVAX VACCINE, VAXCHORA ACTIVE COMPONENT, VAXCHORA VACCINE, VIVOTIF, YF-VAX |
| Talimogene laherparepvec/Selected Immunosuppressants SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Talimogene laherparepvec is a live, attenuated herpes simplex virus.(1) CLINICAL EFFECTS: Concurrent use of talimogene laherparepvec in patients receiving immunosuppressive therapy may cause a life-threatening disseminated herpetic infection.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Talimogene laherparepvec is contraindicated in immunosuppressed patients.(1) The magnitude of immunocompromise and associated risks due to immunosuppressant drugs should be determined by a physician. DISCUSSION: Concurrent use of talimogene laherparepvec in patients receiving immunosuppressive therapy may cause a life-threatening disseminated herpetic infection.(1) |
IMLYGIC |
| Nadofaragene Firadenovec/Selected Immunosuppressants SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Nadofaragene firadenovec may contain low levels of replication-competent adenovirus.(1) CLINICAL EFFECTS: Concurrent use of nadofaragene firadenovec in patients receiving immunosuppressive therapy may cause disseminated adenovirus infection.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Individuals who are immunosuppressed or immune-deficient should not receive nadofaragene firadenovec.(1) DISCUSSION: Nadofaragene firadenovec is a non-replicating adenoviral vector-based gene therapy but may contain low levels of replication-competent adenovirus. Immunocompromised persons, including those receiving immunosuppressant therapy, may be at risk for disseminated adenovirus infection.(1) |
ADSTILADRIN |
There are 6 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Ponesimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ponesimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of ponesimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection, cryptococcal infection, or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The ponesimod US prescribing information states ponesimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects. Initiating treatment with ponesimod after alemtuzumab is not recommended. However, ponesimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections, cryptococcal meningitis, disseminated cryptococcal infections, and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1) |
ABECMA, ABRAXANE, ABRILADA(CF), ABRILADA(CF) PEN, ABRILADA(CF) PEN (2 PACK), ACTEMRA, ACTEMRA ACTPEN, ACTIMMUNE, ADALIMUMAB-AACF(CF), ADALIMUMAB-AACF(CF) (2 PK), ADALIMUMAB-AACF(CF) PEN (2 PK), ADALIMUMAB-AACF(CF) PEN CROHNS, ADALIMUMAB-AACF(CF) PEN PS-UV, ADALIMUMAB-AATY(CF), ADALIMUMAB-AATY(CF) AI CROHNS, ADALIMUMAB-AATY(CF) AUTOINJECT, ADALIMUMAB-ADAZ(CF), ADALIMUMAB-ADAZ(CF) PEN, ADALIMUMAB-ADBM(CF), ADALIMUMAB-ADBM(CF) PEN, ADALIMUMAB-ADBM(CF)PEN, ADALIMUMAB-BWWD(CF), ADALIMUMAB-BWWD(CF) AUTOINJECT, ADALIMUMAB-FKJP(CF), ADALIMUMAB-FKJP(CF) PEN, ADALIMUMAB-RYVK(CF), ADALIMUMAB-RYVK(CF) AUTOINJECT, ADCETRIS, ADRIAMYCIN, ADRUCIL, AFINITOR, AFINITOR DISPERZ, AGAMREE, AKEEGA, ALFERON N, ALKERAN, ALKINDI SPRINKLE, ALUNBRIG, ALYMSYS, AMJEVITA(CF), AMJEVITA(CF) AUTOINJECTOR, AMTAGVI, ANUCORT-HC, ANUSOL-HC, ARAVA, ARCALYST, ARRANON, ARZERRA, ASPARLAS, AUBAGIO, AUCATZYL, AUGTYRO, AVASTIN, AVGEMSI, AVONEX, AVONEX (4 PACK), AVONEX PEN, AVONEX PEN (4 PACK), AVSOLA, AVTOZMA, AVTOZMA AUTOINJECTOR, AXTLE, AZACITIDINE, AZASAN, AZATHIOPRINE, AZATHIOPRINE SODIUM, AZELAIC ACID, BAFIERTAM, BAVENCIO, BECLOMETHASONE DIPROPIONATE, BEIZRAY, BEIZRAY-ALBUMIN, BELEODAQ, BELRAPZO, BENDAMUSTINE HCL, BENDEKA, BESREMI, BETALOAN SUIK, BETAMETHASONE ACETATE MICRO, BETAMETHASONE ACETATE-SOD PHOS, BETAMETHASONE DIPROPIONATE, BETAMETHASONE SOD PHOS-ACETATE, BETAMETHASONE SOD PHOS-WATER, BETAMETHASONE SODIUM PHOSPHATE, BETAMETHASONE VALERATE, BETASERON, BEXAROTENE, BICNU, BIMZELX, BIMZELX AUTOINJECTOR, BLEOMYCIN SULFATE, BLINCYTO, BORTEZOMIB, BORUZU, BOSULIF, BREYANZI, BREYANZI CD4 COMPONENT, BREYANZI CD8 COMPONENT, BRIUMVI, BRUKINSA, BUDESONIDE, BUDESONIDE DR, BUDESONIDE EC, BUDESONIDE ER, BUDESONIDE MICRONIZED, BUPIVACAINE-DEXAMETH-EPINEPHRN, BUSULFAN, BUSULFEX, CAELYX, CALQUENCE, CAMPTOSAR, CAPECITABINE, CARBOPLATIN, CARMUSTINE, CARVYKTI, CELESTONE, CELLCEPT, CHLORAMBUCIL, CIBINQO, CIMZIA, CIMZIA (2 PACK), CISPLATIN, CLADRIBINE, CLOBETASOL PROPIONATE MICRO, CLOFARABINE, COLUMVI, COPAXONE, COPIKTRA, CORTEF, CORTISONE ACETATE, COSENTYX, COSENTYX (2 SYRINGES), COSENTYX SENSOREADY (2 PENS), COSENTYX SENSOREADY PEN, COSENTYX SYRINGE, COSENTYX UNOREADY PEN, CYCLOPHOSPHAMIDE, CYCLOPHOSPHAMIDE MONOHYDRATE, CYCLOSPORINE, CYCLOSPORINE MODIFIED, CYLTEZO(CF), CYLTEZO(CF) PEN, CYTARABINE, DACARBAZINE, DACTINOMYCIN, DANYELZA, DARAPRIM, DARZALEX, DARZALEX FASPRO, DAUNORUBICIN HCL, DECITABINE, DEFERIPRONE, DEFERIPRONE (3 TIMES A DAY), DEFLAZACORT, DEPO-MEDROL, DESONIDE MICRONIZED, DESOXIMETASONE, DEXABLISS, DEXAMETHASONE, DEXAMETHASONE ACETATE, DEXAMETHASONE ACETATE MICRO, DEXAMETHASONE INTENSOL, DEXAMETHASONE ISONICOTINATE, DEXAMETHASONE MICRONIZED, DEXAMETHASONE SOD PHOS-WATER, DEXAMETHASONE SODIUM PHOSPHATE, DEXAMETHASONE-0.9% NACL, DEXRAZOXANE, DIMETHYL FUMARATE, DMT SUIK, DOCETAXEL, DOCIVYX, DOUBLEDEX, DOXIL, DOXORUBICIN HCL, DOXORUBICIN HCL LIPOSOME, DROXIA, EFLORNITHINE