4 24 7
Pain on Injection 12 13 3 0
Sepsis 17 12 14 9
Neurotoxicity 17 10 13 5
Streaking/Erythema 5 4 4 2
Phlebitis 6 3 3 5
Esophagitis 6 3 7 4
Dysphagia 8 0 10 5
Hemorrhage 2 3 2 1
Extravasation 1 3 1 2
Uticaria 2 2 2 0
Recall Skin Reaction 1 1 2 0
The adverse experiences listed above are likely attributable to the FAC regimen with the exception of pain on injection that was observed mainly on the Zinecard arm.
Myelosuppression
Patients receiving FAC with Zinecard experienced more severe leukopenia, granulocytopenia, and thrombocytopenia at nadir than patients receiving FAC without Zinecard, but recovery counts were similar for the two groups of patients.
Hepatic and Renal
Some patients receiving FAC + Zinecard or FAC + placebo experienced marked abnormalities in hepatic or renal function tests, but the frequency and severity of abnormalities in bilirubin, alkaline phosphatase, BUN, and creatinine were similar for patients receiving FAC with or without Zinecard.
Overdosage
There have been no instances of drug overdose in the clinical studies sponsored by either Pharmacia & Upjohn Company or the National Cancer Institute. The maximum dose administered during the cardioprotective trials was 1000 mg/m2 every three weeks.
Disposition studies with Zinecard have not been conducted in cancer patients undergoing dialysis, but retention of a significant dose fraction (>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 it could be removed using conventional peritoneal or hemodialysis.
There is no known antidote for dexrazoxane. Instances of suspected overdose should be managed with good supportive care until resolution of myelosuppression and related conditions is complete. Management of overdose should include treatment of infections, fluid regulation, and maintenance of nutritional requirements.
Zinecard Dosage and Administration
The recommended dosage ratio of Zinecard:doxorubicin is 10:1 (e.g., 500 mg/m2 Zinecard:50 mg/m2 doxorubicin). In patients with moderate to severe renal dysfunction (creatinine clearance values < 40 mL/min), the recommended dosage ratio of Zinecard:doxorubicin is 5:1 (e.g., 250 mg/m2 Zinecard:50 mg/m2 doxorubicin). Creatinine clearance can be determined from a 24-hour urinary creatinine collection or estimated using the Crockroft-Gault equation (assuming stable renal function):
Since a doxorubicin dose reduction is recommended in the presence of hyperbilirubinemia, the Zinecard dosage should be proportionately reduced (maintaining the 10:1 ratio) in patients with hepatic impairment.
Zinecard must be reconstituted with Sterile Water for Injection, USP. For Zinecard 250 mg vials, reconstitute with 25 mL. For Zinecard 500 mg vials, reconstitute with 50 mL. The resultant reconstituted solutions will have a concentration of 10 mg dexrazoxane for each mL of solution. Further dilution with Lactated Ringer's Injection, USP, is necessary prior to administration.
Following reconstitution with Sterile Water for Injection, USP, Zinecard is stable for 30 minutes at room temperature or if storage is necessary, up to 3 hours from the time of reconstitution when stored under refrigeration, 2° to 8°C (36° to 46°F). The pH of the resultant solution is 1.0 to 3.0. DISCARD UNUSED SOLUTIONS. The reconstituted Zinecard sol |
