Depakote ER

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.

Information on pediatric adverse reactions is presented in a section below.

Mania

The incidence of treatment-emergent events has been ascertained based on combined data from two three week placebo-controlled clinical trials of Depakote ER in the treatment of manic episodes associated with bipolar disorder.

Table 3 summarizes those adverse reactions reported for patients in these trials where the incidence rate in the Depakote ER-treated group was greater than 5% and greater than the placebo incidence.

Table 3: Adverse Reactions Reported by > 5% of Depakote-Treated Patients During Placebo-Controlled Trials of Acute Mania1

The following additional adverse reactions were reported by greater than 1% of the Depakote

ER-treated patients in controlled clinical trials:

Body as a Whole: Back Pain, Chills, Chills and Fever, Drug Level Increased, Flu Syndrome, Infection, Infection Fungal, Neck Rigidity.

Cardiovascular System: Arrhythmia, Hypertension, Hypotension, Postural Hypotension.

Digestive System: Constipation, Dry Mouth, Dysphagia, Fecal Incontinence, Flatulence, Gastroenteritis, Glossitis, Gum Hemorrhage, Mouth Ulceration. Hemic and Lymphatic System: Anemia, Bleeding Time Increased, Ecchymosis, Leucopenia.

Metabolic and Nutritional Disorders: Hypoproteinemia, Peripheral Edema.

Musculoskeletal System: Arthrosis, Myalgia.

Nervous System: Abnormal Gait, Agitation, Catatonic Reaction, Dysarthria, Hallucinations, Hypertonia, Hypokinesia, Psychosis, Reflexes Increased, Sleep Disorder, Tardive Dyskinesia, Tremor.

Respiratory System: Hiccup, Rhinitis.

Skin and Appendages: Discoid Lupus Erythematosus, Erythema Nodosum, Furunculosis, Maculopapular Rash, Pruritus, Rash, Seborrhea, Sweating, Vesiculobullous Rash.

Special Senses: Conjunctivitis, Dry Eyes, Eye Disorder, Eye Pain, Photophobia, Taste Perversion.

Urogenital System: Cystitis, Urinary Tract Infection, Menstrual Disorder, Vaginitis.

Epilepsy

Based on a placebo-controlled trial of adjunctive therapy for treatment of complex partial seizures, Depakote was generally well tolerated with most adverse reactions rated as mild to moderate in severity. Intolerance was the primary reason for discontinuation in the Depakotetreated patients (6%), compared to 1% of placebo-treated patients.

Table 4 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 the placebo-controlled 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 4: Adverse Reactions Reported by ≥ 5% of Patients Treated with Valproate During Placebo-Controlled Trial of Adjunctive Therapy for Complex Partial Seizures

Table 5 lists treatment-emergent adverse reactions which were reported by ≥ 5% of patients in the high dose valproate 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 valproate and other antiepilepsy drugs.

Table 5: Adverse Reactions Reported by ≥ 5% of Patients in the High Dose Group in the Controlled Trial of Valproate Monotherapy for Complex Partial Seizures1

The following additional adverse reactions were reported by greater than 1% but less than 5% of the 358 patients treated with valproate 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.

Migraine

Based on two placebo-controlled clinical trials and their long term extension, valproate was generally well tolerated with most adverse reactions rated as mild to moderate in severity. Of the 202 patients exposed to valproate in the placebo-controlled trials, 17% discontinued for intolerance. This is compared to a rate of 5% for the 81 placebo patients. Including the long term extension study, the adverse reactions reported as the primary reason for discontinuation by ≥ 1% of 248 valproate-treated patients were alopecia (6%), nausea and/or vomiting (5%), weight gain (2%), tremor (2%), somnolence (1%), elevated SGOT and/or SGPT (1%), and depression (1%).

Table 6 includes those adverse reactions reported for patients in the placebo-controlled trial where the incidence rate in the Depakote ER-treated group was greater than 5% and was greater than that for placebo patients.

Table 6: Adverse Reactions Reported by > 5% of Depakote ER-Treated Patients During the Migraine Placebo-Controlled Trial with a Greater Incidence than Patients Taking Placebo1

The following additional adverse reactions were reported by greater than 1% but not more than 5% of Depakote ER-treated patients and with a greater incidence than placebo in the placebo-controlled clinical trial for migraine prophylaxis:

Body as a Whole: Accidental injury, viral infection.

Digestive System: Increased appetite, tooth disorder.

Metabolic and Nutritional Disorders: Edema, weight gain.

Nervous System: Abnormal gait, dizziness, hypertonia, insomnia, nervousness, tremor, vertigo.

Respiratory System: Pharyngitis, rhinitis.

Skin and Appendages: Rash.

Special Senses: Tinnitus.

Table 7 includes those adverse reactions reported for patients in the placebo-controlled trials where the incidence rate in the valproate-treated group was greater than 5% and was greater than that for placebo patients.

Table 7: Adverse Reactions Reported by > 5% of Valproate-Treated Patients During Migraine Placebo-Controlled Trials with a Greater Incidence than Patients Taking Placebo1

The following additional adverse reactions were reported by greater than 1% but not more than 5% of the 202 valproate-treated patients in the controlled clinical trials:

Body as a Whole: Chest pain.