HCL, ELAHERE, ELLENCE, ELREXFIO, EMFLAZA, ENBREL, ENBREL MINI, ENBREL SURECLICK, ENHERTU, ENSPRYNG, ENTYVIO, ENTYVIO PEN, EOHILIA, EPIRUBICIN HCL, EPKINLY, ERBITUX, ERLOTINIB HCL, ETOPOPHOS, ETOPOSIDE, EVEROLIMUS, EVOMELA, FERRIPROX, FERRIPROX (2 TIMES A DAY), FERRIPROX (3 TIMES A DAY), FLOXURIDINE, FLUDARABINE PHOSPHATE, FLUNISOLIDE, FLUOCINOLONE ACETONIDE, FLUOCINOLONE ACETONIDE MICRO, FLUOCINONIDE MICRONIZED, FLUOROURACIL, FLUTICASONE PROPIONATE, FLUTICASONE PROPIONATE MICRO, FOLOTYN, FRINDOVYX, FYARRO, GAMIFANT, GAVRETO, GAZYVA, GEFITINIB, GEMCITABINE HCL, GENGRAF, GLATIRAMER ACETATE, GLATOPA, GLEEVEC, GLEOSTINE, GLIADEL, GRAFAPEX, HADLIMA, HADLIMA PUSHTOUCH, HADLIMA(CF), HADLIMA(CF) PUSHTOUCH, HEMADY, HEMMOREX-HC, HEPZATO, HERCEPTIN, HERCEPTIN HYLECTA, HERCESSI, HERZUMA, HEXATRIONE, HICON, HULIO(CF), HULIO(CF) PEN, HUMIRA, HUMIRA PEN, HUMIRA(CF), HUMIRA(CF) PEN, HUMIRA(CF) PEN CROHN'S-UC-HS, HUMIRA(CF) PEN PSOR-UV-ADOL HS, HYCAMTIN, HYDREA, HYDROCORTISONE, HYDROCORTISONE ACETATE, HYDROCORTISONE SOD SUCCINATE, HYDROXYUREA, HYRIMOZ(CF), HYRIMOZ(CF) PEDIATRIC CROHN'S, HYRIMOZ(CF) PEN, HYRIMOZ(CF) PEN CROHN-UC START, HYRIMOZ(CF) PEN PSORIASIS, IBRANCE, ICLUSIG, IDAMYCIN PFS, IDARUBICIN HCL, IFEX, IFOSFAMIDE, ILARIS, IMATINIB MESYLATE, IMBRUVICA, IMDELLTRA, IMFINZI, IMKELDI, IMULDOSA, IMURAN, INFLECTRA, INFLIXIMAB, INFUGEM, INQOVI, INREBIC, IRESSA, IRINOTECAN HCL, IVRA, IWILFIN, IXEMPRA, JAKAFI, JAYPIRCA, JAYTHARI, JEMPERLI, JEVTANA, JOBEVNE, JOENJA, JYLAMVO, KADCYLA, KANJINTI, KEMOPLAT, KENALOG-10, KENALOG-40, KENALOG-80, KEVZARA, KEYTRUDA, KEYTRUDA QLEX, KHINDIVI, KINERET, KYMBEE, KYMRIAH, KYXATA, LEFLUNICLO, LEFLUNOMIDE, LENALIDOMIDE, LEQSELVI, LEUKERAN, LIDOCIDEX-I, LITFULO, LOMUSTINE, LONSURF, LOQTORZI, LUNSUMIO, LUNSUMIO VELO, LUTATHERA, LYMPHIR, LYNOZYFIC, LYNPARZA, MAS CARE-PAK, MATULANE, MECHLORETHAMINE HCL, MEDROL, MEDROLOAN II SUIK, MEDROLOAN SUIK, MEKINIST, MEKTOVI, MELPHALAN HCL, MERCAPTOPURINE, METHOTREXATE, METHOTREXATE SODIUM, METHOTREXATE-NACL, METHYLPREDNISOLONE, METHYLPREDNISOLONE AC MICRO, METHYLPREDNISOLONE ACETATE, METHYLPREDNISOLONE SODIUM SUCC, MILLIPRED, MILLIPRED DP, MITOMYCIN, MITOXANTRONE HCL, MOMETASONE FUROATE, MONJUVI, MUTAMYCIN, MVASI, MYCOPHENOLATE MOFETIL, MYCOPHENOLIC ACID, MYFORTIC, MYHIBBIN, MYLERAN, MYLOTARG, NELARABINE, NEORAL, NIPENT, NULOJIX, OGIVRI, OJJAARA, OLUMIANT, ONCASPAR, ONIVYDE, ONTRUZANT, ONUREG, OPDIVO, OPDIVO QVANTIG, OPDUALAG, ORAPRED ODT, ORENCIA, ORENCIA CLICKJECT, OTULFI, P-PACK PREDNISONE, PACLITAXEL, PACLITAXEL PROTEIN-BOUND, PADCEV, PEGASYS, PEMETREXED, PEMETREXED DISODIUM, PEMFEXY, PEMRYDI RTU, PERJETA, PHESGO, PHOTOFRIN, PLEGRIDY, PLEGRIDY PEN, PLUVICTO, POLIVY, POMALIDOMIDE, POMALYST, POTELIGEO, PRALATREXATE, PREDNISOLONE, PREDNISOLONE ACETATE MICRONIZE, PREDNISOLONE MICRONIZED, PREDNISOLONE SODIUM PHOS ODT, PREDNISOLONE SODIUM PHOSPHATE, PREDNISONE, PREDNISONE INTENSOL, PREDNISONE MICRONIZED, PROCARBAZINE HCL, PROCTOCORT, PROLEUKIN, PROVENGE, PURIXAN, PYQUVI, PYRIMETHAMINE, PYZCHIVA, PYZCHIVA AUTOINJECTOR, RASUVO, REBIF, REBIF REBIDOSE, REMICADE, RENFLEXIS, REVLIMID, REZUROCK, RIABNI, RINVOQ, RINVOQ LQ, RITUXAN, RITUXAN HYCELA, RUXIENCE, RYLAZE, RYTELO, SANDIMMUNE, SARCLISA, SCEMBLIX, SELARSDI, SIKLOS, SIMLANDI(CF), SIMLANDI(CF) AUTOINJECTOR, SIMPONI, SIMPONI ARIA, SIMULECT, SIROLIMUS, SODIUM IODIDE I-123, SODIUM IODIDE I-131, SOLU-CORTEF, SOLU-MEDROL, SOTYKTU, STARJEMZA, STELARA, STEQEYMA, STRONTIUM-89 CHLORIDE, TABLOID, TALTZ AUTOINJECTOR, TALTZ AUTOINJECTOR (2 PACK), TALTZ AUTOINJECTOR (3 PACK), TALTZ SYRINGE, TALVEY, TALZENNA, TAPERDEX, TARGRETIN, TARPEYO, TECARTUS, TECELRA, TECENTRIQ, TECENTRIQ HYBREZA, TECFIDERA, TECVAYLI, TEMODAR, TEMOZOLOMIDE, TEMSIROLIMUS, TEPADINA, TEPYLUTE, TERIFLUNOMIDE, TEVIMBRA, THIOTEPA, TOFACITINIB CITRATE, TOFIDENCE, TOPOTECAN HCL, TORISEL, TORPENZ, TRAMETINIB, TRAZIMERA, TREANDA, TRETINOIN, TREXALL, TRIAMCINOLONE, TRIAMCINOLONE ACETONIDE, TRIAMCINOLONE DIACETATE, TRIAMCINOLONE DIACETATE MICRO, TRILOAN II SUIK, TRILOAN SUIK, TRODELVY, TRUQAP, TRUXIMA, TYENNE, TYENNE AUTOINJECTOR, TZIELD, UCERIS, UNITUXIN, UNLOXCYT, UPLIZNA, USTEKINUMAB, USTEKINUMAB-AAUZ, USTEKINUMAB-AEKN, USTEKINUMAB-TTWE, UVADEX, VECTIBIX, VEGZELMA, VELCADE, VENCLEXTA, VENCLEXTA STARTING PACK, VERIPRED 20, VERZENIO, VIDAZA, VINBLASTINE SULFATE, VINCASAR PFS, VINCRISTINE SULFATE, VINORELBINE TARTRATE, VITRAKVI, VIVIMUSTA, VOYXACT, VYXEOS, WAYRILZ, WEZLANA, XATMEP, XELJANZ, XELJANZ XR, XOFIGO, XPOVIO, XROMI, YESCARTA, YESINTEK, YONDELIS, YUFLYMA(CF), YUFLYMA(CF) AI CROHN'S-UC-HS, YUFLYMA(CF) AUTOINJECTOR, YUSIMRY(CF) PEN, ZANOSAR, ZCORT, ZEJULA, ZEPZELCA, ZEVALIN, ZILRETTA, ZIRABEV, ZOLINZA, ZORTRESS, ZYDELIG, ZYMFENTRA, ZYMFENTRA PEN, ZYNLONTA, ZYNYZ |
