s not indicated for use in pediatric patients. Some adult patients who received Zinecard in combination with anti-cancer agents known to be carcinogenic have also developed secondary malignancies, including AML and MDS.
Razoxane is the racemic mixture, of which dexrazoxane is the S(+)-enantiomer. Secondary malignancies (primarily acute myeloid leukemia) have been reported in patients treated chronically with oral razoxane. In these patients, the total cumulative dose of razoxane ranged from 26 to 480 grams and the duration of treatment was from 42 to 319 weeks. One case of T-cell lymphoma, one case of B-cell lymphoma, and six to eight cases of cutaneous basal cell or squamous cell carcinoma have also been reported in patients treated with razoxane.
Use in Pregnancy
Zinecard can cause fetal harm when administered to pregnant women. There is no adequate information about the use of Zinecard in pregnant women. In animal studies in rats and rabbits, dexrazoxane administration during the period of organogenesis was embryotoxic and teratogenic at doses significantly lower than the clinically recommended dose (see PREGNANCY). If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
Precautions
General
Doxorubicin should not be given prior to the intravenous injection of Zinecard.
Doxorubicin should be given within 30 minutes after beginning the infusion with Zinecard (see DOSAGE AND ADMINISTRATION).
As Zinecard will always be used with cytotoxic drugs, patients should be monitored closely. While the myelosuppressive effects of Zinecard at the recommended dose are mild, additive effects upon the myelosuppressive activity of chemotherapeutic agents may occur.
Patients with Moderate or Severe Renal Insufficiency
Greater exposure to dexrazoxane may occur in patients with compromised renal function. The Zinecard dose should be reduced by 50% in patients with creatinine clearance values <40 mL/min (see DOSAGE AND ADMINISTRATION).
Laboratory Tests
As Zinecard may add to the myelosuppressive effects of cytotoxic drugs, frequent complete blood counts are recommended (see ADVERSE REACTIONS).
Drug Interactions
Zinecard does not influence the pharmacokinetics of doxorubicin.
Carcinogenesis, Mutagenesis, Impairment of Fertility
(See WARNINGS section for information on human carcinogenicity) - No long-term carcinogenicity studies have been carried out with dexrazoxane in animals. Nevertheless, a study by the National Cancer Institute has reported that long term dosing with razoxane (the racemic mixture of dexrazoxane, ICRF-187, and its enantiomer ICRF-186) is associated with the development of malignancies in rats and possibly in mice. Dexrazoxane was not mutagenic in the Ames test but was found to be clastogenic to human lymphocytes in vitro and to mouse bone marrow erythrocytes in vivo (micronucleus test).
The possible adverse effects of Zinecard on the fertility of humans and experimental animals, male or female, have not been adequately studied. Testicular atrophy was seen with dexrazoxane administration at doses as low as 30 mg/kg weekly for 6 weeks in rats (1/3 the human dose on a mg/m2 basis) and as low as 20 mg/kg weekly for 13 weeks in dogs (approximately equal to the human dose on a mg/m2 basis).
Pregnancy
Pregnancy Category D
Dexrazoxane was toxic to pregnant rats at doses of 2 mg/kg (1/40 the human do |
