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Drug overview for JEMPERLI (dostarlimab-gxly):
Generic name: dostarlimab-gxly (dos-TAR-li-mab)
Drug class: Antineoplastic - Anti-Programmed Death-(PD-1/L1) MC Antibody
Therapeutic class: Antineoplastics
Dostarlimab-gxly, a humanized anti-programmed-death receptor-1 (anti-PD-1) monoclonal antibody, is an antineoplastic agent. The drug is an IgG4 immunoglobulin.
No enhanced Uses information available for this drug.
Generic name: dostarlimab-gxly (dos-TAR-li-mab)
Drug class: Antineoplastic - Anti-Programmed Death-(PD-1/L1) MC Antibody
Therapeutic class: Antineoplastics
Dostarlimab-gxly, a humanized anti-programmed-death receptor-1 (anti-PD-1) monoclonal antibody, is an antineoplastic agent. The drug is an IgG4 immunoglobulin.
No enhanced Uses information available for this drug.
DRUG IMAGES
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The following indications for JEMPERLI (dostarlimab-gxly) have been approved by the FDA:
Indications:
Endometrial carcinoma
Microsatellite instability-high solid malignant tumor
Mismatch repair deficient endometrial cancer
Professional Synonyms:
DMMR cancer
DMMR endometrial cancer
DMMR solid malignant tumor
Mismatch repair deficient solid malignant tumor
MSI-H cancer
MSI-H solid malignant tumor
Indications:
Endometrial carcinoma
Microsatellite instability-high solid malignant tumor
Mismatch repair deficient endometrial cancer
Professional Synonyms:
DMMR cancer
DMMR endometrial cancer
DMMR solid malignant tumor
Mismatch repair deficient solid malignant tumor
MSI-H cancer
MSI-H solid malignant tumor
The following dosing information is available for JEMPERLI (dostarlimab-gxly):
If immune-mediated adverse effects occur, temporary interruption or discontinuance of therapy may be required (see Table 1). Permanently discontinue therapy in patients experiencing life-threatening (grade 4) immune-mediated adverse reactions or recurrent severe (grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, and in those not able to reduce corticosteroid dosage to <10 mg of prednisone daily (or equivalent) within 12 weeks of initiating steroids.
Table 1. Recommended Dosage Modifications for Dostarlimab-gxly Toxicity
Adverse Reaction Dosage Modification Pneumonitis Grade 2: Withhold therapy until recovery to grade 0 to 1; may resume after corticosteroid taper Grade 3 or 4 or recurrent grade 2: Permanently discontinue therapy Colitis Grade 2 or 3: Withhold therapy until recovery to grade 0 to 1; may resume after corticosteroid taper Grade 4: Permanently discontinue therapy. Hepatitis with no tumor involvement AST or ALT elevations >3 times but of the liver <=8 times the upper limit of normal (ULN) or total bilirubin concentrations >1.5 but <= 3 times the ULN: Withhold therapy until recovery to grade 0 to 1; may resume after corticosteroid taper AST or ALT elevations >8 times th e ULN or total bilirubin concentrations >3 times the ULN: Permanently discontinue therapy Hepatitis with tumor involvement of Baseline AST or ALT is >1 but <=3 the liver times the ULN and increases to >5 but <=10 times the ULN or baseline AST or ALT is >3 but <=5 times the ULN and increases to >8 but <=10 times the ULN: Withhold therapy until recovery to grade 0 to 1; may resume after corticoster oid taper AST or ALT elevations >10 times the ULN or total bilirubin concentrations >3 times the ULN: Permanently discontinue therapy Endocrinopathies Grade 2, 3, or 4: Withhold therapy until clinically stable or permanently discontinue, depending on severity; may resume after recovery to grade 0 to 1 and completion of corticosteroid taper Nephritis with renal dysfunction Grade 2 or 3 increased serum creatinine concentrations: Withhold therapy until recovery to grade 0 to 1; may resume after corticosteroid taper Grade 4 increased serum creatinine concentrations: Permanently discontinue therapy Exfoliative dermatologic conditions Suspected Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS): Withhold therapy until recovery to grade 0 to 1; may resume after corticosteroid taper Confirmed SJS, TEN, or DRESS: Permanently discontinue therapy Myocarditis Grade 2, 3, or 4: Permanently discontinue therapy Neurologic toxicities Grade 2: Withhold therapy until recovery to grade 0 to 1; may resume after corticosteroid taper Grade 3 or 4: Permanently discontinue therapy Infusion-related reactions Grade 1 or 2: Interrupt or slow the rate of infusion Grade 3 or 4: Permanently discontinue therapy
Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce corticosteroid dosage to <10 mg of prednisone daily (or equivalent) within 12 weeks of initiating steroids.
If AST and ALT <= ULN at baseline in patients with liver involvement, withhold or permanently discontinue based on recommendations for hepatitis with no liver involvement.
Table 1. Recommended Dosage Modifications for Dostarlimab-gxly Toxicity
Adverse Reaction Dosage Modification Pneumonitis Grade 2: Withhold therapy until recovery to grade 0 to 1; may resume after corticosteroid taper Grade 3 or 4 or recurrent grade 2: Permanently discontinue therapy Colitis Grade 2 or 3: Withhold therapy until recovery to grade 0 to 1; may resume after corticosteroid taper Grade 4: Permanently discontinue therapy. Hepatitis with no tumor involvement AST or ALT elevations >3 times but of the liver <=8 times the upper limit of normal (ULN) or total bilirubin concentrations >1.5 but <= 3 times the ULN: Withhold therapy until recovery to grade 0 to 1; may resume after corticosteroid taper AST or ALT elevations >8 times th e ULN or total bilirubin concentrations >3 times the ULN: Permanently discontinue therapy Hepatitis with tumor involvement of Baseline AST or ALT is >1 but <=3 the liver times the ULN and increases to >5 but <=10 times the ULN or baseline AST or ALT is >3 but <=5 times the ULN and increases to >8 but <=10 times the ULN: Withhold therapy until recovery to grade 0 to 1; may resume after corticoster oid taper AST or ALT elevations >10 times the ULN or total bilirubin concentrations >3 times the ULN: Permanently discontinue therapy Endocrinopathies Grade 2, 3, or 4: Withhold therapy until clinically stable or permanently discontinue, depending on severity; may resume after recovery to grade 0 to 1 and completion of corticosteroid taper Nephritis with renal dysfunction Grade 2 or 3 increased serum creatinine concentrations: Withhold therapy until recovery to grade 0 to 1; may resume after corticosteroid taper Grade 4 increased serum creatinine concentrations: Permanently discontinue therapy Exfoliative dermatologic conditions Suspected Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS): Withhold therapy until recovery to grade 0 to 1; may resume after corticosteroid taper Confirmed SJS, TEN, or DRESS: Permanently discontinue therapy Myocarditis Grade 2, 3, or 4: Permanently discontinue therapy Neurologic toxicities Grade 2: Withhold therapy until recovery to grade 0 to 1; may resume after corticosteroid taper Grade 3 or 4: Permanently discontinue therapy Infusion-related reactions Grade 1 or 2: Interrupt or slow the rate of infusion Grade 3 or 4: Permanently discontinue therapy
Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce corticosteroid dosage to <10 mg of prednisone daily (or equivalent) within 12 weeks of initiating steroids.
