Adult: ≤21 years In patients who have relapsed or are refractory after treatment with ≥2 prior regimens: 52 mg/m2 daily via IV infusion over 2 hours for 5 consecutive days. Repeat cycle every 2-6 weeks after recovery of normal haematopoiesis (ANC ≥0.75 x 109/L) and return to baseline organ function. Calculate BSA using the actual weight and height of the patient before the start of each cycle. Dose reduction, dosing interruption, or discontinuation may be required according to the type or severity of haematologic or non-haematologic toxicities (refer to detailed product guidelines). Child: 1-17 years In patients who have relapsed or are refractory after treatment with ≥2 prior regimens: As monotherapy: 52 mg/m2 daily via IV infusion over 2 hours (consider >2 hours infusion time in patients weighing <20 kg) for 5 consecutive days. Repeat cycle every 2-6 weeks after recovery of normal haematopoiesis (ANC ≥0.75 x 109/L) and return to baseline organ function. Calculate BSA using the actual weight and height of the patient before the start of each cycle. Dose reduction, dosing interruption, or discontinuation may be required if haematological or non-haematological toxicities occur (refer to detailed product guidelines).
Renal Impairment
Severe: Contraindicated.
CrCl (mL/min)
Dosage
30-<60
Reduce dose to 50% of the recommended dose.
Hepatic Impairment
Severe: Contraindicated.
Reconstitution
Filter solution through sterile 0.2 micrometre syringe filter, then dilute with NaCl 0.9% infusion or dextrose 5% in water. Instructions on dilution and recommended final concentration may vary among countries or between individual products (refer to specific product guidelines).
Contraindications
Severe renal and hepatic impairment. Lactation.
Special Precautions
Patient with cardiac disease or taking agents known to affect blood pressure or cardiac function. Patient who has received a haematopoietic stem cell transplant. Avoid concomitant use (particularly during the 5-day clofarabine administration period) with agents associated with renal toxicity and those eliminated by tubular secretion (e.g. NSAIDs, methotrexate, foscarnet, pentamidine, ciclosporin, amphotericin B, tacrolimus, aciclovir, valganciclovir). Mild to moderate renal and hepatic impairment. Pregnancy.
Adverse Reactions
Significant: Bone marrow suppression (e.g. neutropenia, anaemia, thrombocytopenia), renal toxicity (e.g. haematuria, elevated creatinine, acute renal failure), tumour lysis syndrome, infections (including bacterial, viral, and fungal infections), cytokine release syndrome (e.g. tachypnoea, tachycardia, hypotension, pulmonary oedema). Cardiac disorders: Pericardial effusion. Ear and labyrinth disorders: Hypoacusis. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, mouth or gingival bleeding, abdominal pain or upper abdominal pain, stomatitis, haematemesis, proctalgia. General disorders and administration site conditions: Fatigue, mucosal inflammation, pyrexia, pain, chills, oedema, feeling hot or abnormal. Hepatobiliary disorders: Jaundice, hyperbilirubinaemia. Immune system disorders: Hypersensitivity reaction. Injury, poisoning and procedural complications: Contusion. Investigations: Increased ALT and AST; decreased weight. Metabolism and nutrition disorders: Anorexia, dehydration, decreased appetite. Musculoskeletal and connective tissue disorders: Myalgia, bone pain, chest wall pain, arthralgia, neck and back pain, pain in extremity. Nervous system disorders: Headache, dizziness, somnolence, paraesthesia, peripheral neuropathy, tremor. Psychiatric disorders: Anxiety, agitation, mental status change, restlessness, irritability. Respiratory, thoracic and mediastinal disorders: Respiratory distress, dyspnoea, epistaxis, cough. Skin and subcutaneous tissue disorders: Pruritus, palmar-plantar erythrodysaesthesia syndrome, maculopapular rash, petechiae, erythema (including generalised erythema), dry skin, hyperhidrosis, pruritic rash, skin exfoliation, generalised rash, alopecia, hyperpigmentation, erythematous rash. Vascular disorders: Flushing, haematoma. Potentially Fatal: Haemorrhage (including cerebral, gastrointestinal and pulmonary haemorrhage), enterocolitis (e.g. neutropenic colitis, caecitis, Clostridioides difficile colitis), Stevens-Johnson syndrome, toxic epidermal necrolysis, veno-occlusive disease, hepatitis, hepatic failure, sepsis; systemic inflammatory response syndrome with capillary leak syndrome and organ dysfunction.
