Clofarabine — Drug Monograph

Brand names: Clolar

Drug class: Antimetabolite

Mechanism of Action

Clofarabine is a second-generation purine nucleoside antimetabolite designed to combine the favorable properties of fludarabine and cladribine. It is phosphorylated intracellularly to clofarabine triphosphate, which inhibits DNA polymerase alpha and ribonucleotide reductase, thereby depleting the intracellular deoxynucleotide pool and terminating DNA chain elongation. Furthermore, it disrupts mitochondrial membrane integrity, triggering the release of cytochrome C and other pro-apoptotic factors. This multi-pronged approach allows it to be effective in rapidly dividing lymphoblasts.

FDA Indications

• Treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens

Common Side Effects

• Nausea
• Vomiting
• Diarrhea
• Febrile neutropenia
• Pruritus
• Pyrexia
• Tachycardia
• Anxiety
• Headache

Clinical Pearl

Clofarabine carries a high risk for SIRS and capillary leak syndrome, which can rapidly progress to multi-organ failure. Early signs like hypotension or tachypnea require immediate cessation of the drug and aggressive supportive care, including corticosteroids. The drug is primarily used in the pediatric setting for refractory ALL, but its use in adult AML is common off-label, often requiring dose adjustments for age and renal function. Prophylactic antiemetics and vigorous hydration are…

Related Therapies & Mechanisms

• Azacitidine (Vidaza) — Antimetabolite · Leukemia
• Cladribine (Leustatin) — Antimetabolite · Leukemia
• Cytarabine (Cytosar-U) — Antimetabolite · Leukemia
• Decitabine (Dacogen) — Antimetabolite · Leukemia