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Drug overview for BESREMI (ropeginterferon alfa-2b-njft):
Generic name: ropeginterferon alfa-2b-njft
Drug class: Interferon Alfa
Therapeutic class: Antineoplastics
Ropeginterferon alfa-2b-njft consists of interferon alfa-2b (recombinant DNA origin) covalently bound to methoxy polyethylene glycol (mPEG); ropeginterferon alfa-2b exerts cellular effects in bone marrow in the management of polycythemia vera.
No enhanced Uses information available for this drug.
Generic name: ropeginterferon alfa-2b-njft
Drug class: Interferon Alfa
Therapeutic class: Antineoplastics
Ropeginterferon alfa-2b-njft consists of interferon alfa-2b (recombinant DNA origin) covalently bound to methoxy polyethylene glycol (mPEG); ropeginterferon alfa-2b exerts cellular effects in bone marrow in the management of polycythemia vera.
No enhanced Uses information available for this drug.
DRUG IMAGES
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The following indications for BESREMI (ropeginterferon alfa-2b-njft) have been approved by the FDA:
Indications:
Polycythemia vera
Professional Synonyms:
None.
Indications:
Polycythemia vera
Professional Synonyms:
None.
The following dosing information is available for BESREMI (ropeginterferon alfa-2b-njft):
If drug-related toxicities arise during ropeginterferon alfa-2b-njft therapy, reduce the dose to the next lower dose level or interrupt therapy in accordance with Table 1. If there is insufficient efficacy at the decreased dose following dose modification, consider attempting a dose increase to the next higher dose level after recovery to grade 1 toxicity.
Table 1. Recommended Dosage Modification of Ropeginterferon alfa-2b-njft for Adverse Reactions
Adverse Reaction Severity Dosage Modification Liver enzyme elevation Any increase above Interrupt treatment with concomitant baseline until recovery, then bilirubin elevation, or restart at a dose 50 mcg other evidence of lower than the hepatic decompensation interrupted dose. If the interrupted dose is 50 mcg, refrain from treatment until recovery. Consider permanent discontinuation if toxicity persists after four dose modificati ons.
Liver enzyme elevation >5 times the upper limit Decrease dose by 50 mcg; of normal (ULN) but <=20 if toxicity does not times the ULN improve, continue decreasing at biweekly intervals until ALT and AST recover to <3 times the ULN if baseline was normal or to 3 times baseline if baseline was abnormal, and gamma-glutamyltransferas e (GGT) recovers t o <2.5 times the ULN if baseline was normal, or to 2.5 times baseline if baseline was abnormal.
If the interrupted dose is 50 mcg, refrain from treatment until recovery. >20 times the ULN Interrupt treatment until ALT and AST recover to <3 times the ULN if baseline was normal, or to 1.5 times baseline if baseline was abnormal, and GGT recovers to <2.5
times the ULN if baseline was normal, or to 2 times baseline if baseline was abnormal. Cons ider permanent discontinuation if toxicity persists after four dose modifications. Cytopenia Anemia: hemoglobin (Hgb) Decrease dose by 50 mcg; <8 g/dL if toxicity does not Thrombocytopenia: improve, continue platelet count decreasing at biweekly <50,000/mm3 but intervals until recovery >=25,000/mm3 Leukopenia: of Hgb >10 g/dL, white blood cell count platelets >75,000/mm3, (WBC) <2000/mm3 but and WBC >3,000/mm3 If >=1000/mm3 the interrupted dose is 50 mcg, refrain from treatment until recovery. Anemia: Hemoglobin Interrupt treatment levels are life until recovery of Hgb threatening, or urgent >10 g/dL, platelets intervention needed >75,000/mm3, and WBC Thrombocytopenia: >3,000/mm3 Consider platelet count permanent <25,000/mm3 Leukopenia: discontinuation if WBC <1000/mm3 toxicity persists after four dose modifications. Depression Mild, without suicidal Consider psychiatric ideation consultation if persistent (>8 weeks) Moderate, without Consider dose reduction suicidal ideation and psychiatric consultation Severe, or any severity Discontinue therapy, with suicidal ideation recommend psychiatric consultation
Table 1. Recommended Dosage Modification of Ropeginterferon alfa-2b-njft for Adverse Reactions
Adverse Reaction Severity Dosage Modification Liver enzyme elevation Any increase above Interrupt treatment with concomitant baseline until recovery, then bilirubin elevation, or restart at a dose 50 mcg other evidence of lower than the hepatic decompensation interrupted dose. If the interrupted dose is 50 mcg, refrain from treatment until recovery. Consider permanent discontinuation if toxicity persists after four dose modificati ons.
