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Drug overview for LENALIDOMIDE (lenalidomide):
Generic name: LENALIDOMIDE (LEN-a-LID-oh-mide)
Drug class: Thalidomide and Derivative Immunomodulators
Therapeutic class: Antineoplastics
Lenalidomide, a thalidomide analog, is an immunomodulatory agent with antineoplastic and antiangiogenic activity.
No enhanced Uses information available for this drug.
Generic name: LENALIDOMIDE (LEN-a-LID-oh-mide)
Drug class: Thalidomide and Derivative Immunomodulators
Therapeutic class: Antineoplastics
Lenalidomide, a thalidomide analog, is an immunomodulatory agent with antineoplastic and antiangiogenic activity.
No enhanced Uses information available for this drug.
DRUG IMAGES
LENALIDOMIDE 10 MG CAPSULE
LENALIDOMIDE 15 MG CAPSULE
LENALIDOMIDE 25 MG CAPSULE
LENALIDOMIDE 5 MG CAPSULE
LENALIDOMIDE 2.5 MG CAPSULE
LENALIDOMIDE 20 MG CAPSULE
The following indications for LENALIDOMIDE (lenalidomide) have been approved by the FDA:
Indications:
Follicular lymphoma
Mantle cell lymphoma
Marginal zone lymphoma
Multiple myeloma maintenance therapy following autologous hematopoietic stem cell transplantation
Multiple myeloma
Myelodysplastic syndrome with 5q deletion
Progressive diffuse large B-cell lymphoma
Professional Synonyms:
Follicular B-cell lymphoma
Follicular B-cell non-Hodgkin's lymphoma
Mantle cell B-cell lymphoma
Plasma cell myeloma
Indications:
Follicular lymphoma
Mantle cell lymphoma
Marginal zone lymphoma
Multiple myeloma maintenance therapy following autologous hematopoietic stem cell transplantation
Multiple myeloma
Myelodysplastic syndrome with 5q deletion
Progressive diffuse large B-cell lymphoma
Professional Synonyms:
Follicular B-cell lymphoma
Follicular B-cell non-Hodgkin's lymphoma
Mantle cell B-cell lymphoma
Plasma cell myeloma
The following dosing information is available for LENALIDOMIDE (lenalidomide):
Temporary interruption of lenalidomide therapy followed by dosage reduction may be necessary in patients experiencing thrombocytopenia (see Table 3) or neutropenia (see Table 4).
Table 3. Dosage Modification for Thrombocytopenia in Patients with MDS
Severity Lenalidomide Dosage Modification (Lenalidomide Starting Dosage = 10 mg daily) Platelet count <50,000/mm3 occurswithin 4 weeks of therapy Baseline platelet count Withhold therapy until platelet >=100,000/mm3 count >=50,000/mm3, then resume at 5 mg daily Platelet count decreases to 50% of baseline value within 4 weeks of therapy Baseline platelet count >=60,000/mm3 Withhold therapy until platelet to <100,000/mm3 count >=50,000/mm3, then resume at 5 mg daily Platelet count decreases to 50% of baseline value within 4 weeks of therapy Baseline platelet count <60,000/mm3 Withhold therapy until platelet count >=30,000/mm3, then resume at 5 mg daily Thrombocytopenia occurring after 4 weeks of therapy Platelet count <30,000/mm3 or Withhold therapy until platelet <50,000/mm3 and requiring platelet count >=30,000/mm3 (without transfusions hemostatic failure), then resume at 5 mg daily Thrombocytopenia recurs on a reduced dosage of 5 mg daily Platelet count <30,000/mm3 or Withhold therapy until platelet <50,000/mm3 and requiring platelet count >=30,000/mm3 (without transfusions hemostatic failure), then resume at 2.5 mg daily
Table 4. Dosage Modification for Neutropenia in Patients with MDS
Severity Lenalidomide Dosage Modification (Lenalidomide Starting Dosage = 10 mg daily) ANC <750/mm3 occurswithin4 weeks of therapy Baseline ANC >=1,000/mm3 Withhold therapy until ANC >=1000/mm3, then resume at 5 mg daily ANC <500/mm3within4 weeks of therapy Baseline ANC is <1,000/mm3 Withhold therapy until ANC >=500/mm3, then resume at 5 mg daily Neutropenia occurring after 4 weeks of therapy ANC <500/mm3 for >=7 days or Withhold therapy until ANC <500/mm3 with fever (>=38.5degreesC) >=500/mm3, then resume at 5 mg daily Neutropenia recurs on a reduced dosage of 5 mg daily ANC <500/mm3 for >=7 days or Withhold therapy until ANC <500/mm3 with fever (>=38.5degreesC) >=500/mm3, then resume at 2.5 mg on a reduced dosage of 5 mg daily daily
Temporary interruption of lenalidomide therapy followed by dosage reduction may be necessary in patients experiencing hematologic adverse effects (see Table 5).
Table 5. Dosage Modification for Hematologic Adverse Effects in Patients with Mantle Cell Lymphoma
Adverse Reaction and Severity Lenalidomide Dosage Modification (Lenalidomide Starting Dosage = 25 mg daily) Thrombocytopenia Platelet count <50,000/mm3 Withhold therapy and monitor CBC weekly; when platelet count >=50,000/mm3, resume at dosage reduced by 5 mg (do not administer dosages lower than 5 mg daily) Neutropenia ANC <1000/mm3 for >=7 days, or Withhold therapy and monitor CBC <1000/mm3 with fever weekly; when ANC >=1000/mm3, resume (>=38.5degreesC), or <500/mm3 at dosage reduced by 5 mg (do not administer dosages lower than 5 mg daily)
Temporary interruption of lenalidomide therapy followed by dosage reduction may be necessary in patients experiencing hematologic adverse effects (see Table 6).
Table 6. Dosage Modification for Hematologic Adverse Effects in Patients with Follicular Lymphoma or Marginal-zone Lymphoma
Adverse Reaction and Severity Lenalidomide Dosage Modification Lenalidomide Starting Dosage = 20 mg daily) Thrombocytopenia Platelet count <50,000/mm3 Withhold therapy and monitor CBC weekly; when platelet count >=50,000/mm3, resume at dosage reduced by 5 mg (do not administer dosages lower than 5 mg daily; if initial dosage was 10 mg daily, do not administer dosages lower than 2.5 mg daily) Neutropenia ANC <1000/mm3 for >=7 days, or Withhold therapy and monitor CBC <1000/mm3 with fever weekly; when ANC >=1000/mm3, resume (>=38.5degreesC), or <500/mm3 at dosage reduced by 5 mg (do not administer dosages lower than 5 mg daily; if initial dosage was 10 mg daily, do not administer dosages lower than 2.5 mg daily)
If angioedema, anaphylaxis, grade 4 rash, skin exfoliation, bullae, or any other severe dermatologic reaction occurs, lenalidomide therapy should be permanently discontinued. (See Hypersensitivity Reactions and also Cutaneous Reactions under Cautions.)
If grade 3 or 4 nonhematologic toxicities occur, temporarily interrupt lenalidomide therapy; when the toxicity resolves or improves to grade 2 or less, lenalidomide therapy may be resumed at the next lower dosage level.
Table 3. Dosage Modification for Thrombocytopenia in Patients with MDS
Severity Lenalidomide Dosage Modification (Lenalidomide Starting Dosage = 10 mg daily) Platelet count <50,000/mm3 occurswithin 4 weeks of therapy Baseline platelet count Withhold therapy until platelet >=100,000/mm3 count >=50,000/mm3, then resume at 5 mg daily Platelet count decreases to 50% of baseline value within 4 weeks of therapy Baseline platelet count >=60,000/mm3 Withhold therapy until platelet to <100,000/mm3 count >=50,000/mm3, then resume at 5 mg daily Platelet count decreases to 50% of baseline value within 4 weeks of therapy Baseline platelet count <60,000/mm3 Withhold therapy until platelet count >=30,000/mm3, then resume at 5 mg daily Thrombocytopenia occurring after 4 weeks of therapy Platelet count <30,000/mm3 or Withhold therapy until platelet <50,000/mm3 and requiring platelet count >=30,000/mm3 (without transfusions hemostatic failure), then resume at 5 mg daily Thrombocytopenia recurs on a reduced dosage of 5 mg daily Platelet count <30,000/mm3 or Withhold therapy until platelet <50,000/mm3 and requiring platelet count >=30,000/mm3 (without transfusions hemostatic failure), then resume at 2.5 mg daily
Table 4. Dosage Modification for Neutropenia in Patients with MDS
Severity Lenalidomide Dosage Modification (Lenalidomide Starting Dosage = 10 mg daily) ANC <750/mm3 occurswithin4 weeks of therapy Baseline ANC >=1,000/mm3 Withhold therapy until ANC >=1000/mm3, then resume at 5 mg daily ANC <500/mm3within4 weeks of therapy Baseline ANC is <1,000/mm3 Withhold therapy until ANC >=500/mm3, then resume at 5 mg daily Neutropenia occurring after 4 weeks of therapy ANC <500/mm3 for >=7 days or Withhold therapy until ANC <500/mm3 with fever (>=38.5degreesC) >=500/mm3, then resume at 5 mg daily Neutropenia recurs on a reduced dosage of 5 mg daily ANC <500/mm3 for >=7 days or Withhold therapy until ANC <500/mm3 with fever (>=38.5degreesC) >=500/mm3, then resume at 2.5 mg on a reduced dosage of 5 mg daily daily
Temporary interruption of lenalidomide therapy followed by dosage reduction may be necessary in patients experiencing hematologic adverse effects (see Table 5).
