divalproex
Divalproex (Depakote) is an antiepileptic medication used to treat certain types of seizures, bipolar disorder, and prevent migraines. The medication comes as delayed-release (DR) tablets, extended-release (ER) tablets, and sprinkle capsules. You take it by mouth, either once a day or in divided doses, depending on your condition and the form that's prescribed. Common side effects include stomach pain, hair loss, and diarrhea. Serious risks include liver problems, inflammation of the pancreas, and birth defects if taken during pregnancy.
What is Divalproex (Depakote)?
What is Divalproex (Depakote) used for?
- Bipolar disorder
- Seizures
- Migraine prevention
How Divalproex (Depakote) works
Divalproex (Depakote) is an antiepileptic. It's not exactly clear how it works to prevent migraines or treat bipolar disorder. But to help control seizures, divalproex (Depakote) tells your brain to make more of a chemical called gamma-aminobutyric acid (GABA), which calms brain activity.
Drug facts
More on Divalproex (Depakote) essentials
Side effects of Divalproex (Depakote)
The following side effects may get better over time as your body gets used to the medication. Let your healthcare provider know immediately if you continue to experience these symptoms or if they worsen over time.
Common Side Effects
Bipolar disorder
- Sleepiness (19-26%)
- Indigestion (9-23%)
- Nausea (19-22%)
- Vomiting (12-13%)
- Dizziness (12%)
- Accidental injury (6-11%)
- Stomach pain (9-10%)
- Weakness (6-10%)
Seizures
- Nausea (48%)
- Headache (31%)
- Weakness (27%)
- Vomiting (27%)
- Sleepiness (27%)
- Tremor (25%)
- Dizziness (25%)
- Stomach pain (23%)
Migraine
- Nausea (15-31%)
- Weakness (20%)
- Sleepiness (7-17%)
- Infection (15%)
- Indigestion (7-13%)
- Diarrhea (7-12%)
- Dizziness (12%)
- Vomiting (7-11%)
Less Common Side Effects
Bipolar disorder
- Pain
- Sore throat
- Chills
- Fever
- Joint pain
- Dry eyes
- Swelling in the arms and legs
- Stiff neck
Seizures
- Reduced appetite
- Constipation
- Fever
- Blurred vision
- Infection
- Hair loss
- Weight loss
- Dizziness
Migraine
- Stomach pain
- Tremor
- Weight gain
- Back pain
- Hair loss
- Increased appetite
- Trouble sleeping
- Nervousness
Divalproex (Depakote) serious side effects
Contact your healthcare provider immediately if you experience any of the following.
- Serious liver problems: tiredness, nausea, vomiting, not feeling hungry, diarrhea, pain in the right side of the stomach, yellowing of the skin or eyes, dark-colored urine, light-colored stool
- Inflammation of the pancreas: severe upper stomach pain that might also extend to the back, nausea, vomiting, not feeling hungry
- Suicidal thoughts or behaviors: self-harm, depression, anxiety, agitation, panic attacks, trouble sleeping, irritability, aggression, acting on dangerous impulses, unusual behavior
- High blood ammonia levels: tiredness, confusion, vomiting
- Low body temperature: shivering, tiredness, confusion, drowsiness, memory loss, coma
- Severe skin reactions: rash, hives, blistering or peeling of the skin, mouth sores, trouble breathing
- Serious allergic reaction: trouble breathing, swelling in the face or throat
More on Divalproex (Depakote) side effects
The following Divalproex (Depakote) side effects have also been reported
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
More common
Black, tarry stools
bleeding gums
bloating or swelling of the face, arms, hands, lower legs, or feet
blood in the urine or stools
chills
confusion
crying
delusions of persecution, mistrust, suspiciousness, or combativeness
difficult or labored breathing
dysphoria
false beliefs that cannot be changed by facts
false or unusual sense of well-being
feeling of unreality
general feeling of discomfort or illness
headache
hoarseness
joint pain
loss of appetite
lower back or side pain
mental depression
muscle aches and pains
nervousness
painful or difficult urination
pinpoint red spots on the skin
poor insight and judgment
problems with memory or speech
quick to react or overreact emotionally
rapid weight gain
rapidly changing moods
sense of detachment from self or body
shakiness in the legs, arms, hands, or feet
shivering
sleepiness or unusual drowsiness
sweating
tightness in the chest
tingling of the hands or feet
trembling or shaking of the hands or feet
trouble recognizing objects
trouble sleeping
trouble thinking and planning
trouble walking
unusual bleeding or bruising
unusual tiredness or weakness
unusual weight gain or loss
vomiting
Less common
Abnormal dreams
absence of or decrease in body movement
bloody nose
blurred vision
bruising burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
change in personality
change in walking and balance
changes in patterns and rhythms of speech
cloudy urine
clumsiness or unsteadiness
cold sweats
dark urine
deep or fast breathing with dizziness
degenerative disease of the joint
difficulty with moving
