What is Depakote

Depakote (divalproex sodium) is used to treat certain types of seizures (epilepsy). Depakote medication is an anticonvulsant that works in the brain tissue to stop seizures. Depakote (divalproex sodium) is sometimes used together with other seizure medications. Depakote (divalproex sodium) is also used to treat the manic episodes related to bipolar disorder (manic-depressive illness) and to prevent migraine headaches. Do NOT use Depakote to prevent migraine headaches if you are pregnant.

Depakote (divalproex sodium) is a stable coordination compound comprised of sodium valproate and valproic acid with anticonvulsant and antiepileptic activities. Depakote (divalproex sodium) dissociates to the valproate ion in the gastrointestinal tract. Divalproex sodium, valproate sodium, and valproic acid, are all similar medications that are used by the body as valproic acid. Therefore, the term divalproex sodium is interchangeable with valproic acid.

Depakote (divalproex sodium) binds to and inhibits gamma-aminobutyric acid (GABA) transaminase and its anticonvulsant activity may be exerted by increasing brain concentration of GABA and by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. Depakote (divalproex sodium) may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels.

Depakote (divalproex sodium) is available only with your doctor’s prescription.

Depakote (divalproex sodium) is available in the following dosage forms:

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

Depakote and alcohol

Using alcohol with Depakote (divalproex sodium) will add to the central nervous depressant effects of alcohol.

Alcohol can increase the nervous system side effects of Depakote (divalproex sodium) such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. You should avoid or limit the use of alcohol while being treated with divalproex sodium. Do not use more than the recommended dose of Depakote, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. Talk to your doctor or pharmacist if you have any questions or concerns.

What should I avoid while taking Depakote?

Drinking alcohol may increase certain side effects of Depakote (divalproex sodium).

Avoid driving or hazardous activity until you know how this medicine will affect you. Your reactions could be impaired.

Depakote (divalproex sodium) could make you sunburn more easily. Avoid sunlight or tanning beds. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Before using Depakote (divalproex sodium)

In deciding to use Depakote (divalproex sodium), 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.

Depakote special precautions

• tell your doctor and pharmacist if you are allergic to Depakote (divalproex sodium), any other medications, or any of the ingredients in the type of Depakote (divalproex sodium) that has been prescribed for you. Ask your pharmacist for a list of the ingredients.

• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: acyclovir (Zovirax), anticoagulants (‘blood thinners’) such as warfarin (Coumadin), amitriptyline, aspirin, carbamazepine (Tegretol), cholestyramine (Prevalite), clonazepam (Klonopin), diazepam (Valium), doripenem (Doribax), ertapenem (Invanz), ethosuximide (Zarontin), felbamate (Felbatol), certain hormonal contraceptives (birth control pills, rings, patches, implants, injections, and intrauterine devices), imipenem and cilastatin (Primaxin), lamotrigine (Lamictal),medications for anxiety or mental illness, meropenem (Merrem), nortriptyline (Pamelor), phenobarbital, phenytoin (Dilantin), primidone (Mysoline), rifampin (Rifadin), rufinamide (Banzel), sedatives, sleeping pills, tolbutamide, topiramate (Topamax),tranquilizers,and zidovudine (Retrovir). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.

• tell your doctor if you have or have ever had episodes of confusion and loss of ability to think and understand, especially during pregnancy or childbirth; coma (loss of consciousness for a period of time); difficulty coordinating your movements; human immunodeficiency virus (HIV); or cytomegalovirus (CMV; a virus that can cause symptoms in people who have weak immune systems).

• tell your doctor if you are breast feeding.

• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking Depakote (divalproex sodium).

• you should know that Depakote (divalproex sodium) may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.

• remember that alcohol can add to the drowsiness caused by Depakote (divalproex sodium).

• you should know that Depakote (divalproex sodium) can cause extreme drowsiness that may cause you to eat or drink less than you normally would, especially if you are elderly. Tell your doctor if you are not able to eat or drink as you normally do.

