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Drug overview for CYTARABINE (cytarabine/pf):
Generic name: CYTARABINE/PF (sye-TAIR-uh-bean)
Drug class: Pyrimidine Analogs
Therapeutic class: Antineoplastics
Cytarabine, a synthetic pyrimidine antagonist, is an antimetabolite antineoplastic agent.
No enhanced Uses information available for this drug.
Generic name: CYTARABINE/PF (sye-TAIR-uh-bean)
Drug class: Pyrimidine Analogs
Therapeutic class: Antineoplastics
Cytarabine, a synthetic pyrimidine antagonist, is an antimetabolite antineoplastic agent.
No enhanced Uses information available for this drug.
DRUG IMAGES
CYTARABINE 100 MG/5 ML VIAL
CYTARABINE 2 G/20 ML VIAL
The following indications for CYTARABINE (cytarabine/pf) have been approved by the FDA:
Indications:
Acute lymphoid leukemia
Acute myeloid leukemia
Acute promyelocytic leukemia
Blastic phase chronic myeloid leukemia
Meningeal leukemia
Professional Synonyms:
Acute granulocytic leukemia
Acute leukemic myelosis
Acute lymphatic leukemia
Acute lymphocytic leukemia
Acute lymphogenous leukemia
Acute myelocytic leukemia
Acute myelogenic leukemia
Acute myelogenous leukemia
Acute non-lymphoblastic leukemia
Acute non-lymphocytic leukemia
Chronic granulocytic leukemia in blast crisis phase
Chronic leukemic myelosis, blast crisis phase
Chronic myelogenic leukemia in blast crisis phase
Chronic myelogenous leukemia in blast crisis phase
Chronic myeloid leukemia in blast crisis phase
CML blast crisis phase
Leukemic leptomeningitis
Leukemic meningitis
Lymphoblastic leukemia
Promyelocytic leukemia
Indications:
Acute lymphoid leukemia
Acute myeloid leukemia
Acute promyelocytic leukemia
Blastic phase chronic myeloid leukemia
Meningeal leukemia
Professional Synonyms:
Acute granulocytic leukemia
Acute leukemic myelosis
Acute lymphatic leukemia
Acute lymphocytic leukemia
Acute lymphogenous leukemia
Acute myelocytic leukemia
Acute myelogenic leukemia
Acute myelogenous leukemia
Acute non-lymphoblastic leukemia
Acute non-lymphocytic leukemia
Chronic granulocytic leukemia in blast crisis phase
Chronic leukemic myelosis, blast crisis phase
Chronic myelogenic leukemia in blast crisis phase
Chronic myelogenous leukemia in blast crisis phase
Chronic myeloid leukemia in blast crisis phase
CML blast crisis phase
Leukemic leptomeningitis
Leukemic meningitis
Lymphoblastic leukemia
Promyelocytic leukemia
The following dosing information is available for CYTARABINE (cytarabine/pf):
Dosage of conventional (unencapsulated) cytarabine must be based on the clinical and hematologic response and tolerance of the patient to obtain optimum therapeutic results with minimum adverse effects. Although higher total doses of cytarabine can be given by rapid IV injection compared with continuous IV infusion with similar hematologic toxicity, the most effective dosage schedule and method of administration have not been established. Clinicians should consult published protocols for the dosage of cytarabine and other chemotherapeutic agents and the method and sequence of administration.
Reduction of cytarabine dosage in patients with impaired renal function does not appear to be necessary. The manufacturers state that cytarabine should be used with caution and in reduced dosage in patients with poor hepatic function, but some clinicians believe that dosage adjustment is not necessary in patients with impaired hepatic function.
Severe and sometimes fatal CNS, GI, and pulmonary toxicity, which differs from that seen with usual dosages, has been associated with high-dose+ cytarabine regimens for refractory or secondary acute leukemia or refractory non-Hodgkin's lymphomas. Adverse effects associated with these regimens include cerebral and cerebellar dysfunction (e.g., somnolence, coma, personality changes), which are usually reversible; hemorrhagic conjunctivitis and reversible corneal toxicity (e.g., keratitis), which may be minimized or prevented by prophylaxis with ophthalmic corticosteroid preparations; one case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH); severe GI ulceration, including pneumatosis cystoides intestinalis leading to peritonitis; bowel necrosis; necrotizing colitis; sepsis and liver abscess; liver damage with increased hyperbilirubinemia; pericarditis with tamponade; and pulmonary edema. Reversible, acute aseptic meningitis, combined with cerebellar dysfunction, has been reported in at least one patient.
Rarely, severe rash leading to desquamation has occurred. Complete alopecia occurs more commonly with high-dose regimens than with usual dosage regimens of the drug. A syndrome of sudden respiratory distress, rapidly progressing to pulmonary edema and radiographically pronounced cardiomegaly and which was sometimes fatal, has been reported in patients with refractory acute leukemia receiving high-dose therapy.
Cases of cardiomyopathy with subsequent death also have been reported in patients receiving high-dose cytarabine in combination with cyclophosphamide in preparation for bone marrow transplantation; this cardiac toxicity may be schedule dependent.