dizziness
dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
excessive muscle tone
fast, irregular, pounding, or racing heartbeat or pulse
feeling of warmth or heat
flushing or redness of the skin, especially on the face and neck
frequent urge to urinate
heavy non-menstrual vaginal bleeding
increased need to urinate
indigestion
lack of coordination
large, flat, blue or purplish patches in the skin
leg cramps
lip smacking or puckering
loss of bladder control
loss of strength or energy
multiple swollen and inflamed skin lesions
muscle pain or stiffness
muscle tension or tightness
normal menstrual bleeding occurring earlier, possibly lasting longer than expected
numbness of the feet, hands and around mouth
pains in the stomach, side, or abdomen, possibly radiating to the back
passing urine more often
pounding in the ears
puffing of the cheeks
rapid or worm-like movements of the tongue
rapid weight gain
restlessness
seeing, hearing, or feeling things that are not there
shakiness and unsteady walk
slurred speech
small red or purple spots on the skin
sweating
swollen joints
trouble with speaking
twitching
uncontrolled chewing movements
uncontrolled movements of the arms and legs
unsteadiness, trembling, or other problems with muscle control or coordination
vomiting of blood or material that looks like coffee grounds
yellow eyes or skin
Incidence not known
Aggression
bladder pain
blistering, peeling, loosening of the skin
blisters on the skin
bone pain, tenderness, or aching
chest discomfort
cloudy urine
decrease in height
decreased urine output
difficulty swallowing
feeling that others are watching you or controlling your behavior
feeling that others can hear your thoughts
feeling, seeing, or hearing things that are not there
increased sensitivity of the skin to sunlight
increased thirst
irritability
joint or muscle pain
loss of balance control
loss of consciousness
mask-like face
pain in the back, ribs, arms, or legs
pain or swelling in the arms or legs without any injury
puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
red skin lesions, often with a purple center
red, irritated eyes
redness or other discoloration of the skin
seizures
severe mood or mental changes
severe sunburn
shuffling walk
slow heartbeat
slowed movements
slurred speech
sores, ulcers, or white spots in the mouth or on the lips
stiffness of the arms and legs
swelling of the face, ankles, or hands
swollen or painful glands
tic-like (jerky) movements of the head, face, mouth, and neck
unusual behavior
Get emergency help immediately if any of the following symptoms of overdose occur:
Symptoms of overdose
Change in consciousness
fainting
loss of consciousness
slow or irregular heartbeat
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
Belching
body aches or pain
change in vision
congestion
continuing ringing or buzzing or other unexplained noise in the ears
hair loss or thinning of the hair
hearing loss
impaired vision
lack or loss of strength
loss of memory
problems with memory
seeing double
tender, swollen glands in the neck
uncontrolled eye movements
voice changes
Less common
Absent, missed, or irregular menstrual periods
burning, dry, or itching eyes
change in taste or bad unusual or unpleasant (after) taste
coin-shaped lesions on the skin
cough producing mucus
cramps
dandruff
discharge or excessive tearing
excess air or gas in the stomach or bowels
feeling of constant movement of self or surroundings
full feeling
increased appetite
itching of the vagina or genital area
loss of bowel control
neck pain
oily skin
pain during sexual intercourse
pain or tenderness around the eyes and cheekbones
passing gas
rash with flat lesions or small raised lesions on the skin
redness or swelling in the ear
redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
redness, swelling, or soreness of the tongue
sensation of spinning
stiff neck
stopping of menstrual bleeding
thick, white vaginal discharge with no odor or with a mild odor
Incidence not known
Breast enlargement
changes in hair color or texture
discoloration of the fingernails or toenails
increased hair growth, especially on the face
unexpected or excess milk flow from the breasts
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
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Pros and cons of Divalproex (Depakote)
Pros
- Used for seizures, bipolar disorder, and migraine prevention
- Dose is adjusted based on your response
- Available in multiple forms
- Can be used alone or with other medications
Cons
- Won't help if you have a migraine attack
- Interacts with many medications
- Not safe to take in pregnancy
- Requires regular blood work and lab tests
Pharmacist tips for Divalproex (Depakote)
- Different forms of divalproex (Depakote) might have different directions and age limits. If you or your child are starting or switching forms, double check with your prescriber that the dose and directions are correct.
