Clofarabine
Mechanism :
Clofarabine, a purine (deoxyadenosine) nucleoside analog, is metabolized to clofarabine 5'-triphosphate. Clofarabine 5'-triphosphate decreases cell replication and repair as well as causing cell death.
Indication :
- Relapsed or refractory acute lymphoblastic leukemia
- Refractory Langerhans cell histiocytosis
Contraindications :
Hypersensitivity to clofarabine or any component of the formulation; symptomatic CNS involvement; history of serious heart, liver, kidney, or pancreas disease; severe hepatic or renal impairment.
Dosing :
Relapsed or refractory acute lymphoblastic leukemia:
≥1 year:
IV: 52 mg/m²/day days 1 through 5; repeat every 2 to 6 weeks; subsequent cycles should begin no sooner than 14 days from day 1 of the previous cycle (subsequent cycles may be administered when ANC ≥750/mm³).
Refractory Langerhans cell histiocytosis:
1 to 18 years:
IV: 25 mg/m²/day days 1 through 5; repeat every 28 days for 2 to 8 cycles.
Adverse Effect :
Infections, vomiting, nausea, anemia, leukopenia, lymphopenia, febrile neutropenia, thrombocytopenia, diarrhea, abdominal pain, anorexia, dermatitis, pruritus, fatigue, headache, pyrexia, edema, flushing, hypotension, anxiety, pain, erythema, petechiae, palmar-plantar erythrodysesthesia syndrome, gingival bleeding, mucositis, oral candidiasis, cough, dyspnea, pleural effusion, hepatobiliary disorder, hematuria, limb pain, myalgia, contusion, injection site pain, transfusion reaction.
Interaction :
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents.
Clozapine: Myelosuppressive Agents may enhance the adverse/toxic effect of Clozapine. Specifically, the risk for neutropenia may be increased.
Tolvaptan: May increase the serum concentration of OAT3 Substrates.
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines.
Hepatic Dose :
Baseline Hepatic Impairment: No dosage adjustments are recommended.
Treatment-Related Hepatic Impairment: Grade 3 (AST/ALT > 5 times upper limit of normal (ULN) or bilirubin > 2.5 times ULN): Withhold therapy. Restart with 75% dose once bilirubin level returns to baseline.