Table 5. Dosage Modification for Hematologic Adverse Effects in Patients with Mantle Cell Lymphoma
Adverse Reaction and Severity Lenalidomide Dosage Modification (Lenalidomide Starting Dosage = 25 mg daily) Thrombocytopenia Platelet count <50,000/mm3 Withhold therapy and monitor CBC weekly; when platelet count >=50,000/mm3, resume at dosage reduced by 5 mg (do not administer dosages lower than 5 mg daily) Neutropenia ANC <1000/mm3 for >=7 days, or Withhold therapy and monitor CBC <1000/mm3 with fever weekly; when ANC >=1000/mm3, resume (>=38.5degreesC), or <500/mm3 at dosage reduced by 5 mg (do not administer dosages lower than 5 mg daily)
Temporary interruption of lenalidomide therapy followed by dosage reduction may be necessary in patients experiencing hematologic adverse effects (see Table 6).
Table 6. Dosage Modification for Hematologic Adverse Effects in Patients with Follicular Lymphoma or Marginal-zone Lymphoma
Adverse Reaction and Severity Lenalidomide Dosage Modification Lenalidomide Starting Dosage = 20 mg daily) Thrombocytopenia Platelet count <50,000/mm3 Withhold therapy and monitor CBC weekly; when platelet count >=50,000/mm3, resume at dosage reduced by 5 mg (do not administer dosages lower than 5 mg daily; if initial dosage was 10 mg daily, do not administer dosages lower than 2.5 mg daily) Neutropenia ANC <1000/mm3 for >=7 days, or Withhold therapy and monitor CBC <1000/mm3 with fever weekly; when ANC >=1000/mm3, resume (>=38.5degreesC), or <500/mm3 at dosage reduced by 5 mg (do not administer dosages lower than 5 mg daily; if initial dosage was 10 mg daily, do not administer dosages lower than 2.5 mg daily)
If angioedema, anaphylaxis, grade 4 rash, skin exfoliation, bullae, or any other severe dermatologic reaction occurs, lenalidomide therapy should be permanently discontinued. (See Hypersensitivity Reactions and also Cutaneous Reactions under Cautions.)
If grade 3 or 4 nonhematologic toxicities occur, temporarily interrupt lenalidomide therapy; when the toxicity resolves or improves to grade 2 or less, lenalidomide therapy may be resumed at the next lower dosage level.
Lenalidomide capsules should be administered orally with water, with or without food, once daily. The capsules should be swallowed intact and should not be broken, chewed, or opened.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| LENALIDOMIDE 2.5 MG CAPSULE | Maintenance | Adults take 1 capsule (2.5 mg) by oral route once daily |
| LENALIDOMIDE 5 MG CAPSULE | Maintenance | Adults take 1 capsule (5 mg) by oral route once daily |
| LENALIDOMIDE 10 MG CAPSULE | Maintenance | Adults take 1 capsule (10 mg) by oral route once daily |
| LENALIDOMIDE 15 MG CAPSULE | Maintenance | Adults take 1 capsule (15 mg) by oral route once daily on days 1 through 21 of a 28 day treatment cycle |
| LENALIDOMIDE 20 MG CAPSULE | Maintenance | Adults take 1 capsule (20 mg) by oral route once daily on days 1 through 21 of a 28 day treatment cycle |
| LENALIDOMIDE 25 MG CAPSULE | Maintenance | Adults take 1 capsule (25 mg) by oral route once daily on days 1 through 21 of a 28 day treatment cycle |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| LENALIDOMIDE 2.5 MG CAPSULE | Maintenance | Adults take 1 capsule (2.5 mg) by oral route once daily |
| LENALIDOMIDE 5 MG CAPSULE | Maintenance | Adults take 1 capsule (5 mg) by oral route once daily |
| LENALIDOMIDE 10 MG CAPSULE | Maintenance | Adults take 1 capsule (10 mg) by oral route once daily |
| LENALIDOMIDE 25 MG CAPSULE | Maintenance | Adults take 1 capsule (25 mg) by oral route once daily on days 1 through 21 of a 28 day treatment cycle |
| LENALIDOMIDE 15 MG CAPSULE | Maintenance | Adults take 1 capsule (15 mg) by oral route once daily on days 1 through 21 of a 28 day treatment cycle |
| LENALIDOMIDE 20 MG CAPSULE | Maintenance | Adults take 1 capsule (20 mg) by oral route once daily on days 1 through 21 of a 28 day treatment cycle |
The following drug interaction information is available for LENALIDOMIDE (lenalidomide):
There are 4 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Efalizumab; Natalizumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Natalizumab,(1-3) efalizumab,(4) immunosuppressives, and immunomodulators all suppress the immune system. CLINICAL EFFECTS: Concurrent use of natalizumab(1-3) or efalizumab(4) with immunosuppressives or immunomodulators may result in an increased risk of infections, including progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV). PREDISPOSING FACTORS: Previous JCV infection, longer duration of natalizumab treatment - especially if greater than 2 years, and prior or concomitant treatment with immunosuppressant medication are all independent risk factors which increase the risk for PML.(1,5) The FDA has estimated PML incidence stratified by risk factors: If anti-JCV antibody positive, no prior immunosuppressant use and natalizumab treatment less than 25 months, incidence <1/1,000. If anti-JCV antibody positive, history of prior immunosuppressant use and natalizumab treatment less than 25 months, incidence 2/1,000 If anti-JCV antibody positive, no prior immunosuppressant use and natalizumab treatment 25-48 months, incidence 4/1,000 If anti-JCV antibody positive, history of prior immunosuppressant use and natalizumab treatment 25-48 months, incidence 11/1,000. PATIENT MANAGEMENT: The US manufacturer of natalizumab states patients with Crohn's disease should not receive concurrent immunosuppressants, with the exception of limited overlap of corticosteroids, due to the increased risk for PML. For new natalizumab patients currently receiving chronic oral corticosteroids for Crohn's Disease, begin corticosteroid taper when therapeutic response to natalizumab has occurred. If corticosteroids cannot be discontinued within six months of starting natalizumab, discontinue natalizumab.(3) The US manufacturer of natalizumab states that natalizumab should not ordinarily be used in multiple sclerosis patients receiving immunosuppressants or immunomodulators due to the increased risk for PML. Immunosuppressives include, but are not limited to azathioprine, cyclophosphamide, cyclosporine, mercaptopurine, methotrexate, mitoxantrone, mycophenolate, and corticosteroids.(3,6) The UK manufacturer of natalizumab states that concurrent use with immunosuppressives or antineoplastic agents is contraindicated.(1) The Canadian manufacturer of natalizumab states that natalizumab should not be used with immunosuppressive or immunomodulatory agents.(2) The US manufacturer of certolizumab states that concurrent therapy with natalizumab is not recommended.(7) DISCUSSION: Progressive multifocal leukoencephalopathy has been reported in patients receiving concurrent natalizumab were recently or concomitantly taking immunomodulators or immunosuppressants.(1-5,8,9) In a retrospective cohort study of multiple sclerosis patients newly initiated on a disease-modifying therapy, use of high-efficacy agents (alemtuzumab, natalizumab, or ocrelizumab) resulted in the same risk of overall infections as moderate-efficacy agents, but there was an elevated risk of serious infections (adjusted hazard ratio [aHR] = 1.24, 95% confidence interval (CI) = 1.06-1.44) and UTIs (aHR = 1.21, 95% CI = 1.14-1.30).(10) |
TYSABRI |