Liver enzyme elevation >5 times the upper limit Decrease dose by 50 mcg; of normal (ULN) but <=20 if toxicity does not times the ULN improve, continue decreasing at biweekly intervals until ALT and AST recover to <3 times the ULN if baseline was normal or to 3 times baseline if baseline was abnormal, and gamma-glutamyltransferas e (GGT) recovers t o <2.5 times the ULN if baseline was normal, or to 2.5 times baseline if baseline was abnormal.
If the interrupted dose is 50 mcg, refrain from treatment until recovery. >20 times the ULN Interrupt treatment until ALT and AST recover to <3 times the ULN if baseline was normal, or to 1.5 times baseline if baseline was abnormal, and GGT recovers to <2.5
times the ULN if baseline was normal, or to 2 times baseline if baseline was abnormal. Cons ider permanent discontinuation if toxicity persists after four dose modifications. Cytopenia Anemia: hemoglobin (Hgb) Decrease dose by 50 mcg; <8 g/dL if toxicity does not Thrombocytopenia: improve, continue platelet count decreasing at biweekly <50,000/mm3 but intervals until recovery >=25,000/mm3 Leukopenia: of Hgb >10 g/dL, white blood cell count platelets >75,000/mm3, (WBC) <2000/mm3 but and WBC >3,000/mm3 If >=1000/mm3 the interrupted dose is 50 mcg, refrain from treatment until recovery. Anemia: Hemoglobin Interrupt treatment levels are life until recovery of Hgb threatening, or urgent >10 g/dL, platelets intervention needed >75,000/mm3, and WBC Thrombocytopenia: >3,000/mm3 Consider platelet count permanent <25,000/mm3 Leukopenia: discontinuation if WBC <1000/mm3 toxicity persists after four dose modifications. Depression Mild, without suicidal Consider psychiatric ideation consultation if persistent (>8 weeks) Moderate, without Consider dose reduction suicidal ideation and psychiatric consultation Severe, or any severity Discontinue therapy, with suicidal ideation recommend psychiatric consultation
Ropeginterferon alfa-2b-njft is administered by subcutaneous injection every 2 weeks. The drug is commercially available as a 500-mcg/mL solution in a single-dose prefilled syringe for subcutaneous administration. Several peginterferon alfa subtypes (alfa-2a, alfa-2b), dosage forms, and strengths are commercially available.
Verify that the correct preparation is used. Ropeginterferon alfa-2b-njft may be self-administered if the clinician determines that the patient and/or their caregiver is competent to prepare and safely administer the drug after appropriate training is provided. Before each injection, remove the carton that contains the ropeginterferon alfa-2b-njft prefilled syringe from the refrigerator.
Keep the prefilled syringe in the carton and lay it flat on a clean work surface for 15-30 minutes to allow the syringe to reach room temperature. Visually inspect the solution in the prefilled syringe for particulate matter and discoloration before administration. The solution should be clear and colorless to slightly yellowish; do not use the drug if the solution is cloudy, discolored, or contains particulate matter, or if the syringe shows any sign of damage.
Depending on the prescribed dose, the amount of solution in the syringe may need to be adjusted by discarding some of the drug. To administer the subcutaneous injection, pinch the skin; insert the needle at a 45- to 90-degree angle into the pinched skin, then release the skin. After all of the drug is injected, remove the needle from the skin.
Verify that the correct preparation is used. Ropeginterferon alfa-2b-njft may be self-administered if the clinician determines that the patient and/or their caregiver is competent to prepare and safely administer the drug after appropriate training is provided. Before each injection, remove the carton that contains the ropeginterferon alfa-2b-njft prefilled syringe from the refrigerator.
Keep the prefilled syringe in the carton and lay it flat on a clean work surface for 15-30 minutes to allow the syringe to reach room temperature. Visually inspect the solution in the prefilled syringe for particulate matter and discoloration before administration. The solution should be clear and colorless to slightly yellowish; do not use the drug if the solution is cloudy, discolored, or contains particulate matter, or if the syringe shows any sign of damage.
