Aklief Use In Pregnancy & Lactation

Orally administered retinoids have been associated with congenital abnormalities. When used in accordance with the prescribing information, topically administered retinoids are generally assumed to result into low systemic exposure due to minimal dermal absorption. However, there could be individual factors (e.g. damaged skin barrier, excessive use) that contribute to an increased systemic exposure.
It is difficult to determine the exact time frame in which a patient's system would be completely free of trifarotene. The clinical pharmacology results demonstrated that trifarotene 50 μg/g cream under maximal use conditions for 4 weeks in patient with acne vulgaris had a low systemic exposure, being non-quantifiable in most of the subjects. However, the daily application of 100 μg/g cream for 4 weeks resulted in quantifiable drug levels, but still with a low systemic exposure, with a short terminal half-life ranging from 2.4 to 9.1 hours and without accumulation after repeated topical application. One could assume that nearly all the drug would be gone after approximately 3.5 days following the last application. In three and a half days, over 9 half-lives will have been completed. It takes about 5 half-lives for 97% of a drug to be eliminated and 7 half-lives for about 99% of a drug to be eliminated.
Effects on fertility: No human fertility studies were conducted with Aklief.
Trifarotene showed no adverse effects on functional fertility in rats administered orally at exposures of approximately 1755 (males) and 1726 (females) times the 2 g dose in humans. However, after oral administration to dogs, Germ cell degeneration with pyknotic/apoptotic germ cells was evident from the lowest dose tested of 0.2 mg/kg/day corresponding to a systemic exposure 1368 times higher than those observed in humans. All animals with this finding also showed hypospermatogenesis and debris in the epididymides. The findings did not completely recover after 8 weeks, suggesting an extended and possibly chronic effect. As these effects were noted also at the lowest dose tested, the relevance of the findings for lower doses is unknown.
Use in pregnancy: Aklief is contraindicated (see Contraindications) during pregnancy or in women planning a pregnancy. If the product is used during pregnancy, or if the patient becomes pregnant while taking this drug, treatment should be discontinued.
In animal reproduction studies, oral administration of trifarotene in pregnant rats and rabbits during organogenesis was teratogenic and embryotoxic at exposures (AUC) that were >800-times those observed in humans at the maximum recommended human dose (MRHD) of 2 g. Trifarotene was not teratogenic in rats and rabbits at systemic exposures corresponding to approximately 500 and 90-times, respectively, those observed in humans.
Use in lactation: It is unknown whether trifarotene or its metabolites are excreted in human milk.
Available data in animals have shown excretion of trifarotene and/or its 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 Aklief therapy taking into account the benefit of breast-feeding 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 women should not apply trifarotene cream to the chest or breast area.