| Live Vaccines; Live BCG/Selected Immunosuppressive Agents SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: A variety of disease modifying agents suppress the immune system. Immunocompromised patients may be at increased risk for uninhibited replication after administration of live, attenuated vaccines or intravesicular BCG. Immune response to vaccines may be decreased during periods of immunocompromise.(1) CLINICAL EFFECTS: The expected serum antibody response may not be obtained and/or the vaccine may result in illness.(1) After instillation of intravesicular BCG, immunosuppression may interfere with local immune response, or increase the severity of mycobacterial infection following inadvertent systemic exposure.(2) PREDISPOSING FACTORS: Immunosuppressive diseases (e.g. hematologic malignancies, HIV disease), treatments (e.g. radiation) and drugs may all increase the magnitude of immunodeficiency. PATIENT MANAGEMENT: The Centers for Disease Control(CDC) Advisory Committee on Immunization Practices (ACIP) states that live-virus and live, attenuated vaccines should not be administered to patients who are immunocompromised. The magnitude of immunocompromise and associated risks should be determined by a physician.(1) For patients scheduled to receive chemotherapy, vaccination should ideally precede the initiation of chemotherapy by 14 days. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy.(1) Patients who receive anti-B cell therapies should not receive live vaccines for at least 6 months after such therapies due to a prolonged duration of immunosuppression. An exception is the Zoster vaccine, which can be given at least 1 month after receipt of anti-B cell therapies.(1) The US manufacturer of abatacept states live vaccines should not be given during or for up to 3 months after discontinuation of abatacept.(2) The US manufacturer of live BCG for intravesicular treatment of bladder cancer states use is contraindicated in immunosuppressed patients.(3) The US manufacturer of daclizumab states live vaccines are not recommended during and for up to 4 months after discontinuation of treatment.(4) The US manufacturer of guselkumab states that live vaccines should be avoided during treatment with guselkumab.(5) The US manufacturer of inebilizumab-cdon states that live vaccines are not recommended during treatment and after discontinuation until B-cell repletion. Administer all live vaccinations at least 4 weeks prior to initiation of inebilizumab-cdon.(6) The US manufacturer of ocrelizumab states that live vaccines are not recommended during treatment and until B-cell repletion occurs after discontinuation of therapy. Administer all live vaccines at least 4 weeks prior to initiation of ocrelizumab.(7) The US manufacturer of ozanimod states that live vaccines should be avoided during and for up to 3 months after discontinuation of ozanimod.(8) The US manufacturer of siponimod states that live vaccines are not recommended during treatment and for up to 4 weeks after discontinuation of treatment.(9) The US manufacturer of ustekinumab states BCG vaccines should not be given in the year prior to, during, or the year after ustekinumab therapy.(10) The US manufacturer of satralizumab-mwge states that live vaccines are not recommended during treatment and should be administered at least four weeks prior to initiation of satralizumab-mwge.(11) The US manufacturer of ublituximab-xiiy states that live vaccines are not recommended during treatment and until B-cell recovery. Live vaccines should be administered at least 4 weeks prior to initiation of ublituximab-xiiy.(12) The US manufacturer of etrasimod states that live vaccines should be avoided during and for 5 weeks after treatment. Live vaccines should be administered at least 4 weeks prior to initiation of etrasimod.(13) The US manufacturer of emapalumab-lzsg states that live vaccines should not be administered to patients receiving emapalumab-lzsg and for at least 4 weeks after the last dose of emapalumab-lzsg. The safety of immunization with live vaccines during or following emapalumab-lzsg therapy has not been studied.(14) DISCUSSION: Killed or inactivated vaccines do not pose a danger to immunocompromised patients.(1) Patients with a history of leukemia who are in remission and have not received chemotherapy for at least 3 months are not considered to be immunocompromised.(1) |
ACAM2000 (NATIONAL STOCKPILE), ADENOVIRUS TYPE 4, ADENOVIRUS TYPE 4 AND TYPE 7, ADENOVIRUS TYPE 7, BCG (TICE STRAIN), BCG VACCINE (TICE STRAIN), DENGVAXIA, ERVEBO (NATIONAL STOCKPILE), FLUMIST 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 |
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 |
|---|---|
| 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 |
| Erythropoietic agents/Lenalidomide 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 unknown. CLINICAL EFFECTS: Concurrent use of erythropoietic agents, such as darbepoetin or epoetin, with lenalidomide may increase the risk of thrombosis.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of lenalidomide states the risk of venous thromboembolism (VTE) may be increased when patients are taking concomitant therapy with erythropoietin stimulating agents. Use caution with concomitant use after a patient specific risk-benefit assessment has been completed. Observe patients for signs and symptoms of VTE and instruct patients to seek medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling.(1) The National Comprehensive Cancer Network (NCCN) Guidelines include use of erythropoietic stimulating agents as a high risk factor for venous thromboembolism (VTE). Other risk factors include: active cancer, advanced stage cancer, certain cancer types, regional bulky lymphadenopathy, familial and/or acquired hypercoagulability, medical comorbidities, poor performance status, older age, major surgery, central venous catheter, chemotherapy including lenalidomide plus high-dose dexamethasone, hormone replacement therapy, contraceptives, tamoxifen/raloxifene, diethylstilbestrol, smoking, obesity, or activity level/exercise.(3) The NCCN Guidelines utilize a Risk Assessment Model to determine chemoprophylaxis. In patients with 0-1 risk factors, consider VTE chemoprophylaxis with aspirin 81-325 mg once daily. In patients with >/= 2 risk factors, consider VTE chemoprophylaxis with low-molecular weight heparin (LMWH) with a dose equivalent to enoxaparin 40 mg once daily or full-dose warfarin with a dose to maintain a target international normalized ratio (INR) 2-3.(3) DISCUSSION: The National Comprehensive Cancer Network (NCCN) Guidelines include use of erythropoietin as an individual risk factor for venous thromboembolism (VTE). Patients should be assessed for total risk based on NCCN guidelines and recommended for the appropriate VTE chemoprophylaxis agent based on risk category.(3) A pooled analysis of two placebo-controlled trials in multiple myeloma noted an incidence rate for VTE of 23% in patients receiving lenalidomide, dexamethasone and erythropoietic therapy versus 5% in patients without erythropoietic therapy. A multivariate analysis indicated an independent correlation between thrombosis and patients with concomitant erythropoietin therapy.(4) A pooled analysis of 125 patients from 3 trials with multiple myeloma on lenalidomide therapy noted a 17% incidence of VTE in patients on lenalidomide with concurrent erythropoietin therapy.(5) Several studies have evaluated the optimal VTE prophylaxis agent with lenalidomide-treated patients. Patients receiving lenalidomide/dexamethasone and no chemoprophylaxis had a VTE incidence of 11-75%, 26% with the use of aspirin, 17% with the use of aspirin/LMWH/warfarin combination therapy, and 2-15% with the use of LMWH. (6) |
ARANESP, EPOGEN, MIRCERA, PROCRIT, RETACRIT |
| 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, cosibelimab, dostarlimab, durvalumab, nivolumab, pembrolizumab, penpulimab, retifanlimab, sintilimab and toripalimab. |
BAVENCIO, IMFINZI, JEMPERLI, KEYTRUDA, LIBTAYO, LOQTORZI, OPDIVO, OPDIVO QVANTIG, OPDUALAG, TECENTRIQ, TECENTRIQ HYBREZA, TEVIMBRA, ZYNYZ |
| 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 |
