PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Purine Analogs

    DEA CLASS

    Rx

    DESCRIPTION

    A purine nucleoside antimetabolite that inhibits DNA synthesis
    Indicated for the treatment of pediatric patients aged 1 to 21 years with relapsed or refractory acute lymphoblastic leukemia after at least 2 prior regimens
    Severe and prolonged myelosuppression may occur; monitor complete blood counts during therapy

    COMMON BRAND NAMES

    Clolar

    HOW SUPPLIED

    Clofarabine/Clolar Intravenous Sol: 1mg, 1mL

    DOSAGE & INDICATIONS

    For the treatment of acute lymphocytic leukemia (ALL).
    For the treatment of relapsed or refractory ALL after at least 2 prior regimens.
    Intravenous dosage
    Adults 21 years and younger, Adolescents, and Children

    52 mg/m2 IV over 2 hours once daily for 5 consecutive days repeated every 2 to 6 weeks depending on recovery or return to baseline organ function. The next cycle of therapy may be started if the absolute neutrophil count is at least 0.75 X 109 cells/L but no sooner than 14 days from day 1 of the previous cycle. Re-calculate body surface area for dosing using actual height and weight prior to each cycle. Discontinue therapy if hypotension develops in the 5-day treatment period or if early signs of a cytokine release syndrome occur. Supportive care, such as IV fluids, antihyperuricemic treatment, and urine alkalinization is recommended during the 5-day treatment period. Consider the use of prophylactic antiemetics to prevent nausea/vomiting and steroids (e.g., hydrocortisone 100 mg/m2 on days 1, 2, and 3) to prevent cytokine release syndrome. The complete remission (CR) rate was 20% (CR, n = 7; CR without platelet recovery (CRp), n = 5) and the partial remission (PR) rate was 10% (n = 6) in 61 pediatric patients with refractory or relapsed acute lymphoblastic leukemia who received 5 days of clofarabine every 2 to 6 weeks (median time between cycles, 28 days; range, 12 to 55 days) for up to 12 cycles (median of 2 cycles; range, 1 to 11 cycles) in a multicenter, phase II study. The median duration of remission was 9.7 weeks; the overall survival time for all patients in this study was 13 weeks (range, 1 to 89 weeks). In this study, the median age was 12 years (1 to 20 years) and the median number of prior regimens was 3 (range, 2 to 6 regimens). Of the 9 patients who underwent a hematopoietic stem-cell transplant, 4 patients achieved a CR (CR, n = 2; CRp, n = 2) and 3 patients had a PR.

    For the treatment of relapsed or refractory ALL, in combination with etoposide and cyclophosphamide†.
    Intravenous dosage
    Adults 21 years or younger, Adolescents, and Children

    40 mg/m2 daily IV over 2 hours on days 1 to 5 in combination with etoposide 150 mg/m2 daily IV over 2 hours on days 1 to 5 and cyclophosphamide 400 mg/m2 daily IV over 1 hour on days 1 to 5 were given in a clinical study. Clofarabine was administered before cyclophosphamide and etoposide. In patients with a blast count greater than 30 X 109 cells/L, prophylactic steroids were given. Alternately, etoposide 100 mg/m2 daily IV over 2 hours on days 1 to 5 in combination with cyclophosphamide 440 mg/m2 daily IV over 1 hour on days 1 to 5, and clofarabine 40 mg/m2 daily IV over 2 hours on days 1 to 5 has been studied. Each drug was given daily for 4 days if administered as consolidation treatment.

    MAXIMUM DOSAGE

    Adults

    Safety and efficacy have not been established in adults aged older than 21 years.

    Geriatric

    Safety and efficacy have not been established.

    Adolescents

    52 mg/m2 IV daily for 5 days.

    Children

    52 mg/m2 IV daily for 5 days.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Baseline Hepatic Impairment
    There is no recommended dosing guidance from the manufacturer. Clofarabine use has not been evaluated in these patients.
    Treatment-Related Hepatic Impairment
    Grade 3 or higher increased bilirubin level: hold therapy; reduce the clofarabine dose by 25% when the patient is stable and bilirubin level returns to baseline.