• you should know that your mental health may change in unexpected ways and you may become suicidal (thinking about harming or killing yourself or planning or trying to do so) while you are taking Depakote (divalproex sodium) for the treatment of epilepsy, mental illness, or other conditions. A small number of adults and children 5 years of age and older (about 1 in 500 people) who took anticonvulsants such as Depakote (divalproex sodium) to treat various conditions during clinical studies became suicidal during their treatment. Some of these people developed suicidal thoughts and behavior as early as one week after they started taking the medication. There is a risk that you may experience changes in your mental health if you take an anticonvulsant medication such as Depakote (divalproex sodium), but there may also be a risk that you will experience changes in your mental health if your condition is not treated. You and your doctor will decide whether the risks of taking an anticonvulsant medication are greater than the risks of not taking the medication. You, your family, or your caregiver should call your doctor right away if you experience any of the following symptoms: panic attacks; agitation or restlessness; new or worsening irritability, anxiety, or depression; acting on dangerous impulses; difficulty falling or staying asleep; aggressive, angry, or violent behavior; mania (frenzied, abnormally excited mood); talking or thinking about wanting to hurt yourself or end your life; withdrawing from friends and family; preoccupation with death and dying; giving away prized possessions; or any other unusual changes in behavior or mood. Be sure that your family or caregiver knows which symptoms may be serious so they can call the doctor if you are unable to seek treatment on your own.

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to Depakote (divalproex sodium) 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.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of Depakote (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 Depakote’s toxicity, use in children younger than 2 years of age requires extreme caution.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of Depakote (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 Depakote (divalproex sodium).

Pregnancy

Pregnancy Category X: Studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. Depakote (divalproex sodium) should NOT be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit.

Breastfeeding

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

Drug 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 Depakote (divalproex sodium), 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 Depakote (divalproex sodium) 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
• Cisplatin
• Doripenem
• Ertapenem
• Imipenem
• Lamotrigine
• Meropenem
• Orlistat
• Primidone
• Sodium Oxybate
• Vorinostat
• Warfarin

Using Depakote (divalproex sodium) 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

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
• Liver disease
• Mental illness
• Pancreatitis (inflammation of the pancreas)
• Thrombocytopenia (low platelet count)—Use with caution. May make these conditions worse.
• Liver disease
• Mitochondrial disorders, including Alpers-Huttenlocher syndrome (genetic disorder)
• 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.

Depakote Precautions

It is very important that your doctor check your progress closely while you are using Depakote (divalproex sodium) to see if it is working properly and to allow for a change in the dose. Blood tests may be needed to check for any unwanted effects.

Using Depakote (divalproex sodium) while you are pregnant (especially during the first trimester) can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using Depakote (divalproex sodium), 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 Depakote (divalproex sodium), 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.

Depakote (divalproex sodium) may cause some people to become dizzy, lightheaded, 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 dizzy or not alert.

Do not stop taking Depakote (divalproex sodium) 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 taking this medicine. The results of some tests may be affected by this medicine.

Depakote (divalproex sodium) may cause serious allergic reactions affecting multiple body organs (e.g, 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.

Depakote (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.

Depakote (divalproex sodium) 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 (e.g, barbiturates), muscle relaxants, or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are taking this medicine.

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.

What is Depakote used for?

Depakote is used to treat various types of seizure disorders. This medicine is sometimes used together with other seizure medications.

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

Mania

Depakote (divalproex sodium) is a valproate and is indicated for the treatment of the manic episodes associated with bipolar disorder. A manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood. Typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, poor judgment, aggressiveness, and possible hostility.

The safety and effectiveness of Depakote for long-term use in mania, i.e., more than 3 weeks, has not been demonstrated in controlled clinical trials. Therefore, healthcare providers who elect to use Depakote for extended periods should continually reevaluate the long-term usefulness of the drug for the individual patient.

Epilepsy

Depakote is indicated as monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures. Depakote is also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures.

Simple absence is defined as very brief clouding of the sensorium or loss of consciousness accompanied by certain generalized epileptic discharges without other detectable clinical signs. Complex absence is the term used when other signs are also present.

Migraine

Depakote is indicated for prophylaxis of migraine headaches. There is no evidence that Depakote is useful in the acute treatment of migraine headaches.

Depakote dosage

Take Depakote (divalproex sodium) 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.

Depakote (divalproex sodium) comes with a Medication Guide and a patient information insert. Read and follow the instructions in the insert carefully. Ask your doctor if you have any questions.

You may take Depakote (divalproex sodium) with food to avoid stomach upset.

The sprinkle capsules may be opened and the contents may be sprinkled onto 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.

If you are taking the sprinkle capsules, part of the capsules may pass into your stool after your body has absorbed the medicine. This is normal and not something to worry about.

The dose of Depakote (divalproex sodium) 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 Depakote (divalproex sodium). If your dose is different, do not change it unless your doctor tells you to do so.

The amount of Depakote (divalproex sodium) 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 Depakote 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) two 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 two or more times during the day.
  • Children younger than 10 years of age—Use and dose must be determined by your doctor.

