The Pharmacovigilance Risk Assessment Committee (PRAC), based on the assessment of the analysis of Periodic Safety Update Reports (PSURs) for medicinal products containing donepezil (donepezil), made the following conclusions.
In view of several literature reports (Segrec et al. 2015, six case reports published by Triquet 2017, Lo Coco and Cannizzaro 2010, Chemali 2003), in which the temporal relationship between the start of donepezil intake and the onset of hypersexuality, as well as the rapid disappearance of symptoms after discontinuation of donepezil and recurrence soon after restarting treatment in some cases, strongly support a relationship between the occurrence of hypersexuality and the use of donepezil, PRAC recommends adding the terms increased libido and hypersexuality to the instructions for medical use.
Based on the available data, including literature articles and relevant post-marketing cases demonstrating improvement or resolution of sleep-related adverse reactions after switching from evening to morning dosing, PRAC recommends including advice on switching to morning dosing if sleep-related adverse reactions occur.
Given the available data, including post-registration reports and several literature reports indicating a causal relationship between donepezil and pleurothotonus, including a case with a positive test for re-administration and repeated withdrawal (de-challenge), two literature cases with repeated withdrawal of the medicinal product and re-administration (de-challenge, re-challenge), and also taking into account the likely mechanisms of dopaminergic-cholinergic imbalance, PRAC recommends adding Pisa syndrome / pleurothotonus to the instructions for medical use with the frequency “Not known.”
The Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) agrees with the scientific conclusions drawn by the PRAC.
Based on the scientific conclusions, the CMDh considers that the benefit/risk balance of medicinal products containing donepezil remains unchanged, subject to the appropriate changes being made to the instructions for medical use.
Changes that should be included in the relevant sections of the instructions for medical use (new text underlined in bold, deleted text struck through).
Section “Posology and method of administration”
Method of administration
<Name of the medicinal product> should be taken orally, in the evening, immediately before bedtime.
In case of sleep disturbances, including unusual dreams, nightmares or insomnia (see the section "Adverse reactions"), taking <name of the medicinal product> in the morning may be considered.
“Adverse reactions” section
The following adverse reaction with the frequency “not known” should be added to the section “Psychiatric disorders”:
increased libido, hypersexuality
The following adverse reaction with frequency “not known” should be added to the section “Nervous system disorders”:
Pleurothotonus (Pisa syndrome)
Перелік лікарських засобів, що містять донепезил (donepezil) і дозволені до медичного застосування в Україні (за даними Державного реєстру лікарських засобів станом на 07.12.2022).
For the analysis of the published information, the applicant must use the original text available at the link:
