Donepezil: 7 things you should know
Medically reviewed by Carmen Pope, BPharm. Last updated on April 5, 2023.
1. How it works
- Donepezil may be used for the treatment of Alzheimer's Disease (AD).
- Donepezil enhances the effects of acetylcholine (a neurotransmitter) by blocking an enzyme responsible for its breakdown. Deficits in acetylcholine are thought to affect cognition and behavior, impair everyday functioning and contribute to the symptoms of AD.
- Donepezil belongs to the group of medicines known as cholinesterase inhibitors.
- Donepezil may be used to treat mild, moderate, and severe Alzheimer’s disease (AD).
- Modestly relieves the symptoms of AD.
- The initial dosage for oral donepezil is 5mg per day which may be increased to 10mg per day. Dosages above 10mg/day have not been shown to provide any substantially greater clinical benefit. However, some patients may benefit from higher dosages. The maximum recommended dosage is 23 mg/day.
- Available as conventional and orally disintegrating tablets.
- Also available as a transdermal patch (Adlarity) that is applied once a week. This is the first and currently only patch for AD.
- Transdermal patches are available in the 5- and 10-mg/day formulations which allow easy switching for people from oral 5 or 10 mg/day donepezil directly to the transdermal patches by their prescriber.
- Patches can be placed on a hairless region of the back, buttock, or thigh.
- May be used in combination with memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist. A fixed combination of donepezil and memantine (Namzaric) is available to those receiving donepezil at a stable dose of 10mg/day. The initial dosage of Namzaric should be reduced in kidney disease to 10mg donepezil/7mg memantine before increasing after one week to 10mg donepezil/14mg memantine.
- Oral tablets may be administered with or without food.
- No dosage adjustments are needed for people with liver or kidney disease.
- Generic donepezil is available, which has increased the affordability of this treatment for people with AD.
If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:
- Diarrhea, nausea, and vomiting are common; prevalence increases with higher dosages and may be higher in those of a lower weight. Symptoms are usually transient and most resolve after one to three weeks of continued treatment. Muscle cramps, weight loss, and fatigue are also common.
- May increase gastric acid secretion and increase the risk of gastrointestinal bleeding and stomach ulcers. The risk is enhanced in people on concomitant non-steroidal anti-inflammatory drugs (NSAIDs).
- May produce a slow heart rate (bradycardia) or heart block via an effect on the sinoatrial or AV nodes, even in people without any known cardiac conduction abnormalities.
- May cause weight loss at higher dosages, and there is a potential to inhibit urine flow or induce seizures. If a dosage increase from 5 mg/day to 10 mg/day is deemed necessary, then this may be considered after 4 to 6 weeks on 10 mg/day to reduce the incidence of side effects.
- Allow four to six weeks before increasing the dosage from 5mg to 10mg. People with mild-to-moderate AD should take no more than the maximum recommended dose of 10mg once daily. For people with severe AD, the dose may be increased to 23mg once daily after three months of taking 10mg once daily.
- May not be suitable for people with certain heart conditions, a history of seizures, stomach ulcers, difficulty passing urine, or lung conditions such as asthma or COPD.
- Caution is needed in people taking donepezil who require anesthesia. Discuss with an anesthetist.
- May interact with several other drugs including aspirin, those metabolized through CYP2D6, and anticholinergics (such as dicyclomine or scopolamine).
- Only provides a modest benefit and does not alter the underlying disease process.
- Donepezil is not a cure for AD and some people do not respond as well as others.
- Not recommended during pregnancy or lactation.
Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects
4. Bottom Line
Donepezil boosts the effects of acetylcholine, a neurotransmitter that is noticeably depleted in people with Alzheimer's disease. Side effects are more likely at higher dosages and include nausea, vomiting, and diarrhea which may force drug discontinuation.
- Oral donepezil should be taken once daily in the evening, just before going to bed. Can be taken with or without food.
- Take oral donepezil exactly as directed by your doctor. Do not take more than recommended. Do not share your donepezil with other people as it may harm them. If you forget to take a tablet, do not double up on a dose, just take only the next dose at the usual time.
- If you have been prescribed donepezil patches (Adlarity), apply them to a hairless region of your back, buttock, or thigh once a week. Remove the old patch before replacing it with a new patch. Rotate patch sites so you are not applying them in the same place every time.
- Donepezil orally disintegrating tablets (ODT) should be allowed to dissolve slowly on the tongue and then followed with a glass of water.
- Talk to your doctor if the side effects you are experiencing from donepezil are intolerable. Call your doctor straight away if you are having dizzy spells or fainting; suffering from indigestion, dyspepsia, or nausea; have a pre-existing lung condition that seems to be getting worse; your stools look like black tar; you are having seizures, or difficulty passing urine.
- Do not take any other medications or supplements with donepezil until you have checked first that they are compatible.
6. Response and effectiveness
- Peak concentrations are reached in three hours for the 10mg tablets compared to eight hours for the 23mg tablets.
- Metabolized to several active metabolites and accumulates with repeated dosing, reaching maximum concentrations for a particular dosage within 15 days. Metabolism is affected in people who are poor or extensive metabolizers of CYP2D6 substrates.
- Some effects may be noticeable within a few days; however, it may take four to six weeks before any significant differences are apparent. Donepezil may not have the same effects for everybody. Some people seem much better whereas others may only improve slightly or donepezil may just slow the rate of their decline in mental functioning.
- Donepezil has been investigated in people with mild cognitive impairment; however, evidence of a benefit is lacking.
- Donepezil transdermal patches release either 5mg or 10mg of donepezil daily for one week.
Medicines that interact with Donepezil may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Donepezil. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.
Common medications that may interact with Donepezil include:
- antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
- beta-blockers, such as atenolol or metoprolol, or other agents that can slow the heartbeat
- cholinesterase inhibitors or cholinergic agonists (eg, bethanechol): additive effect
- corticosteroids, such as dexamethasone or prednisone
- medications metabolized by the same enzymes (CYP1A2, CYP2D6, CYP3A4) such as carbamazepine, dexamethasone, ketoconazole, phenobarbitone, phenytoin, or rifampin
- medications with anticholinergic properties, such as atropine or benztropine
- neuromuscular blocking agents
Unlikely to cause clinically important induction or inhibition of CYP3A4 or CYP2D6. Little or no inhibition of CYP2B6, 2C8, or 2C19. Potent CYP3A4 inhibitors may increase plasma concentrations of donepezil. Potent CYP2D6 inhibitors may increase the systemic exposure of donepezil by 17% to 20%. CYP3A4 inducers are likely to increase donepezil metabolism.
May exaggerate the effects of some muscle relaxants (eg, succinylcholine) during anesthesia.
Avoid drinking alcohol or taking illegal or recreational drugs while taking Donepezil.
Note that this list is not all-inclusive and includes only common medications that may interact with Donepezil. You should refer to the prescribing information for Donepezil for a complete list of interactions.
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- Donepezil. Updated 12/2022. ACI Healthcare USA, Inc. https://www.drugs.com/pro/donepezil.html
Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use donepezil only for the indication prescribed.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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