For oral Depakote 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 if 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 Depakote  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 two or more times during the day.
  • Children younger than 10 years of age—Use and dose must be determined by your doctor.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for your next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Depakote side effects

Depakote (divalproex sodium) may cause side effects. Common side effects of Depakote include: abdominal pain, asthenia, dizziness, drowsiness, nausea, and anorexia. Other side effects include: abnormality in thinking, alopecia, ataxia, nystagmus, tremor, weight loss, fever, and skin rash.

More common side effects:

• black, tarry stools
• bleeding gums
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blood in the urine or stools
• confusion
• cough or hoarseness
• crying
• delusions
• dementia
• depersonalization
• diarrhea
• difficult or labored breathing
• dysphoria
• euphoria
• fever or chills
• general feeling of discomfort or illness
• headache
• joint pain
• loss of appetite
• lower back or side pain
• mental depression
• muscle aches and pains
• nausea
• nervousness
• painful or difficult urination
• paranoia
• pinpoint red spots on the skin
• quick to react or overreact emotionally
• rapid weight gain
• rapidly changing moods
• runny nose
• 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 sleeping
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain or loss
• vomiting

Less common side effects:

• 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
• chills
• cloudy urine
• clumsiness or unsteadiness
• cold sweats
• constipation
• darkened urine
• degenerative disease of the joint
• difficulty with moving
• dizziness
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
• 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
• hyperventilation
• 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
• 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

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 side effects:

• acid or sour stomach
• 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
• rash
• seeing double
• tender, swollen glands in the neck
• trouble with swallowing
• uncontrolled eye movements
• voice changes
• weight gain
• weight loss

Less common side effects:

• absent, missed, or irregular menstrual periods
• back pain
• 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 intestines
• eye pain
• feeling of constant movement of self or surroundings
• full feeling
• heavy bleeding
• increased appetite
• itching of the vagina or genital area
• itching skin
• 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

Gastrointestinal

• Very common (10% or more): Abdominal pain, diarrhea, dyspepsia, gingival disorder, nausea, vomiting
• Common (1% to 10%): Constipation, dry mouth, eructation, fecal incontinence, flatulence, gastralgia, gastroenteritis, glossitis, periodontal abscess, hematemesis, stomatitis
• Uncommon (0.1% to 1%): Pancreatitis (life-threatening)

Hepatic

• Common (1% to 10%): Increased liver enzymes (particularly early in treatment), liver injury, SGOT increased, SGPT increased
• Frequency not reported: Severe liver damage (including hepatic failure sometimes resulting in death), increased serum bilirubin, abnormal changes in other liver function tests

Nervous system

• Very common (10% or more): Dizziness, headache, somnolence, tremor
• Common (1% to 10%): Abnormal gait, amnesia, catatonic reaction, convulsion, disturbance in attention, dysarthria, extrapyramidal disorder, hypertonia, hypokinesia, incoordination, increased reflexes, memory impairment, nystagmus, paresthesia, speech disorder, stupor, tardive dyskinesia, taste perversion
• Uncommon (0.1% to 1%): Ataxia, coma, encephalopathy, lethargy, reversible Parkinsonism
• Rare (less than 0.1%): Cognitive disorder, reversible dementia associated with reversible cerebral atrophy
• Frequency not reported: Cerebral atrophy, dementia

Hematologic

• Very common (10% or more): Thrombocytopenia
• Common (1% to 10%): Anemia, hemorrhage
• Uncommon (0.1% to 1%): Leucopenia, pancytopenia
• Rare (less than 0.1%): Abnormal coagulation tests (e.g., prolonged prothrombin time, prolonged activated partial thromboplastin time, prolonged thrombin time, prolonged INR), agranulocytosis, bone marrow failure, decreased coagulation factors, including pure red cell aplasia, macrocytosis
• Frequency not reported: Aplastic anemia, bone marrow suppression, bruising, eosinophilia, frank hemorrhage, hypofibrinogenemia, anemia including macrocytic with or without folate deficiency, relative lymphocytosis

Respiratory

• Very common (10% or more): Flu syndrome, respiratory infection
• Common (1% to 10%): Bronchitis, dyspnea, epistaxis, increased cough, pharyngitis, pneumonia, rhinitis, sinusitis
• Uncommon (0.1% to 1%): Pleural effusion

Renal

• Rare (less than 0.1%): Reversible Fanconi’s syndrome, tubulointerstitial nephritis

