Clofarabine (Specialist drug)

SCOPE — READ FIRST: this label states ONE recommended dosage and describes it as a paediatric dose. §2.1 verbatim: 'Administer the recommended pediatric dose of 52 mg/m 2 as an intravenous infusion over 2 hours daily for 5 consecutive days. Repeat treatment cycles following recovery or return to baseline organ function, approximately every 2 to 6 weeks.' §8.4 pins the population: 'Safety and effectiveness have been established in pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia' — which matches this page's stated use. §8.5: 'Safety and effectiveness of clofarabine has not been established in geriatric patients aged 65 and older.' No separate adult regimen is given anywhere in the fetched label. BSA: 'Base dosage on the patient's body surface area (BSA), calculated using the actual height and weight before the start of each cycle.' SUPPORTIVE CARE (§2.1): 'Provide supportive care, such as intravenous fluids, antihyperuricemic treatment, and alkalinize urine throughout the 5 days of clofarabine injection administration to reduce the effects of tumor lysis and other adverse reactions.' 'Discontinue clofarabine injection if hypotension develops during the 5 days of administration.' Monitor renal and hepatic function during the 5 days; monitor patients taking medications known to affect blood pressure; monitor cardiac function during administration. §2.3: consider prophylactic antiemetics (moderately emetogenic) and prophylactic steroids to mitigate SIRS or capillary leak syndrome; minimise exposure to drugs with known renal toxicity during the 5 days; avoid concomitant use of medications known to induce hepatic toxicity. DOSE MODIFICATION (§2.4): Grade 4 neutropenia (ANC below 0.5 x 10^9/L) lasting 4 weeks or more — reduce dose by 25% for the next cycle. Withhold for a clinically significant infection until controlled, then restart at the full dose. Withhold for Grade 3 non-infectious non-haematological toxicity (excluding transient rises in transaminases and/or bilirubin and/or nausea/vomiting controlled by antiemetics) and re-institute at a 25% dose reduction on resolution or return to baseline. Discontinue for Grade 4 non-infectious non-haematological toxicity, for early signs or symptoms of SIRS or capillary leak syndrome, and for Grade 3 or higher rises in creatinine or bilirubin (re-institute with a 25% dose reduction once stable and organ function has returned to baseline). PREPARATION (§2.5): filter through a sterile 0.2 micron syringe filter, then dilute with 5% Dextrose Injection USP or 0.9% Sodium Chloride Injection USP to a final concentration between 0.15 mg/mL and 0.4 mg/mL; use within 24 hours of preparation; store diluted solution at 15 to 30 degrees C. Specialist use only — give within the treating protocol.

BSA DOSING, NOT WEIGHT-BASED — no dose per kg is calculable from this label. §2.1 verbatim: 'Administer the recommended pediatric dose of 52 mg/m 2 as an intravenous infusion over 2 hours daily for 5 consecutive days.' Dosage is based on body surface area calculated from the actual height and weight before the start of each cycle. §8.4: 'Safety and effectiveness have been established in pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia.' Give subsequent cycles no sooner than 14 days from the starting day of the previous cycle and provided the ANC is at or above 0.75 x 10^9/L. Product strength (§3): 'Injection: 20 mg/20 mL (1 mg/mL) clear solution in single-dose vial' — the infusion must be diluted to a final concentration between 0.15 mg/mL and 0.4 mg/mL, so no single mg-per-mL figure applies at the bedside and none is recorded here. Full supportive care, monitoring and dose-modification rules are in the adult notes and apply to this same regimen. Specialist prescribing only: verify against the treating protocol and a children's formulary before use.