    Renal Impairment

    Baseline Renal Impairment
    Creatinine clearance (CrCl) of 30 to 60 mL/min: reduce the initial dose by 50% (i.e., 26 mg/m2 IV daily for 5 days)
    CrCl less than 30 mL/min or patients on hemodialysis: no recommended dosing guidance from the manufacturer. Clofarabine use has not been evaluated in these patients.
    Treatment-Related Renal Impairment
    Grade 3 or higher increased serum creatinine (SCr) level: hold therapy; reduce the clofarabine dose by 25% when the patient is stable and SCr level returns to baseline.

    ADMINISTRATION

    Hazardous Drugs Classification
    NIOSH 2016 List: Group 1
    NIOSH (Draft) 2020 List: Table 1
    Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
    Emetic Risk
    Moderate
    Administer routine antiemetic prophylaxis prior to treatment.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Dilution:
    Filter the clofarabine 1 mg/mL solution with a 0.2 micron syringe filter.
    Withdraw the calculated dose and further dilute the filtered solution with 5% dextrose injection or 0.9% sodium chloride injection to a final concentration between 0.15 mg/mL and 0.4 mg/mL.
    Storage following dilution: The diluted admixture may be stored at room temperature (15 to 30 degrees C) for up to 24 hours.
     
    Intravenous infusion:
    Administer by IV infusion over 2 hours.
    Do not give other medications through the same IV line.

    STORAGE

    Clolar:
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - Protect from direct sunlight
    - Store diluted product in accordance with package insert instructions
    - Store in a cool, well ventilated, dry place
    - Store in carton until contents are used
    - Store in original container
    - Store unreconstituted product at room temperature (77 degrees F), excursions of 59 to 86 degrees F permitted
    - Store upright

    CONTRAINDICATIONS / PRECAUTIONS

    Anemia, bone marrow suppression, fungal infection, herpes infection, infection, neutropenia, sepsis, thrombocytopenia, viral infection

    Dose-dependent myelosuppression/bone marrow suppression (e.g., anemia, neutropenia, and thrombocytopenia) has been reported commonly with clofarabine therapy. Myelosuppression is typically reversible when clofarabine is discontinued. Monitor complete blood counts prior to each cycle and as necessary during clofarabine therapy. Do not administer the next cycle of therapy sooner than 14 days from the start of the last cycle and until the patient’s absolute neutrophil count is 0.75 X 109 cells/L or greater. A dose reduction is required in patients who experience grade 4 neutropenia lasting 4 or more weeks. Infection (e.g., viral infection such as herpes infection, bacterial infection, fungal infection) has also been reported commonly in patients who received clofarabine therapy; severe and fatal sepsis and opportunistic infections have also occurred. Monitor patients for signs and symptoms of infection. Withhold therapy in patients who develop a clinically significant infection; treat infection promptly. Clofarabine may be restarted at the full dose once the infection is controlled.

    Bleeding, GI bleeding, intracranial bleeding, pulmonary bleeding

    Bleeding (e.g., intracranial bleeding, GI bleeding, pulmonary bleeding) has occurred with clofarabine therapy; some cases were fatal. Most cases of bleeding were associated with thrombocytopenia. Monitor coagulation parameters (e.g., fibrinogen, PT/PTT) in addition to platelets during clofarabine therapy; treat as necessary.

    Hypotension

    Hypotension has been reported with clofarabine use; patients receiving blood pressure medication may have an increased risk of developing this adverse event. Monitor cardiac function in all patients during clofarabine administration. Discontinue therapy if hypotension develops in the 5-day treatment period.

    Capillary leak syndrome, pericardial effusion, pleural effusion, pulmonary edema, tachycardia

    A cytokine release syndrome, sometimes progressing to systemic inflammatory response syndrome (SIRS) with capillary leak syndrome, has been reported with clofarabine use; some cases were fatal. Symptoms of these syndromes include respiratory distress, tachycardia, tachypnea, hypotension, pleural effusion, pericardial effusion, pulmonary edema, and/or multi-organ failure. The use of prophylactic steroids (e.g., hydrocortisone 100 mg/m2 on days 1, 2, and 3) may help prevent SIRS/capillary leak syndrome. Monitor patients for signs and symptoms of cytokine release as early intervention may be beneficial. Discontinue therapy if a cytokine release syndrome occurs and provide supportive care (e.g., diuretics, albumin). Clofarabine therapy may be restarted at a reduced dose once the patient is stabilized and organ function normalizes.

