Pronunciation:

dye-VAL-proe-ex SOE-dee-um

Brand Names:

• Depakote
• Depakote DR
• Depakote ER
• Depakote Sprinkles
• Alti-Valproic

Dosage Forms:

• Tablet, Delayed Release
• Capsule, Delayed Release
• Tablet, Extended Release

Warnings:

Hepatotoxicity (some cases fatal), usually occurring during the first 6 months of treatment, has been reported in patients receiving valproate and its derivatives. Children younger than 2 years and patients with hereditary mitochondrial disease are at a considerably increased risk of developing fatal hepatotoxicity. For these patients under 2 years, valproate sodium should be used with extreme caution as a sole agent. Use is contraindicated in patients with known mitochondrial disorders caused by mitochondrial DNA polymerase gamma (POLG) mutations and in children younger than 2 years in which mitochondrial disorder is clinically suspected. Failure of other anticonvulsants is the only indication for divalproex sodium in patients older than 2 years with hereditary mitochondrial disease. Perform POLG mutation screening as clinically indicated. Monitor patients closely and perform liver function tests prior to therapy and at frequent intervals thereafter, especially during the first 6 months. Valproate can impair cognitive development with prenatal exposure and produce major congenital malformations, particularly neural tube defects (eg, spina bifida). Valproate is contraindicated for prophylaxis of migraine headaches in pregnant women and women of childbearing potential who are not using effective contraception. Valproate should not be administered to a woman of childbearing potential unless other medications have failed or are otherwise unacceptable. Effective contraception should be used in such situations. Life-threatening pancreatitis has been reported in both children and adults receiving valproate. Cases have occurred shortly after initiation as well as several years after use. If pancreatitis is diagnosed, valproate should ordinarily be discontinued .

Classifications:

Therapeutic—

Anticonvulsant

Pharmacologic—

Valproic Acid

Chemical—

Valproic Acid

Uses of This Medicine:

Divalproex sodium is used to treat certain types of seizures (epilepsy). This medicine is an anticonvulsant that works in the brain tissue to stop seizures.

Divalproex sodium is also used to treat the manic phase of bipolar disorder (manic-depressive illness) and helps prevent migraine headaches.

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of divalproex sodium in children. However, safety and efficacy have not been established for other indications in children, and to treat seizures in children younger than 10 years of age. Because of divalproex sodium's toxicity, use in children younger than 2 years of age requires extreme caution.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of divalproex sodium in the elderly. However, elderly patients are more likely to have unwanted effects (eg, tremors or unusual drowsiness), which may require an adjustment in the dose for patients receiving divalproex sodium.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

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.

• Apixaban
• Aspirin
• Betamipron
• Calcifediol
• Calcium Oxybate
• Cannabidiol
• Cannabis
• Carbamazepine
• Carvedilol
• Celecoxib
• Cisplatin
• Clarithromycin
• Clonazepam
• Dabigatran Etexilate Mesylate
• Doripenem
• Edoxaban
• Ertapenem
• Estradiol
• Ethinyl Estradiol
• Ethosuximide
• Felbamate
• Fosphenytoin
• Imipenem
• Lamotrigine
• Levoketoconazole
• Magnesium Oxybate
• Meropenem
• Mestranol
• Methotrexate
• Orlistat
• Panipenem
• Pexidartinib
• Phenobarbital
• Phenytoin
• Potassium Oxybate
• Primidone
• Propofol
• Ritonavir
• Rivaroxaban
• Rufinamide
• Sodium Oxybate
• Topiramate
• Vorinostat
• Warfarin
• Zidovudine

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
• Amitriptyline
• Cholestyramine
• Clomipramine
• Erythromycin
• Ginkgo
• Lopinavir
• Lorazepam
• Mefloquine
• Nimodipine
• Nortriptyline
• Olanzapine
• Oxcarbazepine
• Rifampin
• Risperidone
• Valacyclovir

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Congenital metabolism disorders (born with a disease that affects metabolism) or
• Mental retardation with severe seizure disorders—Use with caution. May increase risk for more serious side effects.

• Depression or
• Liver disease, history of or
• Mental illness or
• Pancreatitis (inflammation of the pancreas) or
• Thrombocytopenia (low platelet count) or
• Viral infection (eg, HIV, cytomegalovirus infection)—Use with caution. May make these conditions worse.

• Liver disease or
• Mitochondrial disorders, including Alpers-Huttenlocher syndrome (genetic disorder) or
• Urea cycle disorder (genetic disorder)—Should not be used in patients with these conditions.

• Pregnant women with migraine headaches—Should not be used to prevent migraine headaches in these patients.

Proper Use of This Medicine:

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To keep blood levels constant, take this medicine at the same time each day and do not miss any doses.

This medicine comes with a Medication Guide or patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

You may take this medicine with food to avoid stomach upset.

Swallow the sprinkle capsules whole. It may also be opened and the contents may be sprinkled onto a teaspoonful of soft food, such as applesauce or pudding. This mixture must be swallowed immediately without chewing and followed with a glass of water to ensure complete swallowing of the sprinkles.

Swallow the extended-release tablet or tablet whole with a full glass of water. Do not split, crush, or chew it.

