Class: Antineoplastic Agents
Chemical Name: 2-Chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purin-6-amine
Molecular Formula: C10H11ClFN5O3
CAS Number: 123318-82-1
Uses for Clofarabine
Acute Lymphocytic Leukemia
Treatment of acute lymphocytic (lymphoblastic) leukemia (ALL) refractory to or relapsed after at least 2 prior therapies in patients 1–21 years of age.1 2 3 4 5 6 7 Designated an orphan drug by FDA for this use.2 3
Current indication based on induction of complete responses; randomized studies showing increased survival or other clinical benefits have not been conducted to date.1
Clofarabine Dosage and Administration
Consult specialized references for procedures for proper handling and disposal of antineoplastics.1
Monitor respiratory status and BP during infusion, especially in patients receiving drugs that affect BP or cardiac function.1 (See Systemic Inflammatory Response Syndrome (SIRS)/Capillary Leak Syndrome under Cautions.)
Administer IV fluids continuously throughout the 5 days of clofarabine therapy to reduce the effects of tumor lysis and other adverse effects.1 Administer allopurinol if tumor lysis is expected to prevent hyperuricemia.1 (See Tumor Lysis Syndrome under Cautions.)
Administration of corticosteroids (e.g., hydrocortisone 100 mg/m2 on days 1–3) may prevent signs and symptoms of cytokine release or capillary leak syndrome.1 (See Systemic Inflammatory Response Syndrome (SIRS)/Capillary Leak Syndrome under Cautions.)
Administer by IV infusion.1
Administer IV infusion over 2 hours.1
Other drugs should not be infused through the same IV line.1
Dilute the commercially available injection for IV infusion (1 mg/mL) prior to administration.1
Filter the appropriate dose through a sterile 0.2μm filter and further dilute with 5% dextrose injection or 0.9% sodium chloride injection.1
Dosage is based on the patient’s body surface area and is calculated using the actual body weight and height of the patient before starting each cycle.1
Acute Lymphocytic Leukemia
1–21 years of age: 52 mg/m2 by IV infusion over 2 hours daily for 5 consecutive days.1
Repeat treatment cycle following recovery or return to baseline organ function, approximately every 2–6 weeks.1
Discontinue infusion immediately and initiate appropriate supportive measures if early manifestations of cytokine release or capillary leak syndrome occur.1 Consider reinstitution of therapy, generally at a lower dosage, if patient is stable and organ function has returned to baseline levels.1 (See Systemic Inflammatory Response Syndrome (SIRS)/Capillary Leak Syndrome under Cautions.)
Discontinue infusion immediately if substantial increases in serum creatinine or bilirubin concentrations occur.1 Consider reinstitution of therapy, generally at a lower dosage, once the patient is stable and organ function has returned to baseline levels.1
No special population dosage recommendations at this time.1
Cautions for Clofarabine
Administer only under supervision of clinicians qualified in use of cytotoxic therapy.1
Hematologic Effects and Infectious Complications
Anticipate bone marrow suppression (usually reversible and dose dependent) with use.1
Severe bone marrow suppression (neutropenia, anemia, thrombocytopenia) reported.1
Increased risk of developing infectious complications, including severe sepsis and opportunistic infections.1
Tumor Lysis Syndrome
Monitor for signs and symptoms of tumor lysis syndrome.1
Use appropriate measures (e.g., hydration, allopurinol) to prevent hyperuricemia.1
Systemic Inflammatory Response Syndrome (SIRS)/Capillary Leak Syndrome
Signs and symptoms of cytokine release (i.e., tachypnea, tachycardia, hypotension, pulmonary edema) reported.1
Rapid onset of respiratory distress, hypotension, capillary leak (e.g., pleural and pericardial effusions), and multiorgan failure reported.1
Monitor closely and intervene early by discontinuance of the drug and supportive measures (e.g., corticosteroids, diuretics, and/or albumin).1
Development of SIRS or capillary leak syndrome may be fatal.1 (See Dosage under Dosage and Administration.)
