Class: Purine analog
- Injection, solution 1 mg/mL
Inhibits DNA synthesis by decreasing cellular deoxynucleotide triphosphate pools by an inhibitory 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.
Plasma protein binding, predominantly to albumin, is 47%. Steady state Vd is 172 L/m 2 .
Systemic Cl is 28.8 L/h/m 2 and the terminal half-life is approximately 5.2 h. Based on 24-h urine collection in children, 49% to 60% of the dose is excreted unchanged in the urine.
Indications and Usage
Treatment of patients 1 to 21 y of age with relapsed or refractory acute lymphoblastic leukemia after at least 2 prior regimens.
None well documented.
Dosage and AdministrationAcute Lymphoblastic Leukemia
Patients 1 to 21 y of age
IV 52 mg/m 2 infused over 2 h/day for 5 days. Treatment cycles are repeated following recovery or return to baseline organ function, approximately every 2 to 6 wk.Dosage Adjustment Hematologic Toxicity
Administer subsequent cycles no sooner than 14 days from the starting day of the previous cycle, provided the patient's absolute neutrophil count (ANC) is 0.75 × 10 9 /L or more. If a patient experiences a grade 4 neutropenia (ANC of less than 0.5 × 10 9 /L) lasting 4 wk or more, reduce dose by 25% for the next cycle.Nonhematologic Toxicity
Withhold clofarabine if patient develops a clinically significant infection until the infection is clinically controlled, and then restart at the full dose. Withhold clofarabine if a grade 3 noninfectious nonhematologic toxicity (excluding transient elevations in serum transaminases and/or serum bilirubin and/or nausea/vomiting that were controlled by antiemetic therapy) occurs. Reinstitute clofarabine administration at a 25% dose reduction when resolution or return to baseline occurs.Discontinuation of Therapy
Discontinue administration if hypotension develops during the 5 days of administration, if a grade 4 noninfectious nonhematological toxicity occurs and the patient shows early signs or symptoms of systemic inflammatory response syndrome (SIRS) or capillary leak, or if grade 3 or higher increases in creatinine or bilirubin are noted. Reinstitute clofarabine when the patient is stable and organ function has returned to baseline, generally with a 25% dose reduction.
- For IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, intra-arterial, or oral administration.
- Diligently follow institutional and National Institutes of Health procedures for handling, administration, and disposal of anticancer drugs. Wear appropriate protective equipment when preparing and administering clofarabine.
- Continuously administer IV fluids as ordered throughout the 5 days of clofarabine administration to reduce the effects of tumor lysis and other adverse reactions.
- Administer prophylactic corticosteroids (eg, hydrocortisone 100 mg/m 2 on days 1 to 3) as ordered to help prevent signs or symptoms of SIRS or capillary leak.
- Consider prophylactic antiemetic medications because clofarabine is moderately emetogenic.
- If hyperuricemia is anticipated (tumor lysis), prophylactically administer allopurinol.
- Ensure clofarabine dose is accurately determined before each cycle using BSA, calculated using the actual height and weight of the patient just prior to each cycle.
- Prior to administration, further dilute solution for injection by filtering prescribed dose through 0.2 micron syringe filter and adding to prescribed volume of dextrose 5% or sodium chloride 0.9% injection, for a final concentration between 0.15 and 0.4 mg/mL.
- Do not administer any other medications through same IV line.
Store unopened vials of solution for injection at 59° to 86°F. Diluted infusion solution contains no preservative and must be administered within 24 h of preparation if stored at room temperature.
Drug InteractionsHepatic or renal toxic drugs
Because clofarabine has not been studied in patients with hepatic or renal dysfunction, use great caution when using in these patients. Consider avoiding drugs with known renal toxicity during the 5 days of clofarabine administration and consider avoiding using concomitantly with medications known to induce hepatic toxicity.
Tachycardia (35%); hypotension (29%); flushing (19%); hypertension (13%); pericardial effusion (8%).
Headache (43%); chills, fatigue (34%); anxiety (21%); asthenia, irritability, lethargy, somnolence, tremor (10%); agitation (5%); mental status change (1% to 4%)
Pruritus (43%); rash (38%); petechiae (26%); palmar-plantar erythrodysesthesia syndrome (16%); erythema (11%); cellulitis, rash pruritic (8%); Stevens-Johnson syndrome, TEN (postmarketing).
Vomiting (78%); nausea (73%); diarrhea (56%); abdominal pain (35%); anorexia (30%); gingival bleeding (14%); oral candidiasis (11%); upper abdominal pain (8%); Clostridium difficile colitis, stomatitis (7%); mouth hemorrhage, oral mucosal petechiae (5%); cecitis, gastroenteritis adenovirus, pancreatitis (1% to 4%).
