CLOLAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CLOLAR (CLOLAR).
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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CLOLAR (CLOLAR).
| Breastfeeding | No data available on the excretion of clofarabine into breast milk or its effects on the nursing infant. Due to potential for serious adverse reactions (e.g., myelosuppression, gastrointestinal toxicity), breastfeeding is contraindicated during therapy and for at least 3 months after the last dose. M/P ratio is unknown. |
| 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. |
■ 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 |
Absolute: Hypersensitivity to clofarabine or any component of the formulation. Relative: Severe hepatic impairment (bilirubin >3 mg/dL or transaminases >5x ULN). Severe renal impairment (creatinine clearance <30 mL/min).
| 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. |
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| 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. |