Please wait while the formulary information is being retrieved.
Drug overview for MAVENCLAD (cladribine):
Generic name: cladribine (KLAD-ri-been)
Drug class: Purine Analogues
Therapeutic class: Multiple Sclerosis Agents
Cladribine, a purine nucleoside antimetabolite, has immunomodulatory and disease-modifying activity in multiple sclerosis (MS);
No enhanced Uses information available for this drug.
Generic name: cladribine (KLAD-ri-been)
Drug class: Purine Analogues
Therapeutic class: Multiple Sclerosis Agents
Cladribine, a purine nucleoside antimetabolite, has immunomodulatory and disease-modifying activity in multiple sclerosis (MS);
No enhanced Uses information available for this drug.
DRUG IMAGES
- No Image Available
The following indications for MAVENCLAD (cladribine) have been approved by the FDA:
Indications:
Relapsing form of multiple sclerosis
Professional Synonyms:
Multiple sclerosis, relapsing form
Indications:
Relapsing form of multiple sclerosis
Professional Synonyms:
Multiple sclerosis, relapsing form
The following dosing information is available for MAVENCLAD (cladribine):
The recommended cumulative dosage of cladribine for the treatment of relapsing forms of MS in adults is 3.5 mg/kg, administered over 2 yearly treatment courses (1.75 mg/kg per year). Each treatment course consists of two 4-5 day dosing cycles.
In each dosing cycle, 1-2 tablets (10 or 20 mg of cladribine) should be administered once daily over 4 or 5 consecutive days (depending on the patient's body weight) for a total dose of 1.75 mg/kg; no more than 2 tablets (20 mg) should be administered in one day. (See Table 1 for doses and number of tablets for each cycle based on body weight.) Cladribine has not been evaluated in patients weighing less than 40 kg.
In the first treatment course, the first dosing cycle may be administered at any time, but the second cycle should be administered 23-27 days after the last dose of the first cycle.
In the second treatment course, the first dosing cycle should be administered at least 43 weeks after the last dose of the first treatment course and the second cycle should be administered 23-27 days after the last dose of the first cycle in the second treatment course.
Table 1. Dose of Oral Cladribine per Treatment Cycle.
Body Weight (kg) First Cycle Dose (Number Second Cycle Dose of 10-mg tablets) (Number of 10-mg tablets) 40 to less than 50 40 mg (4 tablets) 40 mg (4 tablets) 50 to less than 60 50 mg (5 tablets) 50 mg (5 tablets) 60 to less than 70 60 mg (6 tablets) 60 mg (6 tablets) 70 to less than 80 70 mg (7 tablets) 70 mg (7 tablets) 80 to less than 90 80 mg (8 tablets) 70 mg (7 tablets) 90 to less than 100 90 mg (9 tablets) 80 mg (8 tablets) 100 to less than 110 100 mg (10 tablets) 90 mg (9 tablets) 110 or greater 100 mg (10 tablets) 100 mg (10 tablets)
If a dose is missed, take the missed dose as soon as it is remembered on the same day; if the day has already passed, the missed dose should be taken the following day and the number of days in the treatment cycle should be extended. If 2 consecutive doses are missed, extend the treatment cycle by 2 days. Do not take additional or double doses to make up for a missed dose.
The risks of cladribine therapy increase beyond 2 courses of treatment and have not been studied beyond 4 courses of treatment. Cladribine should not be administered during the 2 years following the initial 2-year treatment course since additional exposure to the drug during this time period may increase the risk of malignancy. Safety and efficacy of reinitiation of cladribine therapy more than 2 years after completion of 2 treatment courses have not been evaluated.
In each dosing cycle, 1-2 tablets (10 or 20 mg of cladribine) should be administered once daily over 4 or 5 consecutive days (depending on the patient's body weight) for a total dose of 1.75 mg/kg; no more than 2 tablets (20 mg) should be administered in one day. (See Table 1 for doses and number of tablets for each cycle based on body weight.) Cladribine has not been evaluated in patients weighing less than 40 kg.
In the first treatment course, the first dosing cycle may be administered at any time, but the second cycle should be administered 23-27 days after the last dose of the first cycle.
In the second treatment course, the first dosing cycle should be administered at least 43 weeks after the last dose of the first treatment course and the second cycle should be administered 23-27 days after the last dose of the first cycle in the second treatment course.
Table 1. Dose of Oral Cladribine per Treatment Cycle.
Body Weight (kg) First Cycle Dose (Number Second Cycle Dose of 10-mg tablets) (Number of 10-mg tablets) 40 to less than 50 40 mg (4 tablets) 40 mg (4 tablets) 50 to less than 60 50 mg (5 tablets) 50 mg (5 tablets) 60 to less than 70 60 mg (6 tablets) 60 mg (6 tablets) 70 to less than 80 70 mg (7 tablets) 70 mg (7 tablets) 80 to less than 90 80 mg (8 tablets) 70 mg (7 tablets) 90 to less than 100 90 mg (9 tablets) 80 mg (8 tablets) 100 to less than 110 100 mg (10 tablets) 90 mg (9 tablets) 110 or greater 100 mg (10 tablets) 100 mg (10 tablets)
If a dose is missed, take the missed dose as soon as it is remembered on the same day; if the day has already passed, the missed dose should be taken the following day and the number of days in the treatment cycle should be extended. If 2 consecutive doses are missed, extend the treatment cycle by 2 days. Do not take additional or double doses to make up for a missed dose.
The risks of cladribine therapy increase beyond 2 courses of treatment and have not been studied beyond 4 courses of treatment. Cladribine should not be administered during the 2 years following the initial 2-year treatment course since additional exposure to the drug during this time period may increase the risk of malignancy. Safety and efficacy of reinitiation of cladribine therapy more than 2 years after completion of 2 treatment courses have not been evaluated.