If AST and ALT <= ULN at baseline in patients with liver involvement, withhold or permanently discontinue based on recommendations for hepatitis with no liver involvement.
Administer dostarlimab-gxly by IV infusion after dilution. Do not administer as an IV push or bolus injection. Do not co-administer with other drugs through the same infusion line.
Consult the manufacturer's labeling for detailed information on infusion system requirements and procedures for IV infusion of dostarlimab-gxly. Store unopened vials at 2-8degreesC in the original carton to protect the drug from light. After the drug is diluted, the prepared dose may be stored either at room temperature for up to 6 hours (including infusion time) or under refrigeration (2- 8degreesC) for up to 24 hours (including infusion time). If the drug is refrigerated, allow the diluted solution to reach room temperature prior to administration.
Consult the manufacturer's labeling for detailed information on infusion system requirements and procedures for IV infusion of dostarlimab-gxly. Store unopened vials at 2-8degreesC in the original carton to protect the drug from light. After the drug is diluted, the prepared dose may be stored either at room temperature for up to 6 hours (including infusion time) or under refrigeration (2- 8degreesC) for up to 24 hours (including infusion time). If the drug is refrigerated, allow the diluted solution to reach room temperature prior to administration.
DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
---|---|---|
JEMPERLI 500 MG/10 ML VIAL | Maintenance | Adults infuse 1,000 mg over 30 minute(s) by intravenous route every 6 weeks (dose 5 and thereafter) |
No generic dosing information available.
The following drug interaction information is available for JEMPERLI (dostarlimab-gxly):
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) |
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 TRIVALENT 2024-2025, IXCHIQ, JYNNEOS, JYNNEOS (NATIONAL STOCKPILE), 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 21 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 |
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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: Undetected severe neutropenia or agranulocytosis may be fatal. If concurrent use of deferiprone is with clozapine, 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). 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) If concurrent use of deferiprone is with clozapine, the following recommendations should be considered based on clozapine use: 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.(4) 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.(4-5) 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.(4) 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.(1-4, 6-27) 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) |
Tofacitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of tofacitinib and azathioprine, other biologic disease-modifying antirheumatic drugs (DMARDs), or potent immunosuppressants may result in additive or synergistic effects on the immune system.(1) CLINICAL EFFECTS: Concurrent use of tofacitinib and azathioprine, other biologic DMARDs, or potent immunosuppressants use may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Tofacitinib should not be used concurrently with azathioprine, other biologic DMARDs, or cyclosporine.(1) Patient should be monitored for decreases in lymphocytes and neutrophils. Therapy should be adjusted based on the indication. - For all indications: If absolute neutrophil count (ANC) or lymphocyte count is less than 500 cells/mm3, discontinue tofacitinib. - For rheumatoid arthritis or psoriatic arthritis and absolute neutrophil count (ANC) 500 to 1000 cells/mm3: interrupt dosing. When ANC is greater than 1000 cells/mm3, resume Xeljanz 5 mg twice daily or Xeljanz XR 11 mg once daily. - For ulcerative colitis and ANC 500 to 1000 cells/mm3: -If taking Xeljanz 10 mg twice daily, decrease to 5 mg twice daily. When ANC is greater than 1000 cells/mm3, increase to 10 mg twice daily based on clinical response. -If taking Xeljanz 5 mg twice daily, interrupt dosing. When ANC is greater than 1000 cells/mm3, resume 5 mg twice daily. -If taking Xeljanz XR 22 mg once daily, decrease to 11 mg once daily. When ANC is greater than 1000 cells/mm3, increase to 22 mg once daily based on clinical response. -If taking Xeljanz XR 11 mg once daily, interrupt dosing. When ANC is greater than 1000 cells/mm3, resume 11 mg once daily. - For polyarticular course juvenile idiopathic arthritis (pcJIA) and ANC 500 to 1000 cells/mm3: interrupt dosing until ANC is greater than 1000 cells/mm3.(1) DISCUSSION: Concurrent use of tofacitinib and azathioprine, other biologic DMARDs, or potent immunosuppressants may increase the risk of infection.(1) |
TOFACITINIB CITRATE, XELJANZ, XELJANZ XR |
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) Myelosuppressive agents linked to this monograph include: acalabrutinib, adalimumab, ado-trastuzumab emtansine, aflibercept, alemtuzumab, altretamine, aminoglutethimide, amphotericin B, anastrozole, anti-thymocyte globulin, aprepitant, auranofin, avelumab, axitinib, azacitidine, azathioprine, belatacept, bendamustine, bevacizumab, bexarotene, boceprevir, bortezomib, bosutinib, brentuximab, busulfan, cabazitaxel, capecitabine, carbamazepine, carboplatin, carfilzomib, carmustine, chlorambucil, cidofovir, cisplatin, cladribine, clofarabine, copanlisib, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, decitabine, docetaxel, doxorubicin, erdafitinib, etoposide, everolimus, fedratinib, flucytosine, fludarabine, fluorouracil, foscarnet, fostamatinib, ganciclovir, gemcitabine, gemtuzumab ozogamicin, hydroxyurea, ibrutinib, ibritumomab, idarubicin, idecabtagene vicleucel, ifosfamide, imatinib, inebilizumab, infliximab, interferon alfa-2a, interferon alfa-2b, interferon alfacon-1, interferon gamma-1b, interferon beta-1b, irinotecan, ixabepilone, lenalidomide, levamisole, linezolid, lomustine, lurbinectedin, mechlorethamine, melphalan, mercaptopurine, methimazole, methotrexate, mitomycin, mitoxantrone, mosunetuzumab, mycophenolate, nelarabine, niraparib, nitisinone, ofatumumab, olaratumab, omacetaxine, paclitaxel, palbociclib, pegaspargase, peginterferon alfa-2a, pemetrexed, penicillamine, pentostatin, pertuzumab, pomalidomide, ponatinib, pralatrexate, procarbazine, pyrimethamine, radium Ra 223 dichloride, ribavirin, rituximab, ruxolitinib, sacituzumab govitecan-hziy, samarium Sm 153 lexidronam, satralizumab-mwge, selinexor, succimer, sulfasalazine, temozolomide, temsirolimus, teniposide, terbinafine, teriflunomide, thioguanine, thiotepa, ticlopidine, tocilizumab, topotecan, tositumomab, trabectedin, trametinib, trastuzumab, trifluridine-tipiracil, trimethadione, uracil mustard, valganciclovir, vinblastine, vincristine, vindesine, vinflunine, vinorelbine, zanubrutinib and zidovudine. |
CLOZAPINE, CLOZAPINE ODT, CLOZARIL, VERSACLOZ |