Peripheral motor and sensory neuropathies also have occurred occasionally in patients receiving high-dose cytarabine therapy. Neuropathies have involved the lower and/or upper extremities, and have been manifested as muscle weakness, gait disturbances, walking difficulties, handwriting difficulties, paresthesia, numbness, hypoalgesia, hypoesthesia, and myalgia. Patients receiving high-dose cytarabine should be observed for signs of neuropathy; dosage schedule adjustment may be necessary to avoid irreversible neurologic toxicity.
According to the manufacturer, patients with renal or hepatic impairment may be at increased risk of CNS toxicity associated with high-dose cytarabine therapy.
Diffuse interstitial pneumonitis, possibly related to cytarabine therapy, has been reported occasionally in patients receiving relatively high doses (e.g., 1 g/m2) of cytarabine alone or in combination with other antineoplastic agents. Pancreatitis also has occurred in patients receiving high-dose cytarabine therapy. Cases of acute pancreatitis have been reported in patients receiving cytarabine who were previously treated with asparaginase.
There is some evidence to suggest that the incidence of cerebellar dysfunction (e.g., ataxia, dysarthria, dysdiadochokinesia, dysmetria, tremor, nystagmus) associated with high-dose+ (1-3 g/m2 given by IV infusion over 1 hour twice daily for 2-6 days) regimens of cytarabine may be increased when drug manufactured by Quad (no longer commercially available in the US) is used compared with that when cytarabine manufactured by Upjohn is used. A causal relationship of this apparent increased incidence of cerebellar dysfunction associated with the Quad preparation has not been established, but results of a retrospective analysis conducted by FDA of a limited number of case histories (25 received Quad's product and 34 received Upjohn's product) revealed that cerebellar dysfunction occurred in 32% of patients receiving the high-dose regimen with cytarabine manufactured by Quad compared with 9% in those receiving the Upjohn preparation. While both preparations meet USP compendial standards, there are small differences in impurities and potency of the sterile powders manufactured by these companies; however, the clinical importance of these differences has not been established, but it is possible that such differences are of no consequence with usual regimens but may be important at very high dosages. Quad recommends that any remaining cytarabine manufactured by them be used only at the labeled dosages, and that their preparation not be used for high-dose regimens.
Reduction of cytarabine dosage in patients with impaired renal function does not appear to be necessary. The manufacturers state that cytarabine should be used with caution and in reduced dosage in patients with poor hepatic function, but some clinicians believe that dosage adjustment is not necessary in patients with impaired hepatic function.
Severe and sometimes fatal CNS, GI, and pulmonary toxicity, which differs from that seen with usual dosages, has been associated with high-dose+ cytarabine regimens for refractory or secondary acute leukemia or refractory non-Hodgkin's lymphomas. Adverse effects associated with these regimens include cerebral and cerebellar dysfunction (e.g., somnolence, coma, personality changes), which are usually reversible; hemorrhagic conjunctivitis and reversible corneal toxicity (e.g., keratitis), which may be minimized or prevented by prophylaxis with ophthalmic corticosteroid preparations; one case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH); severe GI ulceration, including pneumatosis cystoides intestinalis leading to peritonitis; bowel necrosis; necrotizing colitis; sepsis and liver abscess; liver damage with increased hyperbilirubinemia; pericarditis with tamponade; and pulmonary edema. Reversible, acute aseptic meningitis, combined with cerebellar dysfunction, has been reported in at least one patient.
Rarely, severe rash leading to desquamation has occurred. Complete alopecia occurs more commonly with high-dose regimens than with usual dosage regimens of the drug. A syndrome of sudden respiratory distress, rapidly progressing to pulmonary edema and radiographically pronounced cardiomegaly and which was sometimes fatal, has been reported in patients with refractory acute leukemia receiving high-dose therapy.
Cases of cardiomyopathy with subsequent death also have been reported in patients receiving high-dose cytarabine in combination with cyclophosphamide in preparation for bone marrow transplantation; this cardiac toxicity may be schedule dependent.
Peripheral motor and sensory neuropathies also have occurred occasionally in patients receiving high-dose cytarabine therapy. Neuropathies have involved the lower and/or upper extremities, and have been manifested as muscle weakness, gait disturbances, walking difficulties, handwriting difficulties, paresthesia, numbness, hypoalgesia, hypoesthesia, and myalgia. Patients receiving high-dose cytarabine should be observed for signs of neuropathy; dosage schedule adjustment may be necessary to avoid irreversible neurologic toxicity.
According to the manufacturer, patients with renal or hepatic impairment may be at increased risk of CNS toxicity associated with high-dose cytarabine therapy.
Diffuse interstitial pneumonitis, possibly related to cytarabine therapy, has been reported occasionally in patients receiving relatively high doses (e.g., 1 g/m2) of cytarabine alone or in combination with other antineoplastic agents. Pancreatitis also has occurred in patients receiving high-dose cytarabine therapy. Cases of acute pancreatitis have been reported in patients receiving cytarabine who were previously treated with asparaginase.