Cladribine tablets are administered orally without regard to food. Swallow the tablets whole with water, and do not chew. Administration of cladribine tablets and other oral drugs should be separated by at least 3 hours during the 4-5 day treatment cycle.
Follow proper procedures for handling and disposal of antineoplastic drugs when administering cladribine tablets. Because the tablets are not coated, they must be swallowed immediately once removed from their packaging. Store cladribine tablets at 20-25degreesC, with excursions permitted to 15-30degreesC. Store in the original package and protect from moisture.
Follow proper procedures for handling and disposal of antineoplastic drugs when administering cladribine tablets. Because the tablets are not coated, they must be swallowed immediately once removed from their packaging. Store cladribine tablets at 20-25degreesC, with excursions permitted to 15-30degreesC. Store in the original package and protect from moisture.
No dosing information available.
No generic dosing information available.
The following drug interaction information is available for MAVENCLAD (cladribine):
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) |
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) 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, IXCHIQ, 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 14 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 |
---|---|
Deferiprone/Selected Myelosuppressive Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis may increase the frequency or risk for severe toxicity.(1) CLINICAL EFFECTS: Concurrent use of deferiprone and myelosuppressive agents may result in severe neutropenia or agranulocytosis, which may be fatal. PREDISPOSING FACTORS: Agranulocytosis may be less common in patients receiving deferiprone for thalassemia, and more common in patients treated for other systemic iron overload conditions (e.g. myelodysplastic syndromes, sickle cell disease).(2,3) Inadequate monitoring appears to increase the risk for severe outcomes. Manufacturer post market surveillance found that in all fatal cases of agranulocytosis reported between 1999 and 2005, data on weekly white blood count (WBC) monitoring was missing. In three fatal cases, deferiprone was continued for two to seven days after the detection of neutropenia or agranulocytosis.(2) PATIENT MANAGEMENT: If possible, discontinue one of the drugs associated with risk for neutropenia or agranulocytosis. If alternative therapy is not available, documentation and adherence to the deferiprone monitoring protocol is essential. Baseline absolute neutrophil count (ANC) must be at least 1,500/uL prior to starting deferiprone. Monitor ANC weekly during therapy. If infection develops, interrupt deferiprone therapy and monitor ANC more frequently. If ANC is less than 1,500/uL but greater than 500/uL, discontinue deferiprone and any other drugs possibly associated with neutropenia. Initiate ANC and platelet counts daily until recovery (i.e. ANC at least 1,500/uL). If ANC is less than 500/uL, discontinue deferiprone, evaluate patient and hospitalize if appropriate. Do not resume deferiprone unless potential benefits outweigh potential risks.(1) DISCUSSION: Drugs linked to this monograph have an FDA Boxed Warning for risk of neutropenia, agranulocytosis, or pancytopenia, or have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(1-25) In pooled clinical studies submitted to the FDA, 6.1% of deferiprone patients met criteria for neutropenia and 1.7% of patients developed agranulocytosis.(1) The time to onset of agranulocytosis was highly variable with a range of 65 days to 9.2 years (median, 161 days).(3) |
DEFERIPRONE, DEFERIPRONE (3 TIMES A DAY), FERRIPROX, FERRIPROX (2 TIMES A DAY), FERRIPROX (3 TIMES A DAY) |
Clozapine/Selected Myelosuppressive Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clozapine and other myelosuppressive agents may be associated with neutropenia or agranulocytosis.(2) CLINICAL EFFECTS: Moderate neutropenia, even if due to combination therapy, may require abrupt discontinuation of clozapine resulting in decompensation of the patient's psychiatric disorder (e.g. schizophrenia). The disease treated by the myelosuppressive agent may be compromised if myelosuppression requires dose reduction, delay, or discontinuation of the myelosuppressive agent. Undetected severe neutropenia or agranulocytosis may be fatal. PREDISPOSING FACTORS: Low white blood counts prior to initiation of the myelosuppressive agent may increase risk for clinically significant neutropenia. PATIENT MANAGEMENT: If a patient stabilized on clozapine therapy requires treatment with a myelosuppressive agent, the clozapine prescriber should consult with prescriber of the myelosuppressive agent (e.g. oncologist) to discuss treatment and monitoring options.(2) More frequent ANC monitoring or treatment alternatives secondary to neutropenic episodes may need to be considered. Clozapine is only available through a restricted distribution system which requires documentation of the absolute neutrophil count (ANC) prior to dispensing.(1-2) 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.(2) DISCUSSION: Clozapine is only available through a restricted distribution system which requires documentation of the ANC prior to dispensing.(1) Agents linked to this interaction generally have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(3-26) |
