VALPROICACID (Systemic)

Some commonly used brand names are:

In the U.S.?

• Depacon ²
• Depakene ³
• Depakote ¹
• Depakote Sprinkle ¹

In Canada?

• Alti-Valproic ³
• Depakene ³
• Deproic ³
• Dom-Valproic ³
• Epival ¹
• Med Valproic ³
• Novo-Valproic ³
• Nu-Valproic ³
• Penta-Valproic ³
• pms-Valproic Acid ³
• pms-Valproic Acid E.C. ³

Category

• Anticonvulsant?Divalproex; Valproate Sodium; ValproicAcid
• Antimanic?Divalproex
• Migraine headache prophylactic?Divalproex

Description

Valproic acid, valproatesodium, 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 withother seizure medicine. Divalproex is also used to treat the manic phase ofbipolar disorder (manic-depressive illness), and to help prevent migraineheadaches.

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, inthe following dosage forms:

Oral
• Divalproex
  • Delayed-release capsules (U.S.)
  • Delayed-release tablets (U.S. and Canada)
• Valproic Acid
  • Capsules (U.S. and Canada)
  • Syrup (U.S. and Canada)

Parenteral
• Valproate Sodium
  • Injection (U.S.)

Before Using This Medicine

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

Allergies?Tell your doctor if you have ever had any unusual orallergic reaction to valproic acid, valproate sodium, or divalproex. Alsotell your health care professional if you are allergic to any other substances,such as foods, preservatives, or dyes.

Pregnancy?Valproic acid, valproate sodium, and divalproex havebeen reported to cause birth defects when taken by the mother during the first3 months of pregnancy. Also, animal studies have shown that valproic acid,valproate sodium, and divalproex cause birth defects when taken in doses severaltimes greater than doses used in humans. However, these medicines may be necessaryto control seizures in some pregnant patients. Be sure you have discussedthis with your doctor.

Breast-feeding?Valproic acid, valproate sodium, and divalproexpass 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-feedingduring treatment with valproic acid, valproate sodium, or divalproex. Be sureyou have discussed the risks and benefits of this medicine with your doctor.

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

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

Other medicines?Although certain medicines should not be usedtogether at all, in other cases two different medicines may be used togethereven if an interaction might occur. In these cases, your doctor may want tochange the dose, or other precautions may be necessary. When you are takingvalproic acid, valproate sodium, or divalproex, it is especially importantthat your health care professional knows if you are taking any of the following:

• Acetaminophen (e.g., Tylenol) (with long-term, high-dose use) or
• Amiodarone (e.g., Cordarone) or
• Amitriptyline and nortriptyline
• Anabolic steroids (nandrolone [e.g., Anabolin], oxandrolone [e.g.,Anavar], oxymetholone [e.g., Anadrol], stanozolol [e.g., Winstrol]) or
• Androgens (male hormones) or
• Anticoagulants
• Aspirin
• Barbiturates or
• Carbamazepine (e.g., Tegretol) or
• Carmustine (e.g., BiCNU) or
• Dantrolene (e.g., Dantrium) or
• Daunorubicin (e.g., Cerubidine) or
• Disulfiram (e.g., Antabuse) or
• Estrogens (female hormones) or
• Ethosuximide
• Etretinate (e.g., Tegison) or
• Gold salts (medicine for arthritis) or
• Mercaptopurine (e.g., Purinethol) or
• Methotrexate (e.g., Mexate) or
• Methyldopa (e.g., Aldomet) or
• Naltrexone (e.g., Trexan) (with long-term, high-dose use) or
• Phenothiazines (acetophenazine [e.g., Tindal], chlorpromazine [e.g.,Thorazine], fluphenazine [e.g., Prolixin], mesoridazine [e.g., Serentil],perphenazine [e.g., Trilafon], prochlorperazine [e.g., Compazine], promazine[e.g., Sparine], promethazine [e.g., Phenergan], thioridazine [e.g., Mellaril],trifluoperazine [e.g., Stelazine], triflupromazine [e.g., Vesprin], trimeprazine[e.g., Temaril]) or
• Plicamycin (e.g., Mithracin)?There is an increased risk ofserious side effects to the liver