Cardiovascular

• Common (1% to 10%): Edema, hypertension, hypotension, palpitations, postural hypotension, peripheral edema, tachycardia, vasodilation
• Frequency not reported: Bradycardia, cutaneous vasculitis, hematoma formation

Endocrine

• Uncommon (0.1% to 1%): Hyperandrogenism, syndrome of inappropriate ADH secretion
• Rare (less than 0.1%): Hypothyroidism
• Frequency not reported: Abnormal thyroid function tests, elevated serum testosterone concentrations, parotid gland swelling

Dermatologic

• Very common (10% or more): Alopecia
• Common (1% to 10%): Discoid lupus erythematosus, dry skin, ecchymosis, furunculosis, maculopapular rash, petechia, pruritus, rash, seborrhea
• Uncommon (0.1% to 1%): Abnormal hair texture, abnormal hair growth, hair color changes, sweating
• Rare (0.01% to 0.1%): Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
• Very rare (less than 0.01%): Acne, hirsutism
• Frequency not reported: Angioedema, generalized pruritus, photosensitivity

Genitourinary

• Common (1% to 10%): Amenorrhea, cystitis, dysmenorrhea, dysuria, enuresis, metrorrhagia, urinary incontinence, urinary frequency, vaginal hemorrhage, vaginitis
• Very rare (less than 0.01%): Gynecomastia
• Frequency not reported: Breast enlargement, galactorrhea, polycystic ovary disease

Hypersensitivity

• Frequency not reported: Allergic reaction, anaphylaxis, hypersensitivity

Metabolic

• Very common (10% or more): Anorexia
• Common (1% to 10%): Weight loss/gain, increased appetite, hyponatremia
• Rare (less than 0.1%): Hyperammonemia
• Frequency not reported: Acute intermittent porphyria, minor elevations of LDH (dose related), decreased carnitine concentrations, hyperglycinemia

Musculoskeletal

• Common (1% to 10%): Arthralgia, arthrosis, leg cramps, myalgia, myasthenia, twitching
• Uncommon (0.1% to 1%): Decreased bone mineral density, osteopenia, osteoporosis and fractures on long term therapy
• Rare (less than 0.1%): Rhabdomyolysis, systemic lupus erythematosus
• Frequency not reported: Bone pain

Ocular

• Very common (10% or more): Amblyopia/blurred vision, diplopia
• Common (1% to 10%): Abnormal vision, conjunctivitis, diplopia, dry eyes, eye pain

Oncologic

• Rare (less than 0.1%): Myelodysplastic syndrome

Other

• Very common (10% or more): Asthenia
• Common (1% to 10%): Back pain, chills, deafness, ear disorder, ear pain, face edema, fever, malaise, otitis media, tinnitus, vertigo
• Frequency not reported: Hypothermia, weakness

Psychiatric

• Very common (10% or more): Nervousness
• Common (1% to 10%): Abnormal dreams, agitation, anxiety, aggression, confusion, depression, emotional lability, hallucinations, insomnia, personality disorder, thinking abnormalities
• Rare (less than 0.1%): Abnormal behavior, learning disorder, psychomotor hyperactivity
• Frequency not reported: Behavioral deterioration, hostility, psychosis

Depakote overdose

Get emergency help immediately if any of the following symptoms of overdose occur while taking divalproex sodium:

Symptoms of Depakote overdose:

• change in consciousness
• fainting
• loss of consciousness
• slow or irregular heartbeat

Depakote withdrawal

Valproate withdrawal: epilepsy relapse rates are high, especially during abrupt withdrawal ¹⁾, and there is even a case report of one patient being treated for epilepsy developing new-onset mania following valproate withdrawal ²⁾.

Discontinuation can also be problematic in epilepsy. Observations from the EURAP study showed that withdrawal of valproate in the first trimester (when it is most teratogenic) was associated with a significantly higher rate of generalised tonic clonic seizures (33%) compared to when it was continued (16%) ³⁾. More striking, however, is that the rate of seizures was also elevated (29%) when valproate was switched to another anti-epileptic medication.

Another consideration for bipolar disorder patients should include the risks of puerperal psychosis. Prevalence of this condition in the general population is about 0.1–0.25%, but may be up to 50% in women with bipolar disorder ⁴⁾. Hospitalisation for psychiatric morbidity predicts the risk of puerperal psychosis ⁵⁾, so untreated bipolar disorder may not just affect the mother during pregnancy, but also in the weeks afterwards.

In newborns, the signs of withdrawal are irritability, jitteriness, abnormal tone, seizures, feeding problems and hypoglycemia. The signs occur at birth ⁶⁾.