Depending on the prescribed dose, the amount of solution in the syringe may need to be adjusted by discarding some of the drug. To administer the subcutaneous injection, pinch the skin; insert the needle at a 45- to 90-degree angle into the pinched skin, then release the skin. After all of the drug is injected, remove the needle from the skin.
No dosing information available.
No generic dosing information available.
The following drug interaction information is available for BESREMI (ropeginterferon alfa-2b-njft):
There are 5 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 TRIVALENT 2024-2025, 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 |
| Ropeginterferon alfa-2b/Select Immunosuppressives 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: 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: The US and UK manufacturers of ropeginterferon alfa-2b state that concurrent use of ropeginterferon alfa-2b in transplant patients receiving immunosuppressive agents is contraindicated.(1-2) DISCUSSION: In clinical trials, 20% of patients experienced leukopenia. Interferon alfa products may cause fatal or life-threatening infections.(1-2) |
ASTAGRAF XL, CELLCEPT, CYCLOSPORINE, CYCLOSPORINE MODIFIED, ENVARSUS XR, EVEROLIMUS, GENGRAF, MYCOPHENOLATE MOFETIL, MYCOPHENOLIC ACID, MYFORTIC, MYHIBBIN, NEORAL, PROGRAF, SANDIMMUNE, SIROLIMUS, TACROLIMUS, TACROLIMUS XL, ZORTRESS |
There are 19 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 |
|---|---|
| Hydroxyurea/Interferon SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. CLINICAL EFFECTS: Concurrent or recent use of interferon may increase the risk of cutaneous vascular toxicities, including vasculitic ulcerations and gangrene.(1,2) PREDISPOSING FACTORS: The interaction has been noted in patients treated with hydroxyurea for myeloproliferative disorders.(1,2) PATIENT MANAGEMENT: Monitor patients receiving concurrent therapy and patients receiving hydroxyurea alone who have recently received interferon closely for cutaneous vasculitic ulcerations. Discontinue hydroxyurea in patients who develop cutaneous vasculitic ulcerations.(1,2) DISCUSSION: Cutaneous vasculitic toxicities, including vasculitic ulcerations and gangrene, have occurred in patients with myeloproliferative disorders during therapy with hydroxyurea. These vasculitic toxicities were reported most often in patients with a history of, or currently receiving, interferon therapy.(1,2) |
DROXIA, HYDREA, HYDROXYUREA, SIKLOS, XROMI |
| 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) |
| 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) |
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) 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).(3) |
KESIMPTA PEN, OCREVUS, OCREVUS ZUNOVO |
| 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 |
| 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 |
| 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) |
ABECMA, ABRAXANE, ABRILADA(CF), ABRILADA(CF) PEN, ABRILADA(CF) PEN (2 PACK), 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, ARRANON, ARSENIC TRIOXIDE, ARZERRA, ASPARLAS, 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, 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, BRAFTOVI, BREYANZI, BREYANZI CD4 COMPONENT, BREYANZI CD8 COMPONENT, 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, CHLORAMBUCIL, CIBINQO, CIMZIA, CIMZIA (2 PACK), CISPLATIN, CLOBETASOL PROPIONATE MICRO, CLOFARABINE, COLUMVI, COPAXONE, COPIKTRA, CORTEF, CORTISONE ACETATE, COSENTYX, COSENTYX (2 SYRINGES), COSENTYX SENSOREADY (2 PENS), COSENTYX SENSOREADY PEN, COSENTYX SYRINGE, COSENTYX UNOREADY PEN, COSMEGEN, CYCLOPHOSPHAMIDE, CYCLOPHOSPHAMIDE MONOHYDRATE, CYLTEZO(CF), CYLTEZO(CF) PEN, CYLTEZO(CF) PEN