    Hyperuricemia, tumor lysis syndrome (TLS)

    Tumor lysis syndrome (TLS) has been reported with clofarabine use. Monitor patients for signs and symptoms of TLS (e.g., electrolyte abnormalities, increased creatinine and/or uric acid level). Institute measures to prevent TLS/hyperuricemia (e.g., IV fluids, antihyperuricemic treatment, and urine alkalinization) during the 5-day treatment period.

    Colitis

    Enterocolitis (e.g., neutropenic and clostridium difficile colitis, cecitis) has occurred with clofarabine therapy, most often within 30 days of therapy and when clofarabine was used as part of combination chemotherapy. Some cases were fatal or serious, resulting in bowel necrosis, GI perforation or hemorrhage, or complications from sepsis. Monitor patients for signs and symptoms of enterocolitis; manage promptly.

    Hepatic disease

    Severe hepatotoxicity (e.g., hepatitis, jaundice, hepatic failure) has been reported with clofarabine therapy; some cases were fatal. Therefore, use clofarabine with caution in patients with hepatic disease and avoid the concomitant use of other agents known to cause hepatotoxicity. Additionally, hepatic sinusoidal obstruction syndrome (SOS), previously termed hepatic veno-occlusive disease (VOD), has been reported; the risk of SOS may be higher if clofarabine is used in combination with etoposide and cyclophosphamide in patients who have previously received a hematopoietic stem-cell transplant (off-label use). Monitor hepatic function (e.g., liver function tests) and for signs and symptoms of hepatitis, hepatic failure, and SOS. Discontinue clofarabine in patients who develop SOS or grade 3 or higher elevated hepatic enzymes and/or bilirubin levels. In patients who experience severe elevated bilirubin levels during therapy, clofarabine may be restarted at a reduced dose when the patient is stable and organ function has returned to baseline.

    Renal disease, renal impairment

    Renal toxicity has been reported with clofarabine use; therefore, use clofarabine with caution in patients with renal disease or renal impairment. A dose reduction is necessary in patients with a creatinine clearance between 30 to 60 mL/min. Minimize the concomitant use of other agents known to cause renal toxicity and monitor renal function during the 5-day treatment period. Withhold therapy in patients who develop grade 3 or higher elevated SCr levels during clofarabine therapy; restart at a reduced dose when the patient is stable and organ function has returned to baseline. Patients with infection, sepsis, or tumor lysis syndrome may be at increased risk of developing renal toxicity.

    Serious rash

    Serious rash has been reported with clofarabine therapy; some cases were fatal. Discontinue therapy in patients who develop an exfoliative or bullous rash, or if Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) is suspected.

    Pregnancy

    Clofarabine may cause fetal harm when used during pregnancy, based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid becoming pregnant during clofarabine therapy. Women who become pregnant while receiving clofarabine should be apprised of the potential hazard to the fetus. Although there are no well controlled studies in pregnant women who received clofarabine, teratogenic effects including developmental toxicity (e.g., reduced fetal body weight, increased post-implantation loss) and gross external malformations, soft tissue malformations, and skeletal and retarded ossifications have been observed in rats and rabbits at doses approximately 0.2 to 1 times the maximum recommended human dose of 52 mg/m2 based on body surface area.

    Contraception requirements, infertility, pregnancy testing, reproductive risk

    Counsel patients about the reproductive risk and contraception requirements during clofarabine therapy. Females of reproductive potential should receive pregnancy testing prior to starting clofarabine. These patients should use effective contraception during clofarabine treatment and for 6 months after the last dose. Women who become pregnant while receiving clofarabine should be apprised of the potential hazard to the fetus. Due to a risk of male-mediated teratogenicity, men with female partners should also use effective contraception during clofarabine treatment and for at least 3 months after the last dose. The risk of infertility in humans who have received clofarabine therapy is unknown. However, seminiferous tubule and testicular degeneration and atrophy have been reported with clofarabine use in animal studies in mice, rats, and dogs and ovarian atrophy or degeneration and uterine mucosal apoptosis have occurred with high doses of clofarabine in female mice.

