Child: Relapsed or refractory cases (after receiving at least 2 prior regimens): 1-21 yr 52 mg/m2 daily via infusion over 2 hr (>2 hr infusion time in patients weighing <20 kg) for 5 consecutive days. Treatment cycle is repeated every 2-6 wk, following recovery of normal haematopoiesis (i.e. ANC ≥750 cells/mm3) and return to baseline organ function. If significant toxicities occur, the dose may be reduced by 25% of the previous dose. Discontinue if hypotension and signs/symptoms of capillary leak syndrome occur, or if there is substantial increase in serum creatinine and bilirubin levels.
Renal Impairment
Severe: Contraindicated.
CrCl (mL/min)
Dosage
30-60
Reduce to 50% of the usual
dose.
Hepatic Impairment
Severe: Contraindicated.
Reconstitution
IV infusion: Dilute w/ NaCl 0.9% or dextrose 5% to a final concentration between 0.15 to 0.4 mg/mL.
Contraindications
Severe hepatic and renal impairment. Lactation.
Special Precautions
Mild to moderate hepatic and renal impairment. Childn. Pregnancy.
This drug may cause dizziness, fainting, or lightheadedness, if affected, do not drive or operate machinery.
Monitoring Parameters
Obtain CBC and platelet counts daily during treatment, then 1-2 times wkly or as necessary. Monitor hepatic and renal function during the 5 days of admin; cardiac function, BP, coagulation parameters, and resp function during infusion. Assess signs and symptoms of tumour lysis syndrome, infection, hepatic sinusoidal obstruction syndrome, enterocolitis, and cytokine release syndrome.
Overdosage
Symptoms: Diarrhoea, nausea, vomiting, severe bone marrow depression, hyperbilirubinaemia, elevated transaminase levels, maculopapular rash. Management: Supportive treatment.
Drug Interactions
Risk of hepatotoxicity and nephrotoxicity w/ hepato- or nephrotoxic drugs.
Action
Description: Mechanism of Action: Clofarabine is a purine nucleoside antimetabolite that is converted to the active clofarabine 5′-triphosphate which decreases cell replication by competing w/ deoxyadenosine triphosphate for the enzymes ribonucleotide reductase and DNA polymerase. It also disrupts the mitochondrial membrane by releasing cytochrome C and other proapoptotic factors, thereby causing cell death. Pharmacokinetics: Distribution: Volume of distribution: 172 L/m2. Plasma protein binding: Approx 47%, mainly to albumin. Metabolism: Metabolised intracellularly by deoxycytidine kinase and mono- and diphosphokinases to clofarabine 5’-triphosphate; w/ limited hepatic metabolism (0.2%). Excretion: Via urine (49-60%, as unchanged drug). Terminal elimination half-life: Approx 5 hr.
Chemical Structure
Clofarabine Source: National Center for Biotechnology Information. PubChem Database. Clofarabine, CID=119182, https://pubchem.ncbi.nlm.nih.gov/compound/Clofarabine (accessed on Jan. 21, 2020)
Storage
Store at 25°C.
This is a cytotoxic drug. Wear gloves during receiving, unpacking, and placing in storage. Any unused portions should be disposed of in accordance w/ local requirements. Pregnant staff should not handle this product.
L01BB06 - clofarabine ; Belongs to the class of antimetabolites, purine analogues. Used in the treatment of cancer.
References
Anon. Clofarabine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/09/2017.Buckingham R (ed). Clofarabine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/09/2017 .Clofarabine Injection (Sanofi-Aventis U.S. LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/09/2017.Joint Formulary Committee. Clofarabine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/09/2017.McEvoy GK, Snow EK, Miller J et al (eds). Clofarabine. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 05/09/2017.
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