valproic acid

Generic Name: valproic acid (val PRO ik A sid)
Brand Name: Depakene, Stavzor, Depacon

What is valproic acid?

Valproic acid affects chemicals in the body that may be involved in causing seizures.

Valproic acid is used to treat various types of seizure disorders. Valproic acid is sometimes used together with other seizure medications.

Valproic acid is also used to treat manic episodes related to bipolar disorder (manic depression), and to prevent migraine headaches.

Valproic acid may also be used for purposes not listed in this medication guide.

What is the most important information I should know about valproic acid?

If you take valproic acid for seizures or manic episodes: Do not start or stop taking the medicine during pregnancy without your doctor's advice. Valproic acid may cause harm to an unborn baby, but having a seizure during pregnancy could harm both the mother and the baby.

Do not use valproic acid to prevent migraine headaches if you are pregnant.

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Valproic acid can cause liver failure that may be fatal, especially in children under age 2. This risk may be greater in children taking more than one seizure medication, or those who have a metabolic disorder or brain disease causing mental impairment.

Call your doctor at once if the person taking this medicine has early signs of liver damage, such as: a general ill feeling, weakness, lack of energy, swelling in the face, loss of appetite, and vomiting.

Valproic acid can also cause serious harm to the pancreas, which may get worse quickly. Call your doctor at once if you have symptoms such as: nausea, vomiting, loss of appetite, and severe pain in your upper stomach spreading to your back.

What should I discuss with my healthcare provider before taking valproic acid?

Valproic acid can cause liver failure that may be fatal, especially in children under age 2. This risk may be greater in children taking more than one seizure medication, or those who have a metabolic disorder or brain disease causing mental impairment.

You should not use valproic acid if you are allergic to it, or if you have:

• liver disease; or

• a urea cycle disorder.

To make sure valproic acid is safe for you, tell your doctor if you have:

• a pancreas disorder;

• a bleeding or blood clotting disorder;

• a history of head injury, brain disorder, or coma;

• a family history of a urea cycle disorder or infant deaths with unknown cause; or

• HIV or CMV (cytomegalovirus) infection.

Some young people have thoughts about suicide when first taking valproic acid. Your doctor will need to check your progress at regular visits while you are using this medicine. Your family or other caregivers should also be alert to changes in your mood or symptoms.

If you take valproic acid for seizures or manic episodes: FDA pregnancy category D. Do not start or stop taking the medicine during pregnancy without your doctor's advice. Valproic acid can harm an unborn baby or cause birth defects, and may affect cognitive ability (reasoning, intelligence, problem-solving) later in the child's life. However, having a seizure during pregnancy could harm both the mother and the baby. Tell your doctor right away if you become pregnant.

Seizure control is very important during pregnancy. The benefit of preventing seizures may outweigh any risks posed by taking valproic acid. There may be other seizure medications that can be more safely used during pregnancy. Follow your doctor's instructions about taking valproic acid while you are pregnant.

If you take valproic acid to prevent migraine headaches: FDA pregnancy category X. Do not use valproic acid to prevent migraine headaches if you are pregnant.

Use effective birth control while using valproic acid, and tell your doctor right away if you become pregnant.

Valproic acid can pass into breast milk and may harm a nursing baby. You should not breast-feed while using this medicine.

How should I take valproic acid?

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Drink plenty of water while you are taking this medication. Your dose may need to be changed if you do not get enough fluids each day.

Take with food if this medicine upsets your stomach.

Measure liquid medicine with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Do not crush, chew, break, or open a delayed-release capsule. Swallow it whole.

While using valproic acid, you may need frequent blood tests.

Do not stop using valproic acid suddenly, even if you feel fine. Stopping suddenly may cause a serious, life-threatening type of seizure. If you need to stop taking valproic acid, follow your doctor's instructions about tapering your dose.

Wear a medical alert tag or carry an ID card stating that you take valproic acid. Any doctor, dentist, or emergency medical care provider who treats you should know that you are taking a seizure medication.

Store at room temperature away from moisture and heat.

