"The U.S. Food and Drug Administration today expanded the approved uses of Abraxane (paclitaxel protein-bound particles for injectable suspension, albumin-bound) to treat patients with late-stage (metastatic) pancreatic cancer.
Use in Pregnancy
Pregnancy Category D
Totect® can cause fetal harm when administered to a pregnant woman. There is no adequate information about the use of Totect® 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 the fetus. [see Use in Special Populations].
Patient Counseling Information
See FDA-approved Patient Labeling
Treatment with Totect® is associated with leukopenia, neutropenia, and thrombocytopenia. Perform hematological monitoring. [see WARNINGS AND PRECAUTIONS]
Women who have potential to become pregnant should be advised that Totect® might cause fetal harm. [see WARNINGS AND PRECAUTIONS]
Carcinogenesis, Mutagenesis, Impairment of Fertility
The carcinogenic potential of dexrazoxane has not been investigated. 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 to bacteria in vitro (Ames assay), but caused significant chromosomal aberrations in mammalian cells in vitro. It also increased the formation of micronucleated polychromatic erythrocytes in mice. Thus, dexrazoxane is mutagenic and clastogenic.
The possible adverse effects of Totect® 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 (about 1/5 the human dose on a mg/m² basis) and as low as 20 mg/kg weekly for 13 weeks in dogs (about half the human dose on a mg/m² basis).
Use In Specific Populations
Pregnancy Category D [see WARNINGS AND PRECAUTIONS].
Dexrazoxane was toxic to pregnant rats at doses of 2 mg/kg (1/80 the human dose on an mg/m² basis) and embryotoxic and teratogenic at 8 mg/kg (about 1/20 the human dose on an mg/m² basis) when given daily 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 (about 1/16 the human dose on an mg/m² basis) daily during the period of organogenesis caused maternal toxicity and doses of 20 mg/kg (1/4 the human dose on an 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.
It is not known whether dexrazoxane or its metabolites are 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 to discontinue the drug, taking into account the importance of the drug to the mother.
The safety and effectiveness of Totect® in pediatric patients have not been established.
In total, 21% of the patients treated with Totect® were age 65 years or older and 9% were 75 and older. No differences in safety or efficacy were observed between older and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see DOSAGE AND ADMINISTRATION].
Greater exposure to dexrazoxane may occur in patients with compromised renal function. The Totect® dose should be reduced by 50% in patients with creatinine clearance values < 40 mL/min. [see DOSAGE AND ADMINISTRATION]
Last reviewed on RxList: 5/14/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Totect Information
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