Selected Multiple Sclerosis Agents/Immunosuppressants; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ocrelizumab or ofatumumab in combination with immunosuppressives and immune-modulators all suppress the immune system.(1,2) CLINICAL EFFECTS: Concurrent use of ocrelizumab or ofatumumab 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 ocrelizumab US prescribing information states: - Ocrelizumab and other immune-modulating or immunosuppressive therapies, (including immunosuppressant doses of corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with ocrelizumab. When switching from drugs with prolonged immune effects, such as daclizumab, fingolimod, natalizumab, teriflunomide, or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating ocrelizumab.(1) The ofatumumab US prescribing information states: - Ofatumumab and other immunosuppressive therapies (including systemic corticosteroids) may have the potential for increased immunosuppressive effects and increase the risk of infection. When switching between therapies, the duration and mechanism of action of each therapy should be considered due to the potential for additive immunosuppressive effects. Ofatumumab for MS therapy has not been studied in combination with other MS agents that suppress the immune system.(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) |
KESIMPTA PEN, OCREVUS, OCREVUS ZUNOVO |
PD-1 and PD-L1 Blocking Antibodies/Thalidomide Analogues SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The mechanism of this interaction is not known. CLINICAL EFFECTS: Concurrent use of a thalidomide analogue with dexamethasone and a PD-1 or PD-L1 blocking antibody may increase the risk of mortality. PREDISPOSING FACTORS: Concurrent use of dexamethasone may increase the risk of venous thromboembolism (VTE), ischemic heart disease including myocardial infarction, and stroke. PATIENT MANAGEMENT: Concurrent administration of a thalidomide analogue plus dexamethasone with a PD-1 or PD-L1 blocking antibody is not recommended outside of controlled clinical trials. DISCUSSION: Two randomized clinical trials in multiple myeloma patients showed an increase in mortality associated with the concurrent use of pembrolizumab, a thalidomide analogue, and dexamethasone. In the first clinical trial, patients were randomized to receive pomalidomide, dexamethasone, and pembrolizumab. In this trial, the relative risk of death was increased by more than 50% in the experimental arm containing pembrolizumab and the hazard ratio for overall survival was 1.61. Causes of death in the experimental arm included myocarditis, Stevens-Johnson syndrome, myocardial infarction, pericardial hemorrhage, cardiac failure, respiratory tract infection, neutropenia sepsis, sepsis, multiple organ dysfunction, and respiratory failure. In the second clinical trial, patients were randomized to receive lenalidomide, dexamethasone, and pembrolizumab. In this trial, the relative risk of death was increased by more than 100% in the experimental arm containing pembrolizumab and the hazard ratio for overall survival was 2.06. Causes of death in the experimental arm included intestinal ischemia, cardio-respiratory arrest, pulmonary embolism, cardiac arrest, pneumonia, sudden death, myocarditis, large intestinal perforation, and cardiac failure. PD-1 and PD-L1 blocking antibodies linked to this monograph include atezolizumab, avelumab, cemiplimab, dostarlimab, durvalumab, nivolumab, pembrolizumab, penpulimab, retifanlimab, sintilimab and toripalimab-tpzi. |
LENALIDOMIDE, POMALYST, REVLIMID, THALOMID |
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 |
Leflunomide; Teriflunomide/Selected Immunosuppressants SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of leflunomide or teriflunomide and potent immunosuppressants may result in additive or synergistic effects on the immune system.(1,2) Leflunomide is a prodrug and is converted to its active metabolite teriflunomide.(1) CLINICAL EFFECTS: Concurrent use of leflunomide or teriflunomide with immunosuppressants may result in an increased risk of serious infections, including opportunistic infections, especially Pneumocystis jiroveci pneumonia, tuberculosis (including extra-pulmonary tuberculosis), and aspergillosis. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If leflunomide or teriflunomide is used concurrently with immunosuppressive agents, chronic CBC monitoring should be performed more frequently, every month instead of every 6 to 8 weeks. If bone marrow suppression or a serious infection occurs, leflunomide or teriflunomide should be stopped and rapid drug elimination procedure should be performed.(1,2) DISCUSSION: Pancytopenia, agranulocytosis and thrombocytopenia have been reported in patients receiving leflunomide or teriflunomide alone, but most frequently in patients taking concurrent immunosuppressants.(1,2) Severe and potentially fatal infections, including sepsis, have been reported in patients receiving leflunomide or teriflunomide, especially Pneumocystis jiroveci pneumonia and aspergillosis. Tuberculosis has also been reported.(1,2) |
ARAVA, AUBAGIO, LEFLUNICLO, LEFLUNOMIDE, TERIFLUNOMIDE |
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) |
PONVORY |
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 |
Fingolimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Fingolimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1-3) CLINICAL EFFECTS: Concurrent use of fingolimod 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).(1-3) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: Recommendations for fingolimod regarding this interaction differ between regulatory approving agencies. The fingolimod US prescribing information states: - Antineoplastic, immune-modulating, or immunosuppressive therapies, (including corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with fingolimod. When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating fingolimod.(1) The fingolimod Canadian prescribing information states: - Concurrent use with immunosuppressive or immunomodulatory agents is contraindicated due to the risk of additive immune system effects. However, co-administration of a short course of corticosteroids (up to 5 days) did not increase the overall rate of infection in patients participating Phase III clinical trials.(2) The fingolimod UK specific product characteristics states: - Fingolimod is contraindicated in patients currently receiving immunosuppressive therapies or those immunocompromised by prior therapies. When switching patients from another disease modifying therapy to Gilenya, the half-life and mode of action of the other therapy must be considered in order to avoid an additive immune effect whilst at the same time minimizing the risk of disease activation.(3) 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.(1-3) |
FINGOLIMOD, GILENYA, TASCENSO ODT |
Ozanimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ozanimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of ozanimod 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) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The ozanimod US prescribing information state this information regarding this interaction: -Ozanimod 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 week 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 ozanimod after alemtuzumab is not recommended. However, ozanimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1) 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) |
ZEPOSIA |
Siponimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Siponimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of siponimod 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) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The siponimod US prescribing information state this information regarding this interaction: -Siponimod 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 week 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 siponimod after alemtuzumab is not recommended. However, siponimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1) 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) |
MAYZENT |
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) |
CLADRIBINE, MAVENCLAD |
IgG Antibodies and Derivatives/Efgartigimod-alfa SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3) DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod alfa may decrease concentrations of compounds that bind to the human FcRn.(3) |
VYVGART, VYVGART HYTRULO |
Anifrolumab/Biologic Therapies SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of anifrolumab with other biologic therapies may result in additive or synergistic effects on the immune system.(1) CLINICAL EFFECTS: Concurrent use of anifrolumab with other biologic therapies may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The concurrent use of anifrolumab with other biologic therapies is not recommended.(1) DISCUSSION: The combination of anifrolumab with other biologic therapies has not been studied and is not recommended.(1) |
SAPHNELO |
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 |
Pozelimab/IgG Antibodies and Derivatives SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Pozelimab is an IgG4P antibody. Concurrent use of immunoglobulins and other IgG-based antibodies that bind to FcRn may interfere with the FcRn recycling mechanism of pozelimab and decrease systemic exposure of pozelimab.(3) CLINICAL EFFECTS: The levels and effectiveness of pozelimab may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of pozelimab states that concomitant use of intravenous immunoglobulin should avoided with pozelimab. If concomitant use cannot be avoided, monitor patients for worsening signs and symptoms of CD55-deficient protein-losing enteropathy.(3) DISCUSSION: Clinical drug interaction studies with pozelimab have not been performed. Immunoglobulins may interfere with the endosomal FcRn recycling mechanism of monoclonal antibodies like pozelimab and decrease concentrations of pozelimab.(3) |
VEOPOZ |
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 |
Ropeginterferon alfa-2b/Slt Immunosuppress; Immunomodulator SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ropeginterferon alfa-2b and immunosuppressives both suppress the immune system. CLINICAL EFFECTS: Concurrent use of ropeginterferon alfa-2b with immunosuppressives may result in an increased risk of serious infections. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid concurrent use of myelosuppressive agents.(1-2) If concurrent use cannot be avoided, monitor for effects of excessive immunosuppression. DISCUSSION: In clinical trials, 20% of patients experienced leukopenia. Interferon alfa products may cause fatal or life-threatening infections.(1-2) |
BESREMI |
There are 7 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) |
STELARA |
COVID-19 Vaccines/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Immunosuppressants and immunomodulators may prevent the immune system from properly responding to the COVID-19 vaccine.(1,2) CLINICAL EFFECTS: Administration of a COVID-19 vaccine with immunosuppressants or immunomodulators may interfere with vaccine-induced immune response and impair the efficacy of the vaccine. However, patients should be offered and given a COVID-19 vaccine even if the use and timing of immunosuppressive agents cannot be adjusted.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: In an effort to optimize COVID-19 vaccine response, the American College of Rheumatology (ACR) published conditional recommendations for administration of COVID-19 vaccines with immunosuppressants and immunomodulators.(1) The CDC also provides clinical considerations for COVID-19 vaccination in patients on immunosuppressants.(2) The CDC states that all immunocompromised patients over 6 months of age should receive at least 1 dose of COVID-19 vaccine if eligible. See the CDC's Interim Clinical Considerations for Use of COVID-19 Vaccines for specific recommendations based on age, vaccination history, and vaccine manufacturer.(2) The ACR states that in general, immunosuppressants and immunomodulators should be held for 1-2 weeks after each vaccine dose. See below for specific recommendations for certain agents.(1) The CDC advises planning for vaccination at least 2 weeks before starting or resuming immunosuppressive therapy.(2) Patients should be offered and given a COVID-19 vaccine even if the use and timing of immunosuppressive agents cannot be adjusted.(1,2) B-cell depleting agents, including rituximab: The ACR recommends consulting with the rheumatologist to determine optimal timing of COVID-19 vaccination. Measuring CD19 B cells may be considered to determine need for a booster vaccine dose. If B cell levels are not measured, a supplemental vaccine dose 2-4 weeks before the next scheduled dose of rituximab is recommended.(1) The CDC states that the utility of B-cell quantification to guide clinical care is not known and is not recommended. Patients who receive B-cell depleting therapy should receive COVID-19 vaccines about 4 weeks before the next scheduled dose. For patients who received 1 or more doses of COVID-19 vaccine during treatment with B-cell-depleting therapies that were administered over a limited period (e.g., as part of a treatment regimen for certain malignancies), revaccination may be considered. The suggested interval to start revaccination is about 6 months after completion of the B-cell-depleting therapy.(2) Abatacept: - Subcutaneous abatacept should be withheld for 1-2 weeks after each vaccine dose, as disease activity allows. - For intravenous abatacept, time administration so that vaccination will occur 1 week before the next abatacept infusion.(1) Cyclophosphamide: When feasible, administer cyclophosphamide one week after each COVID-19 vaccine dose.