Aklief Use In Pregnancy & Lactation

Use in Pregnancy: Studies in animals with trifarotene by the oral route have shown reproductive toxicity at high systemic exposure.
If the product is used during pregnancy, or if the patient becomes pregnant while taking this drug, treatment should be discontinued.
Risk Summary: Available data from clinical trials with AKLIEF Cream use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. These are case reports of major birth defects similar to those seen in fetuses exposed to oral retinoids in pregnant women exposed to other topical retinoids, but these case reports do not establish a pattern or association with retinoid-related embryopathy.
In animal reproduction studies, oral doses of trifarotene administered to pregnant rats and rabbits during organogenesis that resulted in systemic exposures more than 800 times the systemic exposure at the maximum recommended human dose (MRHD) of Trifarotene (Aklief) Cream resulted in adverse fetal effects, including fetal deaths and external, visceral, and skeletal malformations.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
Use During Lactation: Risk Summary: There are no data on the presence of trifarotene in human milk, the effects on the breastfed infant, or the effects on milk production. In animal studies, trifarotene was present in rat milk with oral administration of the drug. When a drug is present in animal milk, it is likely that the drug will be present in human milk. It is possible that topical administration of large amounts of trifarotene could result in sufficient systemic absorption to produce detectable quantities in human milk (see Clinical Considerations as follows). The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Trifarotene (Aklief) Cream and any potential adverse effects on the breastfed infant from Trifarotene (Aklief) Cream or from the underlying maternal condition.
Clinical Considerations: To minimize potential exposure to the breastfed infant via breastmilk, use AKLIEF Cream on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply AKLIEF Cream directly to the nipple and areola to avoid direct infant exposure.
It is unknown whether trifarotene or its metabolites are excreted in human milk.
Available pharmacodynamic/toxicological data in animals have shown excretion of Trifarotene/metabolites in milk.
A risk to the suckling child cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Trifarotene (Aklief) therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
To avoid the risk of ingestion by, and/or contact exposure of, an infant, nursing woman should not apply Trifarotene (Aklief) cream to the chest or breast area.
It is unknown whether trifarotene is excreted in human milk following the use of Trifarotene (Aklief) cream.
Oral animal studies have shown that trifarotene is excreted in the milk of lactating rats.
In a two-generation study in rats, no relevant plasma levels were detectable in pups of treated mothers indicating very low exposure during lactation.
No adverse effects due to trifarotene were evident in those animals during development. However, because many drugs are excreted in human milk, precaution should be exercised when Trifarotene (Aklief) is administered to a nursing mother.
To avoid exposure of the infant, application of Trifarotene (Aklief) to the chest should be avoided when used during breast-feeding.
Fertility: No human fertility studies were conducted with Aklief.
No effects of trifarotene on fertility were found in rats in reproductive studies of oral administration. After oral administration to dogs, findings of Germ cell degeneration were observed at doses that resulted in systemic exposure 1170 times those in human at the MRHD of Trifarotene (Aklief) Cream.