| Thalidomide Analogues/Estrogen-Containing Contraceptives SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Both the thalidomide analogues and estrogen-containing contraceptives are associated with an increased risk of thromboembolic disorders.(1-9) The US manufacturer of thalidomide states that it is unknown if these risks are additive.(1) CLINICAL EFFECTS: Use of lenalidomide, pomalidomide, or thalidomide in patients taking estrogen-containing hormonal contraceptives may increase the risk of venous or arterial thromboembolism, including deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), and stroke.(1-9) PREDISPOSING FACTORS: Previous history of thromboembolic events or concomitant administration of erythropoietic agents may increase the thrombotic risk. Modifiable risk factors (e.g., diabetes, hyperlipidemia, hypertension, smoking) should be minimized.(1-9) PATIENT MANAGEMENT: The Canadian manufacturer of the thalidomide analogues states that use of hormonal contraceptives is not recommended.(2-4) The UK manufacturer of the thalidomide analogues states that concurrent combined hormonal contraceptives is not recommended and that patients should be switched to a progesterone-only or non-hormonal contraceptive (e.g., progestin-only pills, progestin implant or intrauterine device, depot medroxyprogesterone acetate, tubal sterilization).(5-7) The US manufacturer of the thalidomide analogues does not recommend against use of hormonal contraceptives but instead includes them as an option for highly effective contraception. Estrogen-containing therapies should be used with caution after assessment of their risks and benefits.(1,8-9) The risk of venous thromboembolism continues for 4-6 weeks after discontinuing combined oral contraception.(5-7) If the estrogen-containing contraceptive is not used, two other simultaneous, effective methods of contraception are still required in the US and Canada.(1-4,8,9) In the UK, at least one effective method of contraception is required.(5-7) DISCUSSION: Lenalidomide, pomalidomide, and thalidomide can all cause thromboembolism. Concurrent use of other agents that may increase the risk of thrombosis, like estrogen-containing therapies, may result in an increased risk of thrombosis. |
2-METHOXYESTRADIOL, AFIRMELLE, ALTAVERA, ALYACEN, AMETHIA, AMETHYST, ANNOVERA, APRI, ARANELLE, ASHLYNA, AUBRA, AUBRA EQ, AUROVELA, AUROVELA 24 FE, AUROVELA FE, AVIANE, AYUNA, AZURETTE, BALCOLTRA, BALZIVA, BEYAZ, BLISOVI 24 FE, BLISOVI FE, BRIELLYN, CAMRESE, CAMRESE LO, CAZIANT, CHARLOTTE 24 FE, CHATEAL EQ, CRYSELLE, CYRED, CYRED EQ, DASETTA, DAYSEE, DESOGESTR-ETH ESTRAD ETH ESTRA, DIETHYLSTILBESTROL, DOLISHALE, DROSPIRENONE-ETH ESTRA-LEVOMEF, DROSPIRENONE-ETHINYL ESTRADIOL, ELINEST, ELURYNG, ENILLORING, ENPRESSE, ENSKYCE, ESTARYLLA, ESTRADIOL, ESTRADIOL BENZOATE, ESTRADIOL CYPIONATE, ESTRADIOL HEMIHYDRATE, ESTRADIOL HEMIHYDRATE MICRO, ESTRADIOL MICRONIZED, ESTRADIOL VALERATE, ESTRIOL, ESTRIOL MICRONIZED, ESTRONE, ETHINYL ESTRADIOL, ETHYNODIOL-ETHINYL ESTRADIOL, ETONOGESTREL-ETHINYL ESTRADIOL, FALMINA, FEIRZA, FEMLYV, FINZALA, GEMMILY, HAILEY, HAILEY 24 FE, HAILEY FE, HALOETTE, ICLEVIA, ISIBLOOM, JAIMIESS, JASMIEL, JOLESSA, JOYEAUX, JULEBER, JUNEL, JUNEL FE, JUNEL FE 24, KAITLIB FE, KALLIGA, KARIVA, KELNOR 1-35, KELNOR 1-50, KURVELO, LARIN, LARIN 24 FE, LARIN FE, LAYOLIS FE, LEENA, LESSINA, LEVONEST, LEVONORG-ETH ESTRAD ETH ESTRAD, LEVONORG-ETH ESTRAD-FE BISGLYC, LEVONORGESTREL-ETH ESTRADIOL, LEVORA-28, LO LOESTRIN FE, LO-ZUMANDIMINE, LOESTRIN, LOESTRIN FE, LOJAIMIESS, LORYNA, LOW-OGESTREL, LUTERA, MARLISSA, MERZEE, MIBELAS 24 FE, MICROGESTIN, MICROGESTIN FE, MILI, MINZOYA, MONO-LINYAH, NATAZIA, NECON, NEXTSTELLIS, NIKKI, NORELGESTROMIN-ETH ESTRADIOL, NORETHIN-ETH ESTRA-FERROUS FUM, NORETHINDRON-ETHINYL ESTRADIOL, NORETHINDRONE-E.ESTRADIOL-IRON, NORGESTIMATE-ETHINYL ESTRADIOL, NORTREL, NUVARING, NYLIA, OCELLA, ORTHO TRI-CYCLEN, ORTHO-NOVUM, PHILITH, PIMTREA, PORTIA, RECLIPSEN, RIVELSA, SAFYRAL, SETLAKIN, SIMLIYA, SIMPESSE, SPRINTEC, SRONYX, SYEDA, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TAYTULLA, TILIA FE, TRI-ESTARYLLA, TRI-LEGEST FE, TRI-LINYAH, TRI-LO-ESTARYLLA, TRI-LO-MARZIA, TRI-LO-MILI, TRI-LO-SPRINTEC, TRI-MILI, TRI-SPRINTEC, TRI-VYLIBRA, TRI-VYLIBRA LO, TRIVORA-28, TURQOZ, TWIRLA, TYBLUME, VALTYA, VELIVET, VESTURA, VIENVA, VIORELE, VOLNEA, VYFEMLA, VYLIBRA, WERA, WYMZYA FE, XARAH FE, XELRIA FE, XULANE, YASMIN 28, YAZ, ZAFEMY, ZARAH, ZOVIA 1-35, ZUMANDIMINE |
| 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 |
| Daprodustat; Roxadustat; Vadadustat/Lenalidomide 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 unknown. CLINICAL EFFECTS: Concurrent use of daprodustat, roxadustat, or vadadustat with lenalidomide may increase the risk of thrombosis.(1-5) PREDISPOSING FACTORS: Predisposing factors include a history of thromboembolic disorder, thrombophilia, malignancy, hyperlipidemia, hypertension, heart failure, diabetes mellitus, chronic kidney disease, COPD, obesity, tobacco smoking, major surgery with prolonged post-operative immobilization, and being bed-ridden. PATIENT MANAGEMENT: The US manufacturer of lenalidomide states the risk of venous thromboembolism (VTE) may be increased when patients are taking concomitant therapy with erythropoietin stimulating agents. Use caution with concomitant use after a patient-specific risk-benefit assessment has been completed. Observe patients for signs and symptoms of VTE and instruct patients to seek medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling.(1) The National Comprehensive Cancer Network (NCCN) Guidelines include use of erythropoietic stimulating agents as a high risk factor for venous thromboembolism (VTE). Other risk factors include: active cancer, advanced stage cancer, certain cancer types, regional bulky lymphadenopathy, familial and/or acquired hypercoagulability, medical comorbidities, poor performance status, older age, major surgery, central venous catheter, chemotherapy including lenalidomide plus high-dose dexamethasone, hormone replacement therapy, contraceptives, tamoxifen/raloxifene, diethylstilbestrol, smoking, obesity, or activity level/exercise.(6) The NCCN Guidelines utilize a Risk Assessment Model to determine chemoprophylaxis. In patients with 0-1 risk factors, consider VTE chemoprophylaxis with aspirin 81-325 mg once daily. In patients with >/= 2 risk factors, consider VTE chemoprophylaxis with low-molecular weight heparin (LMWH) with a dose equivalent to enoxaparin 40 mg once daily or full-dose warfarin with a dose to maintain a target international normalized ratio (INR) 2-3.(6) DISCUSSION: Daprodustat, roxadustat, and vadadustat increase endogenous erythropoietin by increasing transcription of the HIF-responsive genes.(2-5) The National Comprehensive Cancer Network (NCCN) Guidelines include use of erythropoietin as an individual risk factor for venous thromboembolism (VTE). Patients should be assessed for total risk based on NCCN guidelines and recommended for the appropriate VTE chemoprophylaxis agent based on risk category.(6) A pooled analysis of two placebo-controlled trials in multiple myeloma noted an incidence rate for VTE of 23% in patients receiving lenalidomide, dexamethasone and erythropoietic therapy versus 5% in patients without erythropoietic therapy. A multivariate analysis indicated an independent correlation between thrombosis and patients with concomitant erythropoietin therapy.(7) A pooled analysis of 125 patients from 3 trials with multiple myeloma on lenalidomide therapy noted a 17% incidence of VTE in patients on lenalidomide with concurrent erythropoietin therapy.(8) Several studies have evaluated the optimal VTE prophylaxis agent with lenalidomide-treated patients. Patients receiving lenalidomide/dexamethasone and no chemoprophylaxis had a VTE incidence of 11-75%, 26% with the use of aspirin, 17% with the use of aspirin/LMWH/warfarin combination therapy, and 2-15% with the use of LMWH.(9) |
VAFSEO |
| 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) |
BESREMI |
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 |
|---|---|
| Dexamethasone/Lenalidomide; Thalidomide SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The mechanism of this interaction is unknown. CLINICAL EFFECTS: Concurrent use of dexamethasone with lenalidomide or thalidomide may increase the risk of venous thromboembolism (VTE), ischemic heart disease including myocardial infarction, and stroke.(1,2) PREDISPOSING FACTORS: The effects of the interaction are greater with high-dose dexamethasone (480 mg/month or more).(3) Erythropoietic agents may also increase the risk.(1,2) PATIENT MANAGEMENT: The US manufacturer of lenalidomide states the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) is significantly increased when lenalidomide and dexamethasone are given concurrently in patients with multiple myeloma and recommends thromboprophylaxis and the regimen should be selected based on the patient's underlying risks. Observe patients for signs and symptoms of venous thromboembolism (VTE) and instruct patients to see medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling.(1) The US manufacturer of thalidomide states the risk of VTE increases significantly when thalidomide is used with concurrent therapy with standard chemotherapeutic agents including dexamethasone therapy and recommends considering thromboprophylaxis based on an assessment of individual patients' underlying risk factors. Observe patients closely for signs and symptoms of VTE and instruct patients to see medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling.(2) The National Comprehensive Cancer Network (NCCN) Guidelines recommend VTE chemoprophylaxis with low-molecular weight heparin (LMWH) with a dose equivalent to enoxaparin 40 mg once daily or full-dose warfarin with a dose to maintain a target international normalized ratio (INR) 2-3.(3) DISCUSSION: The National Comprehensive Cancer Network (NCCN) Guidelines include lenalidomide/thalidomide plus high-dose dexamethasone as a treatment-related venous thromboembolism (VTE) risk factor for cancer patients. High-dose dexamethasone is defined by NCCN as >/= 480 mg per month. The NCCN Guidelines recommend VTE chemoprophylaxis with low-molecular weight heparin (LMWH) at a dose equivalent to enoxaparin 40 mg once daily or full-dose warfarin with a dose to maintain a target international normalized ratio (INR) 2-3.(3) The US manufacturer states the standard dosing for multiple myeloma includes lenalidomide (25 mg daily) on days 1-21 of the 28-day cycle and dexamethasone (40 mg daily) on days 1, 8, 15, and 22 of the 28-day cycle.(1) The dexamethasone dose is adjusted for patients >75 years old to 20 mg daily on days 1, 8, 15, and 22 of the 28-day cycle.(1) In 2 studies of 703 patients who received at least one dose of lenalidomide/dexamethasone or placebo/dexamethasone, the incidence of DVT was 9.3% and 4.3%, respectively. In the same population, the incidence of grade 3/4 adverse reactions the incidence of DVT was 8.2% and 3.4%, respectively, and the incidence of serious adverse reactions of DVT was 7.4% and 3.1%, respectively. The US manufacturer states the standard dosing for multiple myeloma includes combination therapy with thalidomide (200 mg daily) and dexamethasone (40 mg daily on days 1-4, 9-12, and 17-20) in a 28-day treatment cycle.(2) The overall rate of adverse reactions in clinical trials for multiple myeloma resulting in treatment discontinuation were 30% in the thalidomide/dexamethasone group and 16% in the dexamethasone monotherapy group.(2) In a safety study of 466 subjects, the incidence of DVT was higher in the thalidomide/dexamethasone arm than in the placebo/dexamethasone arm with 13% versus 2%, respectively.(2) In a safety study of Grade 3/4 adverse drug reactions, the thalidomide/dexamethasone arm had a 12% incidence of DVT compared to a 2% incidence in the placebo/dexamethasone arm.(2) A summary article discusses the incidence of VTE in patients receiving treatment for multiple myeloma. The use of thalidomide as a single agent does not significantly increase the risk of VTE in both new diagnoses and relapsed/refractory patients with a VTE incidence of 3-4% and 2-4%, respectively. The addition of dexamethasone to thalidomide increased the risk of VTE in newly diagnosed patients with an incidence of 14-26%. Similarly, the use of lenalidomide as a single agent does not increase the risk of VTE. Lenalidomide with dexamethasone increased the incidence of VTE in newly diagnosed patients as well as relapsed/refractory patients to 75% and 17%, respectively. Concurrent therapy with lenalidomide and dexamethasone showed a difference in the incidence of VTE based on the dexamethasone dose (high dose defined as 480 mg/month and low dose defined as 160 mg/month) with higher doses associated with an increase risk (26% versus 12% incidence, respectively). The incidence of VTE in studies with thalidomide alone range from 1.5-4.6% versus studies with thalidomide/dexamethasone at 7-26%.(4) Several studies have evaluated the optimal VTE prophylaxis agent with lenalidomide-treated patients. Patients receiving lenalidomide/dexamethasone and no chemoprophylaxis had a VTE incidence of 11-75%, 26% with the use of aspirin, 17% with the use of aspirin/LMWH/warfarin combination therapy, and 2-15% with the use of LMWH. (5) Several studies have evaluated the optimal VTE prophylaxis agent in thalidomide-treated patients. Patients receiving thalidomide/dexamethasone and no chemoprophylaxis had a VTE incidence of 26%, 10% with the use of low-dose warfarin and 0% with the use of therapeutic warfarin/LMWH.(5) Lenalidomide/dexamethasone compared to placebo/dexamethasone increased the rate of myocardial infarction (1.7% versus 0.6%, respectively) and stroke (2.3% versus 0.9%, respectively).(1) Thalidomide/dexamethasone compared to placebo/dexamethasone increased the rate of ischemic heart disease (11.1% versus 4.7%, respectively), including myocardial infarction (1.3% versus 1.7%, respectively), and stroke (2.6% versus 0.9%, respectively).(2) |
BUPIVACAINE-DEXAMETH-EPINEPHRN, DEXABLISS, DEXAMETHASONE, DEXAMETHASONE ACETATE, DEXAMETHASONE ACETATE MICRO, DEXAMETHASONE INTENSOL, DEXAMETHASONE ISONICOTINATE, DEXAMETHASONE MICRONIZED, DEXAMETHASONE SOD PHOS-WATER, DEXAMETHASONE SODIUM PHOSPHATE, DEXAMETHASONE-0.9% NACL, DEXONTO, DMT SUIK, DOUBLEDEX, HEMADY, LIDOCIDEX-I, MAS CARE-PAK, TAPERDEX, ZCORT |
| 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-AEKN, 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 LENALIDOMIDE (lenalidomide):
Drug contraindication overview.
*Lenalidomide is contraindicated in women who are pregnant. The drug should be used in women of childbearing potential only when alternative therapies are not available and adequate precautions are taken to avoid pregnancy. (See REMS under Dosage and Administration and also see Fetal/Neonatal Morbidity and Mortality under Cautions.) *Lenalidomide is contraindicated in patients with known hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)) to the drug.
*Lenalidomide is contraindicated in women who are pregnant. The drug should be used in women of childbearing potential only when alternative therapies are not available and adequate precautions are taken to avoid pregnancy. (See REMS under Dosage and Administration and also see Fetal/Neonatal Morbidity and Mortality under Cautions.) *Lenalidomide is contraindicated in patients with known hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)) to the drug.
There are 2 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Lactation |
| Pregnancy |
There are 12 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Acute myocardial infarction |
| Acute thromboembolic stroke |
| Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min |
| Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min |
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Deep venous thrombosis |
| Disease of liver |
| Pulmonary thromboembolism |
| Severe neutropenic disorder |
| Severe thrombocytopenia |
| Thromboembolic disorder |
There are 4 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Hodgkin's lymphoma |
| Hyperthyroidism |
| Hypothyroidism |
| Secondary acute myeloid leukemia |
The following adverse reaction information is available for LENALIDOMIDE (lenalidomide):
Adverse reaction overview.
Adverse effects reported in at least 20% of patients with multiple myeloma receiving lenalidomide include diarrhea, fatigue, anemia, constipation, neutropenia, leukopenia, peripheral edema, insomnia, muscle cramp/spasms, abdominal pain, back pain, nausea, asthenia, pyrexia, upper respiratory tract infection, bronchitis, nasopharyngitis, gastroenteritis, cough, rash, dyspnea, dizziness, decreased appetite, thrombocytopenia, and tremor. Adverse effects reported in more than 15% of patients with MDS receiving lenalidomide include thrombocytopenia, neutropenia, diarrhea, pruritus, rash, fatigue, constipation, nausea, nasopharyngitis, arthralgia, pyrexia, back pain, peripheral edema, cough, dizziness, headache, muscle cramp, dyspnea, pharyngitis, and epistaxis. Adverse effects reported in at least 15% of patients with mantle cell lymphoma, follicular lymphoma, or marginal-zone lymphoma receiving lenalidomide include neutropenia, thrombocytopenia, anemia, leukopenia, diarrhea, constipation, nausea, fatigue, pyrexia, cough, upper respiratory tract infection, and rash.
