Depakote (divalproex sodium) is a brand-name drug prescribed for bipolar disorder and epilepsy and to help prevent migraine. Depakote has interactions with some other drugs and certain supplements. Examples include hormonal birth control and aspirin.
Depakote is prescribed for bipolar disorder, epilepsy, and migraine in adults. The drug is also prescribed for epilepsy in children ages 10 years and older.
An interaction occurs when one substance causes another substance to have a different effect than expected.
Depakote comes in different forms, and they have the same interactions. The forms are:
- extended-release oral tablets*
- delayed-release oral tablets†
- delayed-release sprinkle capsules
To learn more about Depakote’s interactions, keep reading. For additional information about Depakote, including details about its uses, see this article.
* Extended-release means the drug is slowly released into your body over a long period of time.
† Delayed-release means the drug is released into your body after it passes through your stomach.
In some cases, factors or conditions could prevent your doctor from prescribing Depakote due to the risk of harm. These are known as contraindications. The Depakote contraindications include:
Having liver disease
Doctors typically won’t prescribe Depakote for people with liver disease, including liver failure. This is because Depakote may cause liver damage, which can worsen liver disease.
In fact, Depakote has a
If you have liver disease, talk with your doctor before taking Depakote. They’ll likely prescribe a treatment other than Depakote for your condition.
Having a certain mitochondrial disorder
Doctors typically won’t prescribe Depakote for people with a certain mitochondrial disorder that affects the liver.
Mitochondrial disorders are genetic (inherited) conditions. With these disorders, the mitochondria in your body’s cells don’t make enough energy. This can lead to a variety of symptoms that affect many areas of your body.
A specific type of mitochondrial disorder can affect the liver and may lead to liver failure. Depakote may cause liver damage, which can worsen this condition.
In fact, Depakote has a
If you have a mitochondrial disorder that affects your liver, talk with your doctor before taking Depakote. They’ll likely prescribe a treatment other than Depakote.
Having urea cycle disorder
Doctors typically won’t prescribe Depakote for people with a genetic (inherited) condition called urea cycle disorder (UCD).
With UCD, your body doesn’t remove ammonia from the body as well as it should. This can lead to high blood ammonia levels, which may result in a certain type of brain damage. Taking Depakote may further increase this risk in people with UCD.
If you have UCD, talk with your doctor before taking Depakote. They’ll likely prescribe a treatment other than Depakote for your condition.
Having the ability to become pregnant or being pregnant while taking Depakote to prevent migraine
Doctors typically won’t prescribe Depakote to help prevent migraine during pregnancy. They’re also unlikely to prescribe the drug for this use if you’re able to become pregnant and are not using effective birth control.
This is because Depakote may not be safe to take during pregnancy. In fact, the drug has a
For migraine prevention during pregnancy, your doctor can recommend a different treatment that’s safe for use in pregnancy. If you’re able to become pregnant, your doctor can advise you on birth control* options to use while taking Depakote for migraine prevention.
* Depakote can interact with hormonal birth control. To learn more, see “Drug interactions in depth” below.
Having had an allergic reaction to Depakote or any of its ingredients
If you have had an allergic reaction to Depakote or any of its ingredients, your doctor will likely not prescribe Depakote. Taking the drug could cause another allergic reaction. You can ask them about other treatments that may be better choices for you.
Note: Before you start treatment with Depakote, it’s important to tell your doctor if these contraindications apply to you. They can determine whether to prescribe Depakote.
Depakote isn’t known to interact with alcohol. However, your doctor may advise you to avoid or limit alcohol consumption during Depakote treatment.
This is because drinking alcohol while taking the drug can worsen some of Depakote’s side effects. Examples include sleepiness, dizziness, and loss of coordination. (For details about possible side effects of Depakote, see this article.)
If you drink alcohol, talk with your doctor before taking Depakote. They can recommend how much alcohol, if any, is safe to drink while taking this drug.
Before you start treatment with Depakote, tell your doctor and pharmacist which prescription, over-the-counter, and other medications you take. By sharing this information with them, you may help prevent possible interactions. (To learn whether Depakote interacts with supplements, herbs, or vitamins, see the “Depakote and other interactions” section below.)
If you have questions about drug interactions that may affect you, ask your doctor or pharmacist.
Here’s a table of drugs that can interact with Depakote. Keep in mind that this table doesn’t include all drugs that may interact with Depakote. Some of these interactions are described in detail just below in “Drug interactions in depth.”
