May 28, 2017
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Etopophos

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Etopophos




Warnings
Precautions

WARNINGS

Included as part of the "PRECAUTIONS" Section

PRECAUTIONS

Myelos uppression

ETOPOPHOS causes myelosuppression that results in thrombocytopenia and neutropenia. Fatal infections and bleeding have occurred. Obtain complete blood counts prior to each cycle of ETOPOPHOS and more frequently as clinically indicated [see ADVERSE REACTIONS].

Secondary Leukemias

Secondary leukemias have occurred with long term use of ETOPOPHOS.

Hypersensitivity Reactions

ETOPOPHOS can cause hypersensitivity reactions, including rash, urticaria, pruritus, and anaphylaxis [see ADVERSE REACTIONS]. If hypersensitivity reactions occur, immediately interrupt ETOPOPHOS and institute supportive management. Permanently discontinue ETOPOPHOS in patients who experience a severe hypersensitivity reaction.

Embryo-Fetal Toxicity

Based on animal studies and its mechanism of action, ETOPOPHOS can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential hazard to the fetus [see Use In Specific Populations].

Advise females of reproductive potential to use effective contraception during treatment with ETOPOPHOS and for at least 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose [see Use In Specific Populations].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

ETOPOPHOS was non-mutagenic in an in vitro Ames microbial mutagenicity assay; however, ETOPOPHOS is rapidly and completely converted to etoposide in vivo. Therefore, as etoposide is mutagenic in the Ames assay, ETOPOPHOS is considered mutagenic in vivo.

In rats, oral dosing of ETOPOPHOS for 5 consecutive days at doses greater than or equal to 86 mg/kg/day (about 10 times the 50 mg/m2 human dose based on BSA) resulted in irreversible testicular atrophy. Irreversible testicular atrophy was also present in rats treated with ETOPOPHOS intravenously for 30 days at 5.11 mg/kg/day (about 0.5 times the 50 mg/m2 human dose based on BSA).

Use In Specific Populations

Pregnancy

Risk Summary

Based on animal data and its mechanism of action, ETOPOPHOS can cause fetal harm when administered to a pregnant woman. Etoposide, the active moiety of etoposide phosphate is teratogenic in mice and rats [see Data]. Advise pregnant women of the potential hazard to a fetus.

Advise women of childbearing potential to avoid becoming pregnant.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

In rats, an intravenous etoposide dose of 0.4 mg/kg/day (about 0.05 times of the 50 mg/m2 human dose based on body surface area [BSA]) during organogenesis caused maternal toxicity, embryotoxicity, and teratogenicity (skeletal abnormalities, exencephaly, encephalocele, and anophthalmia); higher doses of 1.2 and 3.6 mg/kg/day (about 0.14 and 0.5 times the 50 mg/m2 human dose based on BSA) resulted in 90% and 100% embryonic resorptions. In mice, a single etoposide dose of 1.0 mg/kg (approximately 0.06 times the 50 mg/m2 human dose based on BSA) administered intraperitoneally on days 6, 7, or 8 of gestation caused embryotoxicity, cranial abnormalities, and major skeletal malformations. An intraperitoneal dose of 1.5 mg/kg (about 0.1 times the 50 mg/m2 human based on BSA) on day 7 of gestation caused an increase in the incidence of intrauterine death and fetal malformations and a significant decrease in the average fetal body weight [see Nonclinical Toxicology].

Lactation

There is no information regarding the presence of etoposide in human milk or its effects on breastfed infant milk production. Because of the potential for serious adverse reactions in nursing infants from ETOPOPHOS, advise women not to breastfeed during treatment with ETOPOPHOS.

Females And Males Of Reproductive Potential

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment with ETOPOPHOS and for 6 months after the final dose.

Males

ETOPOPHOS may damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities. Males with female sexual partners of reproductive potential should use effective contraception during treatment with ETOPOPHOS and for 4 months after the final dose.

Infertility

Females

In females of reproductive potential, ETOPOPHOS may cause infertility and result in amenorrhea. Premature menopause can occur with ETOPOPHOS. Recovery of menses and ovulation is related to age at treatment.

Males

In male patients, ETOPOPHOS may result in oligospermia, azoospermia, and permanent loss of fertility. Sperm counts have been reported to return to normal levels in some men, and in some cases, have occurred several years after the end of therapy [See Nonclinical Toxicology].

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of etoposide did not include sufficient numbers (n=71) of patients aged 65 years and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between elderly and younger patients.

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 4/28/2017

Warnings
Precautions

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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