Tykerb Use In Pregnancy & Lactation

Pregnancy: Risk Summary: Based on findings in animal studies and its mechanism of action, TYKERB can cause fetal harm when administered to a pregnant woman [see Pharmacology: Mechanism of Action under Actions]. There are no available human data to inform of the drug-associated risks. In an animal reproduction study, administration of lapatinib to pregnant rats during organogenesis and through lactation led to death of offspring within the first 4 days after birth at maternal exposures that were ≥ 3.3 times the human clinical exposure based on AUC following 1,250 mg dose of lapatinib plus capecitabine. When administered to pregnant animals during the period of organogenesis, lapatinib caused fetal anomalies (rats) or abortions (rabbits) at maternally toxic doses (see Data as follows).
Advise pregnant women and females of reproductive potential of the potential risk to the fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.
Data: Animal Data: In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of lapatinib at 30, 60, and 120 mg/kg/day during the period of organogenesis. Minor anomalies (left-sided umbilical artery, cervical rib, and precocious ossification) occurred in rats at the maternally toxic dose of 120 mg/kg/day (approximately 6.4 times the human clinical exposure based on AUC following 1,250 mg dose of lapatinib plus capecitabine). In rabbits, lapatinib was associated with maternal toxicity at 60 and 120 mg/kg/day (approximately 0.07 and 0.2 times the human clinical exposure, respectively, based on AUC following 1,250 mg dose of lapatinib plus capecitabine) and abortions at 120 mg/kg/day. Maternal toxicity was associated with decreased fetal body weights and minor skeletal variations.
In a pre- and post-natal development study, rats were given oral doses of 20, 60, and 120 mg/kg/day during gestation through lactation up to weaning. In rats, doses of 60 and 120 mg/kg/day (approximately 3.3 and 6.4 times the human clinical exposure, respectively, based on AUC following 1,250 mg dose of lapatinib plus capecitabine) led to decrease in F1 postnatal survival (91% and 34% of the pups died by the fourth day after birth, at 60 and 120 mg/kg/day, respectively).
Lactation: Risk Summary: There are no data on the presence of lapatinib in human milk, or its effects on the breastfed child, or milk production. Because of the potential for serious adverse reactions in a breastfed child from TYKERB, advise lactating women not to breastfeed during treatment with TYKERB and for 1 week after the last dose.
Females and Males of Reproductive Potential: Pregnancy Testing: Verify the pregnancy status of females of reproductive potential prior to the initiation of TYKERB.
Contraception: Females: Based on findings in animal studies, TYKERB can cause fetal harm when administered to a pregnant woman [see Pregnancy as previously mentioned]. Advise females of reproductive potential to use effective contraception during treatment with TYKERB and for 1 week after the last dose.
Males: Based on findings in animal reproduction studies, advise male patients with female partners of reproductive potential to use effective contraception during treatment with TYKERB and for 1 week after the last dose [see Pregnancy as previously mentioned].