Overview
11 DESCRIPTION Clofarabine injection contains clofarabine, a purine nucleoside metabolic inhibitor. The chemical name of clofarabine is 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purin-6-amine. Its molecular formula is C 10 H 11 ClFN 5 O 3 with a molecular weight of 303.68 Daltons.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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.
Indications
- 1 INDICATIONS AND USAGE 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. (1)
Common Doses
- 52 mg
- 30 mL
- 60 mL
- 0.15 mg
Dosage
2 DOSAGE AND ADMINISTRATION 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. (2.1) 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. (2.1) Discontinue clofarabine injection if hypotension develops during the 5 days of administration. ( 2.
Contraindications
- 4 CONTRAINDICATIONS None. None. (4)
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the label: Myelosuppression [see Warnings and Precautions (5.1) ] Hemorrhage [see Warnings and Precautions (5.2) ] Serious Infections [see Warnings and Precautions (5.3) ] Hyperuricemia (tumor lysis syndrome) [see Warnings and Precautions (5.4) ] Systemic Inflammatory Response Syndrome (SIRS) and Capillary Leak Syndrome [see Warnings and Precautions (5.5) ] Venous Occlusive Disease of the Liver [see Warnings and Precautions (5.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.