    Breast-feeding

    It is not known if clofarabine is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Due to the risk of serious adverse reactions in a nursing child (e.g., genotoxicity), women should discontinue breast-feeding during clofarabine therapy and for at least 2 weeks after the last dose.

    Vaccination

    Vaccination with live vaccines should be avoided due to neutropenia and immunosuppression during clofarabine therapy.

    ADVERSE REACTIONS

    Severe

    leukopenia / Delayed / 88.0-88.0
    lymphopenia / Delayed / 82.0-82.0
    thrombocytopenia / Delayed / 80.0-80.0
    anemia / Delayed / 75.0-75.0
    neutropenia / Delayed / 64.0-64.0
    elevated hepatic enzymes / Delayed / 36.0-43.0
    hypotension / Rapid / 19.0-19.0
    nausea / Early / 15.0-15.0
    fever / Early / 14.0-14.0
    hyperbilirubinemia / Delayed / 13.0-13.0
    epistaxis / Delayed / 13.0-13.0
    diarrhea / Early / 12.0-12.0
    anorexia / Delayed / 12.0-12.0
    pleural effusion / Delayed / 12.0-12.0
    infection / Delayed / 1.0-11.0
    vomiting / Early / 9.0-9.0
    pericardial effusion / Delayed / 8.0-8.0
    palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / 7.0-7.0
    rash / Early / 0-7.0
    abdominal pain / Early / 1.0-7.0
    dyspnea / Early / 7.0-7.0
    petechiae / Delayed / 6.0-6.0
    tumor lysis syndrome (TLS) / Delayed / 6.0-6.0
    colitis / Delayed / 5.0-5.0
    pancreatitis / Delayed / 0-5.0
    hypertension / Early / 5.0-5.0
    sinus tachycardia / Rapid / 5.0-5.0
    renal failure (unspecified) / Delayed / 5.0-5.0
    headache / Early / 5.0-5.0
    pulmonary edema / Early / 0-5.0
    tachypnea / Early / 5.0-5.0
    fatigue / Early / 5.0-5.0
    capillary leak syndrome / Early / 4.0-4.0
    bone pain / Delayed / 3.0-3.0
    back pain / Delayed / 3.0-3.0
    arthralgia / Delayed / 3.0-3.0
    chills / Rapid / 3.0-3.0
    candidiasis / Delayed / 1.0-2.0
    edema / Delayed / 2.0-2.0
    hematuria / Delayed / 2.0-2.0
    jaundice / Delayed / 2.0-2.0
    sinusoidal obstruction syndrome (SOS) / Delayed / 2.0-2.0
    veno-occlusive disease (VOD) / Delayed / 2.0-2.0
    anxiety / Delayed / 2.0-2.0
    asthenia / Delayed / 2.0-2.0
    pruritus / Rapid / 1.0-1.0
    stomatitis / Delayed / 1.0-1.0
    drowsiness / Early / 1.0-1.0
    lethargy / Early / 1.0-1.0
    irritability / Delayed / 1.0-1.0
    agitation / Early / 1.0-1.0
    toxic epidermal necrolysis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    GI perforation / Delayed / Incidence not known
    enterocolitis / Delayed / Incidence not known
    bowel necrosis / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    intracranial bleeding / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known

    Moderate

    erythema / Early / 11.0-11.0
    bullous rash / Early / Incidence not known
    hyperuricemia / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    bleeding / Early / Incidence not known

    Mild

    flushing / Rapid / 19.0-19.0
    myalgia / Early / 14.0-14.0
    influenza / Delayed / 0-5.0
    sinusitis / Delayed / 0-5.0