• Central nervous system (CNS) depressants (medicines that cause drowsiness)or
• Tricyclic antidepressants (medicine for depression)?There maybe an increase in CNS depressant effects

• Carbenicillin by injection (e.g., Geopen) or
• Dipyridamole (e.g., Persantine) or
• Inflammation or pain medicine, except narcotics, or
• Pentoxifylline (e.g., Trental) or
• Sulfinpyrazone (e.g., Anturane) or
• Ticarcillin (e.g., Ticar)?Valproic acid, valproate sodium,or divalproex may increase the chance of bleeding because of decreased bloodclotting ability; the potential of aspirin, medicine for inflammation or pain,or sulfinpyrazone to cause stomach ulcer and bleeding may also increase thechance of bleeding in patients taking valproic acid, valproate sodium, ordivalproex

• Heparin?There is an increased risk of side effects that maycause bleeding

• Mefloquine?The amount of valproic acid, valproate sodium, ordivalproex that you need to take may change

• Other anticonvulsants (medicine for seizures)?There is an increasedrisk of seizures or other unwanted effects

Other medical problems?The presence of other medicalproblems may affect the use of these medicines. Make sure you tell your doctorif 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 divalproexmay make the condition worse

• Pancreatitis?may be life threatening, stop using valproateif you have this condition

• Urea cycle disorders?my lead to serious side effects or death

Proper Use of This Medicine

For patientstaking 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 amountof 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 irritationof the stomach.

For patients taking the syrup form of valproicacid:

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

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

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

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

Dosing?The dose of valproic acid, valproate sodium,or divalproex will be different for different patients. Follow your doctor's orders or the directions on the label. The followinginformation includes only the average doses of valproic acid, valproate sodium,or divalproex. If your dose is different, do not changeit unless your doctor tells you to do so.

The number of capsules or tablets or teaspoonfuls of syrup that you takeor the number of injections you receive depends on the strength of the medicine.Also, the number of doses you take each day, the timeallowed between doses, and the length of time you take the medicine dependon the medical problem for which you are using valproic acid, valproate sodium,or divalproex.

• If valproic acid or divalproex is the only medicine you are takingfor seizures:
  • Adults and adolescents: Dose is based on body weight. The usual doseis 5 to 15 milligrams (mg) per kilogram (kg) (2.3 to 6.9 mg per pound) ofbody weight to start. Your doctor may increase your dose gradually every weekby 5 to 10 mg per kg of body weight if needed. However, the dose is usuallynot more than 60 mg per kg of body weight a day. If the total dose a day isgreater than 250 mg, it is usually divided into smaller doses and taken twoor more times during the day.
  • Children 1 to 12 years of age: Dose is based on body weight. Theusual dose is 15 to 45 mg per kg (6.9 to 20.7 mg per pound) of body weightto start. The doctor may increase the dose gradually every week by 5 to 10mg 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 doseis 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 perkg 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 duringthe day.
  • Children 1 to 12 years of age: Dose is based on body weight. Theusual 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 temporarilycannot 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 dosesand taken two or more times during the day. Your doctor may increase yourdose 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 increaseyour dose if needed. However, the dose is usually not more than 1000 mg aday.
  • Children: Use and dose must be determined by your doctor.

Missed dose?If you miss a dose of this medicine, and your dosingschedule 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 backto your regular dosing schedule. Do not double doses.
• Two or more doses a day?If you remember within 6 hours of themissed dose, take it right away. Then take the rest of the doses for thatday at equally spaced times. Do not double doses.

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

Storage?To store this medicine:

• Keep out of the reach of children.
• Store away from heat and direct light.
• Do not store the capsule or tablet form of this medicine in the bathroom,near the kitchen sink, or in other damp places. Heat or moisture may causethe medicine to break down.
• Keep the syrup form of this medicine from freezing.
• Do not keep outdated medicine or medicine no longer needed. Be surethat any discarded medicine is out of the reach of children.

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 necessaryto allow dose adjustments and to reduce any unwanted effects.

Do not stop taking this medicine without first checkingwith your doctor. Your doctor may want you to gradually reduce theamount you are taking before stopping completely.

