Brand Names:

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

Dosage Forms:

• Syrup
• Capsule, Delayed Release
• Capsule, Liquid Filled
• Tablet, Delayed Release
• Tablet, Extended Release
• Tablet, Enteric Coated

Uses of This Medicine:

Valproic acid, valproate sodium, and divalproex belong to the group of medicines called anticonvulsants. They are used to control certain types of seizures in the treatment of epilepsy. Valproic acid, valproate sodium, and divalproex may be used alone or with other seizure medicine. Divalproex is also used to treat the manic phase of bipolar disorder (manic-depressive illness), and to help prevent migraine headaches.

Divalproex and valproate sodium form valproic acid in the body. Therefore, the following information applies to all of these medicines.

These medicines are available only with your doctor's prescription.

Before Using This Medicine:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group 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

Abdominal or stomach cramps, nausea or vomiting, tiredness or weakness, and yellow eyes or skin may be especially likely to occur in children, who are usually more sensitive to the effects of these medicines. Children up to 2 years of age, those taking more than one medicine for seizure control, and children with certain other medical problems may be more likely to develop serious side effects.

Older adults

Elderly people are especially sensitive to the effects of these medicines. This may increase the chance of side effects during treatment. The dose of this medicine may be lower for older adults.

Pregnancy

Valproic acid, valproate sodium, and divalproex have been reported to cause birth defects when taken by the mother during the first 3 months of pregnancy. Also, animal studies have shown that valproic acid, valproate sodium, and divalproex cause birth defects when taken in doses several times greater than doses used in humans. However, these medicines may be necessary to control seizures in some pregnant patients. Be sure you have discussed this with your doctor.

Breast-feeding

Valproic acid, valproate sodium, and divalproex pass into the breast milk, but their effect on the nursing baby is not known. It may be necessary for you to take another medicine or to stop breast-feeding during treatment with valproic acid, valproate sodium, or divalproex. Be sure you have discussed the risks and benefits of this medicine with your doctor.

Other medicines

Using medicines in this class 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.

• Doripenem
• Ertapenem
• Imipenem
• Lamotrigine
• Meropenem
• Primidone
• Vorinostat

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 medicines in this class. Make sure you tell your doctor if you have any other medical problems, especially:

• Blood disease or
• Brain disease or
• Kidney disease There is an increased risk of serious side effects.

• Liver disease Valproic acid, valproate sodium, or divalproex may make the condition worse.

• Pancreatitis May be life threatening, stop using valproate if you have this condition.

• Urea cycle disorders May lead to serious side effects or death

Proper Use of This Medicine:

For patients taking the capsule form of valproic acid:

• Swallow the capsule whole without chewing, crushing, or breaking. This is to prevent irritation of the mouth or throat.

For patients taking the delayed-release capsule form of divalproex:

• Swallow the capsule whole, or sprinkle the contents on a small amount of soft food, such as applesauce or pudding, and swallow without chewing.

For patients taking the delayed-release tablet form of divalproex:

• Swallow the tablet whole without chewing, breaking, or crushing. This is to prevent damage to the special coating that helps lessen irritation of the stomach.

For patients taking the syrup form of valproic acid:

• The syrup may be mixed with any liquid or added to food for a better taste.

For patients taking the oral dosage forms of valproic acid and divalproex:

• These medicines may be taken with meals or snacks to reduce stomach upset.

This medicine must be taken exactly as directed by your doctor to prevent seizures and lessen the possibility of side effects.

Dosing

The dose medicines in this class 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 these medicines. 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.

• If valproic acid or divalproex is the only medicine you are taking for seizures:
  • Adults and adolescents Dose is based on body weight. The usual dose is 5 to 15 milligrams (mg) per kilogram (kg) (2.3 to 6.9 mg per pound) of body weight to start. 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 a day. If the total dose a day is greater than 250 mg, it is usually divided into smaller doses and taken two or more times during the day.
  • Children 1 to 12 years of age Dose is based on body weight. The usual dose is 15 to 45 mg per kg (6.9 to 20.7 mg per pound) of body weight to start. The doctor may increase the dose gradually every week by 5 to 10 mg per kg of body weight if needed.
• If you are taking more than one medicine for seizures:
  • Adults and adolescents Dose is based on body weight. The usual dose is 10 to 30 mg per kg (4.6 to 13.8 mg per pound) of body weight to start. Your doctor may increase your dose gradually every week by 5 to 10 mg per kg of body weight if needed. If the total dose a day is greater than 250 mg, it is usually divided into smaller doses and taken two or more times during the day.
  • Children 1 to 12 years of age Dose is based on body weight. The usual dose is 30 to 100 mg per kg (13.8 to 45.5 mg per pound) of body weight.
• If you are using valproate sodium for seizures because you temporarily cannot take oral medication:
  • Adults, adolescents, and children Dose is based on body weight, and will be determined by your doctor. The dose is injected into a vein.
• If you are taking divalproex for treatment of mania:
  • Adults At first, 750 mg a day, usually divided into smaller doses and taken two or more times during the day. Your doctor may increase your dose if needed.
  • Children Use and dose must be determined by your doctor.
• If you are taking divalproex for prevention of migraine headaches:
  • Adults At first, 250 mg two times a day. Your doctor may increase your dose if needed. However, the dose is usually not more than 1000 mg a day.
  • Children Use and dose must be determined by your doctor.