There is some evidence to suggest that the incidence of cerebellar dysfunction (e.g., ataxia, dysarthria, dysdiadochokinesia, dysmetria, tremor, nystagmus) associated with high-dose+ (1-3 g/m2 given by IV infusion over 1 hour twice daily for 2-6 days) regimens of cytarabine may be increased when drug manufactured by Quad (no longer commercially available in the US) is used compared with that when cytarabine manufactured by Upjohn is used. A causal relationship of this apparent increased incidence of cerebellar dysfunction associated with the Quad preparation has not been established, but results of a retrospective analysis conducted by FDA of a limited number of case histories (25 received Quad's product and 34 received Upjohn's product) revealed that cerebellar dysfunction occurred in 32% of patients receiving the high-dose regimen with cytarabine manufactured by Quad compared with 9% in those receiving the Upjohn preparation. While both preparations meet USP compendial standards, there are small differences in impurities and potency of the sterile powders manufactured by these companies; however, the clinical importance of these differences has not been established, but it is possible that such differences are of no consequence with usual regimens but may be important at very high dosages. Quad recommends that any remaining cytarabine manufactured by them be used only at the labeled dosages, and that their preparation not be used for high-dose regimens.
No enhanced Administration information available for this drug.
No dosing information available.
No generic dosing information available.
The following drug interaction information is available for CYTARABINE (cytarabine/pf):
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 18 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 |
|---|---|
| Cytarabine; Methotrexate/Asparaginase SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism of the interaction is unknown and may be a combination of mechanisms. Asparaginase has been shown to decrease the cellular uptake of methotrexate. This effect is maximal 24 hours after asparaginase administration and returns to baseline 96 hours later. Asparaginase inhibits DNA synthesis and asparaginase-induced amino acid depletion may cause cells to enter a stationary phase of growth. Since methotrexate is most toxic against cells that are actively synthesizing DNA, its transport and cytocidal effects may be decreased.(1) CLINICAL EFFECTS: When asparaginase is administered prior to or with cytarabine or methotrexate, asparaginase may diminish the effect of cytarabine or methotrexate on malignant cells (1-3). PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Cytarabine and methotrexate should not be administered with or during the period following asparaginase therapy when asparagine levels are below normal.(2-3) A synergistic effect was observed when cytarabine was given before asparaginase therapy and was most prominent with a treatment interval of about 120 hours.(4) The optimal time interval between asparaginase and a subsequent dose of methotrexate has been shown to be 9-10 days. A 24-hour interval between methotrexate and a subsequent dose of asparaginase allows for the return of methotrexate's effects on malignant cells.(1) DISCUSSION: The effects of asparaginase with cytarabine or methotrexate in combination are schedule-dependent. When asparaginase is given concurrently with or prior to cytarabine or methotrexate, asparaginase inhibits the cytocidal effects of cytarabine and methotrexate. However, when given 24 hours after larger doses of cytarabine or methotrexate, asparaginase may decrease some of the toxic effects of cytarabine or methotrexate, allowing the host to tolerate larger doses of chemotherapy. The sequential administration of cytarabine or methotrexate followed by asparaginase may result in synergistic effects and decreased toxicity (1). |
ASPARLAS, ERWINASE, ONCASPAR, RYLAZE |
| 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 |
| Deoxycytidine Kinase Substrates/Cladribine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine and zalcitabine may inhibit the intracellular phosphorylation of cladribine by deoxycytidine kinase (dCK). CLINICAL EFFECTS: Concurrent administration of clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine, or zalcitabine with cladribine may result in decreased clinical efficacy of cladribine. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of lamivudine states that the concurrent use of lamivudine and cladribine is not recommended.(1) The manufacturer of cladribine states that concurrent use of compounds that require activation by intracellular phosphorylation should be avoided.(2) DISCUSSION: Cladribine undergoes a series of phosphorylations to its active metabolites. In a case report, a patient on lamivudine who received cladribine concurrently did not experience a decrease in his lymphocyte count. After discontinuation of lamivudine and readministration of cladribine, his lymphocytes dropped as expected.(3) It is expected that other compounds phosphorylated by dCK would also decrease cladribine's efficacy.(4) Compounds phosphorylated by dCK include: clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine and zalcitabine. |
CLADRIBINE, MAVENCLAD |
| Upadacitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Upadacitinib, immunosuppressives, and immunomodulators all suppress the immune system. CLINICAL EFFECTS: Concurrent use of upadacitinib with immunosuppressives or immunomodulators may result in an increased risk of serious infections. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of upadacitinib states that concurrent use of upadacitinib with immunosuppressives or immunomodulators is not recommended. DISCUSSION: Serious infections have been reported in patients receiving upadacitinib. Reported infections included pneumonia, cellulitis, tuberculosis, multidermatomal herpes zoster, oral/esophageal candidiasis, cryptococcosis. Reports of viral reactivation, including herpes virus reactivation and hepatitis B reactivation, were reported in clinical studies with upadacitinib.(1) |
RINVOQ, RINVOQ LQ |
| Inebilizumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inebilizumab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of inebilizumab with immunosuppressive or immunomodulating agents may result in myelosuppression including neutropenia resulting in an increased risk for serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of inebilizumab states that the concurrent use of inebilizumab with immunosuppressive agents, including systemic corticosteroids, may increase the risk of infection. If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents.(1) DISCUSSION: Inebilizumab has not been studied in combination with other immunosuppressants. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents. The most common infections reported by inebilizumab treated patients in the randomized and open-label clinical trial periods included urinary tract infections (20%), nasopharyngitis (13%), upper respiratory tract infections (8%), and influenza (7%). Although there been no cases of Hepatitis B virus reactivation or progressive multifocal leukoencephalopathy reported in patients taking inebilizumab, these infections have been observed in patients taking other B-cell-depleting antibodies.(1) |
