Dexrazoxane

DAE Class; Rx

Common Brand Names; Totect, Zinecard

• Cardioprotectant Agents

Cytoprotective agent
Used to reduce the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose of 300 mg/m2 and for the treatment of extravasation resulting from IV anthracycline chemotherapy
May increase the myelosuppressive effects of chemotherapy

Doxorubicin-induced Cardiomyopathy

Zinecard, Totect, and generic

Indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose of 300 mg/m2 and who will continue to receive doxorubicin therapy to maintain tumor control

For the treatment of extravasation resulting from IV anthracycline chemotherapy.

Hypersensitivity

Use (Zinecard) in chemotherapy when an anthracycline is not being administered

Most ADRs due to concurrent antineoplastic treatment

Injection site pain, phlebitis, and increased myelosuppression are only major specific ADR

May interfere with activity of antineoplastic drugs; do NOT initiate until cumulative doxorubicin dose reaches 300 mg/m²

Do NOT give doxorubicin prior to dexrazoxane

Does not eliminate potential for anthracycline-induced cardiac toxicity; monitor cardiac function carefully

Secondary malignancies (eg, AML, MDS) reported with combination chemotherapy

Treatment is associated with leukopenia, neutropenia, and thrombocytopenia; grade 2-4 decreased white blood cells (73%), decreased neutrophils (61%), and decreased platelets (26%) occurred in patients; febrile neutropenia occurred in 2.5% of patients; monitor complete blood counts during treatment; myelosuppression and cytotoxic potential and cytotoxic chemotherapy (with a nadir occurring on days 10-12) may be additive to that of chemotherapy administered alone

Hypersensitivity reactions including anaphylactic reaction, angioedema, skin reactions, bronchospasm, respiratory distress, hypotension and loss of consciousness have occurred in patients treated with dexrazoxane products and anthracyclines; previous history of allergy to dexrazoxane products should be carefully considered prior to administration; consider permanent discontinuation in patients with severe hypersensitivity reactions

Therapy has not been studied in patients with hepatic impairment; since liver dysfunction (increases in transaminases and bilirubin) may occur (especially after doses of above 1000 mg/m² dexrazoxane), it is recommended that routine liver function tests be performed before each administration of dexrazoxane in patients with known liver function disorders; use in patients with hepatic impairment not recommended

Pregnancy

Based on findings from animal studies and mechanism of action, therapy can cause fetal harm when administered to a pregnant woman; limited available data in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes

Lactation

There are no data on presence in human milk, effects on breastfed child, or on milk production; because of potential for serious adverse reactions, such as myelosuppression, in a breastfed child, advise women not to breastfeed during treatment and for 2 weeks following final dose

Adults

Maximum dose as a cytoprotective agent is dependent on the doxorubicin dose; Maximum dose as extravasation treatment is 1,000 mg/m2 (up to 2,000 mg).

Geriatric

Maximum dose as a cytoprotective agent is dependent on the doxorubicin dose; Maximum dose as extravasation treatment is 1,000 mg/m2 (up to 2,000 mg).

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Dexrazoxane