Adverse effects reported in at least 20% of patients with multiple myeloma receiving lenalidomide include diarrhea, fatigue, anemia, constipation, neutropenia, leukopenia, peripheral edema, insomnia, muscle cramp/spasms, abdominal pain, back pain, nausea, asthenia, pyrexia, upper respiratory tract infection, bronchitis, nasopharyngitis, gastroenteritis, cough, rash, dyspnea, dizziness, decreased appetite, thrombocytopenia, and tremor. Adverse effects reported in more than 15% of patients with MDS receiving lenalidomide include thrombocytopenia, neutropenia, diarrhea, pruritus, rash, fatigue, constipation, nausea, nasopharyngitis, arthralgia, pyrexia, back pain, peripheral edema, cough, dizziness, headache, muscle cramp, dyspnea, pharyngitis, and epistaxis. Adverse effects reported in at least 15% of patients with mantle cell lymphoma, follicular lymphoma, or marginal-zone lymphoma receiving lenalidomide include neutropenia, thrombocytopenia, anemia, leukopenia, diarrhea, constipation, nausea, fatigue, pyrexia, cough, upper respiratory tract infection, and rash.
There are 89 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Anemia Dyspnea Leukopenia Neutropenic disorder Thrombocytopenic disorder |
Atrial fibrillation Bronchitis Chest pain Deep venous thrombosis Dehydration Edema Hypocalcemia Hypokalemia Hypophosphatemia Infection Lymphopenia Peripheral neuropathy Pneumonia Squamous cell carcinoma Thromboembolic disorder |
| Rare/Very Rare |
|---|
|
Abnormal desquamation Abnormal hepatic function tests Acute cerebral infarction Acute hepatic failure Acute leukemia Acute myocardial infarction Altered mental status Anaphylaxis Angioedema Arterial aneurysm Atrial flutter Autoimmune hemolytic anemia Bacteremia Bacterial sepsis Bullous dermatitis Cerebral edema Cerebral ischemia Cerebrovascular accident Cholestatic hepatitis Clostridioides difficile infection Delirium Diabetes mellitus DRESS syndrome Drug-induced psychosis Encephalitis Eosinophilia Exfoliative dermatitis Gastritis Gastrointestinal hemorrhage Heart failure Hematuria Hemorrhage Hepatitis Herpes zoster Hodgkin's lymphoma Hypersensitivity pneumonitis Hypertension Hypomagnesemia Hypotension Hypothyroidism Hypoxia Increased alanine transaminase Kidney disease with reduction in glomerular filtration rate (GFr) Lymphadenopathy Lymphedema Myelodysplastic syndrome Organ transplant rejection Orthostatic hypotension Pancreatitis Pancytopenia Phlebitis Progressive multifocal leukoencephalopathy Pulmonary edema Pulmonary thromboembolism Reactivation of hepatitis B Renal failure Renal tubular necrosis Rhabdomyolysis Stevens-johnson syndrome Sudden visual loss Supraventricular tachycardia Sweet's syndrome Thrombophlebitis Thrombotic disorder Toxic epidermal necrolysis Tumor flare reaction Tumor lysis syndrome Urinary retention Vision impairment |
There are 71 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acute abdominal pain Arthralgia Back pain Constipation Cough Cramps Diarrhea Dizziness Dry skin Epistaxis Fatigue Fever General weakness Headache disorder Hypoesthesia Nausea Peripheral edema Pharyngitis Pruritus of skin Skin rash Tremor Upper respiratory infection Weight loss |
Anorexia Basal cell carcinoma of skin Blurred vision Bruising Cellulitis Chills Depression Dysgeusia Ecchymosis Erythema Hyperglycemia Hyperhidrosis Insomnia Loose stools Muscle weakness Myalgia Non-cardiac chest pain Pain in extremities Paresthesia Rhinitis Sinusitis Urinary tract infection Vomiting Xerostomia |
| Rare/Very Rare |
|---|
|
Angina Ataxia Drowsy Dysuria Erectile dysfunction Flushing Gait abnormality Hallucinations Hirsutism Hoarseness Hyperthyroidism Hyperuricemia Libido changes Malaise Mood changes Night sweats Ocular hypertension Pallor Palpitations Petechiae Raynaud's phenomenon Skin pigmentation enhancement Sore tongue Varicose veins |
The following precautions are available for LENALIDOMIDE (lenalidomide):
Safety and efficacy of lenalidomide have not been established in pediatric patients.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Lenalidomide is a thalidomide analog and is contraindicated for use during pregnancy. (See REMS under Dosage and Administration and also see Fetal/Neonatal Morbidity and Mortality under Cautions.)
Not known whether lenalidomide is distributed into human milk; discontinue nursing or the drug, taking into account the importance of the drug to the woman.
In clinical trials of lenalidomide in patients with newly diagnosed multiple myeloma, 94% of patients were 65 years of age or older and 35% of patients were over 75 years of age. Overall, patients over 75 years of age experienced more adverse reactions (including serious adverse reactions) than younger adults regardless of treatment arm. In clinical trials evaluating maintenance therapy with lenalidomide in patients with multiple myeloma, 10% of patients were 65 years of age or older and no patients were over 75 years of age.
Grade 3 or 4 adverse reactions occurred more frequently in patients 65 years of age or older receiving lenalidomide maintenance therapy than in younger patients. Experience in patients 65 years of age or older receiving lenalidomide maintenance therapy is insufficient to determine whether they respond differently to the drug than younger adults. In clinical trials in patients with previously treated multiple myeloma, 45% of patients were 65 years of age or older and 12% patients were over 75 years of age.
In the studies of previously treated patients, deep-vein thrombosis (DVT), pulmonary embolism (PE), atrial fibrillation, and renal failure were more common in patients over 65 years of age than younger adults treated with lenalidomide. In clinical trials in patients with MDS or mantle cell lymphoma, 38 or 63% of patients, respectively, were 65 years of age or older. In patients with MDS or mantle cell lymphoma, 33 or 22% of patients, respectively, were 75 years of age or older.
All patients with MDS experienced an adverse reaction; however, the frequency of serious adverse reactions was higher in patients over 65 years of age (54%) compared with younger adults (33%). In patients with mantle cell lymphoma, the frequency of overall adverse events was similar among patients over 65 years of age than in younger patients; however, serious adverse reactions were more common among patients over 65 years than in younger patients (55% versus 41%). In clinical trials in patients with follicular lymphoma or marginal-zone lymphoma, 48% of patients were 65 years of age or older and 14% patients were over 75 years of age.
The overall frequency of adverse reactions was 98% in both patients 65 years of age or older and younger adults. Serious adverse reactions were higher among lenalidomide-treated patients 65 years of age or older versus younger adults (37% versus 18%).
Grade 3 or 4 adverse reactions occurred more frequently in patients 65 years of age or older receiving lenalidomide maintenance therapy than in younger patients. Experience in patients 65 years of age or older receiving lenalidomide maintenance therapy is insufficient to determine whether they respond differently to the drug than younger adults. In clinical trials in patients with previously treated multiple myeloma, 45% of patients were 65 years of age or older and 12% patients were over 75 years of age.
In the studies of previously treated patients, deep-vein thrombosis (DVT), pulmonary embolism (PE), atrial fibrillation, and renal failure were more common in patients over 65 years of age than younger adults treated with lenalidomide. In clinical trials in patients with MDS or mantle cell lymphoma, 38 or 63% of patients, respectively, were 65 years of age or older. In patients with MDS or mantle cell lymphoma, 33 or 22% of patients, respectively, were 75 years of age or older.
All patients with MDS experienced an adverse reaction; however, the frequency of serious adverse reactions was higher in patients over 65 years of age (54%) compared with younger adults (33%). In patients with mantle cell lymphoma, the frequency of overall adverse events was similar among patients over 65 years of age than in younger patients; however, serious adverse reactions were more common among patients over 65 years than in younger patients (55% versus 41%). In clinical trials in patients with follicular lymphoma or marginal-zone lymphoma, 48% of patients were 65 years of age or older and 14% patients were over 75 years of age.
The overall frequency of adverse reactions was 98% in both patients 65 years of age or older and younger adults. Serious adverse reactions were higher among lenalidomide-treated patients 65 years of age or older versus younger adults (37% versus 18%).