Drug class or drug name | Drug examples | Interaction result with Depakote |
certain other antiseizure drugs* | • carbamazepine (Carbatrol, Epitol, others) • phenytoin (Dilantin, Phenytek) • phenobarbital (Sezaby) • lamotrigine (Lamictal, Lamictal XR, others) • topiramate (Topamax, Qudexy XR, others) | can increase the risk of side effects with Depakote† and certain other antiseizure drugs, or make Depakote and certain other antiseizure drugs less effective |
certain benzodiazepines | • diazepam (Valium) • clonazepam (Klonopin) • alprazolam (Xanax) | can increase the risk of side effects of certain benzodiazepines |
certain antibiotics | • ertapenem (Invanz) • meropenem (Merrem) • rifampin (Rifadin, Rimactane) | can increase the risk of side effects with Depakote† or make Depakote less effective |
certain tricyclic antidepressants (TCAs) | • amitriptyline • nortriptyline (Pamelor) | can increase the risk of side effects of TCAs |
certain HIV drugs | • ritonavir (Norvir) • zidovudine (Retrovir) | can make Depakote less effective or increase the risk of side effects of certain HIV drugs |
hormonal birth control | • drospirenone/ethinyl estradiol (Yasmin, Yaz, others) • levonorgestrel/ethinyl estradiol (Seasonale, Seasonique, others) • drospirenone/estetrol (Nexstellis) | can make Depakote less effective |
methotrexate (Otrexup, Rasuvo, others) | — | can make Depakote less effective |
aspirin | — | can increase the risk of side effects with Depakote† |
warfarin (Jantoven) | — | can increase the risk of side effects of warfarin or make warfarin less effective |
* Depakote is a type of antiseizure drug.
† To learn more about Depakote’s side effects, see this article.
Here’s a closer look at certain drug interactions of Depakote.
Certain tricyclic antidepressants
Tricyclic antidepressants (TCAs) are a type of antidepressant. They’re prescribed to treat depression.
Interaction result. Taking Depakote with certain TCAS can increase the risk of side effects of TCAs.
Interaction explained. Depakote may prevent certain TCAs from being broken down in the body as well as they should. As a result, taking Depakote with certain TCAs can raise the level of these TCAs in your body. Having a high level of certain TCAs in your system can increase your risk of side effects from the TCAs.
Examples of TCA drugs. TCAs that may interact with Depakote include amitriptyline and nortriptyline (Pamelor).
Steps you or your doctor may take. Before starting Depakote treatment, tell your doctor if you’re taking a TCA. They can recommend whether it’s safe to take these medications together.
If your doctor tells you it’s safe to take Depakote with a TCA, they may lower your dosage of the TCA. Doing so may help reduce your risk of side effects from the TCA when these drugs are taken together.
Hormonal birth control
Hormonal birth control is prescribed to help prevent pregnancy.
Interaction result. Taking Depakote with hormonal birth control can make Depakote less effective.
Interaction explained. Hormonal birth control may speed up the breakdown of Depakote in your body. This can lead to low levels of Depakote in your system. Having low levels of Depakote in your body may make the drug less effective.
Examples of hormonal birth control. Here are some hormonal birth control drugs that may interact with Depakote:
- drospirenone/ethinyl estradiol (Yasmin, Yaz, others)
- levonorgestrel/ethinyl estradiol (Seasonale, Seasonique, others)
- drospirenone/estetrol (Nextstellis)
Steps you or your doctor may take. If you’re able to become pregnant, your doctor will likely recommend using an effective form of birth control while taking Depakote. This is because Depakote may not be safe to take during pregnancy. In fact, the drug has a
Before taking Depakote, talk with your doctor about your birth control needs. If you take hormonal birth control, your doctor can advise whether it’s safe to take it with Depakote. They may recommend a different form of birth control that’s less likely to affect Depakote. Examples include barrier methods such as condoms or diaphragms.
Aspirin
Aspirin can be used for several purposes. Examples include relieving pain, reducing inflammation, and reducing the risk of heart attack or stroke.
Interaction result. Taking Depakote with aspirin can increase the risk of side effects of Depakote.
Interaction explained. Aspirin may prevent your body from breaking down Depakote as it should. Taking Depakote with aspirin can increase the level of Depakote in your system. Having a high level of Depakote in your body may increase your risk of side effects from the drug. (For details about Depakote’s side effects, see this article.)
