Dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol.
Note: Consider prophylactic corticosteroids (hydrocortisone 100 mg/m2 on days 1 to 3) to prevent signs/symptoms of capillary leak syndrome or systemic inflammatory response syndrome (SIRS). Provide IV hydration, antihyperuricemic therapy, and alkalinize the urine to reduce the risk of tumor lysis syndrome/hyperuricemia. Calculate BSA prior to each cycle utilizing actual body weight. Clofarabine is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (POGO [Dupuis 2011]).
Acute lymphocytic leukemia (ALL), relapsed or refractory:
Monotherapy: Children and Adolescents: IV infusion: 52 mg/m2/day once daily for days 1 to 5 of each cycle; repeat cycle every 2 to 6 weeks following recovery or return to baseline organ function; subsequent cycles should begin no sooner than 14 days from the start of the previous cycle and when ANC ≥750/mm3
Combination therapy: Limited data available: IV Infusion:
Infants: Dosing regimens variable with very limited data available:
Weight-directed dosing: 1.33 mg/kg/day for 5 days in combination with cyclophosphamide and etoposide (O’Connor 2011)
BSA-directed dosing: 40 mg/m2/day for 5 days in combination with cyclophosphamide and etoposide (Inaba 2012); and with topotecan, vinorelbine, thiotepa (TVTC regimen), and dexamethasone in a Phase I trial (Steinherz 2010)
Children and Adolescents: Usual dose: 40 mg/m2/day for 5 days in combination with cyclophosphamide and etoposide has been most frequently studied (Hijiya 2011; Hijiya 2012; Inaba 2012; Locatelli 2009; O’Connor 2011); and with topotecan, vinorelbine, thiotepa (TVTC regimen), and dexamethasone in a Phase I trial (Steinherz 2010). In one trial, the protocol included 5 days of clofarabine therapy during induction and 4 days of therapy for consolidation; this study was also amended to exclude patients with prior hematopoietic stem cell transplantation due to a high incidence of veno-occlusive disease (Hijiya 2011).
Acute myeloid leukemia (AML), relapsed or refractory: Limited data available: Children and Adolescents: IV infusion:
Monotherapy: 52 mg/m2/day once daily for days 1 to 5 of each cycle; repeat cycle every 2 to 6 weeks for up to 12 cycles following recovery or return to baseline organ function; subsequent cycles should begin no sooner than 14 days from the start of the previous cycle and when ANC ≥750/mm3; the trial did not have minimum exclusion age (patient age ≤21 years at time of diagnosis); the youngest patient was 2 years of age (Jeha 2009)
Combination therapy: 40 mg/m2/day once daily for days 1 to 5 of each cycle in combination with cyclophosphamide and etoposide (Inaba 2012)
Langerhans cell histiocytosis, refractory: Limited data available: Children and Adolescents: IV: 25 mg/m2/day days 1 through 5; repeat every 28 days for 2 to 8 cycles (Simko 2014).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Children and Adolescents:
Hematologic toxicity: ANC <500/mm3 lasting ≥4 weeks: Reduce clofarabine dose by 25% for next cycle
Nonhematologic toxicity:
Clinically significant infection: Withhold treatment until infection is under control, then restart clofarabine at full dose
Grade 3 toxicity, excluding infection, nausea, and vomiting, and transient elevations in transaminases and bilirubin: Withhold treatment; may reinitiate clofarabine with a 25% dose reduction with resolution or return to baseline
Grade ≥3 increase in creatinine or bilirubin: Discontinue clofarabine; may reinitiate with 25% dosage reduction when creatinine or bilirubin return to baseline and patient is stable; administer antihyperuricemic therapy for elevated uric acid
Grade 4 toxicity (noninfectious): Discontinue clofarabine treatment
Capillary leak or systemic inflammatory response syndrome (SIRS) early signs/symptoms (eg, hypotension, tachycardia, tachypnea, pulmonary edema): Discontinue clofarabine; institute supportive measures. May consider reinitiating with a 25% dose-reduction after patient is stable and after organ function recovers to baseline.