The following prioritized warning is available for LENALIDOMIDE (lenalidomide):
WARNING: Lenalidomide is very similar to thalidomide, a drug which has caused severe (possibly fatal) birth defects when used during pregnancy. If lenalidomide is taken during pregnancy, it may also cause severe (possibly fatal) birth defects. Women who are pregnant or who may become pregnant must not use lenalidomide.
Women must have two negative pregnancy tests before starting lenalidomide (the first test 10 to 14 days before the first dose and the second test within 24 hours before the first dose). Women must also continue to have pregnancy tests regularly during treatment (every 2 to 4 weeks). Female patients must use 2 effective forms of birth control (or completely avoid sexual intercourse) for 4 weeks before starting lenalidomide, during use, and for 4 weeks after stopping this drug.
Talk to your doctor about reliable birth control choices. If your period is late or if you have irregular bleeding, or if you have sexual intercourse at any time without using 2 effective forms of birth control, stop taking this medication and contact your doctor right away. Because lenalidomide also passes into semen, men who use this drug and have sex with women must use a latex condom during all sexual contact, even if they have had a vasectomy.
Keep using condoms and other birth control as directed until 4 weeks after lenalidomide treatment has been stopped. You should have a blood test for hepatitis B virus before starting treatment. Some people with this virus may have a serious flare-up when using lenalidomide.
To receive lenalidomide in the United States, you must understand, agree to, and carefully follow the requirements of the REMS Program for this medication. If you live in Canada or any other country, consult your doctor and pharmacist for your country's regulations. This medication may cause a low number of white blood cells and platelets.
Your doctor will monitor you closely while you take this medication and may adjust the dose of the medication or stop the medication based on your lab test results. Get medical help right away if you develop any of the following symptoms: signs of infection (such as sore throat that doesn't go away, fever, swollen lymph nodes, chills), easy bleeding/bruising. Lenalidomide may rarely cause serious problems from blood clots (such as heart attack, stroke, blood clots in the lungs or legs).
You may be at increased risk for blood clots if you smoke, or have a history of blood clots, high blood pressure, or high cholesterol, or if you are immobile (such as on very long plane flights or being bedridden). If you use estrogen-containing products, these may also increase your risk. To lower your risk, your doctor may prescribe an additional medication.
Before using lenalidomide, if you have any of these conditions report them to your doctor or pharmacist. Get medical help right away if any of these side effects occur: shortness of breath/rapid breathing, chest/jaw/left arm pain, unusual sweating, confusion, sudden dizziness/fainting, pain/swelling/warmth in the groin/calf, sudden/severe headaches, trouble speaking, weakness on one side of the body, sudden vision changes.
WARNING: Lenalidomide is very similar to thalidomide, a drug which has caused severe (possibly fatal) birth defects when used during pregnancy. If lenalidomide is taken during pregnancy, it may also cause severe (possibly fatal) birth defects. Women who are pregnant or who may become pregnant must not use lenalidomide.
Women must have two negative pregnancy tests before starting lenalidomide (the first test 10 to 14 days before the first dose and the second test within 24 hours before the first dose). Women must also continue to have pregnancy tests regularly during treatment (every 2 to 4 weeks). Female patients must use 2 effective forms of birth control (or completely avoid sexual intercourse) for 4 weeks before starting lenalidomide, during use, and for 4 weeks after stopping this drug.
Talk to your doctor about reliable birth control choices. If your period is late or if you have irregular bleeding, or if you have sexual intercourse at any time without using 2 effective forms of birth control, stop taking this medication and contact your doctor right away. Because lenalidomide also passes into semen, men who use this drug and have sex with women must use a latex condom during all sexual contact, even if they have had a vasectomy.
Keep using condoms and other birth control as directed until 4 weeks after lenalidomide treatment has been stopped. You should have a blood test for hepatitis B virus before starting treatment. Some people with this virus may have a serious flare-up when using lenalidomide.
To receive lenalidomide in the United States, you must understand, agree to, and carefully follow the requirements of the REMS Program for this medication. If you live in Canada or any other country, consult your doctor and pharmacist for your country's regulations. This medication may cause a low number of white blood cells and platelets.
Your doctor will monitor you closely while you take this medication and may adjust the dose of the medication or stop the medication based on your lab test results. Get medical help right away if you develop any of the following symptoms: signs of infection (such as sore throat that doesn't go away, fever, swollen lymph nodes, chills), easy bleeding/bruising. Lenalidomide may rarely cause serious problems from blood clots (such as heart attack, stroke, blood clots in the lungs or legs).
You may be at increased risk for blood clots if you smoke, or have a history of blood clots, high blood pressure, or high cholesterol, or if you are immobile (such as on very long plane flights or being bedridden). If you use estrogen-containing products, these may also increase your risk. To lower your risk, your doctor may prescribe an additional medication.
Before using lenalidomide, if you have any of these conditions report them to your doctor or pharmacist. Get medical help right away if any of these side effects occur: shortness of breath/rapid breathing, chest/jaw/left arm pain, unusual sweating, confusion, sudden dizziness/fainting, pain/swelling/warmth in the groin/calf, sudden/severe headaches, trouble speaking, weakness on one side of the body, sudden vision changes.
The following icd codes are available for LENALIDOMIDE (lenalidomide)'s list of indications:
| Follicular lymphoma | |
| C82 | Follicular lymphoma |
| C82.0 | Follicular lymphoma grade I |
| C82.00 | Follicular lymphoma grade i, unspecified site |
| C82.01 | Follicular lymphoma grade i, lymph nodes of head, face, and neck |
| C82.02 | Follicular lymphoma grade i, intrathoracic lymph nodes |
| C82.03 | Follicular lymphoma grade i, intra-abdominal lymph nodes |
| C82.04 | Follicular lymphoma grade i, lymph nodes of axilla and upper limb |
| C82.05 | Follicular lymphoma grade i, lymph nodes of inguinal region and lower limb |
| C82.06 | Follicular lymphoma grade i, intrapelvic lymph nodes |
| C82.07 | Follicular lymphoma grade i, spleen |
| C82.08 | Follicular lymphoma grade i, lymph nodes of multiple sites |
| C82.09 | Follicular lymphoma grade i, extranodal and solid organ sites |
| C82.1 | Follicular lymphoma grade II |
| C82.10 | Follicular lymphoma grade Ii, unspecified site |
| C82.11 | Follicular lymphoma grade Ii, lymph nodes of head, face, and neck |
| C82.12 | Follicular lymphoma grade Ii, intrathoracic lymph nodes |
| C82.13 | Follicular lymphoma grade Ii, intra-abdominal lymph nodes |
| C82.14 | Follicular lymphoma grade Ii, lymph nodes of axilla and upper limb |
| C82.15 | Follicular lymphoma grade Ii, lymph nodes of inguinal region and lower limb |
| C82.16 | Follicular lymphoma grade Ii, intrapelvic lymph nodes |
| C82.17 | Follicular lymphoma grade Ii, spleen |
| C82.18 | Follicular lymphoma grade Ii, lymph nodes of multiple sites |
| C82.19 | Follicular lymphoma grade Ii, extranodal and solid organ sites |
| C82.2 | Follicular lymphoma grade IIi, unspecified |
| C82.20 | Follicular lymphoma grade IIi, unspecified, unspecified site |
| C82.21 | Follicular lymphoma grade IIi, unspecified, lymph nodes of head, face, and neck |