- Swallow the divalproex (Depakote) tablet whole. Don't crush it since breaking delayed-release or extended-release tablets can cause the medication to release too quickly and in higher amounts than intended.
- You might need to get regular blood tests while taking divalproex (Depakote) to check your liver health. Tell your prescriber right away if you feel very tired, have upper right stomach pain, yellowing of the skin or eyes, or dark urine.
- Rarely, divalproex (Depakote) can cause high blood ammonia levels. Let your prescriber know if you feel very tired, confused, or vomit without a clear reason.
- If you can become pregnant, use birth control while taking divalproex (Depakote) since the medication can harm an unborn baby. If you're pregnant or planning on getting pregnant, contact your prescriber right away.
- Divalproex (Depakote) can raise the risk of suicidal thoughts or behavior. Tell your prescriber immediately if you notice depression, unusual mood changes, or thoughts of self-harm. Families and caregivers should also watch for these signs.
- Divalproex (Depakote) may cause drowsiness, especially if you also drink alcohol or take other medications that cause drowsiness. Don’t drive, use heavy machinery, or do risky activities until you know how it affects you.
- Tell your prescriber if you're taking aspirin or blood thinners like warfarin. These can interact with divalproex (Depakote) and raise your risk of bleeding or side effects.
- Divalproex (Depakote) can sometimes cause rash and serious skin reactions. Call your prescriber right away if you notice a rash, blisters, skin pain, or peeling.
- If you notice what looks like a pill in your stool, contact your prescriber. This could mean your body isn’t absorbing divalproex (Depakote) properly.
- If you want to stop divalproex (Depakote), talk with your prescriber. Don’t stop suddenly, especially if you have seizures, since this could cause seizures that won't stop. Your prescriber can lower your dose slowly to stop safely.
Directions for divalproex (Depakote) sprinkle capsules:
- If you have trouble swallowing, you can open up the capsule and sprinkle the contents on soft food like applesauce or yogurt.
- Hold the capsule with the end marked "This end up" facing upright, then twist it open over the soft food.
- Eat the entire mixture right away without chewing. Chewing can change how the medication is absorbed. Drink water after to make sure you swallow all of the medication.
Common questions about Divalproex (Depakote)
Possibly. In clinical studies, some people taking divalproex (Depakote) reported weight gain, while others reported weight loss. Higher doses are more likely to cause weight gain, and older adults are more likely to lose weight. Talk with your prescriber if you're concerned about weight changes while taking this medication.
Yes, taking divalproex (Depakote) can make you feel sleepy, weak, or very drowsy. These side effects can be stronger for older adults. To be safe, don't drive, use machines, or do anything that needs a lot of focus until you know how this medication affects you. Talk with your prescriber if these side effects become bothersome or don’t go away.
No, divalproex (Depakote) isn't a controlled substance because it's not likely to cause dependence or lead to abuse.
It can take several weeks to a few months to find the right dose of divalproex (Depakote) that helps manage your condition without causing too many side effects. Your prescriber will adjust your dose until they find the best balance for you. If you’ve been taking this medication for a month or two and haven’t noticed improvement, talk with your prescriber.
Not exactly, but they are very similar. Divalproex (Depakote) and valproic acid are both medications used to treat certain types of seizures. They have similar chemical structures. In fact, divalproex (Depakote) turns into valproic acid once it's in your body. Divalproex (Depakote) is often easier on your stomach and might cause fewer stomach-related side effects than valproic acid. Talk to your prescriber if you have questions comparing the two medications.
