Depakote and Depakote ER Interactions: Alcohol, Medications, and Others

Depakote and Depakote ER (divalproex sodium) are prescription drugs that are used to:

• treat certain types of seizures in adults and some children
• treat bipolar disorder in adults
• prevent migraine headaches in adults

Like other drugs, Depakote and Depakote ER may have interactions.

Some interactions occur because one substance causes another substance to have a different effect than expected. For example, sometimes alcohol, another drug, or a supplement can affect how a drug acts in your body. Interactions can also occur if you have certain health conditions.

Keep reading to learn about possible interactions with these drugs, including what you should not take with Depakote or Depakote ER. And for more information about Depakote and Depakote ER, including details about its uses, see this article.

Certain health conditions or other factors could raise your risk of harm if you take Depakote or Depakote ER. In such cases, your doctor may not prescribe Depakote or Depakote ER for you. These are known as contraindications. The list below includes contraindications of Depakote and Depakote ER.

If you have liver problems. Depakote and Depakote ER can cause severe liver damage, which can be life threatening. In some cases, liver damage can interfere with how these drugs work to manage seizures. Due to this risk, it’s not recommended that you take Depakote or Depakote ER if you have liver problems or have had them in the past.

If you have mitochondrial disorders. Mitochondrial disorders are rare conditions caused by gene mutations affecting the mitochondria. Having certain mitochondrial disorders can raise your risk of liver damage from Depakote or Depakote ER. Due to this risk, doctors typically will not prescribe these drugs if you have certain mitochondrial disorders.

If you have urea cycle disorders. With urea cycle disorders, your body doesn’t get rid of urea as well as usual. (Urea is a chemical made from ammonia.) Depakote and Depakote ER can cause ammonia to build up in your body. Taking Depakote or Depakote ER if you have urea cycle disorders can raise your risk of having high ammonia levels. High ammonia level can harm your brain function. Because of this, your doctor may not prescribe these medications if you have this kind of condition.

If you’re pregnant. Depakote and Depakote ER can cause harm to a fetus if taken during pregnancy. Due to this risk, these drugs should not be taken during pregnancy.

If you take topiramate (Topamax). Taking topiramate (Topamax) with Depakote or Depakote ER has been known to cause high blood ammonia level, which may harm your brain function. Taking these drugs together may also cause hypothermia (dangerously low body temperature).

If you’ve had an allergic reaction. If you have had an allergic reaction to Depakote or Depakote ER or any of its ingredients, your doctor likely won’t prescribe Depakote and Depakote ER. This is because taking the drug could cause another allergic reaction. You can ask your doctor about other treatments that may be better options for you.

Before you start taking Depakote and Depakote ER, talk with your doctor if any of the factors above apply to you. Your doctor can determine whether Depakote and Depakote ER are safe for you to take.

Depakote and Depakote are not known to interact with alcohol. But your doctor might recommend that you avoid alcohol while taking either of these drugs. This is because drowsiness or dizziness are side effects of Depakote, Depakote ER, and alcohol. So, combining alcohol with either of these drugs may make any drowsiness or dizziness that you experience worse.

If you drink alcohol, talk with your doctor to learn how much alcohol, if any, may be safe to consume during your treatment with Depakote or Depakote ER.

Before you start taking Depakote or Depakote ER, tell your doctor and pharmacist about any prescription, over-the-counter, or other drugs you take. Sharing this information with them may help prevent possible interactions. (To learn whether Depakote and Depakote ER interact with supplements, herbs, and vitamins, see the “Are there other interactions with Depakote and Depakote ER?” section below.)

If you have questions about drug interactions that may affect you, talk with your doctor or pharmacist.

The chart below lists drugs that may interact with Depakote and Depakote ER. Keep in mind that this chart does not include all drugs that may interact with these drugs. For more information about some of these interactions, see the “Drug interactions explained” section below.

Learn more about certain drug interactions that can occur with Depakote and Depakote ER.

Interaction with Lamictal

Lamotrigine (Lamictal) can interact with Depakote and Depakote ER. Lamotrigine is a drug prescribed to treat bipolar disorder and certain kinds of seizures.

Doctors may prescribe lamotrigine along with Depakote or Depakote ER to treat these conditions.

What could happen

Depakote or Depakote ER can make your body get rid of lamotrigine more slowly. This can cause lamotrigine to build up in your body, which could raise your risk of serious side effects from lamotrigine. Examples include serious skin side effects such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

For more information about lamotrigine’s skin-related side effects, see this article.