| C82.22 | Follicular lymphoma grade IIi, unspecified, intrathoracic lymph nodes |
| C82.23 | Follicular lymphoma grade IIi, unspecified, intra-abdominal lymph nodes |
| C82.24 | Follicular lymphoma grade IIi, unspecified, lymph nodes of axilla and upper limb |
| C82.25 | Follicular lymphoma grade IIi, unspecified, lymph nodes of inguinal region and lower limb |
| C82.26 | Follicular lymphoma grade IIi, unspecified, intrapelvic lymph nodes |
| C82.27 | Follicular lymphoma grade IIi, unspecified, spleen |
| C82.28 | Follicular lymphoma grade IIi, unspecified, lymph nodes of multiple sites |
| C82.29 | Follicular lymphoma grade IIi, unspecified, extranodal and solid organ sites |
| C82.3 | Follicular lymphoma grade IIia |
| C82.30 | Follicular lymphoma grade IIia, unspecified site |
| C82.31 | Follicular lymphoma grade IIia, lymph nodes of head, face, and neck |
| C82.32 | Follicular lymphoma grade IIia, intrathoracic lymph nodes |
| C82.33 | Follicular lymphoma grade IIia, intra-abdominal lymph nodes |
| C82.34 | Follicular lymphoma grade IIia, lymph nodes of axilla and upper limb |
| C82.35 | Follicular lymphoma grade IIia, lymph nodes of inguinal region and lower limb |
| C82.36 | Follicular lymphoma grade IIia, intrapelvic lymph nodes |
| C82.37 | Follicular lymphoma grade IIia, spleen |
| C82.38 | Follicular lymphoma grade IIia, lymph nodes of multiple sites |
| C82.39 | Follicular lymphoma grade IIia, extranodal and solid organ sites |
| C82.4 | Follicular lymphoma grade IIib |
| C82.40 | Follicular lymphoma grade IIib, unspecified site |
| C82.41 | Follicular lymphoma grade IIib, lymph nodes of head, face, and neck |
| C82.42 | Follicular lymphoma grade IIib, intrathoracic lymph nodes |
| C82.43 | Follicular lymphoma grade IIib, intra-abdominal lymph nodes |
| C82.44 | Follicular lymphoma grade IIib, lymph nodes of axilla and upper limb |
| C82.45 | Follicular lymphoma grade IIib, lymph nodes of inguinal region and lower limb |
| C82.46 | Follicular lymphoma grade IIib, intrapelvic lymph nodes |
| C82.47 | Follicular lymphoma grade IIib, spleen |
| C82.48 | Follicular lymphoma grade IIib, lymph nodes of multiple sites |
| C82.49 | Follicular lymphoma grade IIib, extranodal and solid organ sites |
| C82.5 | Diffuse follicle center lymphoma |
| C82.50 | Diffuse follicle center lymphoma, unspecified site |
| C82.51 | Diffuse follicle center lymphoma, lymph nodes of head, face, and neck |
| C82.52 | Diffuse follicle center lymphoma, intrathoracic lymph nodes |
| C82.53 | Diffuse follicle center lymphoma, intra-abdominal lymph nodes |
| C82.54 | Diffuse follicle center lymphoma, lymph nodes of axilla and upper limb |
| C82.55 | Diffuse follicle center lymphoma, lymph nodes of inguinal region and lower limb |
| C82.56 | Diffuse follicle center lymphoma, intrapelvic lymph nodes |
| C82.57 | Diffuse follicle center lymphoma, spleen |
| C82.58 | Diffuse follicle center lymphoma, lymph nodes of multiple sites |
| C82.59 | Diffuse follicle center lymphoma, extranodal and solid organ sites |
| C82.6 | Cutaneous follicle center lymphoma |
| C82.60 | Cutaneous follicle center lymphoma, unspecified site |
| C82.61 | Cutaneous follicle center lymphoma, lymph nodes of head, face, and neck |
| C82.62 | Cutaneous follicle center lymphoma, intrathoracic lymph nodes |
| C82.63 | Cutaneous follicle center lymphoma, intra-abdominal lymph nodes |
| C82.64 | Cutaneous follicle center lymphoma, lymph nodes of axilla and upper limb |
| C82.65 | Cutaneous follicle center lymphoma, lymph nodes of inguinal region and lower limb |
| C82.66 | Cutaneous follicle center lymphoma, intrapelvic lymph nodes |
| C82.67 | Cutaneous follicle center lymphoma, spleen |
| C82.68 | Cutaneous follicle center lymphoma, lymph nodes of multiple sites |
| C82.69 | Cutaneous follicle center lymphoma, extranodal and solid organ sites |
| C82.8 | Other types of follicular lymphoma |
| C82.80 | Other types of follicular lymphoma, unspecified site |
| C82.81 | Other types of follicular lymphoma, lymph nodes of head, face, and neck |
| C82.82 | Other types of follicular lymphoma, intrathoracic lymph nodes |
| C82.83 | Other types of follicular lymphoma, intra-abdominal lymph nodes |
| C82.84 | Other types of follicular lymphoma, lymph nodes of axilla and upper limb |
| C82.85 | Other types of follicular lymphoma, lymph nodes of inguinal region and lower limb |
| C82.86 | Other types of follicular lymphoma, intrapelvic lymph nodes |
| C82.87 | Other types of follicular lymphoma, spleen |
| C82.88 | Other types of follicular lymphoma, lymph nodes of multiple sites |
| C82.89 | Other types of follicular lymphoma, extranodal and solid organ sites |
| C82.9 | Follicular lymphoma, unspecified |
| C82.90 | Follicular lymphoma, unspecified, unspecified site |
| C82.91 | Follicular lymphoma, unspecified, lymph nodes of head, face, and neck |
| C82.92 | Follicular lymphoma, unspecified, intrathoracic lymph nodes |
| C82.93 | Follicular lymphoma, unspecified, intra-abdominal lymph nodes |
| C82.94 | Follicular lymphoma, unspecified, lymph nodes of axilla and upper limb |
| C82.95 | Follicular lymphoma, unspecified, lymph nodes of inguinal region and lower limb |
| C82.96 | Follicular lymphoma, unspecified, intrapelvic lymph nodes |
| C82.97 | Follicular lymphoma, unspecified, spleen |
| C82.98 | Follicular lymphoma, unspecified, lymph nodes of multiple sites |
| C82.99 | Follicular lymphoma, unspecified, extranodal and solid organ sites |
| Mantle cell lymphoma | |
| C83.1 | Mantle cell lymphoma |
| C83.10 | Mantle cell lymphoma, unspecified site |
| C83.11 | Mantle cell lymphoma, lymph nodes of head, face, and neck |
| C83.12 | Mantle cell lymphoma, intrathoracic lymph nodes |
| C83.13 | Mantle cell lymphoma, intra-abdominal lymph nodes |
| C83.14 | Mantle cell lymphoma, lymph nodes of axilla and upper limb |
| C83.15 | Mantle cell lymphoma, lymph nodes of inguinal region and lower limb |
| C83.16 | Mantle cell lymphoma, intrapelvic lymph nodes |
| C83.17 | Mantle cell lymphoma, spleen |
| C83.18 | Mantle cell lymphoma, lymph nodes of multiple sites |
| C83.19 | Mantle cell lymphoma, extranodal and solid organ sites |
| Marginal zone lymphoma | |
| C83.0 | Small cell b-cell lymphoma |
| C83.00 | Small cell b-cell lymphoma, unspecified site |
| C83.01 | Small cell b-cell lymphoma, lymph nodes of head, face, and neck |
| C83.02 | Small cell b-cell lymphoma, intrathoracic lymph nodes |
| C83.03 | Small cell b-cell lymphoma, intra-abdominal lymph nodes |
| C83.04 | Small cell b-cell lymphoma, lymph nodes of axilla and upper limb |
| C83.05 | Small cell b-cell lymphoma, lymph nodes of inguinal region and lower limb |
| C83.06 | Small cell b-cell lymphoma, intrapelvic lymph nodes |
| C83.07 | Small cell b-cell lymphoma, spleen |
| C83.08 | Small cell b-cell lymphoma, lymph nodes of multiple sites |
| C83.09 | Small cell b-cell lymphoma, extranodal and solid organ sites |
| Multiple myeloma | |
| C90.0 | Multiple myeloma |
| C90.00 | Multiple myeloma not having achieved remission |
| C90.02 | Multiple myeloma in relapse |
| Multiple myeloma maintenance therapy following auto-HSCT | |
| C90.0 | Multiple myeloma |
| C90.00 | Multiple myeloma not having achieved remission |
| Myelodysplastic syndrome with 5q deletion | |
| D46.C | Myelodysplastic syndrome with isolated del(5q) chromosomal abnormality |
| Progressive diffuse large b-cell lymphoma | |
| C83.3 | Diffuse large b-cell lymphoma |
| C83.30 | Diffuse large b-cell lymphoma, unspecified site |
| C83.31 | Diffuse large b-cell lymphoma, lymph nodes of head, face, and neck |
| C83.32 | Diffuse large b-cell lymphoma, intrathoracic lymph nodes |
| C83.33 | Diffuse large b-cell lymphoma, intra-abdominal lymph nodes |
| C83.34 | Diffuse large b-cell lymphoma, lymph nodes of axilla and upper limb |
| C83.35 | Diffuse large b-cell lymphoma, lymph nodes of inguinal region and lower limb |
| C83.36 | Diffuse large b-cell lymphoma, intrapelvic lymph nodes |
| C83.37 | Diffuse large b-cell lymphoma, spleen |
| C83.38 | Diffuse large b-cell lymphoma, lymph nodes of multiple sites |
| C83.39 | Diffuse large b-cell lymphoma, extranodal and solid organ sites |
Formulary Reference Tool