(1) Recipients of hematopoietic cell transplant or CAR-T-cell therapy who received one or more doses of COVID-19 vaccine prior to or during treatment should undergo revaccination following the current CDC recommendations for unvaccinated patients. Revaccination should start at least 3 months (12 weeks) after transplant or CAR-T-cell therapy.(2) TNF-alpha inhibitors and cytokine inhibitors: The ACR was not able to reach consensus on whether to modify dosing or timing of these agents with COVID-19 vaccination.(1) The CDC includes these agents in their general recommendation to hold therapy for at least 2 weeks following vaccination.(2) DISCUSSION: The ACR convened a COVID-19 Vaccine Guidance Task Force to provide guidance on optimal use of COVID-19 vaccines in rheumatology patients. These recommendations are based on limited clinical evidence of COVID-19 vaccines in patients without rheumatic and musculoskeletal disorders and evidence of other vaccines in this patient population.(1) The ACR recommendation for rituximab is based on studies of humoral immunity following receipt of other vaccines. These studies have uncertain generalizability to vaccination against COVID-19, as it is unknown if efficacy is attributable to induction of host T cells versus B cell (antibody-based) immunity.(1) The ACR recommendation for mycophenolate is based on preexisting data of mycophenolate on non-COVID-19 vaccine immunogenicity. Emerging data suggests that mycophenolate may impair SARS-CoV-2 vaccine response in rheumatic and musculoskeletal disease and transplant patients.(1) The ACR recommendation for methotrexate is based on data from influenza vaccines and pneumococcal vaccines with methotrexate.(1) The ACR recommendation for JAK inhibitors is based on concerns related to the effects of JAK inhibitors on interferon signaling that may result in a diminished vaccine response.(1) The ACR recommendation for subcutaneous abatacept is based on several studies suggesting a negative effect of abatacept on vaccine immunogenicity. The first vaccine dose primes naive T cells, naive T cell priming is inhibited by CTLA-4, and abatacept is a CTLA-4Ig construct. CTLA-4 should not inhibit boosts of already primed T cells at the time of the second vaccine dose.(1) |
COMIRNATY 2024-2025, MODERNA COVID 24-25(6M-11Y)EUA, NOVAVAX COVID 2024-2025 (EUA), PFIZER COVID 2024-25(5-11Y)EUA, PFIZER COVID 2024-25(6M-4Y)EUA, SPIKEVAX 2024-2025 |
Sarilumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Sarilumab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of sarilumab 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 sarilumab recommends caution because the concurrent use of sarilumab 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: Sarilumab was studied as monotherapy and in combination with methotrexate or conventional disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis studies. Sarilumab has not been studied with biological DMARDs and concurrent use should be avoided. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents.(1) The most common infections reported by sarilumab treated patients in the clinical trial periods included pneumonia and cellulitis. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving sarilumab. Cases of tuberculosis, candidiasis, and pneumocystis with sarilumab have been reported.(1) |
KEVZARA |
Ublituximab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ublituximab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of ublituximab with immunosuppressive or immunomodulating agents may result in an increased risk for serious infections.(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The US manufacturer of ublituximab recommends caution because the concurrent use of ublituximab with immunomodulating or immunosuppressive agents, including immunosuppressant doses of corticosteroids, may increase the risk of infection.(1) If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents. When switching from agents with immune effects, the half-life and mechanism of action of these drugs must be taken into consideration in order to prevent additive immunosuppressive effects.(1) DISCUSSION: The most common infections reported by ublituximab-treated patients in the clinical trial periods included upper respiratory tract infections and urinary tract infections. Serious, including life-threatening or fatal, bacterial and viral infections were observed in patients receiving ublituximab.(1) Serious and/or fatal bacterial, fungal, and new or reactivated viral infections have been associated with other anti-CD20 B-cell depleting therapies. There were no cases of progressive multifocal leukoencephalopathy (PML) reported during the clinical trials; however, there have been reports of PML during or following completion of other anti-CD20 B-cell depleting therapies.(1) |
BRIUMVI |
Belimumab/Biologic Therapies SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of belimumab with other biologic therapies may result in additive or synergistic effects on the immune system.(1) CLINICAL EFFECTS: Concurrent use of belimumab with other biologic therapies may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The concurrent use of belimumab with other biologic therapies should be approached with caution.(1) DISCUSSION: In a randomized, double-blind, placebo-controlled trial, more patients who received belimumab and rituximab experienced serious adverse events, serious infections, and post-injection systemic reactions (22.2%, 9%, and 13.2%, respectively) than patients who received belimumab with placebo (13.9%, 2.8%, 9.7%) or standard therapy (19.7%, 5.3%, 5.3%).(1) The combination of belimumab with other biologic therapies has not been studied and should be used cautiously.(1) |
BENLYSTA |
IgG Antibodies and Derivatives/Rozanolixizumab-noli SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3) DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3) |
RYSTIGGO |
Tocilizumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tocilizumab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of tocilizumab 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 tocilizumab recommends caution because the concurrent use of tocilizumab 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: Tocilizumab was studied as monotherapy and in combination with methotrexate, non-biologic DMARDs or corticosteroids, depending on the indication. Tocilizumab has not been studied with biological DMARDs and concurrent use should be avoided. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents.(1) The most common infections reported by tocilizumab treated patients in the clinical trial periods included pneumonia, urinary tract infection, cellulitis, herpes zoster, gastroenteritis, diverticulitis, sepsis and bacterial arthritis. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving tocilizumab. Cases of tuberculosis, cryptococcus, aspergillosis, candidiasis, and pneumocystosis have been reported.(1) |
ACTEMRA, ACTEMRA ACTPEN, TOFIDENCE, TYENNE, TYENNE AUTOINJECTOR |
The following contraindication information is available for JEMPERLI (dostarlimab-gxly):
Drug contraindication overview.