Missed dose

Call your doctor or pharmacist for instructions.

If you miss a dose of this medicine, and your dosing schedule is:

• One dose a day Take the missed dose as soon as possible. However, if you do not remember until the next day, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
• Two or more doses a day If you remember within 6 hours of the missed dose, take it right away. Then take the rest of the doses for that day at equally spaced times. Do not double doses.

If you have any questions about this, check with your doctor.

Storage

Keep out of the reach of children.

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

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using This Medicine:

Your doctor should check your progress at regular visits, especially for the first few months that you take this medicine. This is necessary to allow dose adjustments and to reduce any unwanted effects.

Do not stop taking this medicine without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are taking before stopping completely.

Before you have any medical tests, tell the doctor in charge that you are taking this medicine. The results of the metyrapone and thyroid function tests may be affected by this medicine.

Before having any kind of surgery, dental treatment, or emergency treatment, tell the medical doctor or dentist in charge that you are taking this medicine. Valproic acid, valproate sodium, or divalproex may change the time it takes your blood to clot, which may increase the chance of bleeding. Also, taking valproic acid, valproate sodium, or divalproex together with medicines that are used during surgery or dental or emergency treatments may increase the CNS depressant effects.

Valproic acid, valproate sodium, and divalproex will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). 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; barbiturates; medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine.

For diabetic patients:

• This medicine may interfere with urine tests for ketones and give false-positive results.

Your doctor may want you to carry a medical identification card or bracelet stating that you are taking this medicine.

This medicine may cause some people to become drowsy or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are drowsy or not alert.

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 as soon as possible if any of the following side effects occur:

More common

Body aches or pain

congestion

cough

dryness or soreness of throat

fever

hoarseness

runny nose

tender, swollen glands in neck

trouble in swallowing

voice changes

Less common

Abdominal or stomach cramps (severe)

behavioral, mood, or mental changes

blurred vision

confusion

continuous, uncontrolled back-and-forth and/or rolling eye movements

dizziness

double vision

earache

faintness, or light-headedness when getting up from a lying or sitting position suddenly

fast, irregular, pounding, or racing heartbeat or pulse

heavy, nonmenstrual vaginal bleeding

increase in seizures

loss of appetite

nausea or vomiting (continuing)

rapid weight gain

redness or swelling in ear

spots before eyes

sweating

swelling of face, arms, hands, lower legs, or feet

tingling of hands or feet

tiredness and weakness

unusual bleeding or bruising

unusual tiredness or weakness

unusual weight gain or loss

vomiting of blood or material that looks like coffee ground

yellow eyes or skin

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

Abdominal or stomach cramps (mild)

acid or sour stomach

belching

change in menstrual periods

crying

depersonalization

dysphoria

diarrhea

euphoria

hair loss

heartburn

indigestion

lack or loss of strength

loss of appetite

loss of bowel control

mental depression

nausea and vomiting

paranoia

quick to react or overreact emotionally;

rapidly changing moods

sleepiness or unusual drowsiness

stomach discomfort, upset or pain

trembling of hands and arms

weight loss or gain

Less common or rare

Absence of or decrease in body movement

absent, missed, or irregular menstrual periods

anxiety; nervousness; restlessness

bloated full feeling

bloody or cloudy urine

bloody nose

bruising

burning, crawling, itching, numbness, prickling, "pins and needles" , or tingling feelings

burning, dry or itching eyes

change in taste

chills

clumsiness or unsteadiness

coin-shaped lesions on skin

cold sweats

confusion

constipation

cramps

decreased awareness or responsiveness

degenerative disease of the joint

difficult, burning, or painful urination

difficulty in moving

difficult or labored breathing

discharge; excessive tearing of eye

discouragement

dizziness

drowsiness

dry mouth

excess air or gas in stomach or intestines

excessive muscle tone; muscle tension or tightness

feeling of constant movement of self or surroundings

feeling sad or empty

feeling of warmth or heat

flushing or redness of skin, especially on face and neck

frequent urge to urinate

headache

heavy bleeding

hyperventilation

irregular heartbeats

irritability

joint pain; swollen joints

lack of appetite

lip smacking ; uncontrolled chewing movements

loss of hair

loss of interest or pleasure

loss of memory

problems with memory

mimicry of speech or movements

muscle aching or cramping

muscle pains or stiffness

mutism

negativism

normal menstrual bleeding occurring earlier, possibly lasting longer than expected

pain

passing gas

peculiar postures or movements, mannerisms or grimacing

puffing of cheeks

rapid or worm-like movements of tongue

redness, pain, swelling of eye, eyelid, or inner lining of eyelid

redness, swelling, or soreness of tongue

runny nose

seeing, hearing, or feeling things that are not there

sensation of spinning

severe sleepiness

shaking

shortness of breath

skin rash

small red or purple spots on skin

sneezing

stopping of menstrual bleeding

stuffy nose

sweating

tightness in chest

tiredness

trouble concentrating

trouble in speaking

slurred speech

trouble sleeping

uncontrolled chewing movements

uncontrolled movements of arms and legs

unusual excitement, restlessness, or irritability

wheezing

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.