CROHN'S-UC-HS, CYLTEZO(CF) PEN PSORIASIS-UV, CYTARABINE, 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, EFLORNITHINE HCL, ELAHERE, ELLENCE, ELREXFIO, EMFLAZA, ENBREL, ENBREL MINI, ENBREL SURECLICK, ENHERTU, ENSPRYNG, ENTYVIO, ENTYVIO PEN, EOHILIA, EPIRUBICIN HCL, EPKINLY, ERBITUX, ERWINASE, ETOPOPHOS, ETOPOSIDE, EVEROLIMUS, EVOMELA, FARYDAK, FLOXURIDINE, FLUDARABINE PHOSPHATE, FLUNISOLIDE, FLUOCINOLONE ACETONIDE, FLUOCINOLONE ACETONIDE MICRO, FLUOCINONIDE MICRONIZED, FLUOROURACIL, FLUTICASONE PROPIONATE, FLUTICASONE PROPIONATE MICRO, FOLOTYN, FRINDOVYX, FYARRO, GAMIFANT, GAVRETO, GAZYVA, GEFITINIB, GEMCITABINE HCL, GLATIRAMER ACETATE, GLATOPA, GLEEVEC, GLEOSTINE, GLIADEL, GRAFAPEX, HADLIMA, HADLIMA PUSHTOUCH, HADLIMA(CF), HADLIMA(CF) PUSHTOUCH, HEMADY, HEMMOREX-HC, HEPZATO, HERCEPTIN, HERCEPTIN HYLECTA, HERCESSI, HERZUMA, HEXATRIONE, 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, HYDROCORTISONE, HYDROCORTISONE ACETATE, HYDROCORTISONE SOD SUCCINATE, HYRIMOZ, HYRIMOZ PEN, HYRIMOZ(CF), HYRIMOZ(CF) PEDIATRIC CROHN'S, HYRIMOZ(CF) PEN, HYRIMOZ(CF) PEN CROHN-UC START, HYRIMOZ(CF) PEN PSORIASIS, IBRANCE, ICLUSIG, IDAMYCIN PFS, IDARUBICIN HCL, IFEX, IFOSFAMIDE, ILARIS, IMATINIB MESYLATE, IMBRUVICA, IMDELLTRA, IMFINZI, IMKELDI, IMURAN, INFLECTRA, INFLIXIMAB, INFUGEM, INQOVI, INREBIC, IRESSA, IRINOTECAN HCL, ISTODAX, IVRA, IWILFIN, IXEMPRA, JAKAFI, JAYPIRCA, JEMPERLI, JEVTANA, JOENJA, JYLAMVO, KADCYLA, KANJINTI, KEMOPLAT, KENALOG-10, KENALOG-40, KENALOG-80, KEYTRUDA, KINERET, KISQALI, KYMRIAH, LEMTRADA, LENALIDOMIDE, LEUKERAN, LIDOCIDEX-I, LONSURF, LOQTORZI, LUNSUMIO, LUTATHERA, LYNPARZA, MARGENZA, 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, MYLERAN, MYLOTARG, NELARABINE, NILOTINIB HCL, NIPENT, NULOJIX, OGIVRI, OJJAARA, 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, PROLEUKIN, PROVENGE, PURIXAN, PYRIMETHAMINE, QUALAQUIN, QUININE HCL, QUININE SULFATE, RASUVO, RAYOS, REBIF, REBIF REBIDOSE, REMICADE, RENFLEXIS, REVLIMID, REVUFORJ, REZUROCK, RIABNI, RITUXAN, RITUXAN HYCELA, ROMIDEPSIN, RUBRACA, RUXIENCE, RYDAPT, RYLAZE, RYTELO, SARCLISA, SCEMBLIX, SIMLANDI(CF), SIMLANDI(CF) AUTOINJECTOR, SIMPONI, SIMPONI ARIA, SIMULECT, SODIUM IODIDE I-123, SOLU-CORTEF, SOLU-MEDROL, SOTYKTU, SPRYCEL, STRONTIUM-89 CHLORIDE, SUNITINIB MALATE, SUTENT, TABLOID, 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, TEVIMBRA, THIOGUANINE, THIOTEPA, TOPOTECAN HCL, TORISEL, TORPENZ, TRAMETINIB, TRAZIMERA, TREANDA, TRETINOIN, TREXALL, TRIAMCINOLONE, TRIAMCINOLONE ACETONIDE, TRIAMCINOLONE DIACETATE, TRIAMCINOLONE DIACETATE MICRO, TRIFLURIDINE, TRILOAN II SUIK, TRILOAN SUIK, TRISENOX, TRODELVY, TRUQAP, TRUXIMA, 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, VYXEOS, XALKORI, XATMEP, XELODA, XOFIGO, XPOVIO, YESCARTA, YONDELIS, YUFLYMA(CF) (2 PACK), YUFLYMA(CF) AI CROHN'S-UC-HS, YUFLYMA(CF) AUTOINJECT (2 PCK), YUFLYMA(CF) AUTOINJECTOR, YUSIMRY(CF) PEN, ZCORT, ZEJULA, ZEPZELCA, ZEVALIN, ZILRETTA, ZIRABEV, ZOKINVY, ZOLINZA, ZYDELIG, ZYMFENTRA, ZYMFENTRA (2 PACK), ZYMFENTRA PEN (2 PACK), ZYNLONTA, ZYNYZ |
| Erlotinib/Ropeginterferon alfa-2b SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ropeginterferon alfa-2b and erlotinib both suppress the immune system. The exact mechanism of gastrointestinal perforation with erlotinib is unknown. CLINICAL EFFECTS: Concurrent use of ropeginterferon alfa-2b with erlotinib may result in an increased risk of serious infections and gastrointestinal perforation. Fatal cases of gastrointestinal perforation have been reported.(1) PREDISPOSING FACTORS: Patients with a history of peptic ulceration or diverticular disease or who are receiving concomitant corticosteroids, NSAIDs, and/or taxane-based chemotherapy may be an increased risk of gastrointestinal perforation.