See also: Valproic acid dosage (in more detail)

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking valproic acid?

Drinking alcohol can increase certain side effects of valproic acid.

Valproic acid may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid exposure to sunlight or tanning beds. Valproic acid can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Valproic acid side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; fever, swollen glands, difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if the person taking this medicine has early signs of liver damage, such as: a general ill feeling, weakness, lack of energy, swelling in the face, loss of appetite, and vomiting. Later symptoms may include upper stomach pain, itching, dark urine, clay-colored stools, or yellowing of the skin or the whites of the eyes.

Call your doctor at once if you have symptoms of pancreatitis, which can get worse quickly: nausea, vomiting, loss of appetite, and severe pain in your upper stomach spreading to your back.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, depression, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have any of these other side effects:

• worsening seizures;

• swelling in your hands or feet;

• bronchospasm (wheezing, chest tightness, trouble breathing);

• fever, chills, body aches, sore throat, flu symptoms;

• easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

• double vision, back-and-forth movements of the eyes, seeing flashes of light or "floaters" in your vision;

• extreme drowsiness, lack of coordination, confusion, hallucinations, tremors, jerking muscle movements; or

• severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

• indigestion, stomach pain, diarrhea, constipation;

• headache, dizziness, nervousness, problems with thinking or memory;

• mild drowsiness, feeling unsteady, feeling cold;

• back pain;

• thinning hair;

• runny nose;

• blurred vision, ringing in your ears; or

• increased appetite, weight changes, sleep problems (insomnia).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

See also: valproic acid side effects (in more detail)

Valproic acid Dosing Information

Usual Adult Dose for Seizure Prophylaxis:

Valproate sodium injection:
Initial dose: 10 to 15 mg/kg/day intravenously divided over 4 doses administered every 6 hours.
Maintenance dose: 30 to 60 mg/kg/day intravenously divided over 4 doses administered every 6 hours.

Intravenous doses may be broken into 2 to 3 divided doses/day. However, if this frequency is chosen, trough levels should be carefully monitored.

Use of valproate sodium injection for periods of more than 14 days has not been studied. Patients should be switched to oral valproate products as soon as it is clinically feasible.

Capsules or syrup:
Initial dose: 10 to 15 mg/kg/day orally in 1 to 3 divided doses
Maintenance dose: 30 to 60 mg/kg/day orally in 2 to 3 divided doses

Total daily doses in excess of 250 mg should be given in divided doses.

Usual Adult Dose for Mania:

Initial dose: 750 mg valproic acid delayed release capsules orally daily in divided doses. Delayed release capsules must be swallowed whole.

The dose should be increased as rapidly as possible to achieve the lowest therapeutic dose which produces the desired clinical effect or the desired range of plasma concentrations. In placebo-controlled clinical trials of acute mania, patients were dosed to a clinical response with a trough plasma concentration between 50 and 125 mcg per mL. Maximum concentrations were generally achieved within 14 days.

The maximum recommended dosage is 60 mg/kg/day.

There is no body of evidence available from controlled trials to guide a clinician in the longer-term management of a patient who improves during valproic acid delayed release capsules treatment of an acute manic episode. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no systematically obtained data to support the benefits of valproic acid delayed release capsules in such longer-term treatment.

Usual Adult Dose for Migraine Prophylaxis:

Initial dose: 250 mg valproic acid delayed release capsules orally twice daily. Valproic acid delayed release capsules must be swallowed whole.

Some patients may benefit from doses up to 1000 mg/day. In clinical trials, there was no evidence that higher doses led to greater efficacy.

Usual Pediatric Dose for Seizure Prophylaxis:

Limited data are available for neonatal dosing; further studies are needed.
Refractory seizures: Oral: Loading dose: 20 to 25 mg/kg, followed by a maintenance dose of 5 to 10 mg/kg every 12 hours; a report of 6 neonates (30-41 weeks gestation) showed oral valproic acid effectively controlled seizure activity in 5 of 6 patients; therapy was discontinued in 50% of the patients due to hyperammonemia; frequent monitoring is recommended.
Refractory status epilepticus: IV: Loading dose: 20 to 40 mg/kg followed by a continuous infusion of 5 mg/kg/hour was used in 5 neonates; once patients were seizure free for 12 hours and no longer had seizure activity on EEG, the infusion rate was decreased every 2 hours by 1 mg/kg/hour.