Hematuria (13%); proctalgia (8%); acute renal failure (3%).
Leukopenia (88%); anemia (83%); lymphopenia (82%); thrombocytopenia (81%); neutropenia (64%); febrile neutropenia (55%); bone marrow failure (postmarketing).
Jaundice (8%); hyperbilirubinemia (1% to 4%).
Elevated ALT (81%); elevated AST (74%); elevated creatinine (50%); elevated total bilirubin (45%).
Catheter-related infection (12%).
Pain in extremity (30%); myalgia (14%); back pain, bone pain (10%); arthralgia (9%).
Dyspnea (13%); pleural effusion (12%); pneumonia, respiratory distress (10%); tachypnea (9%); upper respiratory tract infection (5%); pneumonia fungal, pneumonia primary atypical, pulmonary edema, respiratory syncytial virus infection, sinusitis (1% to 4%).
Pyrexia (39%); mucosal inflammation (16%); pain (15%); edema (12%); herpes simplex, sepsis (10%); bacteremia (9%); candidiasis, herpes zoster, septic shock (7%); staphylococcal bacteremia, tumor lysis syndrome (6%); staphylococcal sepsis (5%); capillary leak syndrome (4%); SIRS (2%); bacterial infection, enterococcal bacteremia, Escherichia bacteremia, Escherichia sepsis, fungal infection, fungal sepsis, hypersensitivity, infection, influenza, parainfluenzae virus infection, staphylococcal infection (1% to 4%).
Monitor BP frequently during the 5 days of clofarabine administration. Stop therapy if patient develops hypotension for any reason. If hypotension is transient and resolves without pharmacologic intervention, consider reinstituting therapy at a lower dose.CBC
Ensure CBC with differential and platelet count are evaluated before starting therapy and then at regular intervals during clofarabine administration. Monitor blood and platelet counts more frequently if cytopenia develops.Hyperuricemia
Ensure risk of developing hyperuricemia is evaluated before starting therapy and that supportive care, including adequate fluid intake, administration of allopurinol, and monitoring of uric acid, is provided throughout the 5 days of clofarabine administration in patients determined to be at risk for developing hyperuricemia and urate precipitation.Renal/Hepatic function
Ensure renal and hepatic function are monitored closely during the 5 days of clofarabine administration. Discontinue therapy if substantial increases in creatinine or bilirubin are noted. Consider reinstituting clofarabine at a lower dose when patient is stable and organ function has returned to normal.Tumor lysis syndrome/cytokine release
Monitor patient closely for signs or symptoms of tumor lysis syndrome and cytokine release (eg, hypotension, pulmonary edema, tachycardia, tachypnea) that could develop into SIRS, capillary leak, and organ dysfunction. Immediately discontinue infusion if SIRS or capillary leak syndrome is noted or suspected. Be prepared to provide supportive measures (eg, albumin, corticosteroids, diuretics). Consider reinstituting clofarabine at a lower dose when patient is stable.WBC
Implement infection control measures if WBC drops; implement bleeding precautions if platelet count drops.
Category D .
Hepatic/Renal function impairment
Use with caution.
Safety and efficacy not established.
Bone marrow suppression
Should be anticipated; anemia, neutropenia, and thrombocytopenia have been reported.
Ensure that women who are breast-feeding discontinue breast-feeding during treatment with clofarabine.
Because clofarabine primarily is excreted by the kidneys, avoid renal toxic drugs during the 5 days of clofarabine administration.
The risk of infection, including severe sepsis, is likely to increase as a result of bone marrow suppression.
Hyperbilirubinemia, maculopapular rash, vomiting.
- Explain name, action, and potential side effects of the treatment regimen. Review the treatment regimen, including dosing schedule, duration of treatment, and monitoring that will be required.
- Advise patient, family, or caregiver that medication will be prepared and administered by health care providers in a health care setting.
- Advise patient, family, or caregiver that medication may be used in combination with other agents to achieve maximum benefit possible.
- Advise patient, family, or caregiver to immediately report any of the following to health care provider: bleeding or unusual bruising; dark urine; decreased urination; dizziness; fainting spells; fever, chills, or other signs of infection; hives; light-headedness; pain, redness, or swelling at injection site; rapid heartbeat; rapid or difficult breathing; rash; sores in mouth; yellowing of the skin or eyes.
- Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, diarrhea, or appetite loss; persistent or worsening general body weakness.
- Caution women of childbearing potential to avoid becoming pregnant during therapy and to use effective contraception.
- Advise patients of signs and symptoms of SIRS, such as dyspnea, fever, symptoms of hypotension, tachycardia, and tachypnea.
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