Dermatologic toxicity: Exfoliative or bullous rash, or suspected Stevens-Johnson syndrome or toxic epidermal necrolysis: Discontinue clofarabine.
Hypotension (during the 5 days of infusion): Discontinue clofarabine. If hypotension is transient and resolves (without pharmacologic intervention), some have suggested that may reinitiate with 25% dosage reduction (Clolar Canadian product monograph).
Children and Adolescents: Clofarabine undergoes renal elimination and exposure is increased as creatinine clearance decreases (Bonate 2011).
Baseline renal impairment:
CrCl >60 mL/minute: No dosage adjustment recommended
CrCl 30 to 60 mL/minute: Reduce dose by 50%
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; use with caution (insufficient evidence)
Renal toxicity during therapy: Grade 3 or higher increase in serum creatinine: Discontinue clofarabine; may reinitiate with a 25% dose reduction after patient is stable and organ function recovers to baseline
Children and Adolescents:
Baseline hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied)
Hepatotoxicity during therapy: Grade 3 or higher increase in bilirubin: Discontinue clofarabine; may reinitiate with a 25% dose reduction after patient is stable and organ function recovers to baseline.
(For additional information see "Clofarabine: Drug information")
Note: Calculate BSA prior to each cycle, utilizing actual body weight.
Premedications: Clofarabine is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]). Consider prophylactic corticosteroids (hydrocortisone 100 mg/m2 on days 1 to 3) to prevent signs/symptoms of capillary leak syndrome or systemic inflammatory response syndrome (SIRS). Provide supportive care, such as IV fluids and antihyperuricemic treatment, and alkalinize urine (to reduce the risk of tumor lysis syndrome/hyperuricemia).
Acute lymphoblastic leukemia, relapsed or refractory: Adults ≤21 years of age: IV: 52 mg/m2/day days 1 through 5; repeat every ~2 to 6 weeks; subsequent cycles should begin no sooner than 14 days from day 1 of the previous cycle (subsequent cycles may be administered when ANC ≥750/mm3).
Off-label dosing: CLOVE regimen: IV: 20 to 30 mg/m2 once daily on days 1 through 5 (in combination with cyclophosphamide and etoposide) as a bridging regimen to hematopoietic stem cell transplant in patients with relapsed or very high risk disease (Gossai 2014).
Acute lymphoblastic leukemia, relapsed/refractory (off-label population):
Induction: IV: 40 mg/m2 once daily for 5 days; may repeat induction cycle once in 3 to 6 weeks if needed (depending on marrow response and recovery) (Kantarjian 2003).
Consolidation: IV: 30 mg/m2 once daily for 5 days (or last tolerated induction dose, whichever is lower); repeat every 4 weeks for up to a maximum of 6 consolidation cycles (Kantarjian 2003).
Acute myeloid leukemia, refractory (off-label use): Adults <70 years of age:
Induction: IV: 25 mg/m2/day for 5 days (in combination with cytarabine and filgrastim) may repeat one time after 21 days if needed (Becker 2011).
Consolidation: IV: 20 mg/m2/day for 5 days (in combination with cytarabine and filgrastim) for 1 or 2 cycles (Becker 2011).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Clofarabine undergoes renal elimination and exposure is increased as creatinine clearance decreases (Bonate 2011). Minimize the concomitant use of nephrotoxic medications during clofarabine treatment.
Renal impairment at baseline:
CrCl >60 mL/minute: No dosage adjustment necessary.
CrCl 30 to 60 mL/minute: Reduce dose to 50% of the usual dose.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling. Use is not recommended (Krens 2019).
Dialysis: There are no dosage adjustments provided in the manufacturer's labeling. Use is not recommended (Krens 2019).
Renal toxicity during treatment: Serum creatinine increase ≥ grade 3: Discontinue clofarabine; may reinitiate with a 25% dose reduction after patient is stable and organ function recovers to baseline.