| Ponesimod/Beta-Blockers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Initiation of ponesimod has caused transient decreases in heart rate and atrioventricular conduction delays after the first dose. Decreases in heart rate start within the first hour and maximal decrease in heart rate was seen at approximately 2-4 hours. The first dose has also been associated with heart block. Beta-blockers further increase the risk for symptomatic bradycardia or heart block.(1) CLINICAL EFFECTS: The heart rate lowering effect of ponesimod is transient and is usually seen with the first dose. Bradycardia may be associated with an increase in the QTc interval, increasing the risk for torsade de pointes.(1) PREDISPOSING FACTORS: Pre-existing cardiovascular disease (e.g. heart failure, ischemic heart disease, history of myocardial infarction, stroke, history of torsades de pointes, or heart block), severe untreated sleep apnea, a prolonged QTc interval prior to siponimod initiation, or factors associated with QTc prolongation (e.g. hypokalemia, hypomagnesemia, bradycardia, female gender, or advanced age) may increase risk for cardiovascular toxicity due to siponimod. Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: The prescribing information states temporary interruption in beta-blocker therapy may be needed before initiation of ponesimod. Beta-blocker therapy can be initiated in patients receiving stable doses of ponesimod.(1) Treatment initiation recommendations include: - Obtain an ECG in all patients to determine whether preexisting conduction abnormalities are present. - In all patients, a dose titration is recommended for initiation of ponesimod treatment to help reduce cardiac effects. - In patients with sinus bradycardia (HR less than 55 bpm), first- or second-degree [Mobitz type I] AV block, or a history of myocardial infarction or heart failure with onset > 6 months prior to initiation, ECG testing and first dose monitoring is recommended. - Since significant bradycardia may be poorly tolerated in patients with history of cardiac arrest, cerebrovascular disease, uncontrolled hypertension, or severe untreated sleep apnea, ponesimod is not recommended in these patients. If treatment is considered, advice from a cardiologist should be sought prior to initiation of treatment in order to determine the most appropriate monitoring strategy. - Use of ponesimod in patients with a history of recurrent syncope or symptomatic bradycardia should be based on an overall benefit-risk assessment. If treatment is considered, advice from a cardiologist should be sought prior to initiation of treatment in order to determine the most appropriate monitoring. - For patients receiving a stable dose of a beta-blocker, the resting heart rate should be considered before introducing ponesimod treatment. If the resting heart rate is greater than 55 bpm under chronic beta-blocker treatment, ponesimod can be introduced. If resting heart rate is less than or equal to 55 bpm, beta-blocker treatment should be interrupted until the baseline heart-rate is greater than 55 bpm. Treatment with ponesimod can then be initiated and treatment with a beta-blocker can be reinitiated after ponesimod has been up-titrated to the target maintenance dosage. - If a titration dose is missed or if 4 or more consecutive daily doses are missed during maintenance treatment, reinitiate Day 1 of the dose titration and follow titration monitoring recommendations.(1) DISCUSSION: After the first titration dose of ponesimod the heart rate decrease starts within an hour, and the Day 1 decline is maximal at approximately 2-4 hours. With continued up-titration, further heart rate decreases are seen on subsequent days, with maximal decrease from Day 1-baseline reached on Day 4-5. The highest daily post-dose decrease in absolute hourly mean heart rate is observed on Day 1, with the pulse declining on average 6 bpm. Post-dose declines on the following days are less pronounced. With continued dosing, heart rate starts increasing after Day 6 and reaches placebo levels within 10 days after treatment initiation. In a study, bradycardia occurred in 5.8% of ponesimod-treated patients compared to 1.6% of patients receiving placebo. Patients who experienced bradycardia were generally asymptomatic. Few patients experienced symptoms, including dizziness or fatigue, and these symptoms resolved within 24 hours without intervention.(1) Beta-Blockers linked to this monograph are: atenolol, betaxolol, bisoprolol, carvedilol, esmolol, landiolol, labetalol, metoprolol, nadolol, nebivolol, propranolol and timolol. |
ACEBUTOLOL HCL, ATENOLOL, ATENOLOL-CHLORTHALIDONE, BETAXOLOL HCL, BISOPROLOL FUMARATE, BISOPROLOL-HYDROCHLOROTHIAZIDE, BREVIBLOC, BYSTOLIC, CARVEDILOL, CARVEDILOL ER, COREG, COREG CR, ESMOLOL HCL, ESMOLOL HCL-SODIUM CHLORIDE, ESMOLOL HCL-WATER, HEMANGEOL, INDERAL LA, INDERAL XL, INNOPRAN XL, KAPSPARGO SPRINKLE, LABETALOL HCL, LABETALOL HCL-WATER, LOPRESSOR, METOPROLOL SUCCINATE, METOPROLOL TARTRATE, METOPROLOL-HYDROCHLOROTHIAZIDE, NADOLOL, NEBIVOLOL HCL, PINDOLOL, PROPRANOLOL HCL, PROPRANOLOL HCL ER, PROPRANOLOL-HYDROCHLOROTHIAZID, RAPIBLYK, TENORETIC 100, TENORETIC 50, TENORMIN, TIMOLOL MALEATE, TOPROL XL |
