Medical Editor: John P. Cunha, DO, FACOEP
What Is Depakene?
Depakene (valproic acid) is an antiepileptic used to treat various types of seizure disorders. Depakene is sometimes used together with other seizure medications. Depakene is available in generic form.
What Are Side Effects of Depakene?
Common side effects of Depakene include:
- diarrhea,
- constipation,
- upset stomach,
- dizziness,
- drowsiness,
- weakness,
- hair loss,
- blurred/double vision or other vision changes,
- changes in menstrual periods,
- enlarged breasts,
- ringing in the ears,
- shakiness (tremor),
- unsteadiness,
- weight changes, or
- unusual or unpleasant taste in your mouth.
Some patients have suicidal thoughts while taking Depakene. Tell your doctor if this occurs. Tell your doctor if you have serious side effects of Depakene including:
- signs of infection (e.g., fever, persistent sore throat, swollen lymph nodes),
- chest pain,
- easy bruising or unexplained bleeding,
- fast/slow/irregular heartbeat,
- swelling of hands or feet,
- uncontrolled eye movement (nystagmus),
- feeling cold/shivering,
- rapid breathing, or
- loss of consciousness.
Dosage for Depakene
For adults and children over 10 years of age, initial dose of Depakene is 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal response. Maximum optimal dose is usually below 60 mg/kg/day.
What Drugs, Substances, or Supplements Interact with Depakene?
Cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for depression or anxiety can add to sleepiness caused by Depakene. This drug may also interact with topiramate, tolbutamide, blood thinners, aspirin or acetaminophen, zidovudine, clozapine, diazepam, meropenem or imipenem and cilastatin, rifampin, or ethosuximide.
Depakene During Pregnancy and Breastfeeding
Depakene is not recommended for use during pregnancy. It may cause birth defects. However, since untreated seizures are a serious condition that can harm both a pregnant woman and her fetus, do not stop taking this medication unless directed by your doctor. Your doctor may switch the type of medication you use during pregnancy. This medication passes into breast milk. While there have been no reports of harm to nursing infants, consult your doctor before breastfeeding.
Additional Information
Our Depakene (valproic acid) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
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.

QUESTION
If you have had a seizure, it means you have epilepsy. See AnswerGet emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).
Seek medical treatment if you have a serious drug reaction that can affect many parts of your body. Symptoms may include: skin rash, fever, swollen glands, muscle aches, severe weakness, unusual bruising, or yellowing of your skin or eyes.
Call your doctor at once if the person taking this medicine has signs of liver or pancreas problems, such as: loss of appetite, upper stomach pain (that may spread to your back), ongoing nausea or vomiting, dark urine, swelling in the face, or jaundice (yellowing of the skin or eyes).
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:
- confusion, tiredness, cold feeling, vomiting, change in your mental state;
- easy bruising, unusual bleeding (nose, mouth, or gums), purple or red pinpoint spots under your skin;
- severe drowsiness; or
- worsening seizures.
Severe drowsiness may be more likely in older adults.
Common side effects may include:
- nausea, vomiting, stomach pain, diarrhea;
- dizziness, drowsiness, weakness;
- headache;
- tremors, problems with walking or coordination;
- blurred vision, double vision;
- hair loss; or
- changes in appetite, weight gain.
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.
Read the entire detailed patient monograph for Depakene (Valproic Acid)

IMAGES
See ImagesSIDE EFFECTS
The following serious adverse reactions are described below and elsewhere in the labeling:
- Hepatic failure [see WARNINGS AND PRECAUTIONS]
- Birth defects [see WARNINGS AND PRECAUTIONS]
- Decreased IQ following in utero exposure [see WARNINGS AND PRECAUTIONS]
- Pancreatitis [see WARNINGS AND PRECAUTIONS]
- Hyperammonemic encephalopathy [see WARNINGS AND PRECAUTIONS]
- Suicidal behavior and ideation [see WARNINGS AND PRECAUTIONS]
- Bleeding and other hematopoietic disorders [see WARNINGS AND PRECAUTIONS]
- Hypothermia [see WARNINGS AND PRECAUTIONS]
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan hypersensitivity reactions [see WARNINGS AND PRECAUTIONS]
- Somnolence in the elderly [see WARNINGS AND PRECAUTIONS]
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Epilepsy
The data described in the following section were obtained using Depakote (divalproex sodium) tablets.