Divalproex (Depakote) should help you feel more steady and calm. If you have bipolar disorder, it can even out mood swings so you feel less agitated. If you take it for seizures, it helps calm the activity in your brain. But when you first start taking it, you might feel tired or dizzy, and some people have an upset stomach or nausea. If any side effects become bothersome or won't go away, talk to your prescriber so they can adjust your dose or check for other causes.
Yes, stopping divalproex (Depakote) suddenly can lead to withdrawal symptoms. If you have seizures, stopping all at once might cause seizures that don't stop, which is very dangerous. If you want to stop taking this medication, work with your prescriber so they can help you slowly lower your dose in a safe way.
It's best not to drink alcohol while taking divalproex (Depakote). Alcohol can make side effects like sleepiness, dizziness, and confusion worse, which can be unsafe if you’re driving or doing other activities that need focus. If you drink, talk with your prescriber about how much is safe for you, or if you should avoid alcohol completely.
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Risks and warnings for Divalproex (Depakote)
Divalproex (Depakote) can cause some serious health issues. This risk may be even higher for certain groups. If this worries you, talk to your doctor or pharmacist about other options.
Liver problems
- Risk factors: Children under 2 years old | History of liver problems | Taking many antiepileptic medications | Severe seizure condition | Certain genetic metabolic problems | Certain brain condition
Divalproex (Depakote) can cause liver problems that can be life-threatening. These are more likely to happen in the first 6 months of treatment. Your risk is higher if you've had liver problems, take more than one antiepileptic medication, are under 2 years old, or have certain metabolic or brain conditions.
Your prescriber will check your liver with blood tests before you start and while you're taking divalproex (Depakote). Call your prescriber right away if you feel very tired, have pain in the upper right side of your stomach, notice yellow skin or eyes, or have dark urine. In some cases, liver problems can keep getting worse even after stopping the medication, so it’s important to get medical help quickly.
Birth defects
- Risk factors: Pregnancy
Divalproex (Depakote) can cause serious birth defects if you take it during pregnancy. These include problems with the brain or spinal cord, changes to the face, heart problems, and problems affecting the arms and legs. If you can become pregnant, your prescriber might recommend using birth control or taking folic acid during treatment.
If you become pregnant while taking divalproex (Depakote), let your prescriber know right away. You’re also encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 to help track the health of you and your baby.
Inflammation of the pancreas
Though rare, some people taking divalproex (Depakote) have developed inflammation of the pancreas, or pancreatitis. This can happen at any time during treatment. Get medical help right away if you have upper stomach pain, nausea, vomiting, or loss of appetite.
Suicidal thoughts or behavior
- Risk factors: History of depression | Taking anti-epileptics
Like other seizure medications, divalproex (Depakote) can raise the risk of suicidal thoughts or behavior, sometimes as early as 1 week after starting treatment. Let your friends and family know to watch for new or worsening signs of depression, mood changes, or unusual behavior. If you or someone close to you notices suicidal thoughts or actions, call your prescriber right away.
Bleeding and blood conditions
- Risk factors: Higher doses of divalproex (Depakote)
Some people taking divalproex (Depakote) developed a lower platelet count, which can raise the risk of bleeding or bruising. Because of this, you’ll need blood tests before starting treatment and regularly while taking it. Tell your prescriber right away if you notice bleeding, bruising, or any unusual bleeding problems.
High ammonia levels
- Risk factors: History of metabolic conditions | Taking topiramate | Low body temperature
Divalproex (Depakote) can cause high ammonia levels in your blood, especially if you take it with topiramate. This can make you feel very tired, confused, or cause vomit. In some cases, your body temperature might also drop.
Get medical help right away if you notice any of these symptoms. Don't take divalproex (Depakote) if you have a history of metabolic conditions that raise ammonia levels, such as urea cycle problems.
Low body temperature
- Risk factors: Taking topiramate
A drop in body temperature has been reported in people taking divalproex (Depakote). It can happen whether or not you also have high ammonia levels, and it can occur if you’re also taking topiramate, especially after starting or raising the topiramate dose.
If you develop low body temperature, your prescriber might need to stop divalproex (Depakote). Symptoms include feeling very tired, confused, or even becoming unconscious, along with serious problems in your heart or lungs. Your care team will also check your blood ammonia levels if this happens.
Severe skin reactions
Divalproex (Depakote) can sometimes cause rashes and other serious skin reactions. These can include drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Get medical help if you notice a rash, hives, blisters, peeling skin, mouth sores, or trouble breathing.
