Clofarabine

What it is and how it works

Mechanism of Action Clofarabine is sequentially metabolized intracellularly to the 5’-monophosphate metabolite by deoxycytidine kinase and mono- and di-phospho-kinases to the active 5’-triphosphate metabolite. Clofarabine has affinity for the activating phosphorylating enzyme, deoxycytidine kinase, equal to or greater than that of the natural substrate, deoxycytidine. Clofarabine inhibits DNA synthesis by decreasing cellular deoxynucleotide triphosphate pools through 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.

Mechanism class: Nucleic Acid Synthesis Inhibitors

Indications

Clofarabine injection is indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens. Clofarabine injection is a nucleoside metabolic inhibitor indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens.

Dosage and administration (summary)

Administer the recommended pediatric dose of 52 mg/m 2 as an intravenous infusion over 2 hours daily for 5 consecutive days of a 28-day cycle. Repeat cycles every 2 to 6 weeks. Provide supportive care, such as intravenous infusion fluids, antihyperuricemic treatment and alkalinization of urine throughout the 5 days of clofarabine injection administration to reduce the risk of tumor lysis and other adverse reactions. Discontinue clofarabine injection if hypotension develops during the 5 days of administration. Reduce the dose in patients with renal impairment. Use dose modification for toxicity.

Contraindications

None. • None.

Warnings and precautions

Myelosuppression: May be severe and prolonged. Monitor complete blood counts and platelet counts during clofarabine injection therapy. Hemorrhage: Serious and fatal cerebral, gastrointestinal and pulmonary hemorrhage. Monitor platelets and coagulation parameters and treat accordingly. Infections: Severe and fatal sepsis as a result of bone marrow suppression. Monitor for signs and symptoms of infection; discontinue clofarabine injection and treat promptly. Tumor Lysis syndrome: Anticipate, monitor for signs and symptoms and treat promptly.

Pregnancy

Pregnancy Risk Summary In animal reproduction studies, intravenous administration of clofarabine to pregnant rats and rabbits during organogenesis at doses approximately 0.2 to 1-times the maximum recommended human dose of 52 mg/m 2 based on body surface area (BSA) resulted in embryo-fetal mortality, alterations to growth, and structural abnormalit…

Storage and supply

Clofarabine injection is supplied in single-dose flint vials containing 20 mg of clofarabine in 20 mL of solution. Each box contains one clofarabine injection vial (NDC 43598-309-20). The 20 mL flint vials contain 20 mL (20 mg) of solution. The pH range of the solution is 4.5 to 7.5.

Source: Clofarabine (Clofarabine) — US FDA prescribing information, 2024-02-27, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.