Targretin Capsules

Pregnancy

Risk Summary

TARGRETIN, a retinoid, can cause fetal harm based on findings from animal studies when administered to a pregnant female and is contraindicated during pregnancy. Bexarotene was teratogenic and caused developmental mortality in rats following oral administration during organogenesis [see Data]. TARGRETIN must not be given to a pregnant female or a female who intends to become pregnant. If pregnancy does occur during treatment with TARGRETIN, immediately discontinue the drug and advise the pregnant female of the potential risk to a fetus.

The background risk of major birth defects and miscarriage for the indicated populations is unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.

Data

Animal Data

Bexarotene caused malformations when administered orally to pregnant rats during days 7-17 of gestation. Developmental abnormalities included incomplete ossification at 4 mg/kg/day and cleft palate, depressed eye bulge/microphthalmia, and small ears at 16 mg/kg/day. The plasma AUC of bexarotene in rats at 4 mg/kg/day is approximately one third the AUC in humans at the recommended daily dose. At doses greater than 10 mg/kg/day, bexarotene caused developmental mortality. The no effect dose for fetal effects in rats was 1 mg/kg/day (producing an AUC approximately one sixth of the AUC at the recommended human daily dose).

Lactation

Risk Summary

There is no information regarding the presence of TARGRETIN in human milk, the effects on the breast fed infant, or the effects on milk production. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from TARGRETIN, discontinue breastfeeding during treatment with TARGRETIN.

Females and Males of Reproductive Potential

Pregnancy Testing

Obtain a negative serum pregnancy test (e.g., serum beta-human chorionic gonadotropin [beta-HCG]) with a sensitivity of at least 50 mIU/L within 1 week prior to TARGRETIN therapy. Obtain another pregnancy test at monthly intervals while the patient remains on TARGRETIN.

Contraception

Females

TARGRETIN can cause fetal harm when administered to a pregnant female [see Use in Specific Populations (8.1)]. Females of reproductive potential should be advised to avoid becoming pregnant when TARGRETIN is used. Effective contraception must be used for 1 month prior to the initiation of therapy, during therapy and for at least 1 month following discontinuation of therapy; it is recommended that two reliable forms of contraception be used simultaneously unless abstinence is the chosen method. Bexarotene can potentially induce metabolic enzymes and thereby theoretically reduce the plasma concentrations of oral or other systemic hormonal contraceptives [see Drug Interactions (7)]. Thus, if treatment with TARGRETIN is intended in a female with reproductive potential, it is strongly recommended that one of the two reliable forms of contraception should be non-hormonal. TARGRETIN therapy should be initiated on the second or third day of a normal menstrual period. No more than a 1-month supply of TARGRETIN should be given to the patient so that the results of pregnancy testing can be assessed and counseling regarding avoidance of pregnancy and birth defects can be reinforced.

Males

Male patients with sexual partners who are pregnant, possibly pregnant, or who could become pregnant must use condoms during sexual intercourse while taking TARGRETIN and for at least 1 month after the last dose of drug.

Pediatric Use

Safety and effectiveness of TARGRETIN in pediatric patients have not been established.

Geriatric Use

Of the total patients with CTCL in clinical trials of TARGRETIN, 64% were 60 years or older, while 33% were 70 years or older. No overall differences in safety were observed between patients 70 years or older and younger patients, but greater sensitivity of some older individuals to TARGRETIN cannot be ruled out. Responses to TARGRETIN were observed across all age group decades, without preference for any individual age group decade.

Hepatic Impairment

No specific studies have been conducted with TARGRETIN in subjects with hepatic impairment. Hepatic impairment is expected to lead to decreased clearance [see Clinical Pharmacology (12.3)]. If TARGRETIN is used in patients with hepatic impairment, monitor for signs of toxicity that may be due to increased exposure.