Part of the medicine may pass into your stool after your body has absorbed the medicine. Check with your doctor right away if this happens.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage forms (delayed-release tablets or tablets):
  • For mania:
    • Adults—At first, 750 milligrams (mg) once a day, usually divided in smaller doses. Your doctor may increase your dose as needed. However, the dose is usually not more than 60 mg per kilogram (kg) of body weight per day.
    • Children—Use and dose must be determined by your doctor.
  • For migraine:
    • Adults—At first, 250 milligrams (mg) 2 times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 1000 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • For seizures:
    • Adults and children 10 years of age or older—Dose is based on body weight and must be determined by your doctor. At first, the usual dose is 10 to 15 milligrams (mg) per kilogram (kg) of body weight per day. Your doctor may increase your dose gradually every week by 5 to 10 mg per kg of body weight if needed. However, the dose is usually not more than 60 mg per kg of body weight per day. If the total dose a day is greater than 250 mg, it is usually divided into smaller doses and taken 2 or more times during the day.
    • Children younger than 10 years of age—Use and dose must be determined by your doctor.
• For oral dosage form (extended-release tablets):
  • For mania:
    • Adults—Dose is based on body weight and must be determined by your doctor. At first, the usual dose is 25 milligrams (mg) per kilogram (kg) of body weight once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 60 mg per kg of body weight per day.
    • Children—Use and dose must be determined by your doctor.
  • For migraine:
    • Adults—At first, 500 milligrams (mg) once a day for 1 week. Your doctor may increase your dose as needed. However, the dose is usually not more than 1000 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • For seizures:
    • Adults and children 10 years of age or older—Dose is based on body weight and must be determined by your doctor. At first, the usual dose is 10 to 15 milligrams (mg) per kilogram (kg) of body weight per day. Your doctor may increase your dose gradually every week by 5 to 10 mg per kg of body weight if needed. However, the dose is usually not more than 60 mg per kg of body weight per day.
    • Children younger than 10 years of age—Use and dose must be determined by your doctor.
• For oral dosage form (sprinkle capsules):
  • For seizures:
    • Adults and children 10 years of age or older—Dose is based on body weight and must be determined by your doctor. At first, the usual dose is 10 to 15 milligrams (mg) per kilogram (kg) of body weight a day. Your doctor may increase your dose gradually every week by 5 to 10 mg per kg of body weight if needed. However, the dose is usually not more than 60 mg per kg of body weight per day. If the total dose a day is greater than 250 mg, it is usually divided into smaller doses and taken 2 or more times during the day.
    • Children younger than 10 years of age—Use and dose must be determined by your doctor.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using This Medicine:

It is very important that your doctor check your or your child's progress closely while you are using this medicine to see if it is working properly and to allow for a change in the dose. Blood and urine tests may be needed to check for any unwanted effects.

Using this medicine while you are pregnant (especially during the first 3 months of pregnancy) can harm your unborn baby and cause serious unwanted effects (eg, brain or facial problems, heart or blood vessel problems, arm or leg problems, or intelligence or mental problems). Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

It is very important to take folic acid before getting pregnant and during early pregnancy to lower chances of harmful side effects to your unborn baby. Ask your doctor or pharmacist for help if you are not sure how to choose a folic acid product.

Liver problems may occur while you are using this medicine, and some may be serious. Check with your doctor right away if you are having more than one of these symptoms: abdominal or stomach pain or tenderness, clay-colored stools, dark urine, decreased appetite, fever, headache, itching, loss of appetite, nausea and vomiting, skin rash, swelling of the feet or lower legs, unusual tiredness or weakness, or yellow eyes or skin.

Pancreatitis may occur while you are using this medicine. Tell your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.

Check with your doctor right away if you are having unusual drowsiness, dullness, tiredness, weakness or feelings of sluggishness, changes in mental status, low body temperature, or vomiting. These may be symptoms of a serious condition called hyperammonemic encephalopathy.

Divalproex sodium may cause some people to become dizzy, lightheaded, drowsy, or less alert than they are normally. Do not drive or do anything else that could be dangerous until you know how this medicine affects you.

Do not stop using this medicine without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping completely. This may help prevent worsening of seizures and reduce the possibility of withdrawal symptoms.

Before you have any medical tests, tell the medical doctor in charge that you are using this medicine. The results of some tests may be affected by this medicine.

Divalproex sodium may cause serious allergic reactions affecting multiple body organs (eg, liver or kidney). Check with your doctor right away if you have the following symptoms: a fever, dark urine, headache, rash, stomach pain, swollen lymph glands in the neck, armpit, or groin, unusual tiredness, or yellow eyes or skin.

Divalproex sodium may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you notice any of these side effects, tell your doctor right away.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that cause drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds, sedatives, tranquilizers, or sleeping medicine, prescription pain medicine or narcotics, medicine for seizures (eg, barbiturates), muscle relaxants, or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine.

If you plan to have children, talk with your doctor before using this medicine. Some men receiving this medicine have become infertile (unable to have children).

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Side Effects of This Medicine:

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

cough

crying

delusions of persecution, mistrust, suspiciousness, or combativeness

diarrhea

difficult or labored breathing

dysphoria

false beliefs that cannot be changed by facts

false or unusual sense of well-being

feeling of unreality

fever

general feeling of discomfort or illness

headache

hoarseness

joint pain

loss of appetite

lower back or side pain

mental depression

muscle aches and pains

nausea

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

runny nose

sense of detachment from self or body

shakiness in the legs, arms, hands, or feet

shivering

sleepiness or unusual drowsiness

sore throat

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

anxiety

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

chest pain

cloudy urine

clumsiness or unsteadiness

cold sweats

constipation

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

dry mouth

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

hives, itching, skin rash

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

heartburn

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

weight gain

weight loss

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

dry skin

earache

excess air or gas in the stomach or bowels

eye pain

feeling of constant movement of self or surroundings

full feeling

heavy bleeding

increased appetite

itching of the vagina or genital area

loss of bowel control

neck pain

oily skin

pain

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

sneezing

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.