CLOFARABINE
Clinical safety rating
cautionComprehensive clinical and safety monograph for CLOFARABINE (CLOFARABINE).
Comprehensive clinical and safety monograph for CLOFARABINE (CLOFARABINE).
Treatment of relapsed or refractory acute lymphoblastic leukemia (ALL) in pediatric patients aged 1 to 21 yearsOff-label: Treatment of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS)
Clofarabine is a purine nucleoside antimetabolite that inhibits DNA synthesis by reducing intracellular deoxynucleotide triphosphate pools via inhibition of ribonucleotide reductase, and by terminating DNA chain elongation through incorporation into DNA, leading to apoptosis.
| Metabolism | Hepatic; primarily metabolized by deamination via cytidine deaminase to 6-ketoclofarabine, a major metabolite. Also undergoes phosphorylation intracellularly. CYP450 involvement is minimal. |
| Excretion | Renal: 49-60% as unchanged drug; biliary/fecal: minimal (<1%) |
| Half-life | Terminal elimination half-life: 5.2 hours (range 4-6 hours) in adult patients; clinically, this supports a 5-day continuous infusion schedule |
| Protein binding | 47% bound to plasma proteins (primarily albumin) |
| Volume of Distribution | Vd: 14.6 L/kg (range 10-20 L/kg); indicates extensive extravascular distribution and tissue binding |
| Bioavailability | IV: 100% (only IV route); oral: not approved |
| Onset of Action | IV: 1-2 hours after start of infusion; oral: not applicable (only IV formulation available) |
| Duration of Action | Duration of action: 24-48 hours after infusion; clinical effects (e.g., lymphopenia) persist for days to weeks due to prolonged cellular effects |
| Molecular Weight | 303.68 |
52 mg/m^2 intravenously over 2 hours daily for 5 consecutive days, repeated every 28 days.
| Dosage form | SOLUTION |
| Renal impairment | Clcr ≥ 60 mL/min: no adjustment; Clcr 30-59 mL/min: reduce dose to 39 mg/m^2; Clcr < 30 mL/min: not recommended (no data). |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25% (monitor toxicity); Child-Pugh C: not recommended (no data). |
| Pediatric use | 52 mg/m^2 intravenously over 2 hours daily for 5 days every 28 days (same as adult dosing per body surface area; safety and efficacy established in pediatric patients 1 year and older). |
| Geriatric use | No specific dose adjustment based solely on age; monitor renal function closely due to increased risk of nephrotoxicity; use same dosing as adults with renal adjustment as per GFR. |
| 1st trimester | Contraindicated due to teratogenicity; avoid pregnancy. |
| 2nd trimester | Contraindicated; embryotoxic and fetotoxic in animal studies. |
| 3rd trimester | Contraindicated; risk of fetal harm outweighs any potential benefit. |
Clinical note
Comprehensive clinical and safety monograph for CLOFARABINE (CLOFARABINE).
| Placental transfer | Clofarabine crosses the placenta; animal studies demonstrate embryotoxicity and teratogenicity. |
| Breastfeeding | It is unknown if clofarabine is excreted in human milk; however, due to the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy and for at least 2 weeks after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Clofarabine is embryotoxic and teratogenic in animal studies. In humans, it is classified as Pregnancy Category D. First trimester exposure is associated with major congenital malformations including neural tube defects, skeletal anomalies, and cardiovascular defects. Second and third trimester exposure may cause fetal myelosuppression, intrauterine growth restriction, and premature delivery. |
| Fetal Monitoring | Monitor complete blood counts with differential at baseline and throughout therapy. Assess hepatic (ALT, AST, bilirubin) and renal function (serum creatinine, BUN, urinalysis) frequently. Monitor for signs of infection, bleeding, and tumor lysis syndrome. Fetal ultrasound to assess growth and anatomy if exposure occurs during pregnancy. |
| Fertility Effects | Clofarabine may impair fertility in both males and females. In preclinical studies, it caused testicular atrophy and reduced spermatogenesis. In humans, reversible or permanent infertility may occur. Women of reproductive potential should use effective contraception during and for 6 months after therapy; men for 3 months. |
■ FDA Black Box Warning
Clofarabine causes severe bone marrow suppression, including neutropenia, anemia, thrombocytopenia, and increased risk of infection. Hemorrhage and severe infections have been reported. Monitor blood counts regularly.
| Serious Effects |
Hypersensitivity to clofarabine or any component of the formulation
| Precautions | 1) Myelosuppression: monitor CBCs; dose adjustment may be needed. 2) Infections: increased susceptibility. 3) Hemorrhagic cystitis: may occur; manage with hydration and monitoring. 4) Hepatic toxicity: monitor liver function tests; dose reduction in hepatic impairment. 5) Renal toxicity: monitor renal function; dose adjustment for creatinine clearance <60 mL/min. 6) Tumor lysis syndrome: hydrate and use prophylactic allopurinol. 7) Systemic inflammatory response syndrome (SIRS): monitor for signs; discontinue if occurs. |
| Food/Dietary | Grapefruit and grapefruit juice may affect liver enzymes and should be avoided. No specific food restrictions, but avoid alcohol due to potential hepatotoxicity. Maintain adequate hydration; no other known food interactions. |
| Clinical Pearls | Clofarabine is a purine nucleoside antimetabolite used primarily in pediatric relapsed or refractory acute lymphoblastic leukemia (ALL). It is associated with significant myelosuppression; monitor absolute neutrophil count and platelets closely. Capillary leak syndrome and systemic inflammatory response syndrome (SIRS) are rare but serious adverse effects; consider prophylactic corticosteroids. Hepatic veno-occlusive disease (VOD) has been reported, especially in patients with prior stem cell transplant. Administer with adequate hydration and monitor for tumor lysis syndrome. |
| Patient Advice | Clofarabine is a chemotherapy drug that may lower your blood cell counts, increasing risk of infection, bleeding, and fatigue. · Report any signs of infection (fever, chills, sore throat), unusual bleeding or bruising, or shortness of breath immediately. · Drink plenty of fluids (8-10 glasses per day) to prevent kidney problems and tumor lysis syndrome. · Avoid live vaccines and close contact with people who have recently received oral polio vaccine. · Use effective contraception during treatment and for at least 6 months after the last dose. · Do not breastfeed while taking clofarabine. · You may experience nausea, vomiting, or diarrhea; your doctor can prescribe medications to manage these symptoms. |
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