DEXRAZOXANE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DEXRAZOXANE HYDROCHLORIDE (DEXRAZOXANE HYDROCHLORIDE).
Dexrazoxane is a cardioprotective agent that acts as a topoisomerase II inhibitor and iron chelator. It reduces the cardiotoxicity of anthracyclines by binding to iron and preventing the formation of anthracycline-iron complexes that generate reactive oxygen species. It also inhibits topoisomerase II, which may contribute to its cardioprotective effects.
| Metabolism | Dexrazoxane is metabolized by hydrolysis to an active metabolite (ADR-925) via a dihydro-pyrimidine hydrolase enzyme. The parent drug and metabolite undergo further metabolism via unknown pathways. Approximately 70-80% of the dose is excreted in urine as unchanged drug and metabolites. |
| Excretion | Primarily renal (40-60% unchanged drug); minor biliary/fecal (<10%) |
| Half-life | Terminal elimination half-life: 2.5-4 hours; clinical context: supports every-3-week dosing schedule |
| Protein binding | Low, <5% (primarily albumin) |
| Volume of Distribution | 1-2 L/kg; Vd approx 70 L (total body water); indicates extensive tissue distribution |
| Bioavailability | Intravenous (only route): 100% |
| Onset of Action | Intravenous: immediate pharmacodynamic effect (cardioprotection) within infusion; clinical onset of cardioprotection not directly measurable |
| Duration of Action | Pharmacodynamic effect persists through anthracycline infusion and up to 24 hours post-dose; cardioprotection duration: multiple cycles |
500 mg/m² IV over 15-30 minutes, starting within 30 minutes before doxorubicin, at a 10:1 ratio (dexrazoxane:doxorubicin).
| Dosage form | INJECTABLE |
| Renal impairment | CrCl <40 mL/min: reduce dose by 50%; CrCl ≥40 mL/min: no adjustment. |
| Liver impairment | No specific Child-Pugh based guidelines; use caution in severe hepatic impairment. |
| Pediatric use | Same as adult: 500 mg/m² IV, 10:1 ratio to doxorubicin, approved for ages ≥1 year. |
| Geriatric use | No specific dose adjustments; monitor renal function and myelosuppression closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DEXRAZOXANE HYDROCHLORIDE (DEXRAZOXANE HYDROCHLORIDE).
| Breastfeeding | M/P ratio unknown. Dexrazoxane is excreted in breast milk in rats; not studied in humans. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy and for at least 2 weeks after last dose. |
| Teratogenic Risk | Pregnancy Category D. Dexrazoxane is embryotoxic and teratogenic in animal studies. First trimester: potential for major malformations; avoid unless maternal benefit outweighs risk. Second/third trimester: may cause fetal harm due to cytotoxic effects; use only if clearly needed. |
■ FDA Black Box Warning
Do not use dexrazoxane with chemotherapy regimens that are not anthracycline-based. The use of dexrazoxane may increase the risk of secondary malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), particularly when used in pediatric patients or in combination with other chemotherapeutic agents. It may also cause injection site reactions and severe myelosuppression.
| Serious Effects |
["Concomitant use with non-anthracycline chemotherapeutic agents","Severe pre-existing myelosuppression","Hypersensitivity to dexrazoxane or any component of the formulation","Pregnancy (may cause fetal harm)","Lactation (discontinue nursing or drug based on importance to mother)"]
| Precautions | ["May cause severe myelosuppression; monitor blood counts regularly","Increased risk of secondary malignancies (AML/MDS), especially in pediatric patients","Injection site reactions including phlebitis, cellulitis, and necrosis","Cardiotoxicity: Paradoxically, dexrazoxane may impair the anticancer efficacy of anthracyclines; use only in patients who need continued anthracycline therapy","Liver and renal impairment: Dose adjustment may be necessary"] |
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| Fetal Monitoring |
| Monitor complete blood counts (CBC) with differential and platelets, liver function tests, serum creatinine, and cardiac function (ejection fraction) before and during therapy. In pregnancy, monitor fetal growth and development via ultrasound. Assess for signs of myelosuppression in mother. |
| Fertility Effects | Dexrazoxane may cause gonadal suppression and infertility in both males and females, potentially irreversible. Animal studies show testicular atrophy and reduced fertility. Effects on human fertility are not fully characterized but anticipated based on its mechanism of action. |