Use is not recommended.

US FDA pregnancy category: Not assigned.

Risk Summary: Based on findings from animal studies and the mechanisms of action, this combination drug can cause fetal harm when administered to a pregnant woman. Administration of letrozole to pregnant animals during organogenesis caused increased post-implantation pregnancy loss and resorptions, fewer live fetuses, and fetal malformations affecting the renal and skeletal systems. Administration of ribociclib to pregnant animals during organogenesis resulted in increased incidences of postimplantation loss and reduced fetal weights increased incidences of fetal abnormalities.

Comments:
Based on animal studies and mechanisms of action, this combination drug can cause fetal harm when administered to a pregnant woman.
-Obtain a pregnancy test in females of reproductive potential prior to therapy initiation.
-Advise females of reproductive potential to use effective contraception (methods that result in less than 1% pregnancy rates) during therapy and for at least 3 weeks after the last dose.
-Animal studies indicate the potential for fertility impairment in both males and females.

-Animal data with letrozole have revealed evidence of embryotoxicity, fetotoxicity, and teratogenicity with doses much smaller than the daily maximum recommended human dose on a mg/m2 basis. Adverse effects included intrauterine mortality, pre- and post-implantation pregnancy loss and resorptions, fewer live fetuses, congenital malformations affecting the renal and skeletal systems, and reduced fertility including decreased incidence of successful mating and pregnancy, sexual inactivity in females, and reproductive tract atrophy in males and females.
-Animal studies with ribociclib have shown reduced maternal body weight gain, reduced fetal weights (accompanied by skeletal changes), and increased incidences of post-implantation loss and fetal abnormalities (malformations, and external, visceral, and skeletal variants) at exposures approximately 0.6 and 1.5 times the exposure in humans at the highest recommended dose of 600 mg/day based on AUC. Administration of ribociclib to animals also resulted in atrophic changes in testes (e.g., degeneration of seminiferous tubular epithelia in the testes; hypospermia, luminal cellular debris, and vacuolation of epithelia in the epididymides) with a trend towards reversibility after a 4-week non-dosing period.
-There are no controlled data in human pregnancy.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D and X are being phased out.

See references

Use is not recommended.

Excreted into human milk: Unknown (letrozole, ribociclib)
Excreted into animal milk: Yes (letrozole, ribociclib)

Comments:
-Because of the potential for serious adverse reactions in breastfed infants from this combination drug, advise lactating women not to breastfeed while taking it and for at least 3 weeks after.

-Animal data with letrozole have shown doses as low as 0.003 mg/kg/day (approximately 0.01 the maximum recommended human dose on a mg/m2 basis) administered on day 0 to day 20 of lactation resulted in impaired reproductive performance of the male offspring (as reflected by decreased mating and pregnancy ratios), but no effects on the reproductive performance of female offspring were observed.
-In lactating animals administered a ribociclib dose of 50 mg/kg, drug exposure was 3.56-fold higher in milk compared to maternal plasma. Because protein binding of ribociclib is 70%, clinically important amounts of the drug might pass into breastmilk.

See references