CLOZAPINE, CLOZAPINE ODT, CLOZARIL, VERSACLOZ |
Deoxycytidine Kinase Substrates/Cladribine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine and zalcitabine may inhibit the intracellular phosphorylation of cladribine by deoxycytidine kinase (dCK). CLINICAL EFFECTS: Concurrent administration of clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine, or zalcitabine with cladribine may result in decreased clinical efficacy of cladribine. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of lamivudine states that the concurrent use of lamivudine and cladribine is not recommended.(1) The manufacturer of cladribine states that concurrent use of compounds that require activation by intracellular phosphorylation should be avoided.(2) DISCUSSION: Cladribine undergoes a series of phosphorylations to its active metabolites. In a case report, a patient on lamivudine who received cladribine concurrently did not experience a decrease in his lymphocyte count. After discontinuation of lamivudine and readministration of cladribine, his lymphocytes dropped as expected.(3) It is expected that other compounds phosphorylated by dCK would also decrease cladribine's efficacy.(4) Compounds phosphorylated by dCK include: clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine and zalcitabine. |
ABACAVIR-LAMIVUDINE, ARRANON, BIKTARVY, CIMDUO, CLOFARABINE, COMPLERA, CYTARABINE, DELSTRIGO, DESCOVY, DOVATO, EFAVIRENZ-EMTRIC-TENOFOV DISOP, EFAVIRENZ-LAMIVU-TENOFOV DISOP, EMTRICITABINE, EMTRICITABINE-RILPIVIRNE-TENOF, EMTRICITABINE-TENOFOVIR DISOP, EMTRIVA, EPIVIR, FLUDARABINE PHOSPHATE, GEMCITABINE HCL, GENVOYA, INFUGEM, LAGEVRIO (EUA), LAMIVUDINE, LAMIVUDINE HBV, LAMIVUDINE-ZIDOVUDINE, NELARABINE, ODEFSEY, STRIBILD, SYMFI, SYMTUZA, TRIUMEQ, TRIUMEQ PD, TRUVADA, VYXEOS |
Cladribine/Selected Inhibitors of BCRP SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of BCRP may increase the absorption of cladribine.(1-2) CLINICAL EFFECTS: The concurrent administration of cladribine with an inhibitor of BCRP may result in elevated levels of cladribine and signs of toxicity.(1-2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of cladribine states concurrent use of BCRP inhibitors should be avoided during the 4- to 5-day cladribine treatment.(1-2) Selection of an alternative concurrent medication with no or minimal transporter inhibiting proprieties should be considered. If this is not possible, dose reduction to the minimum mandatory dose of the BCRP inhibitor, separation in timing of administration, and careful patient monitoring is recommended.(1-2) Monitor for signs of hematologic toxicity. Lymphocyte counts should be monitored. DISCUSSION: Cladribine is a substrate of BCRP. Inhibitors of this transporter are expected to increase cladribine levels.(1-2) BCRP inhibitors linked to this monograph include: capmatinib, clopidogrel, curcumin, danicopan, darolutamide, dasabuvir, eltrombopag, enasidenib, febuxostat, fostamatinib, fostemsavir, glecaprevir/pibrentasvir, grazoprevir, lazertinib, oteseconazole, pacritinib, pantoprazole, paritaprevir, regorafenib, resmetirom, ritonavir, rolapitant, roxadustat, selpercatinib, sofosbuvir/velpatasvir/voxilaprevir, tafamidis, ticagrelor, tolvaptan, turmeric, and vadadustat.(1-4) |
ALVAIZ, BRILINTA, CLOPIDOGREL, CLOPIDOGREL BISULFATE, ELTROMBOPAG OLAMINE, FEBUXOSTAT, IDHIFA, JYNARQUE, KALETRA, LAZCLUZE, LOPINAVIR-RITONAVIR, MAVYRET, NORVIR, NUBEQA, PANTOPRAZOLE SODIUM, PANTOPRAZOLE SODIUM-0.9% NACL, PAXLOVID, PLAVIX, PROMACTA, PROTONIX, PROTONIX IV, RETEVMO, REZDIFFRA, RITONAVIR, RUKOBIA, SAMSCA, STIVARGA, TABRECTA, TAVALISSE, TICAGRELOR, TOLVAPTAN, ULORIC, VAFSEO, VARUBI, VIVJOA, VONJO, VOSEVI, VOYDEYA, VYNDAMAX, VYNDAQEL, ZEPATIER |
Cladribine/Selected Inhibitors of CNT or ENT SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of concentrative nucleoside transporters (CNT) or equilibrative nucleoside transporters (ENT) may increase the absorption of cladribine.(1-2) CLINICAL EFFECTS: The concurrent administration of cladribine with an inhibitor of CNT or ENT may result in elevated levels of cladribine and signs of toxicity.(1-2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of cladribine states concurrent use of CNT or ENT inhibitors should be avoided during the 4- to 5-day cladribine treatment.(1-2) Selection of an alternative concurrent medication with no or minimal transporter inhibiting proprieties should be considered. If this is not possible, dose reduction to the minimum mandatory dose of the CNT or ENT inhibitor, separation in timing of administration, and careful patient monitoring is recommended.(1-2) Monitor for signs of hematologic toxicity. Lymphocyte counts should be monitored. DISCUSSION: Cladribine is a substrate of CNT and ENT. Inhibitors of these transporters are expected to increase cladribine levels.(1-2) Nucleoside inhibitors linked to this monograph include: cilostazol, dipyridamole, nifedipine, nimodipine, reserpine, and sulindac.(1-2) |