Steps you or your doctor may take. Before taking Depakote, be sure to tell your doctor if you take aspirin. Also talk with them before taking aspirin during Depakote treatment. They can recommend options other than aspirin that can relieve pain, reduce inflammation, or reduce the risk of heart attack or stroke. For example, acetaminophen (Tylenol) can be used to relieve pain and isn’t known to interact with Depakote.
Depakote may have other interactions, such as with supplements, foods, vaccines, or even lab tests. You’ll find details below. Keep in mind that the following information does not include all other possible interactions with Depakote.
Depakote interactions with supplements
Sodium bicarbonate (baking soda) supplements may interact with Depakote. Taking this supplement with the drug may increase the risk of side effects from Depakote.* Your doctor can tell you whether it’s safe to take Depakote with sodium bicarbonate supplements.
Before you start treatment with Depakote, tell your doctor and pharmacist which supplements, herbs, and vitamins you take. By sharing this information with them, you may help prevent possible interactions.
If you have questions about drug interactions that may affect you, ask your doctor or pharmacist.
Note: Some drugs can contain sodium bicarbonate as an active ingredient. Examples include Zegerid and Alka-Seltzer.
* For details about possible side effects of Depakote, see this article.
Depakote and herbs
There are no specific reports of herbs interacting with Depakote DR tablets, Depakote ER tablets, or Depakote DR sprinkle capsules. However, that doesn’t mean herbal interactions won’t occur or be recognized in the future. Because of this, it’s important to check with your doctor or pharmacist before taking any of these products during Depakote treatment.
Depakote and vitamins
There are no specific reports of vitamins interacting with Depakote DR tablets, Depakote ER tablets, or Depakote DR sprinkle capsules. However, that doesn’t mean vitamin interactions won’t occur or be recognized in the future. Because of this, you should talk with your doctor or pharmacist before taking any vitamin product with Depakote.
Depakote and food
There were no reports of food interactions with Depakote DR tablets, Depakote ER tablets, or Depakote DR sprinkle capsules.
Sodium bicarbonate (baking soda) supplements* may interact with Depakote. However, this isn’t likely to result in interactions with baked goods or other foods that contain baking soda.
This is because the amount of baking soda in foods is typically much less than what’s in a sodium bicarbonate supplement. This small amount of baking soda is not likely to interact with Depakote. So, it should be safe to eat foods containing baking soda during Depakote treatment.
If you’d like to learn more about eating certain foods during treatment with Depakote, talk with your doctor.
* To learn more, see “Depakote interactions with supplements” above.
Depakote and vaccines
There were no reports of vaccine interactions with Depakote DR tablets, Depakote ER tablets, or Depakote DR sprinkle capsules. If you’d like to learn more about getting certain vaccines while taking Depakote, talk with your doctor.
Depakote interactions with lab tests
Depakote may interact with certain lab tests. The tests and their interaction with Depakote are described in the table below.
Lab test | Purpose of lab test | Interaction with Depakote |
urine ketones | to measure levels of ketones (substances made when the body breaks down fat) in the urine | can make urine ketone levels appear higher than they are |
thyroid function test | to measure levels of thyroid hormones in the blood | can make thyroid hormone levels appear higher or lower than they are |
HIV viral load | to measure the amount of HIV in the blood | can make HIV levels appear higher than they are |
cytomegalovirus (CMV) test | to measure the amount of CMV (a type of herpes virus) in the blood | can make CMV levels appear higher than they are |
If you’d like to learn more about getting certain lab tests during treatment with Depakote, talk with your doctor.
DEPAKOTE INTERACTION WITH CANNABIS OR CBDCannabis (often called marijuana) and cannabis products, such as cannabidiol (CBD), have been specifically reported to interact with Depakote DR tablets, Depakote ER tablets, and Depakote DR sprinkle capsules.
Taking Depakote with cannabis or cannabis products may lead to high liver enzyme levels, which can be a sign of liver damage. (An enzyme is a type of protein.) In fact, Depakote has a
boxed warning about the risk of liver damage. This is the most serious warning from the Food and Drug Administration (FDA). For details, see “Boxed warnings” at the beginning of this article.Before you start treatment with Depakote, tell your doctor and pharmacist if you use cannabis. By sharing this information with them, you may help prevent possible interactions.
Note: Cannabis is illegal at a federal level but is legal in many U.S. states to varying degrees.
Certain medical conditions and other factors may increase the risk of interactions with Depakote. Before you take this drug, be sure to talk with your doctor about your health history. Depakote may not be the right treatment option if you have certain medical conditions or other factors affecting your health.