    DRUG INTERACTIONS

    Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Concomitant use of clofarabine and zidovudine, ZDV may result in altered clofarabine levels because both agents are substrates of OAT1 and OAT3. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 and OAT3 substrates.
    Abciximab: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Acyclovir: (Moderate) Concomitant use of clofarabine and acyclovir may result in altered clofarabine levels because both agents are substrates of OAT1 and OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 and OCT1 substrates.
    Adefovir: (Moderate) Concomitant use of clofarabine and adefovir may result in altered clofarabine levels because both agents are substrates of OAT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 substrates.
    Aldesleukin, IL-2: (Major) Avoid the concomitant use of clofarabine and aldesleukin due to the risk of additive hepatotoxicity. Coadministration may also increase the risk of additive myelosuppression and nephrotoxicity.
    Aliskiren; Valsartan: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and valsartan, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving valsartan.
    Alogliptin; Metformin: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Alteplase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Amikacin: (Major) Avoid the concurrent and/or sequential use of amikacin and other nephrotoxic drugs such as clofarabine; coadministration may result in additive nephrotoxicity.
    Amlodipine; Celecoxib: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Amlodipine; Valsartan: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and valsartan, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving valsartan.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and valsartan, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving valsartan.
    Anagrelide: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Anticoagulants: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Antithrombin III: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Apixaban: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Argatroban: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Aspirin, ASA; Dipyridamole: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Aspirin, ASA; Pravastatin: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and pravastatin, a substrate of OAT protein (OATP), may result in altered clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP substrates.
    Azelastine; Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system
    Beclomethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Betamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Betrixaban: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Bivalirudin: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Bosentan: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and bosentan, a substrate of OAT protein (OATP), may result in altered clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP substrates.
    Budesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Budesonide; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Budesonide; Glycopyrrolate; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Bupivacaine; Meloxicam: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Canagliflozin; Metformin: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Cefadroxil: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and cefadroxil, an inhibitor of OAT1 and OAT3, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 and OAT3 inhibitors.
    Cefazolin: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and cefazolin, an inhibitor of OAT1 and OAT3, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 and OAT3 inhibitors.
    Celecoxib: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Celecoxib; Tramadol: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Cerivastatin: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and cerivastatin, a substrate of OAT protein (OATP), may result in altered clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP substrates.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
    Ciclesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Cidofovir: (Contraindicated) The concomitant use of cidofovir and clofarabine is contraindicated due to the potential for additive nephrotoxicity. Discontinue clofarabine 7 days prior to starting cidofovir.
    Cilostazol: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Cimetidine: (Moderate) The concomitant use of clofarabine and cimetidine resulted in decreased clofarabine renal excretion in a preclinical study in rats. Cimetidine is a substrate for OAT3 and OCT2. Monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OAT3 or OCT2 substrates or inhibitors.
    Clindamycin: (Moderate) Concomitant use of clofarabine and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
    Clopidogrel: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
    Corticosteroids: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Cortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Cyclosporine: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and cyclosporine, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP inhibitors.
    Cytarabine, ARA-C: (Minor) Clofarabine-cytarabine combination trials have not been completed to date; however, clofarabine is mechanistically like fludarabine. Thus, theoretically, a sequence-related interaction may occur during concurrent clofarabine and cytarabine treatment. The anti-cancer activity of cytarabine may be increased if clofarabine is given prior; while the activity of clofarabine may be decreased if cytarabine is given prior.
    Dabigatran: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Dalteparin: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Danaparoid: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Dapagliflozin; Metformin: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and ritonavir, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
    Deflazacort: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Desipramine: (Moderate) Concomitant use of clofarabine, a substrate of OCT1 and OCT2, and desipramine, a substrate of OCT1 and an inhibitor of OCT2, may result in altered clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 and OCT2 substrates or inhibitors.
    Desirudin: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Dexamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Dextromethorphan; Quinidine: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and quinidine, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
    Diclofenac: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diclofenac; Misoprostol: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diflunisal: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
    Diphenhydramine; Ibuprofen: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diphenhydramine; Naproxen: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Dipyridamole: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Disopyramide: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and disopyramide, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
    Donepezil; Memantine: (Moderate) Concomitant use of clofarabine and memantine may result in altered clofarabine levels because both agents are a substrate of OCT2. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT2 substrates.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Major) Avoid the concomitant use of clofarabine and tenofovir; coadministration may result in additive nephrotoxicity. Additionally, taking these drugs together may alter clofarabine concentrations; clofarabine and tenofovir are both substrates of OAT1 and OAT3.