ASPIRIN-DIPYRIDAMOLE ER, CILOSTAZOL, DIPYRIDAMOLE, NIFEDIPINE, NIFEDIPINE ER, NIFEDIPINE MICRONIZED, NIMODIPINE, NYMALIZE, PROCARDIA XL, RESERPINE, SULINDAC |
Hormonal Contraceptives/Cladribine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Cladribine may lower the efficacy of hormonal contraceptives. The mechanism of this potential interaction is unknown.(1) CLINICAL EFFECTS: Concurrent use of cladribine may reduce the effectiveness of hormonal contraceptives.(1) Cladribine may cause birth defects and/or miscarriage if used by pregnant women. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Women of reproductive age should be counseled not to rely on hormonal contraception (including oral contraceptives, patches, implants, and/or IUDs) for contraception. Women should add a back-up method of birth control during cladribine therapy and for at least 4 weeks after the final dose of each treatment course.(1) DISCUSSION: It is unknown whether cladribine reduces the effectiveness of hormonal contraceptives. Cladribine is teratogenic and contraindicated in pregnancy.(1) |
2-METHOXYESTRADIOL, AFIRMELLE, ALTAVERA, ALYACEN, AMETHIA, AMETHYST, ANNOVERA, APRI, ARANELLE, ASHLYNA, AUBRA, AUBRA EQ, AUROVELA, AUROVELA 24 FE, AUROVELA FE, AVERI, AVIANE, AYUNA, AZURETTE, BALCOLTRA, BALZIVA, BEYAZ, BLISOVI 24 FE, BLISOVI FE, BRIELLYN, CAMILA, CAMRESE, CAMRESE LO, CAZIANT, CHARLOTTE 24 FE, CHATEAL EQ, CRYSELLE, CYRED, CYRED EQ, DASETTA, DAYSEE, DEBLITANE, DEPO-PROVERA, DEPO-SUBQ PROVERA 104, DESOGESTR-ETH ESTRAD ETH ESTRA, DIETHYLSTILBESTROL, DOLISHALE, DROSPIRENONE-ETH ESTRA-LEVOMEF, DROSPIRENONE-ETHINYL ESTRADIOL, ELINEST, ELLA, ELURYNG, EMZAHH, ENILLORING, ENPRESSE, ENSKYCE, ERRIN, ESTARYLLA, ESTRADIOL, ESTRADIOL BENZOATE, ESTRADIOL CYPIONATE, ESTRADIOL HEMIHYDRATE, ESTRADIOL HEMIHYDRATE MICRO, ESTRADIOL MICRONIZED, ESTRADIOL VALERATE, ESTRIOL, ESTRIOL MICRONIZED, ESTRONE, ETHINYL ESTRADIOL, ETHYNODIOL-ETHINYL ESTRADIOL, ETONOGESTREL-ETHINYL ESTRADIOL, FALMINA, FEIRZA, FEMLYV, FINZALA, GALBRIELA, GEMMILY, HAILEY, HAILEY 24 FE, HAILEY FE, HALOETTE, HEATHER, ICLEVIA, INCASSIA, ISIBLOOM, JAIMIESS, JASMIEL, JENCYCLA, JOLESSA, JOYEAUX, JULEBER, JUNEL, JUNEL FE, JUNEL FE 24, KAITLIB FE, KALLIGA, KARIVA, KELNOR 1-35, KELNOR 1-50, KURVELO, LARIN, LARIN 24 FE, LARIN FE, LAYOLIS FE, LEENA, LESSINA, LEVONEST, LEVONORG-ETH ESTRAD ETH ESTRAD, LEVONORG-ETH ESTRAD-FE BISGLYC, LEVONORGESTREL-ETH ESTRADIOL, LEVORA-28, LO LOESTRIN FE, LO-ZUMANDIMINE, LOESTRIN, LOESTRIN FE, LOJAIMIESS, LORYNA, LOW-OGESTREL, LUTERA, LYLEQ, LYZA, MARLISSA, MEDROXYPROGESTERONE ACETATE, MELEYA, MERZEE, MIBELAS 24 FE, MICROGESTIN, MICROGESTIN FE, MILI, MINZOYA, MONO-LINYAH, NATAZIA, NECON, NEXPLANON, NEXTSTELLIS, NIKKI, NORA-BE, NORELGESTROMIN-ETH ESTRADIOL, NORETHIN-ETH ESTRA-FERROUS FUM, NORETHINDRON-ETHINYL ESTRADIOL, NORETHINDRONE, NORETHINDRONE-E.ESTRADIOL-IRON, NORGESTIMATE-ETHINYL ESTRADIOL, NORTREL, NUVARING, NYLIA, OCELLA, ORTHO TRI-CYCLEN, ORTHO-NOVUM, PHILITH, PIMTREA, PORTIA, RECLIPSEN, RIVELSA, ROSYRAH, SAFYRAL, SETLAKIN, SHAROBEL, SIMLIYA, SIMPESSE, SLYND, SPRINTEC, SRONYX, SYEDA, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TAYTULLA, TILIA FE, TRI-ESTARYLLA, TRI-LEGEST FE, TRI-LINYAH, TRI-LO-ESTARYLLA, TRI-LO-MARZIA, TRI-LO-MILI, TRI-LO-SPRINTEC, TRI-MILI, TRI-SPRINTEC, TRI-VYLIBRA, TRI-VYLIBRA LO, TULANA, TURQOZ, TWIRLA, TYBLUME, VALTYA, VELIVET, VESTURA, VIENVA, VIORELE, VOLNEA, VYFEMLA, VYLIBRA, WERA, WYMZYA FE, XARAH FE, XELRIA FE, XULANE, YASMIN 28, YAZ, ZAFEMY, ZARAH, ZOVIA 1-35, ZUMANDIMINE |
Upadacitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Upadacitinib, immunosuppressives, and immunomodulators all suppress the immune system. CLINICAL EFFECTS: Concurrent use of upadacitinib with immunosuppressives or immunomodulators may result in an increased risk of serious infections. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of upadacitinib states that concurrent use of upadacitinib with immunosuppressives or immunomodulators is not recommended. DISCUSSION: Serious infections have been reported in patients receiving upadacitinib. Reported infections included pneumonia, cellulitis, tuberculosis, multidermatomal herpes zoster, oral/esophageal candidiasis, cryptococcosis. Reports of viral reactivation, including herpes virus reactivation and hepatitis B reactivation, were reported in clinical studies with upadacitinib.(1) |
RINVOQ, RINVOQ LQ |
Inebilizumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inebilizumab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of inebilizumab with immunosuppressive or immunomodulating agents may result in myelosuppression including neutropenia resulting in an increased risk for serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of inebilizumab states that the concurrent use of inebilizumab with immunosuppressive agents, including systemic corticosteroids, may increase the risk of infection. If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents.(1) DISCUSSION: Inebilizumab has not been studied in combination with other immunosuppressants. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents. The most common infections reported by inebilizumab treated patients in the randomized and open-label clinical trial periods included urinary tract infections (20%), nasopharyngitis (13%), upper respiratory tract infections (8%), and influenza (7%). Although there been no cases of Hepatitis B virus reactivation or progressive multifocal leukoencephalopathy reported in patients taking inebilizumab, these infections have been observed in patients taking other B-cell-depleting antibodies.(1) |