(1) PATIENT MANAGEMENT: Avoid concurrent use of ropeginterferon alfa-2b and erlotinib.(1-2) If concurrent use cannot be avoided, monitor for effects of excessive immunosuppression and gastrointestinal perforation. Discontinue erlotinib in patients who develop gastrointestinal perforation.(1) DISCUSSION: In a phase II trial of concurrent bevacizumab plus erlotinib, 2 of 13 patients suffered fatal gastrointestinal perforations.(3) In another phase II trial of concurrent bevacizumab with erlotinib, 1 of 104 patients died of gastrointestinal perforation.(4) In clinical trials of ropeginterferon alfa-2b, 20% of patients experienced leukopenia. Interferon alfa products may cause fatal or life-threatening infections.(2) |
ERLOTINIB HCL, TARCEVA |
There are 6 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 |
|---|---|
| Theophylline Derivatives/Selected CYP1A2 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: CYP1A2 inhibitors may reduce the elimination rate of theophylline derivatives. CLINICAL EFFECTS: The concurrent administration of selected CYP1A2 inhibitors and theophylline or their derivatives may result in increased levels and toxicity of theophylline.(1-19) PREDISPOSING FACTORS: Concomitant therapy with inhibitors of CYP3A4 (e.g. clarithromycin, itraconazole, ritonavir) which block a secondary metabolic pathway for theophylline, may increase the magnitude of this interaction. PATIENT MANAGEMENT: Theophylline levels should be closely monitored in patients receiving concurrent therapy. The dosage of theophylline may need to be decreased after a CYP1A2 inhibitor is initiated. If the CYP1A2 inhibitor is discontinued in a patient stabilized on the combination, the theophylline level may fall. Monitor theophylline levels and adjust dose accordingly. DISCUSSION: A study in 5 patients with active hepatitis B and 4 healthy subjects examined the effects of a single dose of interferon alpha (9 million units in 8 subjects, 18 million units in 1 subject). There was no effect on theophylline in 1 subject. In the other 8 subjects, interferon increased theophylline half-life by 70% and decreased theophylline clearance by 49% (range 33% to 81%).(1) A study in 11 healthy subjects examined the effects of interferon alpha (3 million International Units daily for 3 days) on a single aminophylline (4 mg/kg) infusion. Interferon increased the half-life, area-under-curve (AUC), and mean residence time by 13.7%, 17.9%, and 16.3%, respectively. Theophylline clearance decreased by 9.1%.(2) In a study in healthy males, peginterferon alfa-2a (180 mcg once weekly for 4 weeks) increased theophylline AUC by 25%.(3,4) Concurrent interferon alfa has been shown to increase theophylline levels by 100%.(5) A study in 7 patients with chronic hepatitis C examined the effects of interferon beta (3 million to 9 million International Units daily for 8 weeks) on theophylline ethylenediamine (single 250 mg infusion). Interferon decreased theophylline clearance by 26.3% and increased theophylline half-life by 39.3%. There was no correlation between interferon dose and effect. The greatest effect was seen in a patient who received 3 million International Units daily, while no effect was seen in a patient who received 9 million International Units daily.(6) Increased serum theophylline levels with signs and symptoms of theophylline toxicity have been reported in patients following the addition of mexiletine to their treatment.(7-15) In a study evaluated the combination of disulfiram and theophylline in 20 recovering alcoholics. Patients received a single IV dose of theophylline while being given either 250 mg or 500 mg of disulfiram daily. Both dosages of disulfiram decreased the clearance of theophylline. However, the effect was greatest in patients receiving disulfiram 500 mg daily.(16) Increases in serum theophylline concentration and half-life have been reported during concurrent administration of theophylline and ticlopidine.(17) In healthy subjects, rofecoxib (12.5 mg/day, 25 mg/day, or 50 mg/day for seven days) increased the area-under-curve (AUC) of a single dose of theophylline (300 mg) by 38% to 60%. Therefore, the manufacturer of rofecoxib recommends that theophylline levels be monitored if rofecoxib is initiated or changed in patients receiving theophylline.(18) Selected CYP1A2 inhibitors linked to this monograph include: Angelica dahurica, artemisinin, cannabidiol, curcumin, danshen, dipyrone, disulfiram, echinacea, enasidenib, fexinidazole, genistein, ginseng, interferons, methoxsalen, mexiletine, parsley, phenylpropanolamine, pipemidic acid, piperine, propafenone, ribociclib, rofecoxib, rucaparib, simeprevir, ticlopidine, triclabendazole, verapamil.(19) |
AMINOPHYLLINE, DYPHYLLINE, ELIXOPHYLLIN, THEO-24, THEOPHYLLINE, THEOPHYLLINE ANHYDROUS, THEOPHYLLINE ER, THEOPHYLLINE ETHYLENEDIAMINE |
| 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) |
OTULFI, PYZCHIVA, SELARSDI, STELARA, STEQEYMA, USTEKINUMAB, USTEKINUMAB-TTWE, WEZLANA, YESINTEK |
| 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 |
| 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 BESREMI (ropeginterferon alfa-2b-njft):
Drug contraindication overview.
*Current or prior history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt. *Known hypersensitivity to interferons or any component of the preparation. *Moderate or severe hepatic impairment (Child-Pugh class B or C).
*History or presence of active serious or untreated autoimmune disease. *Immunosuppressed transplant recipients.
*Current or prior history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt. *Known hypersensitivity to interferons or any component of the preparation. *Moderate or severe hepatic impairment (Child-Pugh class B or C).
*History or presence of active serious or untreated autoimmune disease. *Immunosuppressed transplant recipients.
There are 7 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Acute pancreatitis |
| Child-pugh class B hepatic impairment |
| Child-pugh class C hepatic impairment |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Hepatic failure |
| Lactation |
| Severe hepatic disease |
There are 17 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Anemia |
| Autoimmune disease |
| Cardiac arrhythmia |
| Cerebrovascular accident |
| Chronic heart failure |
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Depression |
| Diabetic retinopathy |
| Hypertensive retinopathy |
| Kidney disease with likely reduction in glomerular filtration rate (GFr) |
| Myocardial ischemia |
| Neutropenic disorder |
| Pregnancy |
| Psychotic disorder |
| Retinal thrombosis |
| Suicidal ideation |
| Thrombocytopenic disorder |
There are 6 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Diabetes mellitus |
| Hyperlipidemia |
| Hyperthyroidism |
| Hypoglycemic disorder |
| Hypothyroidism |
| Pulmonary disease |
The following adverse reaction information is available for BESREMI (ropeginterferon alfa-2b-njft):
Adverse reaction overview.
The most common adverse reactions reported in >40% of patients receiving ropeginterferon alfa-2b-njft in clinical studies include influenza-like illness, arthralgia, fatigue, pruritus, nasopharyngitis, and musculoskeletal pain.
The most common adverse reactions reported in >40% of patients receiving ropeginterferon alfa-2b-njft in clinical studies include influenza-like illness, arthralgia, fatigue, pruritus, nasopharyngitis, and musculoskeletal pain.
