Dracenax Use In Pregnancy & Lactation

Pregnancy: Risk summary: Letrozole is contraindicated in women who are pregnant (see Contraindications). Letrozole may cause fetal harm when administered to a pregnant woman. The patient should be apprised of the potential risk to the fetus, if letrozole is used during pregnancy or if the patient becomes pregnant while taking this drug.
There are no clinical trials conducted in pregnant women with letrozole. However, there are post-marketing reports of spontaneous abortions and congenital anomalies in infants of mothers who took letrozole during pregnancy (see Precautions). Reproductive toxicity studies in rats demonstrated letrozole induced embryotoxicity and fetotoxicity as well as teratogenicity. Letrozole caused adverse pregnancy outcomes, including congenital malformations, in rats and rabbits at doses much smaller than the daily maximum recommended human dose (MHRD) on a mg/m² basis. Observed effects included increased post-implantation pregnancy loss and resorptions, fewer live fetuses, and fetal malformations affecting the renal and skeletal systems.
Isolated cases of birth defects (labial fusion, ambiguous genitalia) have been reported in infants born to women exposed off label use (infertility treatment, ovulation induction) of letrozole during pregnancy.
Animal data: In embryo-fetal development studies, pregnant rats received oral doses of letrozole up to 0.03 mg/kg/day during the period of organogenesis. Reproduction studies in rats showed embryotoxicity and fetotoxicity at letrozole doses ≥0.003 mg/kg during organogenesis which is equal to or greater than 1/100 the MHRD (mg/m² basis). Embryo-and fetotoxic effects observed at doses ≥0.003 mg/kg included intrauterine mortality, increased resorption, increased post-implantation loss, decreased number of live fetuses and fetal anomalies including shortening of renal papilla, dilation of ureter, edema and skeletal variations. Letrozole doses of 0.03 mg/kg which is 1/10 the MHRD (mg/m² basis) were teratogenic and caused fetal domed head and cervical/centrum vertebral fusion.
In the embryo-fetal development study in pregnant rabbits, oral administration of letrozole was associated with signs of embryotoxicity and fetotoxicity at doses ≥0.006 mg/kg/day, as indicated by increased resorption, increased post implantation loss and decreased numbers of live fetuses. There was no evidence of teratogenicity.
Lactation: Risk summary: Letrozole is contraindicated during lactation (see Contraindications).
It is not known if letrozole is excreted in human milk. There are no data on the effects of letrozole on the breastfed child or the effects of letrozole on milk production. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from letrozole, a nursing woman should be advised on the potential risks to the child. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for letrozole and any potential adverse effects on the breast-fed child from letrozole or from the underlying maternal condition.
Data: Animal data: Exposure of lactating rats to letrozole was associated with an impaired reproductive performance of the male offspring at a letrozole dose as low as 0.003 mg/kg/day. There were no effects on the reproductive performance of female offspring.
Females and males of reproductive potential: Contraception: The physician needs to discuss the necessity of adequate contraception with women who have the potential to become pregnant including women who are perimenopausal or who recently became postmenopausal, until their postmenopausal status is fully established.
Letrozole of reproductive potential should be advised that human data and animal studies have shown letrozole to be harmful to the developing fetus. Sexually-active females of reproductive potential should use effective contraception (methods that result in less than 1% pregnancy rates) when using letrozole during treatment and for 20 days (5 x T½) after stopping treatment with letrozole.
Infertility: Fertility studies in rats showed that letrozole has adverse effects on male and female fertility at doses relevant to man. Exposure of letrozole to lactating rats was associated with an impaired reproductive performance of the male offspring at a letrozole dose as low as 0.003 mg/kg/day. There were no effects on the reproductive performance of female offspring.
In a juvenile rat study, decreased fertility at all doses (lowest dose at 0.003 mg/kg/day) was accompanied by hypertrophy of the hypophysis, testicular changes which included a degeneration of the seminiferous tubular epithelium and atrophy of the female reproductive tract. With the exception of bone size in females and morphological changes in the testes, all effects were at least partially reversible. Based on animal studies, letrozole may impair fertility in males of reproductive potential.