| Ponesimod/Agents That Cause Bradycardia SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Initiation of ponesimod has caused transient decreases in heart rate and atrioventricular conduction delays after the first dose. Decreases in heart rate start within the first hour and maximal decrease in heart rate was seen at approximately 2-4 hours. The first dose has also been associated with heart block. Additional agents that cause bradycardia further increase the risk for symptomatic bradycardia.(1) CLINICAL EFFECTS: The heart rate lowering effect of ponesimod is transient and is usually seen with the first dose. Bradycardia may be associated with an increase in the QTc interval, increasing the risk for torsade de pointes.(1) PREDISPOSING FACTORS: Pre-existing cardiovascular disease (e.g. heart failure, ischemic heart disease, history of myocardial infarction, stroke, history of torsades de pointes, or heart block), severe untreated sleep apnea, a prolonged QTc interval prior to siponimod initiation, or factors associated with QTc prolongation (e.g. hypokalemia, hypomagnesemia, bradycardia, female gender, or advanced age) may increase risk for cardiovascular toxicity due to siponimod.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: The prescribing information states ponesimod treatment should generally not be initiated in patients who are on concurrent therapy with additional agents that cause bradycardia. If treatment with ponesimod is considered, advice from a cardiologist should be sought regarding switching to non-heart rate lowering drugs or monitoring during treatment initiation. Treatment initiation recommendations include: - Obtain an ECG in all patients to determine whether preexisting conduction abnormalities are present. - In all patients, a dose titration is recommended for initiation of ponesimod treatment to help reduce cardiac effects. - In patients with sinus bradycardia (HR less than 55 bpm), first- or second-degree [Mobitz type I] AV block, or a history of myocardial infarction or heart failure with onset > 6 months prior to initiation, ECG testing and first dose monitoring is recommended. - Since significant bradycardia may be poorly tolerated in patients with history of cardiac arrest, cerebrovascular disease, uncontrolled hypertension, or severe untreated sleep apnea, ponesimod is not recommended in these patients. If treatment is considered, advice from a cardiologist should be sought prior to initiation of treatment in order to determine the most appropriate monitoring strategy. - Use of ponesimod in patients with a history of recurrent syncope or symptomatic bradycardia should be based on an overall benefit-risk assessment. If treatment is considered, advice from a cardiologist should be sought prior to initiation of treatment in order to determine the most appropriate monitoring. - If a titration dose is missed or if 4 or more consecutive daily doses are missed during maintenance treatment, reinitiate Day 1 of the dose titration and follow titration monitoring recommendations.(1) DISCUSSION: Initiation of ponesimod treatment has been associated with transient atrioventricular (AV) conduction delays that follow a similar temporal pattern as the observed decrease in heart rate during dose titration. The AV conduction delays manifested in most of the cases as first-degree AV block (prolonged PR interval on ECG), which occurred in 3.4% of ponesimod treated patients and in 1.2% of patients receiving teriflunomide in Study 1. Second-degree or third-degree AV blocks have not been reported in patients in clinical trials. The conduction abnormalities typically were transient, asymptomatic, resolved within 24 hours, and did not require discontinuation of ponesimod treatment.(1) |
CARDIZEM, CARDIZEM CD, CARDIZEM LA, CARTIA XT, CATAPRES-TTS 1, CATAPRES-TTS 2, CATAPRES-TTS 3, CLONIDINE, CLONIDINE HCL, CLONIDINE HCL ER, CORLANOR, DEXMEDETOMIDINE HCL, DEXMEDETOMIDINE-0.9% NACL, DEXMEDETOMIDINE-D5W, DIGITEK, DIGOXIN, DIGOXIN MICRONIZED, DILT-XR, DILTIAZEM 12HR ER, DILTIAZEM 24HR ER, DILTIAZEM 24HR ER (CD), DILTIAZEM 24HR ER (LA), DILTIAZEM 24HR ER (XR), DILTIAZEM HCL, DILTIAZEM HCL-0.7% NACL, DILTIAZEM HCL-0.9% NACL, DILTIAZEM HCL-NACL, DILTIAZEM-D5W, IVABRADINE HCL, JAVADIN, LANOXIN, LANOXIN PEDIATRIC, MATZIM LA, NEXICLON XR, ONYDA XR, PRECEDEX, R.E.C.K.(ROPIV-EPI-CLON-KETOR), ROPIVACAINE-CLONIDINE-KETOROLC, TIADYLT ER, TIAZAC, TRANDOLAPRIL-VERAPAMIL ER, VERAPAMIL ER, VERAPAMIL ER PM, VERAPAMIL HCL, VERAPAMIL SR |
| Ponesimod/Immunosuppressives; Immunomodulators that Prolong QT SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ponesimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1) Initiation of ponesimod has a negative chronotropic effect leading to a mean decrease in heart rate of 6 beats per minute (bpm) after the first dose. The first dose has also been associated with heart block.(1) CLINICAL EFFECTS: Concurrent use of ponesimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection, cryptococcal infection, or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1) The heart rate lowering effect of ponesimod reaches an initial decrease within an hour and reaches its nadir within 2-4 hours. The heart rate typically recovers to baseline levels 4-5 hours after administration. All patients recovered from bradycardia. The conduction abnormalities typically were transient, asymptomatic, resolved within 24 hours. Second- and third-degree AV blocks were not reported. With up-titration after Day 1, the post-dose decrease in heart rate is less pronounced. Bradycardia may be associated with an increase in the QTc interval, increasing the risk for torsades de pointes.