12 Donepezil Side Effects You Should Know About

Donepezil is a go-to medication for treating Alzheimer’s-related dementia. It’s a cholinesterase inhibitor, and it works by enhancing acetylcholine levels in the brain. Acetylcholine is a chemical messenger that helps promote memory, attention, and learning.

Donepezil is available as a regular tablet (Aricept), an orally disintegrating tablet (Aricept ODT), and a patch that’s applied to the skin (Adlarity). Donepezil tablets are taken once daily at bedtime, while the patches are applied to the skin once weekly. Both versions are approved to treat mild, moderate, and severe stages of Alzheimer’s-related dementia.

While donepezil can be a beneficial treatment option for Alzheimer’s-related dementia, there are possible side effects to be aware of. And since Aricept, Aricept ODT, and Adlarity contain the same active ingredient, they share many of the same side effects. The patches, however, are less likely to cause stomach issues than the tablets.

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Below, we’ll discuss 12 of the most notable donepezil side effects and how to manage them.

Donepezil side effects at a glance

Donepezil can cause several side effects. Some are mild and pass quickly, while others are more intense.

Common donepezil side effects include:

• Nausea and vomiting

• Diarrhea

• Constipation

• Less appetite

• Weight changes

• Application site reactions (patches only)

• Insomnia

• Headache

• Dizziness

• Fatigue

• Muscle cramps

Rare but serious donepezil side effects include:

• Slower heartbeat

• Stomach bleeding

• Fainting

• Bladder problems

• Complications during anesthesia

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1. Nausea and vomiting

Gut-related side effects, such as nausea and vomiting, can make it difficult to continue taking the medication. Here are some strategies to help manage these common donepezil side effects.

Nausea

Nausea is one of the most common gut-related donepezil side effects. In clinical trials, more than 10% of people taking the tablets had nausea. However, nausea wasn’t seen with Adlarity.

Thankfully, this side effect is usually short-lived. It’s more likely when you first start taking donepezil or increase your dose. It should improve as your body gets used to the medication.

There are a few things you can do to minimize nausea in the meantime:

• Take donepezil with food.

• Eat smaller meals and lower-fat foods.

• Ask a pharmacist or neurologist if you can take an over-the-counter (OTC) antinausea medication, such as dimenhydrinate (Dramamine), for short-term relief.

Vomiting

It’s less common to experience vomiting from donepezil, but it’s possible. Vomiting happens as a result of uncontrolled nausea.

Vomiting is especially concerning among older adults. Loss of fluids from persistent or intense vomiting can cause dehydration. When older adults are dehydrated, they’re more likely to experience confusion, low blood pressure, or bladder problems. 

Sometimes, oral rehydration — such as sports drinks or coconut water — can help you recover from symptoms of vomiting. But it’s important to know when to go to the ER. If you’re vomiting and also having severe abdominal pain, trouble urinating, or confusion, seek medical attention right away. You might need to receive fluid through a vein to get rehydrated.

2. Diarrhea

Donepezil, especially donepezil tablets, are linked to diarrhea. Like nausea, this side effect usually improves as your body gets used to the medication.

If you experience diarrhea after taking donepezil, make sure you stay hydrated and watch for symptoms of dehydration. Small diet changes may help with mild cases of diarrhea. Avoid spicy and greasy foods, as well as foods high in fiber, such as lentils, broccoli, and granola.

You can also try an OTC antidiarrheal medication, such as loperamide (Imodium A-D). But these medications should only be used for a couple of days at a time. Talk to your neurologist if you need treatment for longer than that.

3. Appetite and weight changes

In some cases, nausea and vomiting can lead to a decreased appetite and weight loss. Appetite and weight changes are more likely with higher donepezil doses and should go away with time. Appetite and weight changes aren’t commonly reported with Adlarity.

Regardless, it’s always ideal to avoid unintended weight loss. If you’re caring for a loved one taking donepezil and are concerned about significant weight loss, talk to their neurologist. They can give you tips on preventing further weight loss. This may include tracking meals and talking with a dietitian.

4. Trouble sleeping

Some people taking donepezil can experience insomnia (trouble sleeping) and nightmares. This side effect is more common with higher doses, but it should improve within a few weeks.

In cases like these, minor changes to your medication routine can make a big difference. Ask your neurologist about taking donepezil in the morning instead of the evening if insomnia or nightmares continue.

However, dementia itself can also cause sleep troubles. If donepezil isn’t the only possible culprit for insomnia, a neurologist can offer other tips for relief.

5. Headache

People taking donepezil may experience headaches. They’re reported relatively often for both the tablets and patches.