*None.
*None.
There are 1 contraindications.
Absolute contraindication.
Contraindication List |
---|
Lactation |
There are 4 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
Severe List |
---|
Hyperglycemia |
Hypophysitis |
Organ transplant rejection |
Pregnancy |
There are 0 moderate contraindications.
The following adverse reaction information is available for JEMPERLI (dostarlimab-gxly):
Adverse reaction overview.
Most common adverse reactions (>=20%) reported with dostarlimab-gxly as a single agentin patients with dMMR solid tumors include fatigue/asthenia, nausea, diarrhea, and anemia. Most common adverse reactions (>=20%) reported with dostarlimab-gxly as combination therapy in patients with dMMR/MSI-H endometrial cancer include rash, diarrhea, hypothroidism, and hypertension.
Most common adverse reactions (>=20%) reported with dostarlimab-gxly as a single agentin patients with dMMR solid tumors include fatigue/asthenia, nausea, diarrhea, and anemia. Most common adverse reactions (>=20%) reported with dostarlimab-gxly as combination therapy in patients with dMMR/MSI-H endometrial cancer include rash, diarrhea, hypothroidism, and hypertension.
There are 49 severe adverse reactions.
More Frequent | Less Frequent |
---|---|
Hypoalbuminemia Increased alkaline phosphatase Lymphopenia |
Colitis Hypothyroidism Interstitial pneumonitis Leukopenia |
Rare/Very Rare |
---|
Adrenocortical insufficiency Aplastic anemia Autoimmune hemolytic anemia Autoimmune hepatitis Autoimmune thrombocytopenia Bullous dermatitis Demyelinating disorder Diabetes mellitus Duodenitis Elevated serum amylase Elevated serum lipase Encephalitis Exfoliative dermatitis Gastritis Graft-versus-host disease Guillain-barre syndrome Hemophagocytic lymphohistiocytosis Hepatocellular damage Histiocytic necrotizing lymphadenitis Hyperthyroidism Hypoparathyroidism Hypophysitis Interstitial nephritis Iritis Meningitis Myelitis Myocarditis Myositis Organ transplant rejection Pancreatitis Pericarditis Peripheral demyelinating neuropathy Polymyalgia rheumatica Polymyositis Renal failure Rhabdomyolysis Sarcoidosis Stevens-johnson syndrome Thyroiditis Toxic epidermal necrolysis Uveitis Vasculitis |
There are 14 less severe adverse reactions.
More Frequent | Less Frequent |
---|---|
Anemia Constipation Diarrhea Fatigue General weakness Nausea |
Anorexia Cough Myalgia Urinary tract infection Vomiting |
Rare/Very Rare |
---|
Arthritis Hashimoto thyroiditis Muscle weakness |
The following precautions are available for JEMPERLI (dostarlimab-gxly):
Safety and efficacy of dostarlimab have not been established in pediatric patients.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
None |
Severe Precaution
None |
Management or Monitoring Precaution
Dostarlimab-gxly | 1 Day – 18 Years | Safety and efficacy not established in age < 18 years. |
Dostarlimab may cause fetal harm if administered to pregnant women based on its mechanism of action. Verify pregnancy status in women of childbearing potential prior to initiation of dostarlimab therapy.
Drug/Drug Class | Severity | Precaution Description | Pregnancy Category Description |
---|---|---|---|
Dostarlimab-gxly | D | Based on drug pharmacology developmental toxicity is possible. | Positive evidence of human fetal risk based on investigation or marketing information but potential benefits may warrant use of drug in pregnant women despite potential risks. |
It is not known whether dostarlimab is distributed into human milk or if the drug has any effect on milk production or the nursing infant. Maternal IgG is known to be present in human milk. The effects of local GI exposure and limited systemic exposure in the breastfed child to dostarlimab are unknown. Because of the potential for adverse reactions in nursing infants, advise women not to breast-feed while receiving the drug and for 4 months after the drug is discontinued.
Contraindicated
Absolute contraindication. (Human data usually available to support recommendations.) This drug should not be given to breast feeding mothers.
Contraindicated
Absolute contraindication. (Human data usually available to support recommendations.) This drug should not be given to breast feeding mothers.
Drug Name | Excretion Potential | Effect on Infant | Notes |
---|---|---|---|
Dostarlimab-gxly | Unknown. It is unknown whether the drug is excreted in human breast milk. | It is not known whether this drug has an adverse effect on the nursing infant. (No data or inconclusive human data) | Manufacturer does not rec during treatment and 4 mo after last dose |
Among patients receiving dostarlimab-gxly as a single agentin clinical trials, 36.9% were 65-75 years of age, and 11.5% were >=75 years of age.
Among patients administered dostarlimab-gxly in combination with carboplatin and paclitaxel in clinical trials, 36.5% were 65-75 years of age, and 11.2% were>=75 years of age. No overall differences in safety or effectiveness were observed between geriatric patients and younger adults.
Among patients administered dostarlimab-gxly in combination with carboplatin and paclitaxel in clinical trials, 36.5% were 65-75 years of age, and 11.2% were>=75 years of age. No overall differences in safety or effectiveness were observed between geriatric patients and younger adults.