    Echinacea: (Major) Echinacea possesses immunostimulatory activity and may theoretically reduce the response to drugs that alter immune system activity like antineoplastic drugs. Although documentation is lacking, coadministration of echinacea with immunosuppressants is not recommended by some resources.
    Edoxaban: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Avoid the concomitant use of clofarabine and tenofovir; coadministration may result in additive nephrotoxicity. Additionally, taking these drugs together may alter clofarabine concentrations; clofarabine and tenofovir are both substrates of OAT1 and OAT3.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid the concomitant use of clofarabine and tenofovir; coadministration may result in additive nephrotoxicity. Additionally, taking these drugs together may alter clofarabine concentrations; clofarabine and tenofovir are both substrates of OAT1 and OAT3.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid the concomitant use of clofarabine and tenofovir; coadministration may result in additive nephrotoxicity. Additionally, taking these drugs together may alter clofarabine concentrations; clofarabine and tenofovir are both substrates of OAT1 and OAT3.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Empagliflozin; Metformin: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Avoid the concomitant use of clofarabine and tenofovir; coadministration may result in additive nephrotoxicity. Additionally, taking these drugs together may alter clofarabine concentrations; clofarabine and tenofovir are both substrates of OAT1 and OAT3.
    Emtricitabine; Tenofovir disoproxil fumarate: (Major) Avoid the concomitant use of clofarabine and tenofovir; coadministration may result in additive nephrotoxicity. Additionally, taking these drugs together may alter clofarabine concentrations; clofarabine and tenofovir are both substrates of OAT1 and OAT3.
    Enoxaparin: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Eptifibatide: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Ertugliflozin; Metformin: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Etodolac: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Famotidine; Ibuprofen: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
    Fenoprofen: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
    Fludrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Flunisolide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Flurbiprofen: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fluticasone; Salmeterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fluticasone; Umeclidinium; Vilanterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fluticasone; Vilanterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fondaparinux: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Formoterol; Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Foscarnet: (Major) Avoid the concomitant use of clofarabine and foscarnet; coadministration may result in additive nephrotoxicity.
    Gallium Ga 68 Dotatate: (Major) Avoid the concomitant use of clofarabine and mannitol; coadministration may result in additive nephrotoxicity. The kidney is the primary route of elimination for both oral and IV mannitol.
    Ganciclovir: (Moderate) Concomitant use of clofarabine and ganciclovir may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Gemfibrozil: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and gemfibrozil, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP inhibitors.
    Gentamicin: (Major) Avoid the concurrent and/or sequential use of gentamicin and other nephrotoxic drugs such as clofarabine; coadministration may result in additive nephrotoxicity.
    Glipizide; Metformin: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Glyburide; Metformin: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Heparin: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Hydrocodone; Ibuprofen: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Hydrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Ibuprofen: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ibuprofen; Oxycodone: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Indomethacin: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Intranasal Influenza Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system
    Ketoprofen: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ketorolac: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Concomitant use of clofarabine and zidovudine, ZDV may result in altered clofarabine levels because both agents are substrates of OAT1 and OAT3. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 and OAT3 substrates.
    Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid the concomitant use of clofarabine and tenofovir; coadministration may result in additive nephrotoxicity. Additionally, taking these drugs together may alter clofarabine concentrations; clofarabine and tenofovir are both substrates of OAT1 and OAT3.
    Lansoprazole; Naproxen: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Lepirudin: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Linagliptin; Metformin: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system
    Lopinavir; Ritonavir: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and ritonavir, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
    Mannitol: (Major) Avoid the concomitant use of clofarabine and mannitol; coadministration may result in additive nephrotoxicity. The kidney is the primary route of elimination for both oral and IV mannitol.
    Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system
    Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system
    Meclofenamate Sodium: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Mefenamic Acid: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Meloxicam: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Memantine: (Moderate) Concomitant use of clofarabine and memantine may result in altered clofarabine levels because both agents are a substrate of OCT2. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT2 substrates.
    Metformin: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Metformin; Repaglinide: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates. (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and repaglinide, a substrate of OAT protein (OATP), may result in altered clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP substrates.
    Metformin; Rosiglitazone: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Metformin; Saxagliptin: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Metformin; Sitagliptin: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Methotrexate: (Major) Avoid the concomitant use of clofarabine and methotrexate due to the risk of additive hepatotoxicity. Coadministration may also increase the risk of additive nephrotoxicity. Additionally, taking these drugs together may alter clofarabine concentrations; clofarabine and methotrexate are both substrates of OAT1 and OAT3.
    Methylprednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Midazolam: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and midazolam, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
    Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Nabumetone: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen; Esomeprazole: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Nebivolol; Valsartan: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and valsartan, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving valsartan.
    Neomycin: (Major) Avoid the concurrent and/or sequential use of neomycin and other nephrotoxic drugs such as clofarabine; coadministration may result in additive nephrotoxicity.
    Nirmatrelvir; Ritonavir: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and ritonavir, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