(1,2) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications may increase the risk from this interaction. Pre-existing cardiovascular or cerebrovascular disease (e.g. heart failure, ischemic heart disease, history of myocardial infarction, stroke, or heart block), severe untreated sleep apnea, a prolonged QTc interval prior to ponesimod initiation, factors associated with QTc prolongation, or concomitant treatment with QT prolonging agents may increase risk for cardiovascular toxicity due to ponesimod.(1) The risk of QT prolongation or torsades de pointes may also be increased in patients with a history of torsades de pointes, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of the QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: The ponesimod US prescribing information states ponesimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects. Initiating treatment with ponesimod after alemtuzumab is not recommended. However, ponesimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1) Ponesimod is generally not recommended in patients receiving concurrent treatment with a QT prolonging agent, anti-arrhythmic drugs, or drugs that may decrease heart rate. Consultation with a cardiologist is recommended. Consult the prescribing information for recommendations regarding cardiac monitoring.(1) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections, cryptococcal meningitis, disseminated cryptococcal infections, and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1) After the first dose of ponesimod, heart rate decrease may begin within the first hour. Decline is usually maximal at approximately 4 hours. With continued, chronic dosing, post-dose decrease in heart rate is less pronounced. Heart rate gradually returns to baseline in about 4-5 hours.(1) |
ARSENIC TRIOXIDE, ASTAGRAF XL, BESPONSA, BRAFTOVI, DANZITEN, DASATINIB, DAURISMO, ENVARSUS XR, FARYDAK, ISTODAX, KISQALI, KOMZIFTI, LAPATINIB, NILOTINIB D-TARTRATE, NILOTINIB HCL, OXALIPLATIN, PAZOPANIB HCL, PHYRAGO, PROGRAF, QUALAQUIN, QUININE HCL, QUININE SULFATE, REVUFORJ, ROMIDEPSIN, RUBRACA, RYDAPT, SPRYCEL, SUNITINIB MALATE, SUTENT, TACROLIMUS, TACROLIMUS XL, TASIGNA, TRISENOX, TYKERB, VANFLYTA, VOTRIENT, XALKORI, ZOKINVY |
| Clozapine/Ponesimod SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of clozapine with other agents that prolong the QTc interval may result in additive effects on the QTc interval.(1) Initiation of ponesimod has a negative chronotropic effect and may cause bradycardia, which may increase the risk of QT prolongation.(2) Clozapine and concurrent use with other myelosuppressive agents, including ponesimod, may be associated with additive risk of neutropenia or agranulocytosis.(1) CLINICAL EFFECTS: Concurrent use of clozapine with agents that prolong the QTc interval may result in life-threatening cardiac arrhythmias.(1) Ponesimod lowers heart rate (HR) within 1 hour of the 1st dose. HR reaches its nadir within 2-4 hours and typically recovers to baseline levels 4-5 hours after dose. The conduction abnormalities typically were transient, asymptomatic, and resolved within 24 hours. With up-titration after Day 1, the post-dose decrease in heart rate is less pronounced. Bradycardia may be associated with an increase in the QTc interval.(2) Moderate neutropenia may require abrupt discontinuation of clozapine resulting in decompensation of the patient's psychiatric disorder. Ponesimod therapy may be compromised if myelosuppression requires dose reduction, delay, or discontinuation of ponesimod. Undetected severe neutropenia or agranulocytosis may be fatal. PREDISPOSING FACTORS: The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(3) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of the QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(3) Low white blood counts prior to initiation of the myelosuppressive agent may increase risk for clinically significant neutropenia.(1) PATIENT MANAGEMENT: Approach the concurrent use of clozapine and other agents that prolong the QTc interval with caution.(1) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. If a patient stabilized on clozapine therapy requires treatment with other myelosuppressive agents the clozapine prescriber should consult with the prescriber of the myelosuppressive agent to discuss treatment and monitoring options. More frequent absolute neutrophil count (ANC) monitoring or treatment alternatives secondary to neutropenic episodes may need to be considered. The U.S. Food and Drug Administration (FDA) recommends that prescribers monitor patients' ANC according to the monitoring frequencies described in the prescribing information. Severe neutropenia remains a serious, potentially fatal risk that is greatest in the first several months of clozapine treatment. ANC monitoring can help identify neutropenia early to allow for timely intervention.(5) Australia, Canada and U.K.: Clozapine is only available through a restricted distribution system which requires documentation of the ANC prior to dispensing. For most clozapine patients, clozapine treatment must be interrupted for a suspected clozapine-induced ANC < 1000 cells/microliter. For patients with benign ethnic neutropenia (BEN), treatment must be interrupted for suspected clozapine-induced neutropenia < 500 cells/microliter.(1) Patients receiving concurrent treatment with a QT prolonging agent at the time ponesimod is initiated or resumed should be referred to a cardiologist. Consult the prescribing information for recommendations regarding cardiac monitoring.(2) DISCUSSION: Treatment with clozapine has been associated with QT prolongation as well as ventricular arrhythmia, torsades de pointes, cardiac arrest, and sudden death.(1) After the first dose of ponesimod, heart rate decrease may begin within the first hour. Decline is usually maximal at approximately 4 hours. With continued, chronic dosing, post-dose decrease in heart rate is less pronounced. Heart rate gradually returns to baseline in about 4-5 hours.(2) |