What you can do

It’s important to let your doctor know about all the medications you take before you start treatment with Depakote, Depakote ER, or lamotrigine.

If your doctor prescribes lamotrigine and you’re already taking Depakote or Depakote ER, they’ll likely prescribe a lower dose of lamotrigine. If you start Depakote or Depakote ER while you’re already taking lamotrigine, your doctor may need to adjust your lamotrigine dosage.

If you stop taking Depakote or Depakote ER during your lamotrigine treatment, you may need a lamotrigine dosage increase.

If you have questions about taking lamotrigine with Depakote, talk with your doctor or pharmacist.

Interaction with birth control that contains estrogen

Certain kinds of birth control have the hormone estrogen in them. Estrogen interacts with Depakote and Depakote ER.

Many birth control pills contain a combination of hormones, which may include a type of estrogen.

Examples of hormonal birth control pills with estrogen include

• ethinyl estradiol, levonorgestrel (Aviane, Nordette, Seasonique)
• ethinyl estradiol, norethindrone (Balziva, Necon 0.5/35, Loestrin)
• ethinyl estradiol, norgestimate (Ortho-Tri-Cyclen, Ortho-Cyclen, Sprintec)
• ethinyl estradiol, drospirenone (Gianvi, Ocella, Yasmin)

What could happen

Estrogen in birth control can lower the levels of Depakote or Depakote ER in your body. If this happens, Depakote or Depakote ER may be less effective. If you take these medications to manage seizures, taking birth control with estrogen may raise your risk of having seizures.

What you can do

Before you start treatment with Depakote or Depakote ER, tell your doctor if you take birth control. Also, let your doctor know if you start taking any new drugs, including birth control, while you’re taking Depakote or Depakote ER.

If you start taking birth control with estrogen during your Depakote or Depakote ER treatment, your doctor will likely monitor your levels of valproic acid (the active drug in Depakote and Depakote ER). They may adjust your Depakote or Depakote ER dosage if needed.

Interaction with certain other seizure drugs

Your doctor may prescribe other seizure medications with Depakote or Depakote ER to help manage your seizures. But some of these drugs may interact with Depakote or Depakote ER.

Interactions may increase your risk of side effects from either drug. They may also make Depakote and Depakote ER less effective.

What could happen

Some seizure medications can decrease the level of Depakote or Depakote ER in your body. This can make Depakote or Depakote ER less effective than usual.

Examples of seizure drugs that may lower Depakote or Depakote ER levels include:

• phenytoin (Dilantin)
• carbamazepine (Tegretol)
• primidone (Mysoline)

Other seizure drugs, such as felbamate (Felbatol) and topiramate (Topamax), can interfere with how your body breaks down Depakote or Depakote ER. Taking these drugs together can raise the levels of Depakote or Depakote ER in your body. It could also raise your risk of side effects from Depakote or Depakote ER.

Depakote or Depakote ER can also increase the levels of certain other seizure drugs in your body. These include phenytoin (Dilantin), ethosuximide (Zarontin), and lamotrigine (Lamictal). To learn more about the interaction between Depakote or Depakote ER and lamotrigine, see the “Interaction with Lamictal” section above.

Taking Depakote or Depakote ER with phenytoin or lamotrigine may increase your risk of side effects from lamotrigine or phenytoin.

What you can do

Talk with your doctor about any medications you take before you start treatment with Depakote or Depakote ER. Also, let them know if you start or stop taking any other seizure medications during your treatment. Your doctor may adjust your dosages if needed.

Depakote and Depakote ER may have other interactions. They could occur with foods, supplements, vaccines, or even lab tests. See below for details. Note that the information below does not include all other possible interactions with Depakote and Depakote ER.

Do Depakote and Depakote ER interact with food?

There are currently no reports of Depakote or Depakote ER interacting with food.

But caffeine, which is found in certain foods and drinks such as coffee, chocolate, and tea, may worsen some side effects of Depakote or Depakote ER.

These side effects can include:

• nervousness
• insomnia (trouble sleeping)
• tremor

Although there are no reported interactions between Depakote and caffeine, you may want to avoid foods and drinks with caffeine while you’re taking Depakote or Depakote ER.

If you have questions about consuming certain foods or drinks during your treatment with Depakote or Depakote ER, talk with your doctor.

Do Depakote and Depakote ER interact with supplements?

There aren’t any supplements that have been reported to interact with Depakote or Depakote ER. But it’s possible that interactions could be identified in the future.