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

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

Valproic acid, valproate sodium, and divalproex will add to the effectsof alcohol and other CNS depressants (medicines that make you drowsy or lessalert). Some examples of CNS depressants are antihistamines or medicine forhay fever, other allergies, or colds; sedatives, tranquilizers, or sleepingmedicine; prescription pain medicine or narcotics; barbiturates; medicinefor seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the abovewhile you are using this medicine.

For diabetic patients:

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

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

This medicine may cause some people to become drowsy or less alert thanthey are normally. Make sure you know how you react tothis medicine before you drive, use machines, or do anything else that couldbe 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 mayneed medical attention.

Check with your doctor as soon as possible if any of the following sideeffects occur:

More common

body aches or pain ; congestion; cough; dryness or soreness of throat; fever ; hoarsenessrunny 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; earache, redness or swelling in ear; dizziness,; double vision; faintness,or light-headedness when getting up from a lying or sitting position suddenly;sweating; unusual tiredness or weakness; fast, irregular,pounding, or racing heartbeat or pulse; heavy, nonmenstrualvaginal bleeding; increase in seizures; loss of appetite; nausea or vomiting(continuing); rapid weight gain; spots before eyes; swelling of face, arms, hands,lower legs, or feet; tingling of hands or feet; tiredness and weakness; unusual bleedingor bruising; unusual weight gain or loss; vomiting of blood or material that looks like coffee grounds; yellow eyes or skin

Other side effects may occurthat usually do not need medical attention. These side effects may go awayduring treatment as your body adjusts to the medicine. However, check withyour doctor if any of the following side effects continue or are bothersome:

More common

Abdominal or stomach cramps (mild); acid or sour stomach; belching; heartburn; indigestion; stomach discomfort,upset or pain; change in menstrual periods; crying paranoia; quick to react or overreact emotionally; rapidlychanging moods; depersonalization; dysphoria; diarrhea; euphoria; hair loss; indigestion; lack or loss of strength; loss of appetite; loss of bowel control; mental depression; nausea and vomiting; paranoia; quick to reactor overreact emotionally; rapidly changing moods; sleepiness or unusual drowsiness; trembling of handsand arms; unusual weight loss or gain

Less common or rare

Absence of or decrease in body movement; absent, missed, or irregular menstrual periods; stopping of menstrual bleeding; anxiety; nervousness; restlessness; bloated full feeling; bloody or cloudyurine; 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 awarenessor responsiveness; degenerative disease of the joint; difficult, burning, or painful urination; difficulty in moving; discharge; excessivetearing of eye; discouragement; dizziness; drowsiness; dry mouth; excess air or gas in stomach or intestines; excessive muscle tone; muscle tension or tightness;muscle stiffness; feeling of constant movement ofself or surroundings; feeling sad or empty; feeling of warmth or heat; ; flushingor redness of skin, especially on face and neck; frequent urge to urinate; headache; heavy bleeding; irregular heartbeats; irritability; joint pain;swollen joints; lack of appetite; lip smacking ; uncontrolled chewing movements; lossof hair; loss of interest or pleasure; loss of memory; problems with memory; mimicry of speech or movements; muscle aching orcramping; muscle pains or stiffness; mutism; negativism; normal menstrual bleeding occurring earlier, possibly lasting longer thanexpected; pain; passinggas; peculiar postures or movements, mannerisms orgrimacing; puffing of cheeks; rapid or worm-like movements of tongue; redness,swelling, or soreness of tongue; severe sleepiness; shortness of breath; difficult or labored breathing; small red or purple spots on skin; stuffy nose; runny nose; sneezing; redness, pain, swelling of eye, eyelid, or inner lining of eyelid; seeing, hearing, or feeling things that are not there; sensation of spinning; shaking; shortness of breath; hyperventilation; skin rash; sweating; tightnessin chest; tiredness; troubleconcentrating; trouble in speaking; slurred speech; trouble sleeping; uncontrolledchewing movements; uncontrolled movements of armsand legs; unusual excitement, restlessness, or irritability; wheezing

Other side effects not listed above may also occur in some patients. Ifyou notice any other effects, check with your doctor.