UPLIZNA |
Baricitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of baricitinib with other biologic disease-modifying antirheumatic drugs (DMARDs) or potent immunosuppressants such as azathioprine or cyclosporine may result in additive or synergistic effects on the immune system. CLINICAL EFFECTS: Concurrent use of baricitinib with other biologic DMARDs or potent immunosuppressants such as azathioprine or cyclosporine may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of baricitinib states that concurrent use of baricitinib with biologic DMARDs or potent immunosuppressants is not recommended.(1) DISCUSSION: Most patients who developed serious infections while being treated with baricitinib were on concomitant immunosuppressants like methotrexate and corticosteroids. The combination of baricitinib with other biologic DMARDs has not been studied.(1) |
OLUMIANT |
Sodium Iodide I 131/Myelosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1) DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1) |
HICON, SODIUM IODIDE I-131 |
Cladribine/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Cladribine in combination with immunosuppressives and immune-modulators all suppress the immune system.(1-2) CLINICAL EFFECTS: Concurrent use of cladribine with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1-2) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: Recommendations for cladribine regarding this interaction differ between regulatory approving agencies. The cladribine US prescribing information states: -Concomitant use with myelosuppressive or other immunosuppressive drugs is not recommended. Acute short-term therapy with corticosteroids can be administered. In patients who have previously been treated with immunomodulatory or immunosuppressive drugs, consider potential additive effect, the mode of action, and duration of effect of the other drugs prior to initiation of cladribine.(1) The cladribine Canadian prescribing information states: -Use of cladribine in immunocompromised patients is contraindicated because of a risk of additive effects on the immune system. Acute short-term therapy with corticosteroids can be administered during cladribine treatment.(2) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1-2) |
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) (2 PACK), ADALIMUMAB-AATY(CF) (2 PK), ADALIMUMAB-AATY(CF) AI CROHNS, ADALIMUMAB-AATY(CF) AUTOINJ(2), ADALIMUMAB-AATY(CF) AUTOINJECT, ADALIMUMAB-ADAZ(CF), ADALIMUMAB-ADAZ(CF) PEN, ADALIMUMAB-ADBM(CF), ADALIMUMAB-ADBM(CF) PEN, ADALIMUMAB-ADBM(CF) PEN CROHNS, ADALIMUMAB-ADBM(CF) PEN PS-UV, ADALIMUMAB-ADBM(CF)PEN, ADALIMUMAB-FKJP(CF), ADALIMUMAB-FKJP(CF) PEN, ADALIMUMAB-RYVK(CF), ADALIMUMAB-RYVK(CF) AUTOINJECT, ADCETRIS, ADRIAMYCIN, ADRUCIL, AFINITOR, AFINITOR DISPERZ, AGAMREE, AKEEGA, ALFERON N, ALIMTA, ALIQOPA, ALKERAN, ALKINDI SPRINKLE, ALUNBRIG, ALYMSYS, AMJEVITA(CF), AMJEVITA(CF) AUTOINJECTOR, AMTAGVI, ANUCORT-HC, ANUSOL-HC, ARCALYST, ARSENIC TRIOXIDE, ARZERRA, ASPARLAS, ASTAGRAF XL, AUCATZYL, AUGTYRO, AVASTIN, AVONEX, AVONEX (4 PACK), AVONEX PEN, AVONEX PEN (4 PACK), AVSOLA, AXTLE, AZACITIDINE, AZASAN, AZATHIOPRINE, AZATHIOPRINE SODIUM, AZELAIC ACID, BAFIERTAM, BAVENCIO, BECLOMETHASONE DIPROPIONATE, BELEODAQ, BELRAPZO, BENDAMUSTINE HCL, BENDEKA, BESPONSA, BESREMI, BETA 1, 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, BSP 0820, BUDESONIDE, BUDESONIDE DR, BUDESONIDE EC, BUDESONIDE ER, BUDESONIDE MICRONIZED, BUPIVACAINE-DEXAMETH-EPINEPHRN, BUSULFAN, BUSULFEX, CAELYX, CALQUENCE, CAMPATH, CAMPTOSAR, CAPECITABINE, CARBOPLATIN, CARMUSTINE, CARVYKTI, CELESTONE, CELLCEPT, CHLORAMBUCIL, CIBINQO, CIMZIA, CIMZIA (2 PACK), CISPLATIN, CLADRIBINE, CLOBETASOL PROPIONATE MICRO, COLUMVI, COPAXONE, COPIKTRA, CORTEF, CORTISONE ACETATE, COSENTYX, COSENTYX (2 SYRINGES), COSENTYX SENSOREADY (2 PENS), COSENTYX SENSOREADY PEN, COSENTYX SYRINGE, COSENTYX UNOREADY PEN, COSMEGEN, CYCLOPHOSPHAMIDE, CYCLOPHOSPHAMIDE MONOHYDRATE, CYLTEZO(CF), CYLTEZO(CF) PEN, CYLTEZO(CF) PEN CROHN'S-UC-HS, CYLTEZO(CF) PEN PSORIASIS-UV, DACARBAZINE, DACTINOMYCIN, DANYELZA, DANZITEN, DARAPRIM, DARZALEX, DARZALEX FASPRO, DASATINIB, DAUNORUBICIN HCL, DAURISMO, DECITABINE, 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, ENVARSUS XR, EOHILIA, EPIRUBICIN HCL, EPKINLY, ERBITUX, ERLOTINIB HCL, ERWINASE, ETOPOPHOS, ETOPOSIDE, EVEROLIMUS, EVOMELA, FARYDAK, FLOXURIDINE, FLUNISOLIDE, FLUOCINOLONE ACETONIDE, FLUOCINOLONE ACETONIDE MICRO, FLUOCINONIDE MICRONIZED, FLUOROURACIL, FLUTICASONE PROPIONATE, FLUTICASONE PROPIONATE MICRO, FOLOTYN, FRINDOVYX, FYARRO, GAMIFANT, GAVRETO, GAZYVA, GLATIRAMER ACETATE, GLATOPA, GLEOSTINE, GLIADEL, GRAFAPEX, HADLIMA, HADLIMA PUSHTOUCH, HADLIMA(CF), HADLIMA(CF) PUSHTOUCH, HEMADY, HEMMOREX-HC, HEPZATO, HERCEPTIN, HERCEPTIN HYLECTA, HERCESSI, HERZUMA, HEXATRIONE, 