Based on a placebo-controlled trial of adjunctive therapy for treatment of complex partial seizures, Depakote (divalproex sodium) was generally well tolerated with most adverse reactions rated as mild to moderate in severity. Intolerance was the primary reason for discontinuation in the Depakote-treated patients (6%), compared to 1% of placebo-treated patients.
Table 3 lists treatment-emergent adverse reactions which were reported by ≥ 5% of Depakotetreated patients and for which the incidence was greater than in the placebo group, in a placebocontrolled trial of adjunctive therapy for treatment of complex partial seizures. Since patients were also treated with other antiepilepsy drugs, it is not possible, in most cases, to determine whether the following adverse reactions can be ascribed to Depakote alone, or the combination of Depakote and other antiepilepsy drugs.
Table 3. Adverse Reactions Reported by ≥ 5% of Patients Treated with Depakote During
Placebo-Controlled Trial of Adjunctive Therapy for Complex Partial Seizures
Body System/Reaction | Depakote (%) (n = 77) |
Placebo (%) (n = 70) |
Body as a Whole | ||
Headache | 31 | 21 |
Asthenia | 27 | 7 |
Fever | 6 | 4 |
Gastrointestinal System | ||
Nausea | 48 | 14 |
Vomiting | 27 | 7 |
Abdominal Pain | 23 | 6 |
Diarrhea | 13 | 6 |
Anorexia | 12 | 0 |
Dyspepsia | 8 | 4 |
Constipation | 5 | 1 |
Nervous System | ||
Tremor | 25 | 6 |
Somnolence | 27 | 11 |
Dizziness | 25 | 13 |
Amblyopia/Blurred Vision | 12 | 9 |
Diplopia | 16 | 9 |
Ataxia | 8 | 1 |
Nystagmus | 8 | 1 |
Emotional Lability | 6 | 4 |
Thinking Abnormal | 6 | 0 |
Amnesia | 5 | 1 |
Respiratory System | ||
Flu Syndrome | 12 | 9 |
Infection | 12 | 6 |
Bronchitis | 5 | 1 |
Rhinitis | 5 | 4 |
Other | ||
Alopecia | 6 | 1 |
Weight Loss | 6 | 0 |
Table 4 lists treatment-emergent adverse reactions which were reported by ≥ 5% of patients in the high dose Depakote group, and for which the incidence was greater than in the low dose group, in a controlled trial of Depakote monotherapy treatment of complex partial seizures. Since patients were being titrated off another antiepilepsy drug during the first portion of the trial, it is not possible, in many cases, to determine whether the following adverse reactions can be ascribed to Depakote alone, or the combination of Depakote and other antiepilepsy drugs.
Table 4. Adverse Reactions Reported by ≥ 5% of Patients in the High Dose Group in the
Controlled Trial of Depakote Monotherapy for Complex Partial Seizures1
Body System/Reaction | High Dose (%) (n = 131) |
Low Dose (%) (n = 134) |
Body as a Whole | ||
Asthenia | 21 | 10 |
Digestive System | ||
Nausea | 34 | 26 |
Diarrhea | 23 | 19 |
Vomiting | 23 | 15 |
Abdominal Pain | 12 | 9 |
Anorexia | 11 | 4 |
Dyspepsia | 11 | 10 |
Hemic/Lymphatic System | ||
Thrombocytopenia | 24 | 1 |
Ecchymosis | 5 | 4 |
Metabolic/Nutritional | ||
Weight Gain | 9 | 4 |
Peripheral Edema | 8 | 3 |
Nervous System | ||
Tremor | 57 | 19 |
Somnolence | 30 | 18 |
Dizziness | 18 | 13 |
Insomnia | 15 | 9 |
Nervousness | 11 | 7 |
Amnesia | 7 | 4 |
Nystagmus | 7 | 1 |
Depression | 5 | 4 |
Respiratory System | ||
Infection | 20 | 13 |
Pharyngitis | 8 | 2 |
Dyspnea | 5 | 1 |
Skin and Appendages | ||
Alopecia | 24 | 13 |
Special Senses | ||
Amblyopia/Blurred Vision | 8 | 4 |
Tinnitus | 7 | 1 |
1 Headache was the only adverse reaction that occurred in ≥ 5% of patients in the high dose group and at an equal or greater incidence in the low dose group. |
The following additional adverse reactions were reported by greater than 1% but less than 5% of the 358 patients treated with Depakote in the controlled trials of complex partial seizures:
Body as a Whole: Back pain, chest pain, malaise.