    Nonsteroidal antiinflammatory drugs: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and ritonavir, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
    Oxaprozin: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
    Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
    Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
    Pentamidine: (Major) Avoid the concomitant use of clofarabine and pentamidine if possible; coadministration may result in additive nephrotoxicity. Monitor patients closely for signs of renal toxicity if concomitant use is required.
    Pentosan: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Pentoxifylline: (Minor) Clofarabine is mechanistically similar to fludarabine. Therefore, documented drug-drug interactions with fludarabine may potentially occur with clofarabine. These interactions are theoretic. While combination regimens containing clofarabine and pentoxifylline have not been studied, additive cytotoxic effects of fludarabine may be seen when the drug is given in combination with pentoxifylline.
    Phenoxybenzamine: (Moderate) Concomitant use of clofarabine, a substrate of OCT1 and OCT2, and phenoxybenzamine, an inhibitor of OCT1 and OCT2, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 and OCT2 inhibitors.
    Pioglitazone; Metformin: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
    Piroxicam: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Pitavastatin: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and pitavastatin, a substrate of OAT protein (OATP), may result in altered clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP substrates.
    Platelet Inhibitors: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Prasugrel: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Pravastatin: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and pravastatin, a substrate of OAT protein (OATP), may result in altered clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP substrates.
    Prednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Prednisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Probenecid: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and probenecid, an inhibitor of OAT1 and OAT3, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 and OAT3 inhibitors.
    Probenecid; Colchicine: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and probenecid, an inhibitor of OAT1 and OAT3, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 and OAT3 inhibitors.
    Quinidine: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and quinidine, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
    Quinine: (Moderate) Concomitant use of clofarabine, a substrate of OCT1 and OCT2, and quinine, an inhibitor of OCT1 and OCT2, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 and OCT2 inhibitors.
    Repaglinide: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and repaglinide, a substrate of OAT protein (OATP), may result in altered clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP substrates.
    Reteplase, r-PA: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Ritonavir: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and ritonavir, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
    Rivaroxaban: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Rofecoxib: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Rosuvastatin: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and rosuvastatin, a substrate of OAT protein (OATP), may result in altered clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP substrates.
    Rosuvastatin; Ezetimibe: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and rosuvastatin, a substrate of OAT protein (OATP), may result in altered clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP substrates.
    Rotavirus Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system
    Rubella Virus Vaccine Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system
    Sacubitril; Valsartan: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and valsartan, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving valsartan.
    SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
    Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system
    Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system
    Streptokinase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Streptomycin: (Major) Avoid the concurrent and/or sequential use of streptomycin and other nephrotoxic drugs such as clofarabine; coadministration may result in additive nephrotoxicity.
    Streptozocin: (Major) Avoid the concomitant use of clofarabine and streptozocin due to the risk of additive hepatotoxicity. Coadministration may also increase the risk of additive nephrotoxicity.
    Sulindac: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Sumatriptan; Naproxen: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
    Telaprevir: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and telaprevir, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP inhibitors.
    Telithromycin: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and telithromycin, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP inhibitors.
    Tenecteplase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Tenofovir, PMPA: (Major) Avoid the concomitant use of clofarabine and tenofovir; coadministration may result in additive nephrotoxicity. Additionally, taking these drugs together may alter clofarabine concentrations; clofarabine and tenofovir are both substrates of OAT1 and OAT3.
    Teriflunomide: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and teriflunomide, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP inhibitors.
    Thrombolytic Agents: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Ticagrelor: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Ticlopidine: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Tinzaparin: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Tirofiban: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Tobramycin: (Major) Avoid the concurrent and/or sequential use of tobramycin (IV injection and inhalation solution) and other nephrotoxic drugs such as clofarabine; coadministration may result in additive nephrotoxicity. If the use of tobramycin inhalation solution and clofarabine is required, monitor tobramycin serum concentrations and renal function.
    Tolmetin: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Trandolapril; Verapamil: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and verapamil, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
    Triamcinolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
    Typhoid Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system
    Urokinase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Valdecoxib: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Valsartan: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and valsartan, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving valsartan.
    Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and valsartan, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving valsartan.
    Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system
    Verapamil: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and verapamil, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
    Voclosporin: (Moderate) Concomitant use of voclosporin and clofarabine may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
    Vorapaxar: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Warfarin: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Yellow Fever Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system
    Zidovudine, ZDV: (Moderate) Concomitant use of clofarabine and zidovudine, ZDV may result in altered clofarabine levels because both agents are substrates of OAT1 and OAT3. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 and OAT3 substrates.