UPLIZNA |
| Baricitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of baricitinib with other biologic disease-modifying antirheumatic drugs (DMARDs) or potent immunosuppressants such as azathioprine or cyclosporine may result in additive or synergistic effects on the immune system. CLINICAL EFFECTS: Concurrent use of baricitinib with other biologic DMARDs or potent immunosuppressants such as azathioprine or cyclosporine may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of baricitinib states that concurrent use of baricitinib with biologic DMARDs or potent immunosuppressants is not recommended.(1) DISCUSSION: Most patients who developed serious infections while being treated with baricitinib were on concomitant immunosuppressants like methotrexate and corticosteroids. The combination of baricitinib with other biologic DMARDs has not been studied.(1) |
OLUMIANT |
| Leflunomide; Teriflunomide/Selected Immunosuppressants SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of leflunomide or teriflunomide and potent immunosuppressants may result in additive or synergistic effects on the immune system.(1,2) Leflunomide is a prodrug and is converted to its active metabolite teriflunomide.(1) CLINICAL EFFECTS: Concurrent use of leflunomide or teriflunomide with immunosuppressants may result in an increased risk of serious infections, including opportunistic infections, especially Pneumocystis jiroveci pneumonia, tuberculosis (including extra-pulmonary tuberculosis), and aspergillosis. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If leflunomide or teriflunomide is used concurrently with immunosuppressive agents, chronic CBC monitoring should be performed more frequently, every month instead of every 6 to 8 weeks. If bone marrow suppression or a serious infection occurs, leflunomide or teriflunomide should be stopped and rapid drug elimination procedure should be performed.(1,2) DISCUSSION: Pancytopenia, agranulocytosis and thrombocytopenia have been reported in patients receiving leflunomide or teriflunomide alone, but most frequently in patients taking concurrent immunosuppressants.(1,2) Severe and potentially fatal infections, including sepsis, have been reported in patients receiving leflunomide or teriflunomide, especially Pneumocystis jiroveci pneumonia and aspergillosis. Tuberculosis has also been reported.(1,2) |
ARAVA, AUBAGIO, LEFLUNICLO, LEFLUNOMIDE, TERIFLUNOMIDE |
| Ponesimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ponesimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of ponesimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection, cryptococcal infection, or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The ponesimod US prescribing information states ponesimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects. Initiating treatment with ponesimod after alemtuzumab is not recommended. However, ponesimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections, cryptococcal meningitis, disseminated cryptococcal infections, and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1) |
PONVORY |
| Sodium Iodide I 131/Myelosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1) DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1) |
HICON, SODIUM IODIDE I-131 |
| Fingolimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Fingolimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1-3) CLINICAL EFFECTS: Concurrent use of fingolimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1-3) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: Recommendations for fingolimod regarding this interaction differ between regulatory approving agencies. The fingolimod US prescribing information states: - Antineoplastic, immune-modulating, or immunosuppressive therapies, (including corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with fingolimod. When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating fingolimod.(1) The fingolimod Canadian prescribing information states: - Concurrent use with immunosuppressive or immunomodulatory agents is contraindicated due to the risk of additive immune system effects. However, co-administration of a short course of corticosteroids (up to 5 days) did not increase the overall rate of infection in patients participating Phase III clinical trials.(2) The fingolimod UK specific product characteristics states: - Fingolimod is contraindicated in patients currently receiving immunosuppressive therapies or those immunocompromised by prior therapies. When switching patients from another disease modifying therapy to Gilenya, the half-life and mode of action of the other therapy must be considered in order to avoid an additive immune effect whilst at the same time minimizing the risk of disease activation.(3) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1-3) |
FINGOLIMOD, GILENYA, TASCENSO ODT |
| Ozanimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ozanimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of ozanimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The ozanimod US prescribing information state this information regarding this interaction: -Ozanimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during therapy and in the week following administration. When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects. Initiating treatment with ozanimod after alemtuzumab is not recommended. However, ozanimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1) |
ZEPOSIA |
| Siponimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Siponimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of siponimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The siponimod US prescribing information state this information regarding this interaction: -Siponimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during therapy and in the week following administration. When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects. Initiating treatment with siponimod after alemtuzumab is not recommended. However, siponimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1) |
MAYZENT |
| 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 |
|---|---|
| Digoxin, Oral/Antineoplastics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Decreased gastrointestinal digoxin absorption. CLINICAL EFFECTS: The pharmacologic effects of digoxin may be decreased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor serum digoxin concentrations and observe the patient for a decrease in pharmacologic activity. Adjust the dose of digoxin accordingly. Substituting digitoxin or digoxin capsules for digoxin tablets may circumvent this interaction. DISCUSSION: There are a number of factors affecting the outcome of this interaction. The effects of antineoplastic therapy on the gastrointestinal absorption of digoxin have only been studied with certain chemotherapeutic agents or regimens (e.g., bleomycin, carmustine, cyclophosphamide, cytarabine, doxorubicin, methotrexate, procarbazine, vincristine). The interaction appears to occur with the administration of oral digoxin tablets as opposed to digoxin capsules. The gastrointestinal absorption of digitoxin does not seem to be altered by antineoplastic therapy. |
DIGITEK, DIGOXIN, LANOXIN |
| 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 CYTARABINE (cytarabine/pf):
Drug contraindication overview.