Cardiovascular System: Tachycardia, hypertension, palpitation.
Digestive System: Increased appetite, flatulence, hematemesis, eructation, pancreatitis, periodontal abscess.
Hemic and Lymphatic System: Petechia.
Metabolic and Nutritional Disorders: SGOT increased, SGPT increased.
Musculoskeletal System: Myalgia, twitching, arthralgia, leg cramps, myasthenia.
Nervous System: Anxiety, confusion, abnormal gait, paresthesia, hypertonia, incoordination, abnormal dreams, personality disorder.
Respiratory System: Sinusitis, cough increased, pneumonia, epistaxis.
Skin and Appendages: Rash, pruritus, dry skin.
Special Senses: Taste perversion, abnormal vision, deafness, otitis media.
Urogenital System: Urinary incontinence, vaginitis, dysmenorrhea, amenorrhea, urinary frequency.
Mania
Although Depakene has not been evaluated for safety and efficacy in the treatment of manic episodes associated with bipolar disorder, the following adverse reactions not listed above were reported by 1% or more of patients from two placebo-controlled clinical trials of Depakote (divalproex sodium) tablets.
Body as a Whole: Chills, neck pain, neck rigidity.M
Cardiovascular System: Hypotension, postural hypotension, vasodilation.
Digestive System: Fecal incontinence, gastroenteritis, glossitis.
Musculoskeletal System: Arthrosis.
Nervous System: Agitation, catatonic reaction, hypokinesia, reflexes increased, tardive dyskinesia, vertigo.
Skin and Appendages: Furunculosis, maculopapular rash, seborrhea.
Special Senses: Conjunctivitis, dry eyes, eye pain.
Urogenital System: Dysuria.
Migraine
Although Depakene has not been evaluated for safety and efficacy in the prophylactic treatment of migraine headaches, the following adverse reactions not listed above were reported by 1% or more of patients from two placebo-controlled clinical trials of Depakote (divalproex sodium) tablets.
Body as a Whole: Face edema.
Digestive System: Dry mouth, stomatitis.
Urogenital System: Cystitis, metrorrhagia, and vaginal hemorrhage.
Post-Marketing Experience
The following adverse reactions have been identified during post approval use of Depakote.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Dermatologic: Hair texture changes, hair color changes, photosensitivity, erythema multiforme, toxic epidermal necrolysis, nail and nail bed disorders, and Stevens-Johnson syndrome.
Psychiatric: Emotional upset, psychosis, aggression, psychomotor hyperactivity, hostility, disturbance in attention, learning disorder, and behavioral deterioration.
Neurologic: Paradoxical convulsion
There have been several reports of acute or subacute cognitive decline and behavioral changes (apathy or irritability) with cerebral pseudoatrophy on imaging associated with valproate therapy; both the cognitive/behavioral changes and cerebral pseudoatrophy reversed partially or fully after valproate discontinuation.
There have been reports of acute or subacute encephalopathy in the absence of elevated ammonia levels, elevated valproate levels, or neuroimaging changes. The encephalopathy reversed partially or fully after valproate discontinuation.
Musculoskeletal: Fractures, decreased bone mineral density, osteopenia, osteoporosis, and weakness.
Hematologic: Relative lymphocytosis, macrocytosis, leukopenia, anemia including macrocytic with or without folate deficiency, bone marrow suppression, pancytopenia, aplastic anemia, agranulocytosis, and acute intermittent porphyria.
Endocrine: Irregular menses, secondary amenorrhea, hyperandrogenism, hirsutism, elevated testosterone level, breast enlargement, galactorrhea, parotid gland swelling, polycystic ovary disease, decreased carnitine concentrations, hyponatremia, hyperglycinemia, and inappropriate ADH secretion.
There have been rare reports of Fanconi’s syndrome occurring chiefly in children.
Metabolism and nutrition: Weight gain.
Reproductive: Aspermia, azoospermia, decreased sperm count, decreased spermatozoa motility, male infertility, and abnormal spermatozoa morphology.
Genitourinary: Enuresis and urinary tract infection.
Special Senses: Hearing loss.
Other: Allergic reaction, anaphylaxis, developmental delay, bone pain, bradycardia, and cutaneous vasculitis.
Read the entire FDA prescribing information for Depakene (Valproic Acid)

SLIDESHOW
What Is Epilepsy? Symptoms, Causes, and Treatments See Slideshow© Depakene Patient Information is supplied by Cerner Multum, Inc. and Depakene Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.
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