CLOZAPINE, CLOZAPINE ODT, CLOZARIL, VERSACLOZ |
| Etrasimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Etrasimod causes reversible sequestration of lymphocytes in lymphoid tissues, resulting in a mean 55% decrease in peripheral blood lymphocyte count at 52 weeks.(1) Other immunosuppressives and immune-modulators also suppress the immune system. CLINICAL EFFECTS: Concurrent use of etrasimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious and fatal infections, such as disseminated herpetic infection, cryptococcal infection, or progressive multifocal leukoencephalopathy (PML).(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications increases the risk of adverse effects. PATIENT MANAGEMENT: The etrasimod US prescribing information states etrasimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Concomitant administration of these therapies with etrasimod should be avoided because of the risk of additive immune effects during therapy and in the weeks following administration. Etrasimod's effect on peripheral lymphocytes may persist for up to 5 weeks after discontinuation.(1) When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects.(1) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections, cryptococcal meningitis, disseminated cryptococcal infections, and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients treated with other sphingosine-1 phosphate receptor modulators.(1) |
VELSIPITY |
There are 2 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Ponesimod/QT Prolonging Agents SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ponesimod is a sphingosine 1-phosphate (S1P) receptor 1 modulator. Initiation of ponesimod has a negative chronotropic effect leading to a mean decrease in heart rate of 6 beats per minute (bpm) after the first dose. The first dose has also been associated with heart block.(1) CLINICAL EFFECTS: After a dose of ponesimod, a decrease in heart rate typically begins within an hour and reaches its nadir within 2-4 hours. The heart rate typically recovers to baseline levels 4-5 hours after administration. All patients recovered from bradycardia. The conduction abnormalities typically were transient, asymptomatic, and resolved within 24 hours. Second- and third-degree AV blocks were not reported. With up-titration after Day 1, the post-dose decrease in heart rate is less pronounced. Bradycardia may be associated with an increase in the QTc interval, increasing the risk for torsades de pointes.(1,2) PREDISPOSING FACTORS: Pre-existing cardiovascular or cerebrovascular disease (e.g. heart failure, ischemic heart disease, history of myocardial infarction, stroke, or heart block), severe untreated sleep apnea, a prolonged QTc interval prior to ponesimod initiation, factors associated with QTc prolongation, or concomitant treatment with QT prolonging agents may increase risk for cardiovascular toxicity due to ponesimod.(1) The risk of QT prolongation or torsades de pointes may also be increased in patients with a history of torsades de pointes, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of the QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: Prior to initiation of ponesimod, obtain an ECG to determine if preexisting conduction abnormalities are present. Ponesimod is generally not recommended in patients who are receiving concurrent treatment with a QT prolonging agent, anti-arrhythmic drugs, or drugs that may decrease heart rate. Consultation with a cardiologist is recommended.(1) In patients with heart rate (HR) less than 55 beats per minute (bpm), first- or second-degree AV block, or history of myocardial infarction or heart failure, monitor patients for 4 hours after the first dose for signs and symptoms of bradycardia with a minimum of hourly pulse and blood pressure measurements. Obtain an ECG in these patients prior to dosing and at the end of the 4-hour observation period.(1) Additional US monitoring recommendations include: If HR is less than 45 bpm, the heart rate 4 hours post-dose is at the lowest value post-dose or if the ECG shows new onset of second degree or higher AV block at the end of the monitoring period, then monitoring should continue until the finding has resolved. If patient requires treatment for symptomatic bradycardia, second-degree or higher AV block, or QTc interval greater than or equal to 500 msec, perform continuous overnight ECG monitoring and repeat the first dose monitoring strategy for the second dose of ponesimod. Consult the prescribing information for full monitoring recommendations. If fewer than 4 consecutive doses are missed during titration: resume treatment with the first missed titration dose and resume the titration schedule at that dose and titration day. If fewer than 4 consecutive doses are missed during maintenance: resume treatment with the maintenance dosage. If 4 or more consecutive daily doses are missed during treatment initiation or maintenance treatment, reinitiate Day 1 of the dose titration (new starter pack) and follow first-dose monitoring recommendations. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: After the first dose of ponesimod, heart rate decrease may begin within the first hour. Decline is usually maximal at approximately 4 hours. With continued, chronic dosing, post-dose decrease in heart rate is less pronounced. Heart rate gradually returns to baseline in about 4-5 hours.(1) |