    PREGNANCY AND LACTATION

    Pregnancy

    Clofarabine may cause fetal harm when used during pregnancy, based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid becoming pregnant during clofarabine therapy. Women who become pregnant while receiving clofarabine should be apprised of the potential hazard to the fetus. Although there are no well controlled studies in pregnant women who received clofarabine, teratogenic effects including developmental toxicity (e.g., reduced fetal body weight, increased post-implantation loss) and gross external malformations, soft tissue malformations, and skeletal and retarded ossifications have been observed in rats and rabbits at doses approximately 0.2 to 1 times the maximum recommended human dose of 52 mg/m2 based on body surface area.

    Counsel patients about the reproductive risk and contraception requirements during clofarabine therapy. Females of reproductive potential should receive pregnancy testing prior to starting clofarabine. These patients should use effective contraception during clofarabine treatment and for 6 months after the last dose. Women who become pregnant while receiving clofarabine should be apprised of the potential hazard to the fetus. Due to a risk of male-mediated teratogenicity, men with female partners should also use effective contraception during clofarabine treatment and for at least 3 months after the last dose. The risk of infertility in humans who have received clofarabine therapy is unknown. However, seminiferous tubule and testicular degeneration and atrophy have been reported with clofarabine use in animal studies in mice, rats, and dogs and ovarian atrophy or degeneration and uterine mucosal apoptosis have occurred with high doses of clofarabine in female mice.

    MECHANISM OF ACTION

    Clofarabine is metabolized intracellularly to the inactive 5'-monophosphate metabolite by deoxycytidine kinase and to the active 5'-triphosphate metabolite by mono- and di-phosphokinases. Clofarabine has high affinity for the activating phosphorylating enzyme, deoxycytidine kinase, equal to or greater than that of the natural substrate, deoxycytidine. Clofarabine inhibits DNA synthesis by decreasing cellular deoxynucleotide triphosphate pools through an inhibitor action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through incorporation into the DNA chain by competitive inhibition of DNA polymerases. The affinity of clofarabine triphosphate for these enzymes is similar to or greater than that of deoxyadenosine triphosphate. In preclinical models, clofarabine has demonstrated the ability to inhibit DNA repair by incorporation into the DNA chain during the repair process. Clofarabine 5'-triphosphate also disrupts the integrity of mitochondrial membrane, leading to the release of the pro-apoptotic mitochondrial proteins, cytochrome C and apoptosis-inducing factor, leading to programmed cell death. Clofarabine is cytotoxic to rapidly proliferating and quiescent cancer cell types in vitro.

    PHARMACOKINETICS

    Clofarabine is administered by intravenous (IV) infusion. It is 47% plasma protein bound, primarily to albumin.
     
    Affected cytochrome P450 isoenzymes and drug transporters: OAT1, OAT3, OCT1, OCT2
    Although no in vivo drug interaction studies have been performed, clofarabine undergoes limited hepatic metabolism and CYP450 interactions are not expected. Clofarabine appears to be a substrate of OAT1, OAT3, OCT1 based on an in vitro transporter study and an OCT2 inhibitor based on a preclinical study. Therefore, use caution and monitor for clofarabine toxicity in patients receiving concomitant OAT1, OAT3, OCT1, and OCT2 substrates or inhibitors.