Because of this, it’s important to talk with your doctor and pharmacist about any supplements, herbs, and vitamins you take before you start taking Depakote or Depakote ER. Sharing this information with them may help you avoid possible interactions.

If you have questions about interactions that may affect you, talk with your doctor or pharmacist.

Depakote and Depakote ER and herbs

There are currently no reports of Depakote or Depakote ER interacting with herbs. But this doesn’t mean that interactions with herbs won’t be recognized in the future.

For this reason, it’s still important to check with your doctor or pharmacist before taking any of these products while taking Depakote or Depakote ER.

Depakote and Depakote ER and vitamins

There are currently no reports of Depakote and Depakote ER interacting with vitamins. But this doesn’t mean that vitamin interactions won’t be recognized in the future.

For this reason, it’s still important to check with your doctor or pharmacist before taking any of these products while taking Depakote and Depakote ER.

Do Depakote and Depakote ER interact with vaccines?

Depakote and Depakote ER aren’t known to interact with vaccines. If you have questions about receiving vaccines while taking Depakote or Depakote ER, talk with your doctor or pharmacist.

Do Depakote and Depakote ER interact with lab tests?

Depakote and Depakote ER may affect the results of certain lab tests.

For example, your body clears Depakote or Depakote ER as a ketone product in your urine. High urine ketone level can be a sign of high blood sugar levels.

Urine ketone tests are often used to check blood sugar in people with diabetes. So, taking Depakote or Depakote ER may cause urine ketone test results to appear falsely positive for high blood sugar.

Depakote and Depakote ER may also affect the results of thyroid function tests. These are tests used to check how your thyroid is working.

In some cases, Depakote and Depakote ER may increase the amount of human immunodeficiency virus (HIV) or cytomegalovirus (CMV) present in a lab test. These lab tests are used to test how well drugs used to treat these conditions are working.

Do Depakote and Depakote ER interact with cannabis or CBD?

Cannabis (commonly called marijuana) and cannabis products, such as cannabidiol (CBD), have been specifically reported to interact with Depakote and Depakote ER.

Cannabis can increase Depakote and Depakote ER levels in your body which may increase your risk of side effects from Depakote or Depakote ER. These side effects can include elevated liver enzyme levels, which can be a sign of liver damage.

Cannabis, Depakote, and Depakote ER can also cause drowsiness. Taking these drugs together may increase your risk of or worsen this side effect.

Before you start treatment with Depakote or Depakote ER, 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 states to varying degrees.

Certain medical conditions or other health factors may raise the risk of interactions with Depakote or Depakote ER. Before taking either of these drugs, talk with your doctor about your health history. They’ll determine whether Depakote or Depakote ER is right for you.

Health conditions or other factors that might interact with Depakote or Depakote ER include:

Liver problems. Depakote and Depakote ER can cause serious liver damage. Your risk may be higher if you’ve had liver problems in the past. The drugs have a boxed warning about this side effect. For more information, see the “Boxed warnings” section above.

Urea cycle disorders. Taking Depakote or Depakote ER if you have a urea cycle disorder can raise your risk of having elevated ammonia levels. Because of this, doctors typically will not prescribe Depakote or Depakote ER if you have this condition. To learn more, see the “When should I avoid Depakote or Depakote ER?” section above.

Mitochondrial disorders. Certain mitochondrial disorders can increase your risk of liver damage from Depakote or Depakote ER. (Mitochondrial disorders are rare conditions caused by gene mutations affecting the mitochondria.) Due to this risk, doctors typically don’t prescribe Depakote or Depakote ER if you have this kind of condition. For more details, see the “When should I avoid Depakote or Depakote ER?” section above.

Problems with your digestive system. If you have problems with your digestive system, including having a colostomy, ileostomy, or diarrhea, talk with your doctor before taking Depakote or Depakote ER. Having these conditions may prevent your body from fully absorbing the drug, which could make it less effective. Talk with your doctor if you notice part of the tablet or capsule in your stool.

Older age. The risk of certain side effects, such as sleepiness, may be higher in people 65 years or older taking Depakote or Depakote ER. Due to this risk, doctors will likely prescribe a lower dosage of either drug for people in this age group.

Pregnancy. Depakote and Depakote ER are not safe to take during pregnancy. These drugs have a boxed warning about the risk of fetal harm. To learn more, see the “Boxed warnings” section above.

Breastfeeding. It’s not known whether it’s safe to take Depakote or Depakote ER while breastfeeding. But these drugs can pass into breast milk and may cause side effects in a breastfed child. If you’re breastfeeding or planning to breastfeed, talk with your doctor before taking Depakote or Depakote ER. They can discuss your options with you.