Conventional cytarabine is contraindicated in patients with known hypersensitivity to the drug. Liposomal cytarabine is contraindicated in patients who are hypersensitive to cytarabine or any component of the formulation, and in patients with active meningeal infection.
Conventional cytarabine is contraindicated in patients with known hypersensitivity to the drug. Liposomal cytarabine is contraindicated in patients who are hypersensitive to cytarabine or any component of the formulation, and in patients with active meningeal infection.
There are 1 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Lactation |
There are 19 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Acute pancreatitis |
| Acute respiratory distress syndrome |
| Anemia |
| Bacterial infection |
| Bone marrow depression |
| Cardiomyopathy |
| Coma |
| Disease of liver |
| Gastrointestinal ulcer |
| Hyperuricemia |
| Leukopenia |
| Necrotizing enterocolitis |
| Opportunistic fungal infection |
| Opportunistic viral infection |
| Peripheral neuropathy |
| Pregnancy |
| Protozoal infection |
| Pulmonary edema |
| Thrombocytopenic disorder |
There are 5 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Diarrhea |
| Granulocytopenic disorder |
| Kidney disease with likely reduction in glomerular filtration rate (GFr) |
| Stomatitis |
| Vomiting |
The following adverse reaction information is available for CYTARABINE (cytarabine/pf):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 34 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Infection Leukopenia Stomatitis Thrombocytopenic disorder |
CNS toxicity Paresthesia Tumor lysis syndrome Uric acid nephropathy |
| Rare/Very Rare |
|---|
|
Anemia Bone pain Chest pain Coma Conjunctival hemorrhage Drug-induced hepatitis Esophagitis Fever Gastrointestinal hemorrhage Gastrointestinal ulcer Injection site sequelae Interstitial pneumonitis Jaundice Kidney disease with reduction in glomerular filtration rate (GFr) Malaise Megaloblastic anemia Myalgia Necrotizing enterocolitis Pancreatitis Pericarditis Pulmonary edema Sepsis Sinus bradycardia Skin rash Thrombophlebitis Urinary retention |
There are 14 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Anorexia Nausea Vomiting |
Acute abdominal pain Conjunctivitis Dyspnea |
| Rare/Very Rare |
|---|
|
Alopecia Diarrhea Dizziness Drowsy Dyschromia Headache disorder Peripheral sensory neuropathy Pruritus of skin |
The following precautions are available for CYTARABINE (cytarabine/pf):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Cytarabine can cause fetal toxicity when administered to pregnant women, but potential benefits from use of the drug may be acceptable in certain conditions despite the possible risks to the fetus. Because systemic exposure to cytarabine is negligible during intrathecal therapy with liposomal cytarabine, the risk of fetal toxicity is thought to be low. However, there are no formal studies assessing the reproductive toxicity of liposomal cytarabine.
Congenital abnormalities have been reported, particularly when the fetus has been exposed to systemic therapy with cytarabine during the first trimester. There is a definite, but considerably reduced risk to the fetus when therapy is initiated during the second or third trimester. At least 3 cases of major limb malformations have been reported in infants of mothers who received IV cytarabine, alone or in combination with other agents, during the first trimester.
One infant had extremity and ear deformities, and another infant had upper and lower distal limb defects. A few women have received cytarabine with other antineoplastic agents during the second and third trimesters (20th-28th week of gestation) and delivered apparently normal infants. However, in one patient a trisomy C chromosomal abnormality was found in the chorionic tissue following a therapeutic abortion at 24 weeks of gestation after 4 weeks of therapy with cytarabine and thioguanine; the fetus appeared to have no congenital abnormalities.
In animal studies, cytarabine has been shown to cause abnormal cerebellar development in the neonatal hamster. Cytarabine has been shown to be teratogenic in mice and rats. Abnormalities including cleft palate, phocomelia, deformed appendages, and skeletal abnormalities have been observed in the offspring of mice given cytarabine doses of at least 2 mg/kg daily (about 0.2 times the recommended human dose on a mg/m2 basis) administered intraperitoneally during the period of organogenesis.