Note: Use of Depakote-ER (R) in pediatric patients less than 10 years of age is not recommended; do not confuse Depakote-ER (R) with Depakote (R). Erroneous substitution of Depakote (R) (delayed release tablets) for Depakote-ER (R) has resulted in toxicities; only Depakote-ER (R) is intended for once daily administration.

Seizures disorders: Children and Adults:
Oral: Initial: 10 to 15 mg/kg/day in 1 to 3 divided doses; increase by 5 to 10 mg/kg/day at weekly intervals until therapeutic levels are achieved; maintenance: 30 to 60 mg/kg/day in 2 to 3 divided doses; Depakote (R) and Depakote (R) Sprinkle can be given twice daily.
Note: Children receiving more than 1 anticonvulsant (i.e., polytherapy) may require doses up to 100 mg/kg/day in 3 to 4 divided doses. Due to differences in bioavailability, children greater than or equal to 10 years of age and adult epilepsy patients receiving Depakote (R) may be switched to Depakote-ER (R) by using a once daily Depakote-ER (R) dose that is 8 to 20% higher than the total daily dose of Depakote (R) (see Depakote-ER (R) package insert for details).

IV: Total daily IV dose is equivalent to the total daily oral dose, however, IV dose should be divided with a frequency of every 6 hours; if IV form is administered 2 to 3 times/day, close monitoring of trough levels is recommended; switch patients to oral product as soon as possible (IV use has not been studied for greater than 14 days).

Rectal: Dilute syrup 1:1 with water for use as a retention enema; loading dose: 17 to 20 mg/kg one time; maintenance: 10 to 15 mg/kg/dose every 8 hours.

Refractory status epilepticus:
Infants and Children:
IV: Loading dose: Initial: Optimal dosage is not established; pediatric studies have used initial loading doses of 20 to 40 mg/kg.
Note: In one retrospective study, an initial loading dose of 25 mg/kg administered 3 mg/kg/minute was effective in stopping seizure activity within 20 minutes after the end of the infusion in all 18 patients treated for status epilepticus. A separate retrospective trial found a higher efficacy rate in pediatric patients (n=41) who received an initial loading dose of 30 to 40 mg/kg (compared to 20 to 30 mg/kg or greater than 40 mg/kg). In an open label, randomized comparative trial, an initial loading dose of 30 mg/kg was administered (n=20; age range: 7 months to 10 years of age; mean age: 3 years); a repeat bolus of 10 mg/kg could be administered if seizures were not controlled within 10 minutes; mean required dose: 37.5 plus or minus 4.4 mg/kg; median required dose: 40 mg/kg. Further studies are needed.
IV: Maintenance dose: IV infusion: Optimal dosage is not established; pediatric studies used continuous infusions of 5 mg/kg/hour after the loading dose; once patients were seizure free for 6 hours, the infusion rate was decreased by 1 mg/kg/hour every 2 hours. Further studies are needed.

What other drugs will affect valproic acid?

Taking valproic acid with other drugs that make you sleepy or slow your breathing can worsen these effects. Ask your doctor before taking this medicine with a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety or depression.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with valproic acid, especially:

• aspirin;

• tolbutamide;

• topiramate;

• warfarin;

• zidovudine;

• an antibiotic--imipenem/cilastatin, meropenem, rifampin;

• an antidepressant--amitriptyline, nortriptyline;

• a sedative--clonazepam, diazepam, Valium; or

• other seizure medications--carbamazepine, ethosuximide, felbamate, lamotrigine, phenobarbital, phenytoin, primidone.

This list is not complete. Other drugs may interact with valproic acid, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Where can I get more information?

• Your pharmacist can provide more information about valproic acid.