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, IMBRUVICA, IMDELLTRA, IMFINZI, IMURAN, INFLECTRA, INFLIXIMAB, INQOVI, INREBIC, IRINOTECAN HCL, ISTODAX, IVRA, IWILFIN, IXEMPRA, JAKAFI, JEMPERLI, JEVTANA, JYLAMVO, KADCYLA, KANJINTI, KEMOPLAT, KENALOG-10, KENALOG-40, KENALOG-80, KEVZARA, KEYTRUDA, KHINDIVI, KINERET, KISQALI, KYMRIAH, LAPATINIB, LENALIDOMIDE, LEUKERAN, LIDOCIDEX-I, LONSURF, LOQTORZI, LUNSUMIO, LUTATHERA, LYNPARZA, MAS CARE-PAK, MATULANE, MECHLORETHAMINE HCL, MEDROL, MEDROLOAN II SUIK, MEDROLOAN SUIK, MEKINIST, MEKTOVI, MELPHALAN HCL, MERCAPTOPURINE, METHOTREXATE, METHOTREXATE SODIUM, 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, NILOTINIB HCL, NILOTINIB TARTRATE, NIPENT, NULOJIX, OGIVRI, ONCASPAR, ONIVYDE, ONTRUZANT, ONUREG, OPDIVO, OPDIVO QVANTIG, OPDUALAG, ORAPRED ODT, ORENCIA, ORENCIA CLICKJECT, ORTIKOS, OTREXUP, OXALIPLATIN, PACLITAXEL, PACLITAXEL PROTEIN-BOUND, PADCEV, PARAPLATIN, PAZOPANIB HCL, PEDIAPRED, PEGASYS, PEMETREXED, PEMETREXED DISODIUM, PEMFEXY, PEMRYDI RTU, PERJETA, PHESGO, PHOTOFRIN, PLEGRIDY, PLEGRIDY PEN, PLUVICTO, POLIVY, POMALYST, POTELIGEO, PRALATREXATE, PREDNISOLONE, PREDNISOLONE ACETATE MICRONIZE, PREDNISOLONE MICRONIZED, PREDNISOLONE SODIUM PHOS ODT, PREDNISOLONE SODIUM PHOSPHATE, PREDNISONE, PREDNISONE INTENSOL, PREDNISONE MICRONIZED, PRO-C-DURE 5, PRO-C-DURE 6, PROCARBAZINE HCL, PROCTOCORT, PROGRAF, PROLEUKIN, PROVENGE, PURIXAN, PYRIMETHAMINE, QUALAQUIN, QUININE HCL, QUININE SULFATE, RASUVO, RAYOS, REBIF, REBIF REBIDOSE, REMICADE, RENFLEXIS, REVLIMID, REVUFORJ, RIABNI, RITUXAN, RITUXAN HYCELA, ROMIDEPSIN, RUBRACA, RUXIENCE, RYDAPT, RYLAZE, RYTELO, SARCLISA, SIKLOS, SIMLANDI(CF), SIMLANDI(CF) AUTOINJECTOR, SIMPONI, SIMPONI ARIA, SIMULECT, SIROLIMUS, SODIUM IODIDE I-123, SOLU-CORTEF, SOLU-MEDROL, SOTYKTU, SPRYCEL, STRONTIUM-89 CHLORIDE, SUNITINIB MALATE, SUTENT, TABLOID, TACROLIMUS, TACROLIMUS XL, TALTZ AUTOINJECTOR, TALTZ AUTOINJECTOR (2 PACK), TALTZ AUTOINJECTOR (3 PACK), TALTZ SYRINGE, TALVEY, TALZENNA, TAPERDEX, TARGRETIN, TARPEYO, TASIGNA, TECARTUS, TECELRA, TECENTRIQ, TECENTRIQ HYBREZA, TECFIDERA, TECVAYLI, TEMODAR, TEMOZOLOMIDE, TEMSIROLIMUS, TEPADINA, TEPYLUTE, 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, TRISENOX, TRODELVY, TRUQAP, TRUXIMA, TYENNE, TYENNE AUTOINJECTOR, TYKERB, TZIELD, UCERIS, UNITUXIN, UVADEX, VANFLYTA, VECTIBIX, VEGZELMA, VELCADE, VENCLEXTA, VENCLEXTA STARTING PACK, VERIPRED 20, VERZENIO, VIDAZA, VINBLASTINE SULFATE, VINCASAR PFS, VINCRISTINE SULFATE, VINORELBINE TARTRATE, VITRAKVI, VIVIMUSTA, VOTRIENT, XALKORI, XATMEP, XELJANZ, XELJANZ XR, XELODA, XOFIGO, XPOVIO, XROMI, YESCARTA, YONDELIS, YUFLYMA(CF) (2 PACK), YUFLYMA(CF) AI CROHN'S-UC-HS, YUFLYMA(CF) AUTOINJECT (2 PCK), YUFLYMA(CF) AUTOINJECTOR, YUSIMRY(CF) PEN, ZANOSAR, ZCORT, ZEJULA, ZEPZELCA, ZEVALIN, ZILRETTA, ZIRABEV, ZOKINVY, ZOLINZA, ZORTRESS, ZYDELIG, ZYMFENTRA, ZYMFENTRA (2 PACK), ZYMFENTRA PEN (2 PACK), ZYNLONTA, ZYNYZ |
Cladribine/Selected Inhibitors of BCRP with Myelosuppression SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of BCRP may increase the absorption of cladribine.(1-2) Also, cladribine in combination with immunosuppressives and immune-modulators all suppress the immune system.(1-2) CLINICAL EFFECTS: The concurrent administration of cladribine with an inhibitor of BCRP may result in elevated levels of cladribine and signs of toxicity.(1-2) Concurrent use of cladribine with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1-2) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The manufacturer of cladribine states concurrent use of BCRP inhibitors should be avoided during the 4- to 5-day cladribine treatment.(1-2) Selection of an alternative concurrent medication with no or minimal transporter inhibiting proprieties should be considered. If this is not possible, dose reduction to the minimum mandatory dose of the BCRP inhibitor, separation in timing of administration, and careful patient monitoring is recommended.(1-2) Myelosuppression risk recommendations for cladribine regarding this interaction differ between regulatory approving agencies. The cladribine US prescribing information states: -Concomitant use with myelosuppressive or other immunosuppressive drugs is not recommended. Acute short-term therapy with corticosteroids can be administered. In patients who have previously been treated with immunomodulatory or immunosuppressive drugs, consider potential additive effect, the mode of action, and duration of effect of the other drugs prior to initiation of cladribine.(1) The cladribine Canadian prescribing information states: -Use of cladribine in immunocompromised patients is contraindicated because of a risk of additive effects on the immune system. Acute short-term therapy with corticosteroids can be administered during cladribine treatment.(2) Monitor for signs of hematologic toxicity. Lymphocyte counts should be monitored. DISCUSSION: Cladribine is a substrate of BCRP. Inhibitors of this transporter are expected to increase cladribine levels.(1-2) BCRP inhibitors linked to this monograph include: asciminib, belumosudil, cyclosporine, encorafenib, leflunomide, leniolisib, momelotinib, pirtobrutinib, and teriflunomide.(1,2) Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1-2) |