Deformed appendages have been observed in the offspring of rats given cytarabine 20 mg/kg (about 4 times the recommended human dose on a mg/m2 basis) as a single intraperitoneal dose on day 12 of gestation. Reduced prenatal and postnatal brain size and permanent impairment of learning ability were observed in rats given single intraperitoneal doses of cytarabine 50 mg/kg (about 10 times the recommended human dose on a mg/m2 basis) on day 14 of gestation. Cytarabine was embryotoxic in mice when given during the period of organogenesis.
Decreased fetal weight was observed in mice given cytarabine 0.5 mg/kg daily (about 0.05 times the recommended human dose on a mg/m2 basis), and increased early and late resorptions and decreased live litter sizes were observed in mice given cytarabine 8 mg/kg daily (approximately equal to the recommended human dose on a mg/m2 basis). There are no adequate and well-controlled studies to date using conventional or liposomal cytarabine in pregnant women.
Cytarabine should be used during pregnancy only in life-threatening situations or severe disease for which safer drugs cannot be used or are ineffective. When the drug is administered during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus. Women receiving systemic therapy with cytarabine, particularly during the first trimester, should be counseled on the advisability of continuing the pregnancy.
The manufacturers suggest that infants delivered by women who received cytarabine therapy during pregnancy receive follow-up monitoring. Women of childbearing potential should be advised to avoid becoming pregnant while receiving the drug.
Congenital abnormalities have been reported, particularly when the fetus has been exposed to systemic therapy with cytarabine during the first trimester. There is a definite, but considerably reduced risk to the fetus when therapy is initiated during the second or third trimester. At least 3 cases of major limb malformations have been reported in infants of mothers who received IV cytarabine, alone or in combination with other agents, during the first trimester.
One infant had extremity and ear deformities, and another infant had upper and lower distal limb defects. A few women have received cytarabine with other antineoplastic agents during the second and third trimesters (20th-28th week of gestation) and delivered apparently normal infants. However, in one patient a trisomy C chromosomal abnormality was found in the chorionic tissue following a therapeutic abortion at 24 weeks of gestation after 4 weeks of therapy with cytarabine and thioguanine; the fetus appeared to have no congenital abnormalities.
In animal studies, cytarabine has been shown to cause abnormal cerebellar development in the neonatal hamster. Cytarabine has been shown to be teratogenic in mice and rats. Abnormalities including cleft palate, phocomelia, deformed appendages, and skeletal abnormalities have been observed in the offspring of mice given cytarabine doses of at least 2 mg/kg daily (about 0.2 times the recommended human dose on a mg/m2 basis) administered intraperitoneally during the period of organogenesis.
Deformed appendages have been observed in the offspring of rats given cytarabine 20 mg/kg (about 4 times the recommended human dose on a mg/m2 basis) as a single intraperitoneal dose on day 12 of gestation. Reduced prenatal and postnatal brain size and permanent impairment of learning ability were observed in rats given single intraperitoneal doses of cytarabine 50 mg/kg (about 10 times the recommended human dose on a mg/m2 basis) on day 14 of gestation. Cytarabine was embryotoxic in mice when given during the period of organogenesis.
Decreased fetal weight was observed in mice given cytarabine 0.5 mg/kg daily (about 0.05 times the recommended human dose on a mg/m2 basis), and increased early and late resorptions and decreased live litter sizes were observed in mice given cytarabine 8 mg/kg daily (approximately equal to the recommended human dose on a mg/m2 basis). There are no adequate and well-controlled studies to date using conventional or liposomal cytarabine in pregnant women.
Cytarabine should be used during pregnancy only in life-threatening situations or severe disease for which safer drugs cannot be used or are ineffective. When the drug is administered during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus. Women receiving systemic therapy with cytarabine, particularly during the first trimester, should be counseled on the advisability of continuing the pregnancy.
The manufacturers suggest that infants delivered by women who received cytarabine therapy during pregnancy receive follow-up monitoring. Women of childbearing potential should be advised to avoid becoming pregnant while receiving the drug.
It is not known whether cytarabine is distributed into human milk. Because of the potential for serious adverse reactions to conventional cytarabine in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman. Systemic exposure to free cytarabine following intrathecal administration of liposomal cytarabine is negligible, so the risk of the drug being distributed into human milk is thought to be low. However, because many drugs are distributed into human milk and because of the potential for serious adverse reactions in nursing infants, the use of liposomal cytarabine is not recommended in nursing women.
Contraindicated
Absolute contraindication. (Human data usually available to support recommendations.) This drug should not be given to breast feeding mothers.
Contraindicated
Absolute contraindication. (Human data usually available to support recommendations.) This drug should not be given to breast feeding mothers.
| Drug Name | Excretion Potential | Effect on Infant | Notes |
|---|---|---|---|
| Cytarabine | Unknown. It is unknown whether the drug is excreted in human breast milk. | It is not known whether this drug has an adverse effect on the nursing infant. (No data or inconclusive human data) | Potential severe adverse effects including bone marrow depression. |
No enhanced Geriatric Use information available for this drug.
Precaution Exists
Geriatric management or monitoring precaution exists.