Allergic reaction. If you’ve had an allergic reaction to Depakote or Depakote ER or any of its ingredients, your doctor will likely not prescribe these drugs. This is because taking the drug could cause another allergic reaction. You can ask your doctor about other treatments that may be better choices for you.

Depression and other mental health conditions. Taking Depakote or Depakote ER can increase your risk of suicidal thoughts or behaviors. If you already have a mental health condition, such as depression, taking these drugs may raise your risk of having suicidal thoughts or behaviors. Or it could make this side effect worse if you do experience it.

Talk with your doctor about your health history before you start treatment with Depakote or Depakote ER. They can determine whether the drug is safe for you to take.

Find answers to some frequently asked questions about possible interactions with Depakote and Depakote ER.

Can you take ibuprofen with Depakote or Depakote ER?

Yes. There have been no reports of interactions between Depakote or Depakote ER and ibuprofen (Advil, Motrin).

But it’s important to note that aspirin, another nonsteroidal anti-inflammatory drug (NSAID) similar to ibuprofen, can interact with Depakote and Depakote ER. Taking aspirin with Depakote or Depakote ER can raise the level of Depakote or Depakote ER in your body. This may increase your risk of having side effects from Depakote or Depakote ER or make side effects worse if you experience them.

Always check with your doctor or pharmacist before taking any over-the-counter medications, including aspirin, ibuprofen, and other NSAIDs. They’ll let you know if these drugs are safe to take with Depakote or Depakote ER.

Can you take lithium and Depakote together?

In many cases, yes. Doctors may prescribe lithium and Depakote together to treat bipolar disorder.

There are no reported interactions between lithium and Depakote or Depakote ER. But these drugs may have some similar side effects. Taking them together can raise your risk of having these side effects or make the side effects worse if you experience them.

They can include:

• dizziness
• nausea
• blurry vision

If you have concerns about taking lithium and Depakote together, talk with your doctor. They’ll let you know if these medications are safe for you to take together.

Does Depakote or Depakote interact with Wellbutrin?

No. There have not been any reported interactions between bupropion (Wellbutrin) and Depakote or Depakote ER.

But it’s important to note that Wellbutrin should not be prescribed for people who’ve had seizures before. This is because taking Wellbutrin can increase your risk of having seizures. So, if you take Depakote or Depakote ER to treat seizures, your doctor may not prescribe Wellbutrin for you.

If you take Wellbutrin and Depakote or Depakote ER to treat bipolar disorder, tell your doctor right away if you have a seizure while taking these medications. They may have you stop taking Wellbutrin and switch to a different treatment.

Does Depakote or Depakote ER interact with Zyprexa?

No, there are no reported interactions between olanzapine (Zyprexa) and Depakote or Depakote ER.

But these drugs can cause similar side effects, such as the following:

• nausea
• headache
• weight gain

Taking these medications together can raise your risk of these side effects or make the side effects worse if you experience them.

Talk with your doctor or pharmacist if you have questions about taking Depakote or Depakote ER with Zyprexa.

Taking certain steps can help you avoid interactions with Depakote or Depakote ER. Before starting treatment, talk with your doctor and pharmacist. Things to discuss with them include:

• Whether you drink alcohol or use cannabis.
• Other medications you take. Your doctor or pharmacist can help you fill out a medication list.
• What to do if you start taking a new drug during your Depakote or Depakote ER treatment.

It’s also important to read Depakote or Depakote ER’s label and other paperwork that may come with the drug. You may see colored stickers on the label that describe interactions. And the paperwork (sometimes called the patient package insert or medication guide) may have other details about interactions. (If you did not get paperwork with Depakote and Depakote ER, ask your pharmacist to print a copy for you.) If you need help understanding this information, your doctor or pharmacist can help.

Taking Depakote or Depakote ER exactly as prescribed can also help prevent interactions.

If you still have questions about possible interactions with Depakote or Depakote ER, talk with your doctor.

Questions you may want to ask your doctor include:

• Does my risk of interactions depend on my dosage of Depakote or Depakote ER?
• Do I need to space out when I take my medications throughout the day to avoid interactions?
• Does lithium have similar interactions to Depakote and Depakote ER?

To learn more about Depakote and Depakote ER, see these articles:

• Depakote and Depakote ER (divalproex sodium)
• Side Effects of Depakote and Depakote ER: What You Need to Know
• Dosage Details for Depakote and Depakote ER

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Disclaimer: Healthline 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.