Hepatic impairment at baseline: There are no dosage adjustments provided in the manufacturer's labeling. Avoid the concomitant use of medications that may cause hepatotoxicity.
Mild or moderate impairment: No need for dosage adjustment is expected (Krens 2019).
Severe impairment: Use is not recommended (Krens 2019).
Hepatotoxicity during treatment:
Hepatic enzymes and/or bilirubin increase ≥ grade 3: Discontinue clofarabine; may reinitiate with a 25% dose reduction after patient is stable and organ function recovers to baseline.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 1 mg/mL (20 mL)
Solution, Intravenous [preservative free]:
Clolar: 1 mg/mL (20 mL)
Generic: 1 mg/mL (20 mL)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Clolar: 1 mg/mL (20 mL)
Parenteral: IV infusion: Administer by IV infusion over 2 hours per the manufacturer's labeling and in most trials; a few trials have infused over 1 hour (Federl 2005; Jeha 2004; Kantarian 2003). An inline filter is not needed for administration. Do not administer with any other medications through the same intravenous line.
Clofarabine is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (POGO [Dupuis 2011]).
Clofarabine is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).
IV infusion: Infuse over 2 hours for relapsed/refractory ALL. May be infused over 1 hour for some off-label protocols (Becker 2011; Kantarjian 2003). Continuous IV fluids are encouraged to decrease adverse events and tumor lysis effects. Hypotension may be a sign of capillary leak syndrome or systemic inflammatory response syndrome. Do not administer any other medications through the same intravenous line.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Store intact vials at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Solutions diluted for infusion in D5W or NS may be stored for up to 24 hours at room temperature (use within 24 hours of preparation).
Treatment of relapsed or refractory acute lymphoblastic leukemia (ALL) after at least two prior treatment regimens (FDA approved in ages 1 to 21 years); has also been used for the treatment of acute myelogenous leukemia (AML) and refractory Langerhans cell histiocytosis
Clofarabine may be confused with cladribine, clevidipine, cytarabine, nelarabine
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences include off-label use in the treatment of AML.
>10%:
Cardiovascular: Tachycardia (35%), hypotension (29%), flushing (19%), hypertension (13%), edema (12%)
Central nervous system: Headache (43%), chills (34%), fatigue (34%), anxiety (21%), pain (15%)
Dermatologic: Pruritus (43%), skin rash (38%), palmar-plantar erythrodysesthesia (16%), erythema (11%)
Gastrointestinal: Vomiting (78%), nausea (73%), diarrhea (56%), abdominal pain (35%), anorexia (30%), gingival bleeding (17%), mucosal inflammation (16%), oral candidiasis (11%)
Genitourinary: Hematuria (13%)
Hematologic & oncologic: Leukopenia (88%; grades 3/4: 88%), anemia (83%; grades 3/4: 75%), lymphocytopenia (82%; grades 3/4: 82%), thrombocytopenia (81%; grades 3/4: 80%), neutropenia (10% to 64%; grades 3/4: 64%; grade 4: 7%), febrile neutropenia (55%; grade 3: 51%; grade 4: 3%), petechia (26%; grade 3: 6%)
Hepatic: Increased serum ALT (81%), increased serum AST (74%), increased bilirubin (45%)
Infection: Infection (83%; includes bacterial, fungal, and viral), sepsis (including septic shock; 17%)
Local: Catheter infection (12%)
Neuromuscular & skeletal: Limb pain (30%), myalgia (14%)
Renal: Increased serum creatinine (50%)
Respiratory: Epistaxis (27%), dyspnea (13%), pleural effusion (12%)
Miscellaneous: Fever (39%)
1% to 10%:
Cardiovascular: Pericardial effusion (8%), capillary leak syndrome (4%)
Central nervous system: Drowsiness (10%), irritability (10%), lethargy (10%), agitation (5%), mental status changes (1% to 4%)
Dermatologic: Cellulitis (8%), pruritic rash (8%)