If you have a headache after starting donepezil, try to stay hydrated and get plenty of rest. OTC pain relievers such as acetaminophen (Tylenol) may help. But talk to your pharmacist or neurologist before starting any new medication to make sure it’s safe.

6. Muscle cramps

Some people have muscle cramps while taking donepezil — especially with higher doses. They’re more likely to happen in the early stages of taking the medication, while your body is still getting used to it.

Contact a neurologist if you’re experiencing muscle cramps that interfere with your daily routine. They may initially recommend a medication-free remedy like icing or heating the affected areas. Topical OTC pain relief medications such as diclofenac gel (Voltaren) are another option.

7. Constipation

Constipation can become a long-term donepezil side effect — especially if you’re dehydrated from vomiting or diarrhea or not drinking enough water.

Common signs and symptoms of constipation include: 

• Having fewer bowel movements than normal each week

• Straining or having pain during bowel movements

• Producing stool that’s harder or drier than normal

• Feeling like you can’t get all your stool out

Although mild constipation is common, severe constipation can be a medical emergency. If you notice blood in your stool or you have intense stomach pain, you should go to the ER to get treatment and prevent any complications. 

Good to know: Constipation is a common side effect of several medications. There are many lifestyle changes you can make to help reduce or relieve medication-related constipation. Increasing the amount of fiber in your diet is one way to help resolve constipation.

8. Stomach bleeding

Although rare, donepezil may raise the risk of stomach bleeds. This risk is higher if you’ve had stomach ulcers in the past or take nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin) or naproxen (Aleve, Naprosyn).

Let a neurologist know right away if you notice any signs or symptoms of ulcers or bleeding, such as burning stomach pain, blood in your vomit, or tarry black stool. They’ll likely recommend taking a proton pump inhibitor medication such as omeprazole (Prilosec) to help manage your stomach acid levels. They may also suggest an endoscopy to figure out the root of the issue. An endoscopy is a procedure where your healthcare professional uses a flexible tube with a camera to look inside your stomach. 

9. Slower heartbeat

Rarely, donepezil may cause a slow heartbeat (bradycardia). Taking certain medications with donepezil that also slow your heartbeat can add to this risk. Examples include beta blockers, such as carvedilol (Coreg), and medications that regulate your heartbeat, such as amiodarone (Pacerone).

Let your neurologist know if you have a history of heart problems. They’ll decide if donepezil is safe for you to take. Also, if you feel dizzy, out of breath, or notice a really low heartbeat while taking donepezil, let your neurologist know. Make sure they have a complete list of medications you take so they can also screen for drug interactions.

10. Dizziness and fatigue

Dizziness is a potentially dangerous side effect of donepezil, especially in older adults. It can lead to a higher risk for falls. 

Dizziness typically improves as your body adjusts to your medication. If you feel dizzy or unbalanced on your feet, find a safe and sturdy place nearby to sit or lie down. Try not to move suddenly or change positions until the dizziness resolves.

Your neurologist may suggest taking donepezil at night or closer to bedtime if dizziness becomes too bothersome. This way you can sleep through the side effect rather than dealing with it during the day.

Since fatigue is also a common side effect of donepezil, you should make sure you’re getting enough rest. Too much stress, certain medical conditions, and not getting quality sleep can also make you feel tired. Consuming foods and beverages that are rich in electrolytes can combat sluggishness. 

If you feel unusually tired and it doesn’t get better, contact your neurologist. They may recommend a blood draw to see if low electrolyte levels are the cause of your symptoms. 

11. Fainting

Since donepezil can slow down your heartbeat, this can lead to fainting. Fainting is a rare but serious side effect of donepezil. It could also be a sign of another underlying condition. It can result in injury if you’re not careful. 

You may not be able to prevent fainting, but there are other things you can do to help prevent falls or injury. For example, if you’ve been sitting or lying down for a while, try standing up slowly. Sometimes standing up too fast can cause you to faint. Let your neurologist know if you notice a low heartbeat or dizziness while taking donepezil or if you’ve had fainting episodes in the past. 

12. Application site reactions

Application site reactions are possible with Adlarity patches. The most common side effect is skin redness where you applied the patch. Itching, rash, and swelling can also appear. Most application site reactions are mild and improve after a few days.

To keep your skin free from irritation, make sure to apply the patch to a different area every week. Stop using Adlarity and let your neurologist know right away if you have a rash that’s getting worse, swelling, or blistering, or if your symptoms don’t improve within 48 hours of removing the patch.

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Written by:

Taylor K. Clarke, PharmD

Taylor K. Clarke, PharmD, has 8 years of pharmacy experience working in community practice, hospital pharmacy, and ambulatory care pharmacy. Taylor's commitment to patient education motivated her to pursue health communications as a pharmacist.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

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