There are 46 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Abnormal hepatic function tests Increased alanine transaminase Increased aspartate transaminase |
Anemia Depression Dyspnea Hyperbilirubinemia Hypertension Hyperthyroidism Hypothyroidism Leukopenia Thrombocytopenic disorder |
| Rare/Very Rare |
|---|
|
Acute myocardial infarction Aggressive behavior Anaphylaxis Angioedema Atrial fibrillation Bronchospastic pulmonary disease Cardiomyopathy Diabetes mellitus Drug-induced psychosis Hypersensitivity drug reaction Hypertriglyceridemia Infection Interstitial nephritis Interstitial pneumonitis Ischemic colitis Kidney disease with reduction in glomerular filtration rate (GFr) Manic disorder Myocardial ischemia Neutropenic disorder Pancreatitis Pneumonia Pulmonary hypertension Pulmonary infiltrates Retinal detachment Retinal disorder Retinal hemorrhage Retinal vascular occlusion Sarcoidosis Suicidal Suicidal ideation Thyroiditis Ulcerative colitis Urticaria Vision impairment |
There are 41 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Alopecia Anorexia Arthralgia Chills Diarrhea Dizziness Fatigue Fever Flu-like symptoms Headache disorder Injection site sequelae Irritability Musculoskeletal pain Nausea Pharyngitis Pruritus of skin Skin rash |
Acneiform eruption Cataracts Dry eye Edema Erythema Hyperlipidemia Mood changes Muscle spasm Myalgia Sleep disorder Upper respiratory infection Urinary tract infection Vertigo |
| Rare/Very Rare |
|---|
|
Bronchiolitis Drowsy Dry skin General weakness Hallucinations Hyperhidrosis Hyperkeratosis Malaise Migraine Psoriasis Tooth disorder |
The following precautions are available for BESREMI (ropeginterferon alfa-2b-njft):
Safety and effectiveness of ropeginterferon alfa-2b-njft have not been established in pediatric patients.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Available human data with ropeginterferon alfa-2b-njft use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproductive studies have not been conducted. Based on its mechanism of action and the role of interferon alfa in pregnancy and fetal development, ropeginterferon alfa-2b may cause fetal harm and should be assumed to have abortifacient potential when administered to a pregnant woman.
Advise pregnant women of the potential risk to a fetus. Adverse maternal and fetal outcomes such as thrombosis and hemorrhage, including a risk of miscarriage, have been associated with polycythemia vera in pregnant women.
Advise pregnant women of the potential risk to a fetus. Adverse maternal and fetal outcomes such as thrombosis and hemorrhage, including a risk of miscarriage, have been associated with polycythemia vera in pregnant women.
It is not known whether ropeginterferon alfa-2b-njft distributes into human or animal milk, or if the drug has any effects on the breast-fed child or on milk production. Because of the potential for serious adverse reactions in breast-fed infants from ropeginterferon alfa-2b, breastfeeding is not recommended during treatment and for 8 weeks after the final dose.
Clinical studies of ropeginterferon alfa-2b-njft did not include sufficient numbers of patients >= 65 years of age to determine whether they respond differently than younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for geriatric patients should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other therapy.
The following prioritized warning is available for BESREMI (ropeginterferon alfa-2b-njft):
WARNING: This medication may rarely cause or worsen some serious medical conditions, including mental/mood problems (such as depression), autoimmune conditions (such as lupus, rheumatoid arthritis), blood vessel problems (such as heart disease), or infections. Careful monitoring by your doctor may decrease your risk. Tell your doctor right away if you develop any serious symptoms or side effects (see Side Effects section). Some side effects may go away or lessen after stopping treatment with this medication.
WARNING: This medication may rarely cause or worsen some serious medical conditions, including mental/mood problems (such as depression), autoimmune conditions (such as lupus, rheumatoid arthritis), blood vessel problems (such as heart disease), or infections. Careful monitoring by your doctor may decrease your risk. Tell your doctor right away if you develop any serious symptoms or side effects (see Side Effects section). Some side effects may go away or lessen after stopping treatment with this medication.
The following icd codes are available for BESREMI (ropeginterferon alfa-2b-njft)'s list of indications:
| Polycythemia vera | |
| D45 | Polycythemia vera |
Formulary Reference Tool