Gastrointestinal: Rectal pain (8%), upper abdominal pain (8%), pseudomembranous colitis (7%), stomatitis (7%), pancreatitis (1% to 4%), typhlitis (1% to 4%)
Hematologic & oncologic: Tumor lysis syndrome (6%; grade 3: 6%), oral mucosal petechiae (5%; grade 3: 4%)
Hepatic: Jaundice (8%), hyperbilirubinemia (1% to 4%), hepatic sinusoidal obstruction syndrome (formerly known as hepatic veno-occlusive disease: 2%)
Hypersensitivity: Hypersensitivity (1% to 4%)
Infection: Herpes simplex infection (10%), bacteremia (9%), candidiasis (7%), herpes zoster (7%), staphylococcal bacteremia (6%), staphylococcal sepsis (5%), influenza (1% to 4%), sepsis syndrome (2%)
Neuromuscular & skeletal: Back pain (10%), ostealgia (10%), weakness (10%), arthralgia (9%)
Renal: Acute renal failure
Respiratory: Pneumonia (10%), respiratory distress (10%), tachypnea (9%), upper respiratory tract infection (5%), pulmonary edema (1% to 4%), sinusitis (1% to 4%)
<1%, postmarketing, and/or case reports: Enterocolitis (occurs more frequently within 30 days of treatment and with combination chemotherapy), exfoliative dermatitis, gastrointestinal hemorrhage, hallucination (Jeha 2006), hepatic failure, hepatitis, hepatomegaly (Jeha 2006), hypokalemia (Jeha 2006), hyponatremia, hypophosphatemia, increased right ventricular pressure (Jeha 2006), left ventricular systolic dysfunction (Jeha 2006), major hemorrhage (including cerebral and pulmonary; majority of cases associated with thrombocytopenia), Stevens-Johnson syndrome, toxic epidermal necrolysis
There are no contraindications listed in the manufacturer’s US labeling.
Canadian labeling: Hypersensitivity to clofarabine or any component of the formulation; symptomatic CNS involvement; history of serious heart, liver, kidney, or pancreas disease; severe hepatic impairment (AST and/or ALT >5 x ULN, and/or bilirubin >3 x ULN); severe renal impairment (CrCl <30 mL/minute)
Concerns related to adverse effects:
• Bone marrow suppression: Dose-dependent, reversible myelosuppression (neutropenia, thrombocytopenia, and anemia) is common; may be severe and prolonged. Patients may be at increased risk for infection due to neutropenia.
• Capillary leak syndrome/systemic inflammatory response syndrome: Clofarabine may cause a cytokine release syndrome (eg, tachypnea, tachycardia, hypotension, pulmonary edema), which may progress to systemic inflammatory response syndrome with capillary leak syndrome and organ dysfunction; may be fatal.
• Dermatologic reactions: Serious and fatal cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.
• GI toxicity: Serious and fatal enterocolitis (including neutropenic colitis, cecitis, and C. difficile colitis) has been reported, usually occurring within 30 days of treatment, and when used in combination with other chemotherapy. Enterocolitis may lead to necrosis, perforation, hemorrhage, or sepsis complications.
• Hemorrhage: Serious and fatal hemorrhages (including cerebral, GI, and pulmonary hemorrhage) have occurred, usually associated with thrombocytopenia.
• Hepatotoxicity: Transaminases and bilirubin may be increased during treatment (including grade 3 and 4 events); severe and fatal hepatitis and hepatic failure have been reported. Transaminase elevations generally occur within 10 days of administration and resolve to ≤ grade 2 within 15 days. The risk for hepatotoxicity, including hepatic sinusoidal obstruction syndrome (SOS; formerly called veno-occlusive disease), is increased in patients who have previously undergone a hematopoietic stem cell transplant.
• Infection: Clofarabine increases the risk for infections, including opportunistic infection or severe or fatal sepsis. Fungal, bacterial, and viral infections have occurred.
• Renal toxicity: Elevated creatinine, acute renal failure, and hematuria were observed in clinical studies. Infection, sepsis, or tumor lysis syndrome may cause an increased risk of renal toxicity in patients receiving clofarabine.
