No

Cardioprotectant

Reduction of 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 would benefit from continuing therapy with doxorubicin. It is not recommended for use with the initiation of doxorubicin therapy.

C

Clinical effects on the fetus: Avoid use in pregnant women unless the potential benefit justifies the potential risk to the fetus

Breast-feeding/lactation: Discontinue nursing during dexrazoxane therapy

Do not use with chemotherapy regimens that do not contain an anthracycline

Dexrazoxane may add to the myelosuppression caused by chemotherapeutic agents. There is some evidence that the use of dexrazoxane concurrently with the initiation of fluorouracil, doxorubicin, and cyclophosphamide (FAC) therapy interferes with the antitumor efficacy of the regimen, and this use is not recommended. Dexrazoxane should only be used in those patients who have received a cumulative doxorubicin dose of 300 mg/m² and are continuing with doxorubicin therapy. Dexrazoxane does not eliminate the potential for anthracycline-induced cardiac toxicity. Carefully monitor cardiac function.

The adverse experiences are likely attributable to the FAC regimen, with the exception of pain on injection that was observed mainly with dexrazoxane. Patients receiving FAC with dexrazoxane experienced more severe leukopenia, granulocytopenia, and thrombocytopenia at nadir than patients receiving FAC without dexrazoxane; but recovery counts were similar for the two groups.

Management includes good supportive care until resolution of myelosuppression, and related conditions, is complete. Management of overdose should include treatment of infections, fluid regulation, and management of nutritional requirements. Retention of a significant dose fraction of the unchanged drug in the plasma pool, minimal tissue partitioning or binding and availability of >90% of the systemic drug levels in the unbound form suggest that dexrazoxane could be removed using conventional peritoneal or hemodialysis.

Decreased effect: There is some evidence that the use of dexrazoxane concurrently with the initiation of FAC therapy interferes with the antitumor efficacy of the regimen, and this use is not recommended

Store intact vials at controlled room temperature, (15°C to 30°C/59°F to 86°F). Reconstituted and diluted solutions are stable for 6 hours at controlled room temperature or under refrigeration (2°C to 8°C/36°F to 46°F).

Must be reconstituted with 0.167 Molar (M/6) sodium lactate injection to a concentration of 10 mg dexrazoxane/mL sodium lactate. Reconstituted dexrazoxane solution may be diluted with either 0.9% sodium chloride injection or 5% dextrose injection to a concentration of 1.3-5 mg/mL in intravenous infusion bags.

Caution should be exercised in the handling and preparation of the reconstituted solution; the use of gloves is recommended. If dexrazoxane powder or solutions contact the skin or mucosae, immediately wash with soap and water.

Derivative of EDTA and potent intracellular chelating agent. The mechanism of cardioprotectant activity is not fully understood. Appears to be converted intracellularly to a ring-opened chelating agent that interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline-induced cardiomyopathy.

Distribution: V_d: 22-22.4 L/m²; not bound to plasma proteins

Half-life: 2.1-2.5 hours

Elimination: 42% of dose excreted in the urine; renal clearance: 3.35 L/hour/m²; plasma clearance: 6.25-7.88 L/hour/m²

Adults: I.V.: The recommended dosage ratio of dexrazoxane:doxorubicin is 10:1 (eg, 500 mg/m² dexrazoxane:50 mg/m² doxorubicin). Administer the reconstituted solution by slow I.V. push or rapid I.V. infusion from a bag. After completing the infusion, and prior to a total elapsed time of 30 minutes (from the beginning of the dexrazoxane infusion), administer the I.V. injection of doxorubicin.

Since dexrazoxane will always be used with cytotoxic drugs, and since it may add to the myelosuppressive effects of cytotoxic drugs, frequent complete blood counts are recommended

None reported

May cause granulocytopenia; use caution with clozapine or carbamazepine

No information available to require special precautions

No effects or complications reported

This I.V. medication is given to reduce incidence of cardiac complications with doxorubicin. Report promptly any pain at infusion site. Pregnancy/breast-feeding precautions: Inform prescriber if pregnant. Consult prescriber if breast-feeding.

Observe for signs and symptoms of cardiac toxicity, infection, and anemia

Powder for injection, lyophilized: 250 mg, 500 mg (10 mg/mL when reconstituted)

Sehested M, et al, "Dexrazoxane for Protection Against Cardiotoxic Effects of Anthracyclines," J Clin Oncol, 1996, 14:2884.

Speyer JL, Green MD, Kramer E, et al, "Protective Effect of the Bispiperazinedione ICRF-187 Against Doxorubicin-induced Cardiac Toxicity in Women With Advanced Breast Cancer," N Engl J Med, 1988, 319(12):745-52.

Speyer JL, Green MD, Sanger J, et al, "A Prospective Randomized Trial of ICRF-187 for Prevention of Cumulative Doxorubicin-Induced Cardiac Toxicity in Women With Breast Cancer," Cancer Treat Rev, 1990, 17(2-3):161-3.

Speyer JL, Green MD, Zeleniuch-Jacquotte A, et al, "ICRF-187 Permits Longer Treatment With Doxorubicin in Women With Breast Cancer," J Clin Oncol, 1992, 10(1):117-27.

Swain SM, et al, "Cardioprotection With Dexrazoxane for Doxorubicin-Containing Therapy in Advanced Breast Cancer," J Clin Oncol, 1997, 15:1318-32.

Swain SM, et al, "Delayed Administration of Dexrazoxane Provides Cardioprotection for Patients With Advanced Breast Cancer Treated With Doxorubicin-Containing Therapy," J Clin Oncol, 1997, 15:1333-40.

Wexler LH, et al, "Randomized Trial of the Cardioprotective Agent ICRF-187 in Pediatric Sarcoma Patients Treated With Doxorubicin," J Clin Oncol, 1996, 14:362-72.