Dexrazoxane Dosage

Usual Adult Dose for Cardiomyopathy Prophylaxis

Dexrazoxane (marketed as Zinecard)
For use in 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:

The recommended dosage ratio of dexrazoxane:doxorubicin is 10:1 (for example: 500 mg/m2 dexrazoxane:50 mg/m2 doxorubicin).

After completing the infusion of dexrazoxane, and prior to a total elapsed time of 30 minutes (from the beginning of the dexrazoxane infusion), the intravenous injection of doxorubicin should be given.

Usual Adult Dose for Extravasation

Dexrazoxane (marketed as Totect)
For use in the treatment of extravasation resulting from IV anthracycline chemotherapy:

Dexrazoxane should be given once daily for three consecutive days. The first infusion should be initiated as soon as possible and within the first six hours after extravasation.

The recommended doses are:
Day one: 1000 mg/m2
Day two: 1000 mg/m2
Day three: 500 mg/m2

The maximum recommended doses are:
Day one: 2000 mg
Day two: 2000 mg
Day three: 1000 mg

The dose should be administered as an intravenous infusion over 1 to 2 hours in a large caliber vein in an extremity/area other than the one affected by the extravasation.

Cooling procedures such as ice packs, if used, should be removed from the area at least 15 minutes before dexrazoxane administration in order to allow sufficient blood flow to the area of extravasation. Treatment on day 2 and day 3 should start at the same hour (plus or minus 3 hours) as on the first day.

Usual Pediatric Dose for Cardiomyopathy Prophylaxis

Dexrazoxane dose is based on a 10:1 ratio of the doxorubicin dose (example: 300 mg/m2 dexrazoxane; 30 mg/m2 doxorubicin)

Dexrazoxane should be administered 30 minutes before doxorubicin.

This regimen has been used in patients with high-risk acute lymphoblastic leukemia.

Renal Dose Adjustments

The dexrazoxane dose should be reduced by 50% in patients with creatinine clearance values less than 40 mL/min.

For example, when used in patients with a creatinine clearance value less than 40 mL/min for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer, the recommended dosage ratio of dexrazoxane:doxorubicin is 5:1 (for example: 250 mg/m2 dexrazoxane:50 mg/m2 doxorubicin).

Liver Dose Adjustments

The pharmacokinetics of dexrazoxane have not been evaluated in patients with hepatic impairment.

When used for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer, the dexrazoxane dose is dependent upon the dose of doxorubicin. Since a doxorubicin dose reduction is recommended in the presence of hyperbilirubinemia, the dexrazoxane dosage is proportionately reduced in patients with hepatic impairment.

Precautions

In general, elderly patients should be treated with caution due to the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.

Cardiac monitoring should continue during dexrazoxane therapy. Anthracycline/dexrazoxane should be discontinued in patients who develop a decline in left ventricular ejection fraction or clinical congestive heart failure.

Dialysis

Disposition studies with dexrazoxane have not been conducted in cancer patients undergoing dialysis, but retention of a significant dose fraction (greater than 0.4) of the unchanged drug in the plasma pool, minimal tissue partitioning or binding, and availability of greater than 90% of the systemic drug levels in the unbound form suggest that dexrazoxane could be removed using conventional peritoneal or hemodialysis.

Other Comments

Dexrazoxane should not be mixed with other drugs. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.