Serious allergic reaction
Serious allergic reactions have been reported in people taking divalproex (Depakote). Stop taking the medication and get medical help right away if you notice swelling of your face, lips, mouth, or throat.
Sleepiness in older adults
Divalproex (Depakote) can cause sleepiness, especially in older adults. If you're older, your prescriber will raise your dose more slowly and will keep track of your eating, drinking, and alertness. If you get too sleepy or aren’t eating or drinking enough, your prescriber might lower your dose or stop the medication altogether.
Interaction with other medications
Some medications can interact with how your body processes divalproex (Depakote), which can affect how well it works or raise your risk of side effects. For example, taking it with carbapenem antibiotics can lower the amount of divalproex (Depakote) in your body, making it work less well. On the other hand, taking it with aspirin can raise the amount of divalproex (Depakote) in your body and increase side effects.
Divalproex (Depakote) can also interfere with how your body gets rid of other medications. For example, it can raise the level of lamotrigine which can increase your risk of serious side effects like rash. In some cases, your prescriber might lower the dose of the other medication to keep you safe.
For your safety, let your prescriber or pharmacist know what other medications you take, including over-the-counter (OTC) products and supplements so they can help you check for interactions.
Divalproex (Depakote) dosage
Typical dosage for Divalproex (Depakote)
Bipolar disorder (adults only)
- Delayed-release (DR) tablets: The typical starting dose is 750 mg daily, split into smaller doses and taken by mouth throughout the day. Your prescriber will raise your dose quickly to help control your mood better. The maximum daily dose is 60 mg/kg.
- Extended-release (ER) tablets: The typical starting dose is 25 mg/kg by mouth once a day. Your prescriber will raise your dose quickly to help control your mood better. The maximum daily dose is 60 mg/kg.
Seizures (adults and children ages 10 years or older)
- ER tablets, DR tablets, and sprinkle capsules: The typical starting dose ranges from 10 mg/kg to 15 mg/kg by mouth a day, depending on what type of seizure you have. Your prescriber will raise your dose weekly as needed to better control the seizures. The maximum daily dose is 60 mg/kg.
Migraine prevention (adults only)
- DR tablets: The typical starting dose is 250 mg by mouth twice a day. The maximum daily dose is 1000 mg.
- ER tablets: The typical starting dose is 500 mg by mouth once a day. The maximum daily dose is 1000 mg.
Your dose might differ if you're an older adult.
More on Divalproex (Depakote) dosage
Interactions between Divalproex (Depakote) and other drugs
More on Divalproex (Depakote) interactions
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Calcifediol
- Calcium Oxybate
- Cannabidiol
- Carvedilol
- Cisplatin
- Doripenem
- Ertapenem
- Estradiol
- Ethinyl Estradiol
- Imipenem
- Lamotrigine
- Lumateperone
- Magnesium Oxybate
- Meropenem
- Mestranol
- Orlistat
- Pexidartinib
- Potassium Oxybate
- Primidone
- Propofol
- Sodium Oxybate
- Vorinostat
- Warfarin
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Acyclovir
- Aspirin
- Betamipron
- Carbamazepine
- Cholestyramine
- Clomipramine
- Erythromycin
- Ethosuximide
- Felbamate
- Fosphenytoin
- Ginkgo
- Lopinavir
- Lorazepam
- Mefloquine
- Nimodipine
- Nortriptyline
- Olanzapine
- Oxcarbazepine
- Panipenem
- Phenobarbital
- Phenytoin
- Rifampin
- Rifapentine
- Risperidone
- Ritonavir
- Rufinamide
- Topiramate
- Valacyclovir
- Zidovudine
How much does Divalproex (Depakote) cost?
Divalproex (Depakote) contraindications
Contraindications are specific health conditions or situations in which a person should not take a medication due to safety concerns. If you have any of the following conditions or if any of the following apply to you, let your healthcare provider know because Divalproex (Depakote) will not be safe for you to take.
- Liver problems
- Certain genetic conditions, like Alpers-Huttenlocher Syndrome
- Children under 2 with or at risk for POLG
- Urea cycle problems
- Currently pregnant or can become pregnant but not using birth control
What are alternatives to Divalproex (Depakote)?
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