Cardiovascular System: Vasodilatation.

Digestive System: Constipation, dry mouth, flatulence, and stomatitis.

Hemic and Lymphatic System: Ecchymosis.

Metabolic and Nutritional Disorders: Peripheral edema.

Musculoskeletal System: Leg cramps.

Nervous System: Abnormal dreams, confusion, paresthesia, speech disorder, and thinking abnormalities.

Respiratory System: Dyspnea, and sinusitis.

Skin and Appendages: Pruritus.

Urogenital System: Metrorrhagia.

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: 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.

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, decrease 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.

In rare cases, divalproex sodium has caused life-threatening liver failure, especially in children younger than 2 years old. Children of this age may be at even greater risk for liver problems if they use more than one seizure medication, if they have a metabolic disorder, or if they have a brain disease causing mental impairment (such as Creutzfeldt-Jacob disease, Huntington disease, multiple sclerosis, or a brain injury or infection).

Divalproex sodium has also caused rare cases of life-threatening pancreatitis (inflammation of the pancreas). Pancreatitis can come on suddenly and symptoms may start even after you have been taking divalproex sodium for several years.

You should not take this medication if you are allergic to divalproex sodium, or if you have liver disease or a urea cycle disorder.

To make sure you can safely take divalproex sodium, tell your doctor if you have any of these other conditions:

• liver disease;
• 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.

You may have thoughts about suicide while taking this medication. Tell your doctor if you have new or worsening depression or suicidal thoughts during the first several months of treatment, or whenever your dose is changed.

Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits. Do not miss any scheduled appointments.

FDA pregnancy category D. Divalproex sodium can cause birth defects. Do not start taking divalproex sodium without telling your doctor if you are pregnant or planning to become pregnant. Use effective birth control while you are taking divalproex sodium.

Divalproex sodium may also affect cognitive development in children born to mothers who take this medication during pregnancy. Studies have shown that these children may score lower on cognitive tests (reasoning, intelligence, and problem-solving) than children whose mothers took other seizure medications during pregnancy.

Although divalproex sodium may harm an unborn baby, having a seizure during pregnancy could harm both mother and baby. If you become pregnant while taking divalproex sodium, do not stop taking the medicine without your doctor's advice.

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

Divalproex sodium can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Your pharmacist can provide more information about divalproex sodium.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 9.01. Revision date: 7/14/2011.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

• Bipolar Disorder
• Headache
• Prescription Migraine Medications
• Seizure (Epilepsy)

It is very important that your doctor check your progress closely while you are using this medicine 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 this medicine while you are pregnant (especially during 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 the medicine, 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 this medicine, 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.

Valproic acid 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.

Valproic acid may cause serious allergic reactions affecting multiple body organs (eg, 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.

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 fever, sore throat, rash, ulcers in the mouth, nosebleeds, bleeding gums, swollen glands, or small red or purple spots on the skin occur. These could be symptoms of a serious blood problem.

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.

Valproic acid 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 this medicine 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.

This medicine 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 (eg, 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.

Depakote ER 250 mg is available as white ovaloid tablets with the “a” logo and the code (HF). Each Depakote ER tablet contains divalproex sodium equivalent to 250 mg of valproic acid.

Depakote ER 500 mg is available as gray ovaloid tablets with the “a” logo and the code HC. Each Depakote ER tablet contains divalproex sodium equivalent to 500 mg of valproic acid.

1. Meador KJ, Baker GA, Browning N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurology 2013; 12 (3):244-252.

Do not use divalproex sodium to prevent migraine headaches if you are pregnant.

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

You should not use divalproex sodium if you have liver disease, a urea cycle disorder, or a genetic disorder such as Alpers' disease or Alpers-Huttenlocher syndrome (especially in a child younger than 2 years old).

Divalproex sodium can cause liver failure that may be fatal, especially in children under age 2 and in people with liver problems caused by a genetic mitochondrial (MYE-toe-KON-dree-al) disorder.

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).

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.

You may open the divalproex sodium sprinkle capsule and sprinkle the medicine into a spoonful of pudding or applesauce to make swallowing easier. Swallow this mixture right away.

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

While using divalproex sodium, you may need frequent blood tests.

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

If you need surgery, tell the surgeon ahead of time that you are using divalproex sodium.

Do not stop using divalproex sodium suddenly, even if you feel fine. Stopping suddenly may cause a serious, life-threatening type of seizure. Follow your doctor's instructions about tapering your dose.

Store at room temperature away from moisture and heat.

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.

Applies to divalproex sodium: oral delayed release capsule, oral delayed release tablet, oral tablet extended release

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)[Ref]

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[Ref]

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[Ref]

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[Ref]

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[Ref]

Renal

Rare (less than 0.1%): Reversible Fanconi's syndrome, tubulointerstitial nephritis[Ref]

Cardiovascular

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

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[Ref]

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[Ref]

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[Ref]

Hypersensitivity

Frequency not reported: Allergic reaction, anaphylaxis, hypersensitivity[Ref]

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[Ref]

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[Ref]

Ocular

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

Oncologic

Rare (less than 0.1%): Myelodysplastic syndrome[Ref]

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[Ref]

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[Ref]

Some side effects of Depakote ER may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.