ARAVA, AUBAGIO, BRAFTOVI, CYCLOSPORINE, CYCLOSPORINE MODIFIED, GENGRAF, JAYPIRCA, JOENJA, LEFLUNICLO, LEFLUNOMIDE, NEORAL, OJJAARA, REZUROCK, SANDIMMUNE, SCEMBLIX, TERIFLUNOMIDE |
Ritlecitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ritlecitinib, immunosuppressives, and immunomodulators all suppress the immune system. CLINICAL EFFECTS: Concurrent use of ritlecitinib with immunosuppressives or immunomodulators may result in an increased risk of serious infections. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of ritlecitinib states that concurrent use of ritlecitinib with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants is not recommended.(1) DISCUSSION: Serious infections have been reported in patients receiving ritlecitinib. Reported infections included appendicitis, COVID-19 infection (including pneumonia), and sepsis. Reports of viral reactivation, including herpes virus reactivation was reported in clinical studies with ritlecitinib.(1) |
LITFULO |
Deuruxolitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Deuruxolitinib, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of deuruxolitinib and potent immunosuppressants may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of deuruxolitinib states that concurrent use of deuruxolitinib with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants is not recommended.(1) If concurrent use cannot be avoided, patients should be monitored for signs and symptoms of infection. If a patient develops a serious or opportunistic infection, interrupt deuruxolitinib treatment until the infection is controlled. DISCUSSION: Serious infections have been reported in patients receiving treatment with deuruxolitinib.(1) |
LEQSELVI |
There are 1 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 |
---|---|
Ustekinumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ustekinumab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of ustekinumab with immunosuppressive or immunomodulating agents may result in an increased risk for serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of ustekinumab recommends caution because the concurrent use of ustekinumab with immunosuppressive agents may increase the risk of infection. If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents.(1) DISCUSSION: Ustekinumab has not been studied in combination with other immunosuppressants in psoriasis studies. In psoriatic arthritis studies, concomitant methotrexate use did not appear to influence the safety or efficacy of ustekinumab. In Crohn's disease and ulcerative colitis studies, concomitant use of immunosuppressants or corticosteroids did not appear to influence the safety or efficacy of ustekinumab. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents.(1) The most common infections reported by ustekinumab treated patients in the clinical trial periods included nasopharyngitis(8%) and upper respiratory tract infection(5%). Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving ustekinumab. Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia resulting in respiratory failure or prolonged hospitalization have been reported in patients receiving ustekinumab.(1) |
IMULDOSA, OTULFI, PYZCHIVA, SELARSDI, STELARA, STEQEYMA, USTEKINUMAB, USTEKINUMAB-AEKN, USTEKINUMAB-TTWE, WEZLANA, YESINTEK |
The following contraindication information is available for MAVENCLAD (cladribine):
Drug contraindication overview.
*Current malignancy. *Women who are pregnant and in women and men of reproductive potential who do not plan to use effective contraception during therapy and for 6 months after the last dose in each treatment course. *Women intending to breast-feed during treatment and for 10 days after the last dose.
*HIV infection or active chronic infections (e.g., hepatitis, tuberculosis). *History of hypersensitivity to cladribine.
*Current malignancy. *Women who are pregnant and in women and men of reproductive potential who do not plan to use effective contraception during therapy and for 6 months after the last dose in each treatment course. *Women intending to breast-feed during treatment and for 10 days after the last dose.
*HIV infection or active chronic infections (e.g., hepatitis, tuberculosis). *History of hypersensitivity to cladribine.
There are 10 contraindications.
Absolute contraindication.
Contraindication List |
---|
Active tuberculosis |
Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min |
Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min |
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
Hepatitis |
HIV infection |
Immunosuppression |
Lactation |
Pregnancy |
There are 7 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
Severe List |
---|
Anemia |
Bone marrow depression |
Infection |
Lymphopenia |
Malignancy |
Neutropenic disorder |
Thrombocytopenic disorder |
There are 1 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
Moderate List |
---|
Disease of liver |
The following adverse reaction information is available for MAVENCLAD (cladribine):
Adverse reaction overview.
Adverse effects occurring in >20% of patients receiving oral cladribine for the treatment of MS and with an incidence greater than with placebo include upper respiratory tract infection, headache, and lymphopenia.
