Cholinesterase Inhibitor (CNS Agent)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of donepezil in human pregnancy have been located. Because of its indication, such reports should be rare. Moreover, the animal data suggest that the risk to the embryo and/or fetus is low. Therefore, inadvertent exposure to donepezil during pregnancy should not be a reason for pregnancy termination.
FETAL RISK SUMMARY
Donepezil (known previously as E2020) is a reversible cholinesterase inhibitor that is indicated for the treatment of mild-to-moderate dementia of the Alzheimer’s type. Two metabolites of donepezil are known to be active. The drug is extensively protein bound (about 96%) in the plasma, primarily to albumin (about 75%) and α1-acid glycoprotein. The plasma elimination half-life is about 70 hours (1,2).
Reproduction studies have been conducted in rats and rabbits. In rats, doses up to about 13 times the maximum recommended human dose based on BSA (MRHD) were not teratogenic. At 8 times the MRHD given from gestational day 17 through postpartum day 20, there was a slight increase in stillbirths and a slight decrease in pup survival through postpartum day 4. Donepezil had no effect on rat fertility at doses up to about 8 times the MRHD. In rabbits, no teratogenic effects were observed at a dose 16 times the MRHD (1,2).
It is not known if donepezil or its active metabolites cross the human placenta. The molecular weight of the parent compound (about 416) and its long plasma elimination half-life suggest that the drug will cross to the embryo–fetus, but the extensive protein binding will limit this transfer.
BREASTFEEDING SUMMARY
No reports describing the use of donepezil during human lactation have been located. Because of its indication, such reports should be rare. Donepezil has two active metabolites. The molecular weight of the parent compound (about 416) and its long plasma elimination half-life (about 70 hours) suggest that donepezil, and possible the active metabolites, will be excreted into breast milk. The extensive protein binding (about 96%), however, should limit this excretion. The effects of this exposure on a nursing infant are unknown.
References
1.Product information. Aricept. Eisai, 2004.
2.Product information. Aricept. Pfizer, 2004.