The following prioritized warning is available for JEMPERLI (dostarlimab-gxly):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for JEMPERLI (dostarlimab-gxly)'s list of indications:
Endometrial carcinoma | |
C54.1 | Malignant neoplasm of endometrium |
Microsatellite instability-high solid malignant tumor | |
C15 | Malignant neoplasm of esophagus |
C15.3 | Malignant neoplasm of upper third of esophagus |
C15.4 | Malignant neoplasm of middle third of esophagus |
C15.5 | Malignant neoplasm of lower third of esophagus |
C15.8 | Malignant neoplasm of overlapping sites of esophagus |
C15.9 | Malignant neoplasm of esophagus, unspecified |
C16 | Malignant neoplasm of stomach |
C16.0 | Malignant neoplasm of cardia |
C16.1 | Malignant neoplasm of fundus of stomach |
C16.2 | Malignant neoplasm of body of stomach |
C16.3 | Malignant neoplasm of pyloric antrum |
C16.4 | Malignant neoplasm of pylorus |
C16.5 | Malignant neoplasm of lesser curvature of stomach, unspecified |
C16.6 | Malignant neoplasm of greater curvature of stomach, unspecified |
C16.8 | Malignant neoplasm of overlapping sites of stomach |
C16.9 | Malignant neoplasm of stomach, unspecified |
C17 | Malignant neoplasm of small intestine |
C17.0 | Malignant neoplasm of duodenum |
C17.1 | Malignant neoplasm of jejunum |
C17.2 | Malignant neoplasm of ileum |
C17.3 | Meckel's diverticulum, malignant |
C17.8 | Malignant neoplasm of overlapping sites of small intestine |
C17.9 | Malignant neoplasm of small intestine, unspecified |
C18 | Malignant neoplasm of colon |
C18.0 | Malignant neoplasm of cecum |
C18.1 | Malignant neoplasm of appendix |
C18.2 | Malignant neoplasm of ascending colon |
C18.3 | Malignant neoplasm of hepatic flexure |
C18.4 | Malignant neoplasm of transverse colon |
C18.5 | Malignant neoplasm of splenic flexure |
C18.6 | Malignant neoplasm of descending colon |
C18.7 | Malignant neoplasm of sigmoid colon |
C18.8 | Malignant neoplasm of overlapping sites of colon |
C18.9 | Malignant neoplasm of colon, unspecified |
C19 | Malignant neoplasm of rectosigmoid junction |
C20 | Malignant neoplasm of rectum |
C22.3 | Angiosarcoma of liver |
C22.4 | Other sarcomas of liver |
C24 | Malignant neoplasm of other and unspecified parts of biliary tract |
C24.0 | Malignant neoplasm of extrahepatic bile duct |
C24.1 | Malignant neoplasm of ampulla of vater |
C24.8 | Malignant neoplasm of overlapping sites of biliary tract |
C24.9 | Malignant neoplasm of biliary tract, unspecified |
C26.0 | Malignant neoplasm of intestinal tract, part unspecified |
C34 | Malignant neoplasm of bronchus and lung |
C34.1 | Malignant neoplasm of upper lobe, bronchus or lung |
C34.10 | Malignant neoplasm of upper lobe, unspecified bronchus or lung |
C34.11 | Malignant neoplasm of upper lobe, right bronchus or lung |
C34.12 | Malignant neoplasm of upper lobe, left bronchus or lung |
C34.2 | Malignant neoplasm of middle lobe, bronchus or lung |
C34.3 | Malignant neoplasm of lower lobe, bronchus or lung |
C34.30 | Malignant neoplasm of lower lobe, unspecified bronchus or lung |
C34.31 | Malignant neoplasm of lower lobe, right bronchus or lung |
C34.32 | Malignant neoplasm of lower lobe, left bronchus or lung |
C34.8 | Malignant neoplasm of overlapping sites of bronchus and lung |
C34.80 | Malignant neoplasm of overlapping sites of unspecified bronchus and lung |
C34.81 | Malignant neoplasm of overlapping sites of right bronchus and lung |
C34.82 | Malignant neoplasm of overlapping sites of left bronchus and lung |
C34.9 | Malignant neoplasm of unspecified part of bronchus or lung |
C34.90 | Malignant neoplasm of unspecified part of unspecified bronchus or lung |
C34.91 | Malignant neoplasm of unspecified part of right bronchus or lung |
C34.92 | Malignant neoplasm of unspecified part of left bronchus or lung |
C46 | Kaposi's sarcoma |
C46.0 | Kaposi's sarcoma of skin |
C46.1 | Kaposi's sarcoma of soft tissue |
C46.2 | Kaposi's sarcoma of palate |
C46.3 | Kaposi's sarcoma of lymph nodes |
C46.4 | Kaposi's sarcoma of gastrointestinal sites |
C46.5 | Kaposi's sarcoma of lung |
C46.50 | Kaposi's sarcoma of unspecified lung |
C46.51 | Kaposi's sarcoma of right lung |
C46.52 | Kaposi's sarcoma of left lung |
C46.7 | Kaposi's sarcoma of other sites |
C46.9 | Kaposi's sarcoma, unspecified |
C48 | Malignant neoplasm of retroperitoneum and peritoneum |
C48.0 | Malignant neoplasm of retroperitoneum |
C48.8 | Malignant neoplasm of overlapping sites of retroperitoneum and peritoneum |
C49 | Malignant neoplasm of other connective and soft tissue |
C49.0 | Malignant neoplasm of connective and soft tissue of head, face and neck |
C49.1 | Malignant neoplasm of connective and soft tissue of upper limb, including shoulder |
C49.10 | Malignant neoplasm of connective and soft tissue of unspecified upper limb, including shoulder |
C49.11 | Malignant neoplasm of connective and soft tissue of right upper limb, including shoulder |
C49.12 | Malignant neoplasm of connective and soft tissue of left upper limb, including shoulder |
C49.2 | Malignant neoplasm of connective and soft tissue of lower limb, including hip |
C49.20 | Malignant neoplasm of connective and soft tissue of unspecified lower limb, including hip |
C49.21 | Malignant neoplasm of connective and soft tissue of right lower limb, including hip |
C49.22 | Malignant neoplasm of connective and soft tissue of left lower limb, including hip |
C49.3 | Malignant neoplasm of connective and soft tissue of thorax |
C49.4 | Malignant neoplasm of connective and soft tissue of abdomen |
C49.5 | Malignant neoplasm of connective and soft tissue of pelvis |
C49.6 | Malignant neoplasm of connective and soft tissue of trunk, unspecified |
C49.8 | Malignant neoplasm of overlapping sites of connective and soft tissue |
C49.9 | Malignant neoplasm of connective and soft tissue, unspecified |
C50 | Malignant neoplasm of breast |
C50.1 | Malignant neoplasm of central portion of breast |