Fetal/Neonatal Morbidity and Mortality
May cause fetal harm; teratogenicity demonstrated in animals.1
Adequate Patient Monitoring
Perform CBC, including platelet counts at regular intervals; more frequently in patients who develop cytopenias.1
Monitor hepatic and renal function prior to therapy and throughout the 5 days of clofarabine administration.1
Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)1
Not known whether clofarabine or its metabolites are distributed into milk.1
Discontinue nursing because of potential risk to nursing infants.1
Safety and efficacy established for treatment of relapsed or refractory ALL in patients 1–21 years of age.1
Safety and efficacy not established in adults >21 years of age.1
 Not studied in patients with hepatic impairment; use with caution.1
Not studied in patients with renal impairment; use with caution.1
Common Adverse Effects
Nausea, vomiting, diarrhea, anemia, leukopenia, thrombocytopenia, neutropenia (including febrile neutropenia), infections.1
Interactions for Clofarabine
No formal drug interaction studies to date.1
Interaction with drugs that induce or inhibit CYP 450 isoenzymes not expected.1
Avoid concomitant use with nephrotoxic drugs throughout the 5 days of clofarabine administration because clofarabine is eliminated by kidneys.1
Avoid concomitant use with hepatotoxic drugs because clofarabine may cause hepatotoxicity.1
Plasma Protein Binding
47% (mainly albumin) in pediatric patients.1
Undergoes limited hepatic metabolism (0.2%) in pediatric patients.1
Excreted in urine (49–60%) as unchanged drug in pediatric patients.1
Estimated terminal half-life about 5.2 hours in pediatric patients.1
Pharmacokinetics not studied in patients with renal or hepatic impairment.1
Injection for IV infusion
25°C (may be exposed to 15–30°C).1
Store diluted solutions at room temperature; discard after 24 hours.1
Inhibits DNA synthesis, inhibits ribonucleoside reductase, and has direct effects on mitochondria; these effects lead to depletion of intracellular deoxynucleotide triphosphate pools, inhibition of elongation of DNA strands during synthesis, and release of proapoptotic mitochondrial factors in both actively dividing and quiescent tumor cells.1 2 6
Advice to Patients
Advise patients about risk of dehydration secondary to vomiting and diarrhea.1
Importance of advising patients regarding appropriate measures to avoid dehydration.1
Advise patients to notify clinician immediately if symptoms of hypotension (e.g., dizziness, lightheadedness, fainting spell) or decreased urine output occurs.1
Importance of monitoring blood cell counts, renal and hepatic function.1
Necessity of advising women to use an effective method of contraception and to avoid breast-feeding while receiving clofarabine therapy.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
For injection, for IV infusion
1 mg/mL (20 mg)
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions May 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Genzyme Corporation. Clolar (clofarabine) for intravenous infusion prescribing information. Cambridge, MA; 2005.
2. Anon. Clofarabine. Drugs R &D. 2004; 5:213-7.
3. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97 414). Rockville, MD. From FDA website (). Accessed 2005 Jan 25.
4. Jeha S, Razzouk B, Gaynon P et al. Phase II trials of clofarabine in pediatric acute leukemia. Presented at the American Society of Clinical Oncologists Annual Meeting 2005. From the ASCO website (). Abstract No. 6588. Accessed 2005 Jun 21.
5. Jeha S, Gandhi V, Chan KW et al. Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia. Blood. 2004;103:784-9.
6. Faderl S, Gandhi V, Keating MJ et al. The role of clofarabine in hematologic and solid malignancies–development of a next-generation nucleoside analog. Cancer. 2005; 103:1985-95. [IDIS 533862] [PubMed 15803490]
7. Jeha S, Razzouk BI, Rytting ME et al. Phase II trials of clofarabine in relapsed or refractory pediatric leukemia. Presented at the American Society of Hematology Annual Meeting 2004. From the ASH website (). Abstract No. 684. Accessed 2005 Jun 30.
8. Genzyme Corporation, Cambridge, MA: personal communication.