Ensure adequate hydration during treatment. Women of childbearing potential must use effective birth control methods during treatment and for 6 months after the last dose. Men with female partners of childbearing potential must use effective birth control methods during treatment and for 3 months after the last dose. Discontinue breastfeeding before, during and within 2 weeks after the last dose.
Monitoring Parameters
Evaluate pregnancy status before use in women of childbearing potential. Closely monitor CBC with differential and platelets regularly during treatment; renal and hepatic function before, during, and after treatment; respiratory status, blood pressure, fluid balance, and weight during and immediately after the 5-day administration period. Monitor coagulation parameters and hydration status. Assess for signs and symptoms of infection, enterocolitis, tumour lysis syndrome, cytokine release syndrome (e.g. tachycardia, tachypnoea, hypotension, pulmonary oedema), hepatic sinusoidal obstruction syndrome, dermatologic toxicity, haemorrhage, capillary leak syndrome/systemic inflammatory response syndrome (e.g. rapid onset respiratory distress, pleural or pericardial effusion, multiorgan failure), and renal toxicity.
Overdosage
Symptoms: Nausea, vomiting, diarrhoea, hyperbilirubinaemia, increased transaminase levels, maculopapular rash, severe bone marrow suppression. Management: Supportive treatment. Immediately discontinue treatment and carefully observe the patient.
Drug Interactions
Risk of hepatotoxicity with hepatotoxic drugs and risk of nephrotoxicity with drugs eliminated by tubular secretion (e.g. NSAIDs, amphotericin B, methotrexate, foscarnet, pentamidine, ciclosporin, tacrolimus, aciclovir, valganciclovir).
Action
Description: Mechanism of Action: Clofarabine is a purine nucleoside analogue that is metabolised to clofarabine 5'-triphosphate (active metabolite). Clofarabine 5'-triphosphate reduces cell replication by competing with DNA polymerase for incorporation into the DNA chain and by inhibiting ribonucleotide reductase which reduces deoxynucleotide triphosphate that is required for DNA synthesis. It also causes cell death by disrupting the mitochondrial membrane integrity with the release of cytochrome C and other proapoptotic factors. Pharmacokinetics: Distribution: Volume of distribution: 172 L/m2 (children and adolescents aged 2-19 years). Plasma protein binding: Approx 47%, mainly to albumin. Metabolism: Limited metabolism in the liver (0.2%); metabolised intracellularly by deoxycytidine kinase and mono- and diphosphokinases to clofarabine 5'-triphosphate (active metabolite). Excretion: Via urine (49-60% as unchanged drug). Elimination half-life: 5.2 hours (children and adolescents aged 2-19 years).
Chemical Structure
Clofarabine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 119182, Clofarabine. https://pubchem.ncbi.nlm.nih.gov/compound/Clofarabine. Accessed Feb. 25, 2025.
Storage
Intact vials: Store between 20-25°C. Do not freeze. Diluted solution: Store between 2-8°C or up to 25°C for 3 days. Do not freeze. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
L01BB06 - clofarabine ; Belongs to the class of antimetabolites, purine analogues. Used in the treatment of cancer.
References
Brayfield A, Cadart C (eds). Clofarabine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/02/2025.Clofarabine Injection (Dr. Reddy's Laboratories Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/02/2025.Clofarabine Teva 1 mg/mL Concentrate for Solution for Infusion (Teva UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 06/02/2025.Clofarabine. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 06/02/2025.Joint Formulary Committee. Clofarabine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/02/2025.Nuclofar 1 mg/mL Concentrate for Solution for Infusion (Mega Lifesciences Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 06/02/2025.Paediatric Formulary Committee. Clofarabine. BNF for Children [online]. London. BMJ Group, Pharmaceutical Press, and RCPCH Publications. https://www.medicinescomplete.com. Accessed 06/02/2025.
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