The government is now operating in accordance with the Guidance on Caretaker Conventions, pending the outcome of the 2025 federal election.
Cardiac conduction disorders have been reported in patients receiving donepezil. The Product Information (PI) documents for this medicine are being updated to advise caution in patients with known QTc prolongation or a family history of this condition. Additionally, caution is advised in patients also receiving other drugs that affect the QTc interval, or who have certain types of cardiac disease (see below) or electrolyte disturbances. As these adverse effects can be severe and potentially life threatening, clinical monitoring may be required.
Donepezil hydrochloride is a cholinesterase inhibitor that enhances cholinergic function in the central nervous system. It is indicated for the treatment of mild, moderate and severe Alzheimer's disease.
It is marketed in Australia as Aricept and various generic brands.
The following warning has been added to 'Cardiovascular conditions' in the 'Special warnings and precautions for use' section (4.4) of the Aricept PI for donepezil:
'Cases of QTc interval prolongation and Torsades de Pointes have been reported for donepezil (see sections 4.4 and 4.8). Caution is advised when donepezil is used in combination with other medicinal products known to prolong the QTc interval and clinical monitoring may be required. Examples include:
- Class IA antiarrhythmics (e.g. disopyramide)
- Class III antiarrhythmics (e.g. amiodarone, sotalol)
- Certain antidepressants (e.g. citalopram, escitalopram, amitriptyline)
- Other antipsychotics (e.g. phenothiazine derivatives, pimozide, ziprasidone)
- Certain antibiotics (e.g. clarithromycin, erythromycin, moxifloxacin)'
In the 'Adverse effects' section (4.8) of the Aricept PI for donepezil, 'electrocardiogram QT interval prolonged' and 'polymorphic ventricular tachycardia including Torsades de Pointes' have been added to the post-marketing experience list.
Post-marketing adverse event data
The PI updates are based on evidence published in the literature and from post-market adverse event data in Australia and internationally.[1]
To 5 January 2022, there have been 18 cases of atrioventricular block, atrioventricular block complete, atrioventricular block second degree, bundle branch block, bifascicular block or Torsades de Pointes associated with donepezil reported to the TGA and included in our Database of Adverse Event Notifications (DAEN).
Information for health professionals
Health professionals should be aware of any pre-existing or family history of cardiac disease, significant electrolyte changes and relevant drug interactions when prescribing donepezil for a patient.
The cardiac conduction disorders caused by donepezil can be potentially life threatening, so monitoring of cardiac function may be required in at-risk individuals or where this adverse event is suspected.
Reference
| [1] | Kho J, Ioannou A, Mandal AKJ et al. 2021. Long term use of donepezil and QTc prolongation - external site. Clin Toxicol (Phila). 2021 Mar;59(3):208-214. doi: 10.1080/15563650.2020.1788054. Epub 2020 Jul 1. |
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What to report? You don't need to be certain, just suspicious!
The TGA encourages the reporting of all suspected adverse reactions to medicines, including vaccines, over-the-counter medicines, herbal, traditional or alternative remedies.
We particularly request reports of:
- all suspected reactions to new medicines (look for the Black Triangle in PI and CMI documents - this symbol identifies medicines that are new or being used differently)
- all suspected medicines interactions
- suspected reactions causing death, admission to hospital or prolongation of hospitalisation, increased investigations or treatment, or birth defects.
Reports may be submitted:
- online at www.tga.gov.au
- by fax to 02 6232 8392
- by email to ADR.Reports@tga.gov.au
For more information about reporting, visit www.tga.gov.au or contact the TGA's Pharmacovigilance and Special Access Branch ADR.Reports@tga.gov.au.
Disclaimer
Medicines Safety Update is aimed at health professionals. It is intended to provide practical information to health professionals on medicine safety, including emerging safety issues. The information in Medicines Safety Update is necessarily general and is not intended to be a substitute for a health professional's judgment in each case, taking into account the individual circumstances of their patients. Reasonable care has been taken to ensure that the information is accurate and complete at the time of publication. The Australian Government gives no warranty that the information in this document is accurate or complete, and shall not be liable for any loss whatsoever due to negligence or otherwise arising from the use of or reliance on this document.
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For correspondence or further information about Medicines Safety Update, contact the TGA's Pharmacovigilance and Special Access Branch at ADR.Reports@tga.gov.au.
Medicines Safety Update is written by staff from the Pharmacovigilance Branch.
Editor: Dr Catherine Brogan
Deputy Editor: Mr Michael Pittman
Contributors: Mr Gilbert Yeap, Ms Rebecca Page