Precaution Exists
Geriatric management or monitoring precaution exists.
| Drug Name | Narrative | REN | HEP | CARDIO | NEURO | PULM | ENDO |
|---|---|---|---|---|---|---|---|
| Cytarabine | General-May need to reduce dose. | Y | N | N | N | N | N |
The following prioritized warning is available for CYTARABINE (cytarabine/pf):
WARNING: This medication decreases bone marrow function, an effect that may lead to a low number of blood cells such as red cells, white cells, and platelets. This effect can cause anemia, decrease your body's ability to fight an infection, or cause easy bruising/bleeding. Tell your doctor right away if you develop any of the following symptoms: unusual tiredness, pale skin, signs of infection (such as sore throat that doesn't go away, fever, chills), easy bruising/bleeding.
WARNING: This medication decreases bone marrow function, an effect that may lead to a low number of blood cells such as red cells, white cells, and platelets. This effect can cause anemia, decrease your body's ability to fight an infection, or cause easy bruising/bleeding. Tell your doctor right away if you develop any of the following symptoms: unusual tiredness, pale skin, signs of infection (such as sore throat that doesn't go away, fever, chills), easy bruising/bleeding.
The following icd codes are available for CYTARABINE (cytarabine/pf)'s list of indications:
| Acute lymphoid leukemia | |
| C91.0 | Acute lymphoblastic leukemia [ALl] |
| C91.00 | Acute lymphoblastic leukemia not having achieved remission |
| C91.02 | Acute lymphoblastic leukemia, in relapse |
| Acute myeloid leukemia | |
| C92.0 | Acute myeloblastic leukemia |
| C92.00 | Acute myeloblastic leukemia, not having achieved remission |
| C92.02 | Acute myeloblastic leukemia, in relapse |
| C92.4 | Acute promyelocytic leukemia |
| C92.40 | Acute promyelocytic leukemia, not having achieved remission |
| C92.42 | Acute promyelocytic leukemia, in relapse |
| C92.5 | Acute myelomonocytic leukemia |
| C92.50 | Acute myelomonocytic leukemia, not having achieved remission |
| C92.52 | Acute myelomonocytic leukemia, in relapse |
| C92.6 | Acute myeloid leukemia with 11q23-abnormality |
| C92.60 | Acute myeloid leukemia with 11q23-abnormality not having achieved remission |
| C92.62 | Acute myeloid leukemia with 11q23-abnormality in relapse |
| C93.0 | Acute monoblastic/monocytic leukemia |
| C93.00 | Acute monoblastic/monocytic leukemia, not having achieved remission |
| C93.02 | Acute monoblastic/monocytic leukemia, in relapse |
| C94.4 | Acute panmyelosis with myelofibrosis |
| C94.40 | Acute panmyelosis with myelofibrosis not having achieved remission |
| C94.42 | Acute panmyelosis with myelofibrosis, in relapse |
| Acute promyelocytic leukemia | |
| C92.4 | Acute promyelocytic leukemia |
| C92.40 | Acute promyelocytic leukemia, not having achieved remission |
| C92.42 | Acute promyelocytic leukemia, in relapse |
| Blastic phase chronic myeloid leukemia | |
| C92.1 | Chronic myeloid leukemia, BCr/ABl-positive |
| C92.10 | Chronic myeloid leukemia, BCr/ABl-positive, not having achieved remission |
| C92.12 | Chronic myeloid leukemia, BCr/ABl-positive, in relapse |
| C92.2 | Atypical chronic myeloid leukemia, BCr/ABl-negative |
| C92.20 | Atypical chronic myeloid leukemia, BCr/ABl-negative, not having achieved remission |
| C92.22 | Atypical chronic myeloid leukemia, BCr/ABl-negative, in relapse |
| Meningeal leukemia | |
| C90.1 | Plasma cell leukemia |
| C90.10 | Plasma cell leukemia not having achieved remission |
| C90.12 | Plasma cell leukemia in relapse |
| C91.0 | Acute lymphoblastic leukemia [ALl] |
| C91.00 | Acute lymphoblastic leukemia not having achieved remission |
| C91.02 | Acute lymphoblastic leukemia, in relapse |
| C91.1 | Chronic lymphocytic leukemia of b-cell type |
| C91.10 | Chronic lymphocytic leukemia of b-cell type not having achieved remission |
| C91.12 | Chronic lymphocytic leukemia of b-cell type in relapse |
| C91.3 | Prolymphocytic leukemia of b-cell type |
| C91.30 | Prolymphocytic leukemia of b-cell type not having achieved remission |
| C91.32 | Prolymphocytic leukemia of b-cell type, in relapse |
| C91.4 | Hairy cell leukemia |
| C91.40 | Hairy cell leukemia not having achieved remission |
| C91.42 | Hairy cell leukemia, in relapse |
| C91.5 | Adult t-cell lymphoma/leukemia (HTLv-1-associated) |
| C91.50 | Adult t-cell lymphoma/leukemia (HTLv-1-associated) not having achieved remission |
| C91.52 | Adult t-cell lymphoma/leukemia (HTLv-1-associated), in relapse |
| C91.6 | Prolymphocytic leukemia of t-cell type |
| C91.60 | Prolymphocytic leukemia of t-cell type not having achieved remission |
| C91.62 | Prolymphocytic leukemia of t-cell type, in relapse |
| C91.9 | Lymphoid leukemia, unspecified |
| C91.90 | Lymphoid leukemia, unspecified not having achieved remission |
| C91.92 | Lymphoid leukemia, unspecified, in relapse |
| C91.A | Mature b-cell leukemia burkitt-type |
| C91.A0 | Mature b-cell leukemia burkitt-type not having achieved remission |
| C91.A2 | Mature b-cell leukemia burkitt-type, in relapse |
| C91.Z | Other lymphoid leukemia |
| C91.Z0 | Other lymphoid leukemia not having achieved remission |
| C91.Z2 | Other lymphoid leukemia, in relapse |
| C92.0 | Acute myeloblastic leukemia |
| C92.00 | Acute myeloblastic leukemia, not having achieved remission |
| C92.02 | Acute myeloblastic leukemia, in relapse |
| C92.1 | Chronic myeloid leukemia, BCr/ABl-positive |
| C92.10 | Chronic myeloid leukemia, BCr/ABl-positive, not having achieved remission |
| C92.12 | Chronic myeloid leukemia, BCr/ABl-positive, in relapse |
| C92.2 | Atypical chronic myeloid leukemia, BCr/ABl-negative |
| C92.20 | Atypical chronic myeloid leukemia, BCr/ABl-negative, not having achieved remission |
| C92.22 | Atypical chronic myeloid leukemia, BCr/ABl-negative, in relapse |
| C92.4 | Acute promyelocytic leukemia |
| C92.40 | Acute promyelocytic leukemia, not having achieved remission |
| C92.42 | Acute promyelocytic leukemia, in relapse |
| C92.5 | Acute myelomonocytic leukemia |
| C92.50 | Acute myelomonocytic leukemia, not having achieved remission |
| C92.52 | Acute myelomonocytic leukemia, in relapse |
| C92.6 | Acute myeloid leukemia with 11q23-abnormality |
| C92.60 | Acute myeloid leukemia with 11q23-abnormality not having achieved remission |
| C92.62 | Acute myeloid leukemia with 11q23-abnormality in relapse |
| C92.9 | Myeloid leukemia, unspecified |
| C92.90 | Myeloid leukemia, unspecified, not having achieved remission |
| C92.92 | Myeloid leukemia, unspecified in relapse |
| C92.A | Acute myeloid leukemia with multilineage dysplasia |
| C92.A0 | Acute myeloid leukemia with multilineage dysplasia, not having achieved remission |
| C92.A2 | Acute myeloid leukemia with multilineage dysplasia, in relapse |
| C92.Z | Other myeloid leukemia |
| C92.Z0 | Other myeloid leukemia not having achieved remission |
| C92.Z2 | Other myeloid leukemia, in relapse |
| C93.0 | Acute monoblastic/monocytic leukemia |
| C93.00 | Acute monoblastic/monocytic leukemia, not having achieved remission |
| C93.02 | Acute monoblastic/monocytic leukemia, in relapse |
| C93.1 | Chronic myelomonocytic leukemia |
| C93.10 | Chronic myelomonocytic leukemia not having achieved remission |
| C93.12 | Chronic myelomonocytic leukemia, in relapse |
| C93.3 | Juvenile myelomonocytic leukemia |
| C93.30 | Juvenile myelomonocytic leukemia, not having achieved remission |
| C93.32 | Juvenile myelomonocytic leukemia, in relapse |
| C93.9 | Monocytic leukemia, unspecified |
| C93.90 | Monocytic leukemia, unspecified, not having achieved remission |
| C93.92 | Monocytic leukemia, unspecified in relapse |
| C93.Z | Other monocytic leukemia |
| C93.Z0 | Other monocytic leukemia, not having achieved remission |
| C93.Z2 | Other monocytic leukemia, in relapse |
| C94.0 | Acute erythroid leukemia |
| C94.00 | Acute erythroid leukemia, not having achieved remission |
| C94.02 | Acute erythroid leukemia, in relapse |
| C94.2 | Acute megakaryoblastic leukemia |
| C94.20 | Acute megakaryoblastic leukemia not having achieved remission |
| C94.22 | Acute megakaryoblastic leukemia, in relapse |
| C94.3 | Mast cell leukemia |
| C94.30 | Mast cell leukemia not having achieved remission |
| C94.32 | Mast cell leukemia, in relapse |
| C94.8 | Other specified leukemias |
| C94.80 | Other specified leukemias not having achieved remission |
| C94.82 | Other specified leukemias, in relapse |
| C95.0 | Acute leukemia of unspecified cell type |
| C95.00 | Acute leukemia of unspecified cell type not having achieved remission |
| C95.02 | Acute leukemia of unspecified cell type, in relapse |
| C95.1 | Chronic leukemia of unspecified cell type |
| C95.10 | Chronic leukemia of unspecified cell type not having achieved remission |
| C95.12 | Chronic leukemia of unspecified cell type, in relapse |
| C95.9 | Leukemia, unspecified |
| C95.90 | Leukemia, unspecified not having achieved remission |
| C95.92 | Leukemia, unspecified, in relapse |
Formulary Reference Tool