se on a mg/m2 basis) and embryotoxic and teratogenic at 8 mg/kg (approximately 1/10 the human dose on a mg/m2 basis) when given daily to pregnant rats during the period of organogenesis. Teratogenic effects in the rat included imperforate anus, microphthalmia, and anophthalmia. In offspring allowed to develop to maturity, fertility was impaired in the male and female rats treated in utero during organogenesis at 8 mg/kg. In rabbits, doses of 5 mg/kg (approximately 1/10 the human dose on a mg/m2 basis) daily during the period of organogenesis caused maternal toxicity and doses of 20 mg/kg (1/2 the human dose on a mg/m2 basis) were embryotoxic and teratogenic. Teratogenic effects in the rabbit included several skeletal malformations such as short tail, rib and thoracic malformations, and soft tissue variations including subcutaneous, eye and cardiac hemorrhagic areas, as well as agenesis of the gallbladder and of the intermediate lobe of the lung. There are no adequate and well-controlled studies in pregnant women. 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 (see WARNINGS).
Nursing Mothers
It is not known whether dexrazoxane is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from dexrazoxane, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness of dexrazoxane in pediatric patients have not been established.
Geriatric Use
Clinical studies of Zinecard did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. 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.
Adverse Reactions
Zinecard at a dose of 500 mg/m2 has been administered in combination with FAC in randomized, placebo-controlled, double-blind studies to patients with metastatic breast cancer. The dose of doxorubicin was 50 mg/m2 in each of the trials. Courses were repeated every three weeks, provided recovery from toxicity had occurred. Table 3 below lists the incidence of adverse experiences for patients receiving FAC with either Zinecard or placebo in the breast cancer studies. Adverse experiences occurring during courses 1 through 6 are displayed for patients receiving Zinecard or placebo with FAC beginning with their first course of therapy (columns 1 and 3, respectively). Adverse experiences occurring at course 7 and beyond for patients who received placebo with FAC during the first six courses and who then received either Zinecard or placebo with FAC are also displayed (columns 2 and 4, respectively).
Table 3 ADVERSE EXPERIENCE PERCENTAGE (%) OF BREAST CANCER PATIENTS WITH ADVERSE EXPERIENCE
FAC + Zinecard FAC + PLACEBO
Courses 1–6
N = 413 Courses ≥ 7
N = 102 Courses 1–6
N = 458 Course ≥ 7
N = 99
Alopecia 94 100 97 98
Nausea 77 51 84 60
Vomiting 59 42 72 49
Fatigue/Malaise 61 48 58 55
Anorexia 42 27 47 38
Stomatitis 34 26 41 28
Fever 34 22 29 18
Infection 23 19 18 21
Diarrhea 21 1 |
