Pivikto Use In Pregnancy & Lactation

Pregnancy: Risk summary: Based on animal data and its mechanism of action, alpelisib (Pivikto) can cause fetal harm when administered to a pregnant woman.
There are no adequate and well-controlled studies in pregnant women. Embryo-fetal development studies in rats and rabbits have demonstrated that oral administration of alpelisib during organogenesis induced embryo-toxicity, feto-toxicity, and teratogenicity. In rats and rabbits, following prenatal exposure to alpelisib, increased incidences of post-implantation loss, reduced fetal weights, and increased incidences of fetal abnormalities were observed starting at doses below (see animal data) the exposure in humans at the highest recommended dose of 300 mg.
Alpelisib should not be used during pregnancy unless the benefits to the mother outweigh the risk to the fetus. If alpelisib (Pivikto) is used during pregnancy, the patient should be advised of the potential risk to the fetus.
Data: Animal Data: In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of alpelisib up to 30 mg/kg/day, during the period of organogenesis.
In rats, oral administration of alpelisib was associated with maternal body weight loss or stagnation, low food consumption and embryonal death at 30 mg/kg/day, approximately 3.2 times (based on AUC) the exposure in humans at the highest recommended dose of 300 mg. Low maternal body weight gain, increased incidences of enlarged brain ventricle in the fetuses, reduced fetal weight, decreased bone ossification and skeletal malformations were seen at 10 mg/kg/day, that is equal to approximately 0.9 times below the exposure in humans at the highest recommended dose.
In rabbits, at doses of ≥25 mg/kg/day, maternal body weight loss with reduced food intake was observed. At 15mg/kg/day, slight transient body weight loss was observed. At ≥ 15 mg/kg/day increased embryo-fetal deaths and malformations were observed, mostly related to the tail and head, and were associated with increased serum glucose levels in dams. At 25 mg/kg/day, reduced mean fetal weight was observed. The dose of 15 mg/kg/day dose in rabbits is equivalent to approximately 5.5 times (based on AUC) the exposure achieved at the highest recommended human dose.
In rats and rabbits, no fetal effects were observed at 3 mg/kg/day, and considered to be the no-observable-adverse-effect-level (NOAEL) for fetal abnormalities. The maternal systemic exposures (AUC) at the NOAEL were 0.12 (rats) or 0.86 (rabbits) times the exposure in humans at the highest recommended dose of 300 mg.
Lactation: Risk summary: It is not known if alpelisib is transferred into human or animal milk after administration of alpelisib (Pivikto). There are no data on the effects of alpelisib on the breastfed child or the effects of alpelisib on milk production.
Because of the potential for serious adverse drug reactions in the breastfed child from alpelisib (Pivikto), it is recommended that women should not breastfeed during treatment and for at least 4 days after the last dose of alpelisib (Pivikto).
Females and males of reproductive potential: Pregnancy testing: The pregnancy status for females of reproductive potential should be verified prior to starting treatment with alpelisib (Pivikto).
Contraception: Females of reproductive potential should be advised that animal studies and the mechanism of action have shown that alpelisib can 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 alpelisib (Pivikto) during treatment and for at least 4 days after stopping treatment with alpelisib. It is currently unknown whether alpelisib may reduce the effectiveness of systemically acting hormonal contraceptives.
Male patients with sexual partners who are pregnant, possibly pregnant, or who could become pregnant should use condoms during sexual intercourse while taking alpelisib (Pivikto) and for at least 4 days after stopping treatment with alpelisib (Pivikto).
Infertility: There are no clinical data available on the effect of alpelisib on fertility. Based on repeat dose toxicity studies in animals, alpelisib (Pivikto) may impair fertility in males and females of reproductive potential (see PHARMACOLOGY: TOXICOLOGY: NON-CLINICAL SAFETY DATA under ACTIONS). In fertility studies conducted in male and female rats, similar effects were observed (see PHARMACOLOGY: TOXICOLOGY: NON-CLINICAL SAFETY DATA under ACTIONS).