C50.11 | Malignant neoplasm of central portion of breast, female |
C50.111 | Malignant neoplasm of central portion of right female breast |
C50.112 | Malignant neoplasm of central portion of left female breast |
C50.119 | Malignant neoplasm of central portion of unspecified female breast |
C50.12 | Malignant neoplasm of central portion of breast, male |
C50.121 | Malignant neoplasm of central portion of right male breast |
C50.122 | Malignant neoplasm of central portion of left male breast |
C50.129 | Malignant neoplasm of central portion of unspecified male breast |
C50.2 | Malignant neoplasm of upper-inner quadrant of breast |
C50.21 | Malignant neoplasm of upper-inner quadrant of breast, female |
C50.211 | Malignant neoplasm of upper-inner quadrant of right female breast |
C50.212 | Malignant neoplasm of upper-inner quadrant of left female breast |
C50.219 | Malignant neoplasm of upper-inner quadrant of unspecified female breast |
C50.22 | Malignant neoplasm of upper-inner quadrant of breast, male |
C50.221 | Malignant neoplasm of upper-inner quadrant of right male breast |
C50.222 | Malignant neoplasm of upper-inner quadrant of left male breast |
C50.229 | Malignant neoplasm of upper-inner quadrant of unspecified male breast |
C50.3 | Malignant neoplasm of lower-inner quadrant of breast |
C50.31 | Malignant neoplasm of lower-inner quadrant of breast, female |
C50.311 | Malignant neoplasm of lower-inner quadrant of right female breast |
C50.312 | Malignant neoplasm of lower-inner quadrant of left female breast |
C50.319 | Malignant neoplasm of lower-inner quadrant of unspecified female breast |
C50.32 | Malignant neoplasm of lower-inner quadrant of breast, male |
C50.321 | Malignant neoplasm of lower-inner quadrant of right male breast |
C50.322 | Malignant neoplasm of lower-inner quadrant of left male breast |
C50.329 | Malignant neoplasm of lower-inner quadrant of unspecified male breast |
C50.4 | Malignant neoplasm of upper-outer quadrant of breast |
C50.41 | Malignant neoplasm of upper-outer quadrant of breast, female |
C50.411 | Malignant neoplasm of upper-outer quadrant of right female breast |
C50.412 | Malignant neoplasm of upper-outer quadrant of left female breast |
C50.419 | Malignant neoplasm of upper-outer quadrant of unspecified female breast |
C50.42 | Malignant neoplasm of upper-outer quadrant of breast, male |
C50.421 | Malignant neoplasm of upper-outer quadrant of right male breast |
C50.422 | Malignant neoplasm of upper-outer quadrant of left male breast |
C50.429 | Malignant neoplasm of upper-outer quadrant of unspecified male breast |
C50.5 | Malignant neoplasm of lower-outer quadrant of breast |
C50.51 | Malignant neoplasm of lower-outer quadrant of breast, female |
C50.511 | Malignant neoplasm of lower-outer quadrant of right female breast |
C50.512 | Malignant neoplasm of lower-outer quadrant of left female breast |
C50.519 | Malignant neoplasm of lower-outer quadrant of unspecified female breast |
C50.52 | Malignant neoplasm of lower-outer quadrant of breast, male |
C50.521 | Malignant neoplasm of lower-outer quadrant of right male breast |
C50.522 | Malignant neoplasm of lower-outer quadrant of left male breast |
C50.529 | Malignant neoplasm of lower-outer quadrant of unspecified male breast |
C50.6 | Malignant neoplasm of axillary tail of breast |
C50.61 | Malignant neoplasm of axillary tail of breast, female |
C50.611 | Malignant neoplasm of axillary tail of right female breast |
C50.612 | Malignant neoplasm of axillary tail of left female breast |
C50.619 | Malignant neoplasm of axillary tail of unspecified female breast |
C50.62 | Malignant neoplasm of axillary tail of breast, male |
C50.621 | Malignant neoplasm of axillary tail of right male breast |
C50.622 | Malignant neoplasm of axillary tail of left male breast |
C50.629 | Malignant neoplasm of axillary tail of unspecified male breast |
C50.8 | Malignant neoplasm of overlapping sites of breast |
C50.81 | Malignant neoplasm of overlapping sites of breast, female |
C50.811 | Malignant neoplasm of overlapping sites of right female breast |
C50.812 | Malignant neoplasm of overlapping sites of left female breast |
C50.819 | Malignant neoplasm of overlapping sites of unspecified female breast |
C50.82 | Malignant neoplasm of overlapping sites of breast, male |
C50.821 | Malignant neoplasm of overlapping sites of right male breast |
C50.822 | Malignant neoplasm of overlapping sites of left male breast |
C50.829 | Malignant neoplasm of overlapping sites of unspecified male breast |
C50.9 | Malignant neoplasm of breast of unspecified site |
C50.91 | Malignant neoplasm of breast of unspecified site, female |
C50.911 | Malignant neoplasm of unspecified site of right female breast |
C50.912 | Malignant neoplasm of unspecified site of left female breast |
C50.919 | Malignant neoplasm of unspecified site of unspecified female breast |
C50.92 | Malignant neoplasm of breast of unspecified site, male |
C50.921 | Malignant neoplasm of unspecified site of right male breast |
C50.922 | Malignant neoplasm of unspecified site of left male breast |
C50.929 | Malignant neoplasm of unspecified site of unspecified male breast |
C54.1 | Malignant neoplasm of endometrium |
C61 | Malignant neoplasm of prostate |
C64 | Malignant neoplasm of kidney, except renal pelvis |
C64.1 | Malignant neoplasm of right kidney, except renal pelvis |
C64.2 | Malignant neoplasm of left kidney, except renal pelvis |
C64.9 | Malignant neoplasm of unspecified kidney, except renal pelvis |
C73 | Malignant neoplasm of thyroid gland |
C92.3 | Myeloid sarcoma |
C92.30 | Myeloid sarcoma, not having achieved remission |
C92.31 | Myeloid sarcoma, in remission |
C92.32 | Myeloid sarcoma, in relapse |
C96.22 | Mast cell sarcoma |
C96.4 | Sarcoma of dendritic cells (accessory cells) |
C96.A | Histiocytic sarcoma |
Mismatch repair deficient endometrial cancer | |
C54.1 | Malignant neoplasm of endometrium |
Formulary Reference Tool