• Tumor lysis syndrome/hyperuricemia: Tumor lysis syndrome may occur as a consequence of leukemia treatment, including treatment with clofarabine, usually occurring in the first treatment cycle. Tumor lysis syndrome may lead to life-threatening acute renal failure; adequate hydration and prophylactic antihyperuricemic therapy will reduce the risk/effects of tumor lysis syndrome.
Substrate of OAT1/3, OCT1, OCT2
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: In the US, after receipt of the single dose COVID-19 adenovirus vector vaccine (Janssen), administer an additional 2nd dose using an mRNA COVID-19 vaccine, at least 28 days after the primary vaccine dose, in patients taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification
Erdafitinib: May increase the serum concentration of OCT2 Substrates. Risk C: Monitor therapy
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Gilteritinib: May increase the serum concentration of OCT1 Substrates. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitisinone: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Pretomanid: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Tafenoquine: May increase the serum concentration of OCT2 Substrates. Management: Avoid use of OCT2 substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the OCT2 substrate and consider a reduced dose of the OCT2 substrate according to that substrate's labeling. Risk D: Consider therapy modification
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Teriflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Evaluate pregnancy status prior to use in patients who may become pregnant. Patients who may become pregnant should use effective contraception during therapy and for at least 6 months after the last clofarabine dose. Patients with partners who may become pregnant should use effective contraception during therapy and for at least 3 months after the last dose of clofarabine.
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (1-877-635-4499).
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to clofarabine may cause fetal harm.
CBC with differential and platelets (daily during treatment, then 1-2 times weekly or as necessary); liver and kidney function (during 5 days of clofarabine administration); blood pressure, cardiac function, and respiratory status during infusion; signs and symptoms of tumor lysis syndrome, infection, and cytokine release syndrome (tachypnea, tachycardia, hypotension, pulmonary edema); hydration status
Clofarabine, a purine (deoxyadenosine) nucleoside analog, is metabolized to clofarabine 5'-triphosphate. Clofarabine 5'-triphosphate decreases cell replication and repair as well as causing cell death. To decrease cell replication and repair, clofarabine 5'-triphosphate competes with deoxyadenosine triphosphate for the enzymes ribonucleotide reductase and DNA polymerase. Cell replication is decreased when clofarabine 5'-triphosphate inhibits ribonucleotide reductase from reacting with deoxyadenosine triphosphate to produce deoxynucleotide triphosphate which is needed for DNA synthesis. Cell replication is also decreased when clofarabine 5'-triphosphate competes with DNA polymerase for incorporation into the DNA chain; when done during the repair process, cell repair is affected. To cause cell death, clofarabine 5'-triphosphate alters the mitochondrial membrane by releasing proteins, an inducing factor and cytochrome C.
Distribution: Vd: Decreased with increasing age, based on pharmacokinetic simulations: 5.8 L/kg (3 years old); 3.1 L/kg (30 years old); 2.7 L/kg (82 years old) (Bonate 2011); Children and Adolescents 2 to 19 years: 172 L/m2
Protein binding: 47%, primarily to albumin
Metabolism: Intracellulary by deoxycytidine kinase and mono- and diphosphokinases to active metabolite clofarabine 5′-triphosphate; limited hepatic metabolism (0.2%)
Half-life elimination: Children and Adolescents 2 to 19 years: 5.2 hours; Children and Adults: 7 hours; may be prolonged in in the elderly and in patients with renal impairment (Bonate, 2011)
Excretion: Urine (49% to 60%, as unchanged drug)
Renal function impairment: Clofarabine undergoes renal elimination and exposure is increased as creatinine clearance decreases (Bonate 2011). In patients with CrCl 60 to <90 mL/minute, the AUC was increased by 60% and in patients with CrCl 30 to <60 mL/minute, the AUC was increased by 140%.
Solution (Clofarabine Intravenous)
1 mg/mL (per mL): $48.00 - $176.08
Solution (Clolar Intravenous)
1 mg/mL (per mL): $204.25
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.