Health conditions or factors that might interact with Depakote include:
- Liver disease. Depakote may cause liver damage, which could worsen liver disease. In fact, Depakote has a
boxed warning about the risk of liver damage. This is the most serious warning from the Food and Drug Administration (FDA). For details, see the “When to avoid Depakote” and “Boxed warnings” sections above. - Mitochondrial disorder. A specific type of mitochondrial disorder can affect the liver and may lead to liver failure. Depakote may cause liver damage, which can worsen this condition. In fact, Depakote has a boxed warning about the risk of liver damage. This is the most serious warning from the FDA. For details, see the “When to avoid Depakote” and “Boxed warnings” sections above.
- Urea cycle disorder. Taking Depakote may increase the risk of high blood ammonia levels and a certain type of brain damage in people with urea cycle disorder. For details, see the “When to avoid Depakote” section above.
- Gastrointestinal (GI) problem. Before taking Depakote, tell your doctor if you have a GI problem. Examples include having had an ileostomy or colostomy in the past. If you have a GI problem, Depakote may not break down entirely in your body. If this happens, pieces of the capsule or tablet may appear in your stool. This can mean your body isn’t getting enough Depakote to treat your condition. If you have a GI problem, your doctor may prescribe a different medication for you.
- Being age 65 years or older. The risk of certain side effects with Depakote, such as sleepiness, may be higher in people ages 65 years and older. (To learn more about Depakote’s side effects, see this article.) Due to this risk, doctors may prescribe a lower dosage of Depakote for older adults. (For details about Depakote’s dosage, see this article.) Your doctor can tell you more about the safety of Depakote in older adults.
- Pregnancy. Taking Depakote during pregnancy may lead to congenital anomalies (commonly known as birth defects). In fact, Depakote has a boxed warning about the risk of fetal harm. This is the most serious warning from the FDA. For details, see “Boxed warnings” at the beginning of this article.
- Breastfeeding. It isn’t known whether it’s safe to breastfeed while taking Depakote. The drug may pass into breast milk and cause side effects in a breastfed child. If you’re breastfeeding or planning to do so, talk with your doctor before starting Depakote treatment. To learn more about the drug’s use while breastfeeding, see this article.
- Allergic reaction. If you’ve had an allergic reaction to Depakote or any of its ingredients, your doctor will likely not prescribe Depakote. Taking the drug could cause another allergic reaction. You can ask them about other treatments that may be better choices for you.
Here is a frequently asked question about Depakote and possible interactions.
Can I take Depakote and trazodone together?
Yes, you can take Depakote with trazodone if your doctor advises you to do so. These medications aren’t known to interact with each other.
Trazodone is an antidepressant. It’s typically prescribed to treat depression. If you have depression, your doctor may prescribe trazodone for this use while you’re taking Depakote to treat epilepsy or help prevent migraine.
Antidepressants, including trazodone, are not typically recommended for bipolar disorder. This is because antidepressants may trigger a manic episode in people with this condition. Depakote is used to treat bipolar disorder. If you have this condition, your doctor can tell you more about taking trazodone.
To learn more about taking Depakote with trazodone, talk with your doctor or pharmacist.
You can take certain steps to help prevent interactions with Depakote. Your doctor and pharmacist are key resources, so reach out to them before starting treatment. For example, you should plan to do the following:
- Let them know if you drink alcohol or use cannabis.
- Tell them about any other medications you take, as well as any supplements, herbs, and vitamins.
- Create a
medication list , which your doctor and pharmacist can help you fill out.
It’s also important to read the Depakote label and other
If Depakote doesn’t come with paperwork, you can ask your pharmacist to print a copy. If you need help reading or understanding this information, ask your doctor or pharmacist.
You can also help prevent interactions with Depakote by taking it exactly as your doctor prescribes.
Besides learning about interactions, you may want to find out more about Depakote. These resources might help:
- Overview of Depakote. For a general overview of Depakote, you can see this article.
- Side effects. If you’re interested in the side effects of Depakote, see this article. Another option is to refer to the Depakote prescribing information for Depakote DR tablets, Depakote ER tablets, or Depakote DR sprinkle capsules.
- Dosage specifics. To learn about the dosage of Depakote, see this article.
- Facts about Depakote’s uses. To learn more about the conditions Depakote is used to treat, see our headache & migraine hub, epilepsy & seizure hub, and list of bipolar articles.
Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.