Adverse effects occurring in >20% of patients receiving oral cladribine for the treatment of MS and with an incidence greater than with placebo include upper respiratory tract infection, headache, and lymphopenia.
There are 38 severe adverse reactions.
More Frequent | Less Frequent |
---|---|
Infection Lymphopenia Neutropenic disorder |
Acute myocardial infarction Anemia Angioedema Drug-induced hepatitis Fungal infection Hypersensitivity drug reaction Hypertension Thrombocytopenic disorder |
Rare/Very Rare |
---|
Abnormal hepatic function tests Active tuberculosis Coccidioidomycosis Cryptococcosis Graft-versus-host disease Heart failure Hepatic failure Hepatitis Herpes simplex infection Herpes zoster Herpes zoster meningitis Histoplasmosis Hyperbilirubinemia Increased alanine transaminase Increased aspartate transaminase Malignancy Myocarditis Nocardiosis Pancytopenia Pharyngeal edema Progressive multifocal leukoencephalopathy Pyelonephritis Reactivation of hepatitis B Seizure disorder Toxoplasmosis Uveitis Varicella zoster virus infection |
There are 26 less severe adverse reactions.
More Frequent | Less Frequent |
---|---|
Headache disorder Upper respiratory infection |
Acute abdominal pain Alopecia Arthralgia Arthritis Atrial fibrillation Back pain Black tarry stools Bronchitis Cataracts Depression Eosinophilia Fever Gastroenteritis Influenza Insomnia Leukopenia Nausea Ocular irritation Pruritus of skin Skin inflammation Symptoms of anxiety Urticaria Xerostomia |
Rare/Very Rare |
---|
Skin rash |
The following precautions are available for MAVENCLAD (cladribine):
Safety and efficacy of cladribine have not been established in pediatric patients younger than 18 years of age. Use of the drug is not recommended in pediatric patients because of the risk of malignancies.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
None |
Severe Precaution
None |
Management or Monitoring Precaution
None |
Cladribine is contraindicated in pregnant females. There are no adequate data regarding use of cladribine in pregnant females; however, embryolethality and teratogenicity have been demonstrated in animals. The observed developmental effects in animals are consistent with the mechanism of action of cladribine.
Pregnancy should be excluded prior to initiation of cladribine therapy. Cladribine should be discontinued if a patient becomes pregnant during therapy. A pregnancy safety study is monitoring pregnancy and infant outcomes following exposure to cladribine.
Physicians and patients are encouraged to report pregnancies of women with MS exposed to oral cladribine during pregnancy or within 6 months before conception as well as pregnancies fathered by men with MS who had taken oral cladribine within 6 months before conception by calling EMD Serono's Adverse Event reporting line at 1-800-283-8088 ext. 5563 or by faxing 1-781-681-2961.
Pregnancy should be excluded prior to initiation of cladribine therapy. Cladribine should be discontinued if a patient becomes pregnant during therapy. A pregnancy safety study is monitoring pregnancy and infant outcomes following exposure to cladribine.
Physicians and patients are encouraged to report pregnancies of women with MS exposed to oral cladribine during pregnancy or within 6 months before conception as well as pregnancies fathered by men with MS who had taken oral cladribine within 6 months before conception by calling EMD Serono's Adverse Event reporting line at 1-800-283-8088 ext. 5563 or by faxing 1-781-681-2961.
It is not known whether cladribine or its metabolites are distributed into human milk. Because of the potential for serious adverse reactions to cladribine in nursing infants, cladribine is contraindicated in women who are breast-feeding. Breast-feeding is not advised during cladribine treatment and for 10 days after the last dose of the drug. The effects of the drug on nursing infants or on milk production are not known.
Clinical studies of cladribine did not include sufficient numbers of patients 65 years of age or older to determine whether they respond differently than younger patients. Other clinical experience has not identified differences in response between geriatric patients and younger adults. Cladribine should be used with caution in geriatric patients, reflecting the greater frequency of decreased hepatic, renal, and cardiac function and of concomitant disease and other drug therapy.
The following prioritized warning is available for MAVENCLAD (cladribine):
WARNING: Cladribine may rarely increase your risk of getting cancer. Do not take this medication if you have cancer. Discuss the risks and benefits with your doctor if you have had cancer in the past or are at increased risk for cancer.
Talk to your doctor about getting regularly screened for cancer. Tell your doctor right away if you have symptoms such as a change in size/color of a mole, unusual skin changes, new lumps/growths, night sweats, or unexplained/sudden weight loss. Ask your doctor for more details.
This medication must not be used during pregnancy. It may harm an unborn baby. Your doctor will order a pregnancy test before you start this medication.
It is important to prevent pregnancy while taking this medication and for at least 6 months after each treatment course. Men and women using this medication must use reliable forms of birth control during treatment and for at least 6 months after the last dose. If you or your partner become pregnant or think you may be pregnant, tell your doctor right away.
WARNING: Cladribine may rarely increase your risk of getting cancer. Do not take this medication if you have cancer. Discuss the risks and benefits with your doctor if you have had cancer in the past or are at increased risk for cancer.
Talk to your doctor about getting regularly screened for cancer. Tell your doctor right away if you have symptoms such as a change in size/color of a mole, unusual skin changes, new lumps/growths, night sweats, or unexplained/sudden weight loss. Ask your doctor for more details.
This medication must not be used during pregnancy. It may harm an unborn baby. Your doctor will order a pregnancy test before you start this medication.
It is important to prevent pregnancy while taking this medication and for at least 6 months after each treatment course. Men and women using this medication must use reliable forms of birth control during treatment and for at least 6 months after the last dose. If you or your partner become pregnant or think you may be pregnant, tell your doctor right away.
The following icd codes are available for MAVENCLAD (cladribine)'s list of indications:
Relapsing form of multiple sclerosis | |
G35 | Multiple sclerosis |
Formulary Reference Tool