CLOLAR
Clinical safety rating
cautionComprehensive clinical and safety monograph for CLOLAR (CLOLAR).
Comprehensive clinical and safety monograph for CLOLAR (CLOLAR).
FDA: Treatment of relapsed or refractory acute lymphoblastic leukemia (ALL) in pediatric patients aged 1 to 21 years.Off-label: Treatment of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), chronic myeloid leukemia (CML) in blast crisis.
Clolar (clofarabine) is a purine nucleoside antimetabolite that inhibits DNA synthesis and RNA transcription. It is phosphorylated intracellularly to its active triphosphate form, which competes with adenosine triphosphate for incorporation into DNA, leading to chain termination and inhibition of DNA polymerase and ribonucleotide reductase, resulting in apoptosis.
| Metabolism | Clofarabine is partially metabolized by deamination via cytidine deaminase (CDA) to inactive 6-keto-clofarabine. Approximately 50-60% of the drug is excreted unchanged in urine. |
| Excretion | Renal: 50-60% as unchanged drug; biliary/fecal: minimal (<5%) |
| Half-life | Terminal elimination half-life approximately 5.2 hours in patients with normal renal function; prolonged in renal impairment (up to 9.8 hours with CrCl <60 mL/min) and in elderly; clinical context: supports once-daily dosing adjustment for renal function. |
| Protein binding | 47% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | Central Vd approximately 172 L/m² (extensive tissue distribution); in L/kg: ~4.6 L/kg (assuming 70 kg patient with BSA 1.73 m²). Clinical meaning: indicates wide distribution into total body water and tissues, exceeding total body water. |
| Bioavailability | Intravenous: 100% (only route of administration); oral: not available (no oral formulation). |
| Onset of Action | Intravenous: clinical effect (reduction in peripheral blasts) observed within 24-48 hours after first dose. |
| Duration of Action | Duration of pharmacodynamic effect (e.g., lymphocytopenia) persists for 4-7 days after last dose; clinical notes: dosing is typically 5 consecutive days per cycle due to cumulative toxicity. |
| Molecular Weight | 363.76 |
5 mg/m2 intravenously over 2 hours daily for 5 consecutive days. Repeat every 28 days.
| Dosage form | SOLUTION |
| Renal impairment | CrCl >= 60 mL/min: no adjustment. CrCl 30-59 mL/min: reduce dose by 20%. CrCl < 30 mL/min: contraindicated. |
| Liver impairment | No specific guidelines; use caution in severe hepatic impairment (Child-Pugh class C) and consider dose reduction based on tolerability. |
| Pediatric use | 1-21 years: 5 mg/m2 IV over 2 hours daily for 5 days every 28 days; reduce dose by 50% in patients with renal impairment. |
| Geriatric use | No specific dose adjustment, but monitor renal function closely due to age-related decline and increased risk of toxicity. |
| 1st trimester | Avoid. Teratogenic potential based on animal studies; crosses placenta. Use only if benefit outweighs risk. |
| 2nd trimester | Avoid. Potential fetal harm; limited human data. |
| 3rd trimester | Avoid. Risk of neonatal myelosuppression and other adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for CLOLAR (CLOLAR).
| Placental transfer | Clofarabine and its metabolites cross the placenta based on animal studies and molecular weight; human data limited but likely. |
| Breastfeeding | Clofarabine is excreted in human milk. Due to potential serious adverse reactions in nursing infants, breastfeeding is contraindicated during treatment and for at least 2 weeks after last dose. |
| Lactation Rating | L5 |
| Teratogenic Risk | Clofarabine is contraindicated in pregnancy. Based on its mechanism of action (inhibitor of DNA synthesis) and animal studies, there is a high risk of fetal harm if administered during pregnancy. In the first trimester, there is a significant risk of embryolethality and teratogenicity (structural anomalies). In the second and third trimesters, fetal growth restriction and central nervous system damage may occur. Pregnancy must be excluded before initiation. |
| Fetal Monitoring | Monitor complete blood counts (CBC) with differential and platelets, liver function tests (ALT, AST, bilirubin), renal function (serum creatinine), and serum electrolytes (potassium, calcium, phosphate, magnesium) at baseline and frequently during therapy. Monitor for signs of infection, bleeding, and tumor lysis syndrome. During pregnancy if inadvertently used, perform fetal ultrasound to assess for anomalies and growth restriction; monitor fetal heart rate for signs of distress. |
| Fertility Effects | Clofarabine may impair fertility in both males and females based on its cytotoxic mechanism. In males, it may cause oligospermia or azoospermia; in females, it may cause amenorrhea and premature ovarian failure. Fertility preservation counseling is recommended before treatment initiation. |
■ FDA Black Box Warning
WARNING: HEMATOLOGIC TOXICITY, INFECTION, AND HEPATIC TOXICITY. Clolar suppresses bone marrow function, causing severe neutropenia, thrombocytopenia, and anemia. Fatal infections have occurred. Hepatic toxicity, including hepatic failure and death, has been reported. Monitor blood counts and liver function frequently.
| Serious Effects |
Hypersensitivity to clofarabine or any componentPregnancy (unless benefit outweighs risk)Breastfeeding
| Precautions | Bone marrow suppression: severe neutropenia, thrombocytopenia, and anemia require close monitoring. Infections: serious and fatal infections (bacterial, fungal, viral) may occur. Hepatic toxicity: elevation of liver enzymes, bilirubin, and hepatic veno-occlusive disease. Renal toxicity: increased creatinine, hematuria, and hemolytic uremic syndrome-like reactions. Cardiac toxicity: pericardial effusion, hypotension, and ventricular dysfunction. Tumor lysis syndrome. Hypersensitivity reactions. Use in pregnancy: embryo-fetal toxicity. Vaccination: avoid live vaccines. |
| Food/Dietary | No specific food interactions are documented. However, maintain adequate hydration to reduce risk of nephrotoxicity and tumor lysis syndrome. Avoid grapefruit and grapefruit juice as they may affect metabolism via CYP3A4 (theoretical concern, though clofarabine is primarily renally excreted). |
| Clinical Pearls | Clolar (clofarabine) is a purine nucleoside analog indicated for pediatric relapsed/refractory acute lymphoblastic leukemia. Key pearls: (1) Monitor for systemic inflammatory response syndrome (SIRS) and capillary leak syndrome; premedicate with corticosteroids. (2) Requires aggressive hydration and allopurinol for tumor lysis prophylaxis. (3) Dose reductions needed for renal impairment (CrCl < 60 mL/min). (4) Avoid live vaccines during and after treatment. |
| Patient Advice | Clolar is a chemotherapy drug used to treat a type of leukemia in children that has not responded to other treatments. · You may experience side effects like fever, nausea, vomiting, diarrhea, and skin rashes. Report any signs of infection or unusual bleeding. · Drink plenty of fluids as directed to prevent kidney problems. You may receive IV fluids before and after treatment. · Avoid vaccinations without doctor approval, as live vaccines are not safe during treatment. · This drug can cause severe reactions including organ inflammation and fluid retention; seek immediate medical help if you have difficulty breathing, rapid weight gain, or swelling. |
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