ADLARITY, AGRYLIN, ALFUZOSIN HCL ER, AMIODARONE HCL, AMIODARONE HCL-D5W, ANAGRELIDE HCL, APOKYN, APOMORPHINE HCL, ARICEPT, ASPRUZYO SPRINKLE, AZITHROMYCIN, BARHEMSYS, BETAPACE, BETAPACE AF, BLUJEPA, CAPRELSA, CELEXA, CESIUM CHLORIDE, CHLOROQUINE PHOSPHATE, CHLORPROMAZINE HCL, CILOSTAZOL, CIPRO, CIPROFLOXACIN, CIPROFLOXACIN HCL, CIPROFLOXACIN-D5W, CITALOPRAM HBR, CLARITHROMYCIN, CLARITHROMYCIN ER, CLOFAZIMINE, COARTEM, CORVERT, DIFLUCAN, DIPRIVAN, DISKETS, DISOPYRAMIDE PHOSPHATE, DOFETILIDE, DONEPEZIL HCL, DONEPEZIL HCL ODT, DROPERIDOL, E.E.S. 200, E.E.S. 400, EFAVIRENZ, EFAVIRENZ-EMTRIC-TENOFOV DISOP, EFAVIRENZ-LAMIVU-TENOFOV DISOP, EGATEN, ERIBULIN MESYLATE, ERY-TAB, ERYPED 200, ERYPED 400, ERYTHROCIN LACTOBIONATE, ERYTHROCIN STEARATE, ERYTHROMYCIN, ERYTHROMYCIN ESTOLATE, ERYTHROMYCIN ETHYLSUCCINATE, ERYTHROMYCIN LACTOBIONATE, ERZOFRI, ESCITALOPRAM OXALATE, EXXUA, FANAPT, FARESTON, FLECAINIDE ACETATE, FLUCONAZOLE, FLUCONAZOLE-NACL, GALANTAMINE ER, GALANTAMINE HBR, GALANTAMINE HYDROBROMIDE, GATIFLOXACIN SESQUIHYDRATE, GEODON, GRANISETRON HCL, HALAVEN, HALOPERIDOL, HALOPERIDOL DECANOATE, HALOPERIDOL LACTATE, HYDROXYCHLOROQUINE SULFATE, HYDROXYZINE HCL, HYDROXYZINE PAMOATE, IBTROZI, IBUTILIDE FUMARATE, IGALMI, INVEGA, INVEGA HAFYERA, INVEGA SUSTENNA, INVEGA TRINZA, ISTURISA, KALETRA, LANSOPRAZOL-AMOXICIL-CLARITHRO, LENVIMA, LEVOFLOXACIN, LEVOFLOXACIN HEMIHYDRATE, LEVOFLOXACIN-D5W, LEXAPRO, LOFEXIDINE HCL, LOPINAVIR-RITONAVIR, LUCEMYRA, MEMANTINE HCL-DONEPEZIL HCL ER, METHADONE HCL, METHADONE HCL-0.9% NACL, METHADONE HCL-NACL, METHADONE INTENSOL, METHADOSE, MODEYSO, MOXIFLOXACIN, MOXIFLOXACIN HCL, MULTAQ, NAMZARIC, NEBUPENT, NEXAVAR, NEXTERONE, NORPACE, NORPACE CR, NOXAFIL, NUEDEXTA, NUPLAZID, OFLOXACIN, OMECLAMOX-PAK, ONAPGO, ONDANSETRON HCL, ONDANSETRON HCL-0.9% NACL, PACERONE, PALIPERIDONE ER, PENTAM 300, PENTAMIDINE ISETHIONATE, PIMOZIDE, PLAQUENIL, POSACONAZOLE, PROCAINAMIDE HCL, PROPAFENONE HCL, PROPAFENONE HCL ER, PROPOFOL, QUETIAPINE FUMARATE, QUETIAPINE FUMARATE ER, QUINIDINE GLUCONATE, QUINIDINE SULFATE, RALDESY, RANOLAZINE ER, RETEVMO, ROZLYTREK, SANCUSO, SEROQUEL, SEROQUEL XR, SEVOFLURANE, SIGNIFOR, SIGNIFOR LAR, SIRTURO, SORAFENIB, SOTALOL, SOTALOL AF, SOTALOL HCL, SOTYLIZE, SOVUNA, SUSTOL, SYMFI, TAGRISSO, THIORIDAZINE HCL, THIORIDAZINE HYDROCHLORIDE, TIBSOVO, TIKOSYN, TOLTERODINE TARTRATE, TOLTERODINE TARTRATE ER, TOREMIFENE CITRATE, TRAZODONE HCL, ULTANE, UROXATRAL, VFEND, VFEND IV, VIBATIV, VOQUEZNA TRIPLE PAK, VORICONAZOLE, VORICONAZOLE (HPBCD), WAKIX, XENLETA, XOLREMDI, XOSPATA, ZELBORAF, ZIPRASIDONE HCL, ZIPRASIDONE MESYLATE, ZITHROMAX, ZITHROMAX TRI-PAK, ZUNVEYL, ZYKADIA |
| Non-Live or Non-Replicating Vaccines/Ponesimod SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ponesimod is an immunosuppressant and may alter the immune system's response to vaccines.(1) CLINICAL EFFECTS: Administration of a vaccine during and for up to 2 weeks after discontinuation of ponesimod therapy may result in decreased effectiveness of the vaccine. Ponesimod treatment should be paused 1-2 weeks prior and for 4 weeks after vaccination.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Ideally, administer vaccines prior to initiating ponesimod therapy. The immune response to non-live vaccines should be monitored in patients receiving ponesimod or who have received ponesimod in the previous 2 weeks. Vaccinations given during and for up to 2 weeks after discontinuation of ponesimod therapy may need to be repeated.(1) The Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP) states that non-live vaccines should be used with caution in patients who are severely immunosuppressed. Patients who are vaccinated within the 14 days prior to initiating immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after immunosuppressive therapy is discontinued when immune competence is restored.(2) DISCUSSION: Vaccinations may be less effective if administered during and for up to 2 weeks after ponesimod treatment.(1) However they are considered safe to administer. |
