Dexrazoxane

Table of contents

  • Brand Names
  • Chemistry
  • Pharmacologic Category
  • Mechanism of Action
  • Therapeutic Use
  • Pregnancy and Lactation Implications
  • Contraindications
  • Warnings and Precautions
  • Adverse Reactions
  • Genes that may be involved
  • Drug Interactions
  • Dosage
  • Pharmacokinetics and Pharmacodynamics
  • Special Considerations

Brand Names

Europe

Austria: Cardioxane, Savene; Belgium: Savene; Bulgaria: Savene; Cyprus: Savene; Czech Republic: Cardioxane, Savene; Denmark: Cardioxane, Savene; Estonia: Savene; Finland: Cardioxane, Savene; France: Cardioxane; Germany: Cardioxane, Savene; Greece: Cardioxane, Savene, Zinecard; Hungary: Cardioxane; Ireland: Cardioxane, Savene; Italy: Cardioxane, Savene; Latvia: Savene; Lithuania: Cardioxane, Savene; Luxembourg: Savene; Malta: Savene; Netherlands: Cardioxane, Savene; Poland: Cardioxane, Savene; Portugal: Cardioxane, Savene; Romania: Savene; Slovakia: Cardioxane, Savene; Slovenia: Savene; Spain: Cardioxane, Savene; Sweden: Savene; UK: Cardioxane, Savene.

North America

Canada: Zinecard; USA: Dexrazoxane, Totect, Zinecard.

Latin America

Brazil: Cardioxane; Mexico: Cardioxane.

Drug combinations

Chemistry

Dexrazoxane: C~11~H~16~N~4~O~4~. Mw: 268.27. (1) 2,6-Piperazinedione, 4,4′-(1-methyl-1,2-ethanediyl)bis-, (S)-; (2)(+)-(S)-4,4′-Propylenedi-2,6-piperazinedione. CAS-24584-09-6 (1990).

Pharmacologic Category

Miscellaneous Therapeutic Agents; Protective Agents. EDTA derivative. Cardioprotectant. Antioxidant. Reversible Topoisomerase II Inhibitor. Antidotes. (ATC-Code: V03AF02).

Mechanism of action

EDTA derivative. It is a potent intracellular chelating agent. The mechanism of cardioprotectant activity is not fully understood. Appears to be converted intracellularly to a ring-opened chelating agent which interferes with iron-mediated oxygen free radical generation thought to be responsible, in part, for anthracycline-induced cardiomyopathy. In the management of anthracycline-induced extravasation, dexrazoxane may act by reversibly inhibiting topoisomerase II, protecting tissue from anthracycline cytotoxicity, thereby decreasing tissue damage.

Therapeutic use

Used to prevent or decrease cardiomyopathy associated with anthracycline derivatives (e.g. doxorubicin). Designated an orphan drug by the FDA for use in women with metastatic breast cancer who have received a cumulative doxorubicin hydrochloride dose of 300 mg/m^2^ and who, would benefit from continued doxorubicin therapy. Also used for the treatment of anthracycline-induced extravasation.

Pregnancy and lactiation implications

Embryotoxicity and teratogenicity in animal studies. Maternal toxicity also noted. Avoid use in pregnant women unless the potential benefit justifies the potential risk to the fetus. Breast-feeding is not recommended during therapy.

Unlabeled use

Contraindications

Hypersensitivity to dexrazoxane or any component of the formulation. Use with chemotherapy regimens which do not contain an anthracycline.

Warnings and precautions

Hazardous agent. May cause mild myelosuppression activity (may be additive with chemotherapeutic agents). Does not eliminate the potential for anthracycline-induced cardiac toxicity. Avoid dimethylsulfoxide in dexrazoxane therapy for anthracycline-induced extravasation (may diminish efficacy of the drug). May interfere with the antitumor effect of chemotherapy when administered with fluorouracil, doxorubicin, and cyclophosphamide. When used for prevention of cardiomyopathy, it should be administered 30 minutes after the beginning of the infusion. For I.V. administration (not for local infiltration into extravasation site).

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