ACTHIB, ADACEL TDAP, AREXVY, AREXVY ANTIGEN COMPONENT, BEXSERO, BIOTHRAX, BOOSTRIX TDAP, CAPVAXIVE, COMIRNATY 2025-2026 (12Y UP), COMIRNATY 2025-2026(5-11Y), CYFENDUS (NATIONAL STOCKPILE), DAPTACEL DTAP, ENGERIX-B ADULT, ENGERIX-B PEDIATRIC-ADOLESCENT, GARDASIL 9, HAVRIX, HEPLISAV-B, HIBERIX, IMOVAX RABIES VACCINE, INFANRIX DTAP, IPOL, IXIARO, JYNNEOS, JYNNEOS (NATIONAL STOCKPILE), KINRIX, MENQUADFI, MENVEO A-C-Y-W-135-DIP, MENVEO MENA COMPONENT, MENVEO MENCYW-135 COMPONENT, MNEXSPIKE 2025-2026 (12Y UP), MRESVIA, NUVAXOVID 2025-2026, PEDIARIX, PEDVAXHIB, PENBRAYA, PENBRAYA MENACWY COMPONENT, PENBRAYA MENB COMPONENT, PENMENVY MEN A-B-C-W-Y, PENMENVY MENACWY COMPONENT, PENMENVY MENB COMPONENT, PENTACEL, PENTACEL ACTHIB COMPONENT, PENTACEL DTAP-IPV COMPONENT, PNEUMOVAX 23, PREVNAR 20, QUADRACEL DTAP-IPV, RABAVERT, RECOMBIVAX HB, SHINGRIX, SHINGRIX GE ANTIGEN COMPONENT, SPIKEVAX 2025-2026 (12Y UP), SPIKEVAX 2025-2026 (6M-11Y), TENIVAC, TICOVAC, TRUMENBA, TWINRIX, TYPHIM VI, VAQTA, VAXELIS, VAXNEUVANCE, VIMKUNYA |
The following contraindication information is available for PONVORY (ponesimod):
Drug contraindication overview.
*Patients who have experienced MI, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or class III/IV heart failure in the last 6 months. *Presence of Mobitz type II second-degree, third-degree atrioventricular (AV) block, or sick sinus syndrome, unless patient has a functioning pacemaker.
*Patients who have experienced MI, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or class III/IV heart failure in the last 6 months. *Presence of Mobitz type II second-degree, third-degree atrioventricular (AV) block, or sick sinus syndrome, unless patient has a functioning pacemaker.
There are 5 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Acute myocardial infarction |
| Child-pugh class B hepatic impairment |
| Child-pugh class C hepatic impairment |
| History of cerebrovascular accident |
| Progressive multifocal leukoencephalopathy |
There are 8 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Acutely decompensated chronic heart failure |
| Atrioventricular block |
| Bradycardia |
| Congenital long QT syndrome |
| Disease of liver |
| Infection |
| Pregnancy |
| Prolonged QT interval |
There are 7 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Asthma |
| Chronic obstructive pulmonary disease |
| Hypertension |
| Macular retinal edema |
| Pre-malignant skin lesion |
| Pulmonary fibrosis |
| Uveitis |
The following adverse reaction information is available for PONVORY (ponesimod):
Adverse reaction overview.
The most common adverse reactions (occurring in >=10% of patients) in clinical studies of ponesimod include upper respiratory tract infection, elevated liver enzymes, and hypertension.
The most common adverse reactions (occurring in >=10% of patients) in clinical studies of ponesimod include upper respiratory tract infection, elevated liver enzymes, and hypertension.
There are 15 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Abnormal hepatic function tests Increased alanine transaminase Increased aspartate transaminase Infection |
Atrioventricular block Bradycardia Decrease in forced vital capacity Herpes simplex infection Herpes zoster Hyperkalemia Lymphopenia Macular retinal edema Seizure disorder Sinus bradycardia |
| Rare/Very Rare |
|---|
|
Basal cell carcinoma of skin |
There are 24 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Hypertension Upper respiratory infection |
Arthritis Back pain Chest discomfort Cough Depression Dizziness Drowsy Dyspepsia Dyspnea Elevated c-reactive protein Fatigue Fever Hypercholesterolemia Insomnia Migraine Pain in extremities Peripheral edema Rhinitis Sinusitis Urinary tract infection Vertigo Xerostomia |
| Rare/Very Rare |
|---|
| None. |
The following precautions are available for PONVORY (ponesimod):
Safety and efficacy of ponesimod have not been established in pediatric patients.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
There is insufficient data on the developmental risk associated with the use of ponesimod during pregnancy. However, the S1P receptor targeted by ponesimod has been demonstrated to have an important role in embryogenesis, including neural and vascular development. In animal studies, administration of ponesimod during pregnancy had adverse effects on fetal development, including embryolethality, increased fetal malformation, and neurobehavioral changes in the absence of maternal toxicity.
It is not known whether ponesimod is distributed into human milk; however, the drug is distributed into milk in rats. The effects of ponesimod on the nursing infant or on milk production are not known. Consider the developmental and heath benefits of breast-feeding along with the importance of ponesimod to the woman and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.
Clinical studies of ponesimod did not include sufficient numbers of patients >=65 years of age to determine whether they respond differently than younger patients. Use of ponesimod in geriatric patients should be cautious, reflecting greater frequency of decreased hepatic, renal, and cardiac function and of concomitant disease and other drug therapy.
The following prioritized warning is available for PONVORY (ponesimod):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for PONVORY (ponesimod)'s list of indications:
| Relapsing form of multiple sclerosis | |
| G35 | Multiple sclerosis |
| G35.A | Relapsing-remitting multiple sclerosis |
| Secondary progressive multiple sclerosis | |
| G35 | Multiple sclerosis |
| G35.C | Secondary progressive multiple sclerosis |
| G35.C0 | Secondary progressive multiple sclerosis, unspecified |
| G35.C1 | Active secondary progressive multiple sclerosis |
Formulary Reference Tool