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Depakote ER

Depakote ER(Divalproex Sodium) side effects drug center

 

PROFESSIONAL

CONSUMER

SIDE EFFECTS

 

Depakote ER Side Effects Center

What Is Depakote ER?

Depakote ER (divalproex sodium) is an anticonvulsant and mood stabilizer used to treat several conditions, including seizure disorders, acute manic or mixed episodes associated with bipolar disorder, and migraine headaches. Depakote is available in generic form.

What Are Side Effects of Depakote ER?

Common side effects of Depakote ER include:

Tell your doctor if you experience serious side effects of Depakote ER 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 or shivering,
  • rapid breathing, or
  • loss of consciousness.

Dosage for Depakote ER

Dosage of Depakote ER is based on weight, medical condition, and response to therapy.

What Drugs, Substances, or Supplements Interact with Depakote ER?

Depakote ER may interact with topiramate, blood thinners, aspirin, acetaminophen, zidovudine, clozapine, diazepam, meropenem, rifampin, or ethosuximide. Discuss all medications you are taking with your doctor.

Depakote ER During Pregnancy and Breastfeeding

Depakote ER is not recommended for use during pregnancy. It may harm a fetus. 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 a doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately talk to your doctor about the benefits and risks of using this medication. This medication passes into breast milk. While there have been no reports of harm to nursing infants, consult your doctor before breast-feeding. If Depakote ER is used for seizures, do not stop taking it without consulting your doctor. Your condition may become worse if the drug is suddenly stopped.

Additional Information

Our Depakote ER Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Depakote ER Consumer Information

Get 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:

  • easy bruising, unusual bleeding (nose, mouth, or gums), purple or red pinpoint spots under your skin;
  • fever, swollen glands, mouth sores;
  • confusion, tiredness, cold feeling, vomiting, change in your mental state;
  • severe drowsiness; or
  • worsening seizures.

Common side effects may include:

  • nausea, vomiting, stomach pain, diarrhea, constipation;
  • headache, back pain;
  • dizziness, drowsiness, weakness, tremors;
  • memory problems, mood changes, trouble sleeping;
  • bruising or bleeding;
  • runny nose, sore throat, cough, wheezing, trouble breathing;
  • fever, flu symptoms;
  • problems with walking or coordination;
  • swelling in your hands or feet;
  • blurred vision, double vision, unusual eye movements;
  • ringing in your ears;
  • rash, hair loss; or
  • changes in weight or appetite.

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 Depakote ER (Divalproex Sodium)

 

Depakote ER Professional Information

SIDE EFFECTS

The following serious adverse reactions are described below and elsewhere in the labeling:

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

Adverse Event Depakote ER
(n=338)		 Placebo
(n=263)
Somnolence 26% 14%
Dyspepsia 23% 11%
Nausea 19% 13%
Vomiting 13% 5%
Diarrhea 12% 8%
Dizziness 12% 7%
Pain 11% 10%
Abdominal pain 10% 5%
Accidental injury 6% 5%
Asthenia 6% 5%
Pharyngitis 6% 5%
1 The following adverse reactions/event occurred at an equal or greater incidence for placebo than for Depakote ER: headache

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

Body System/Event 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
  Somnolence 27 11
  Tremor 25 6
  Dizziness 25 13
  Diplopia 16 9
  Amblyopia/Blurred Vision 12 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 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

Body System/Event 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 event 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 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

Body System Event Depakote ER
(n=122)		 Placebo
(n=115)
Gastrointestinal System
  Nausea 15% 9%
  Dyspepsia 7% 4%
  Diarrhea 7% 3%
  Vomiting 7% 2%
  Abdominal Pain 7% 5%
Nervous System
  Somnolence 7% 2%
Other
  Infection 15% 14%
1 The following adverse reactions occurred in greater than 5% of Depakote ER-treated patients and at a greater incidence for placebo than for Depakote ER: asthenia and flu syndrome.

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

Body System Reaction Depakote
(n=202)		 Placebo
(n=81)
Gastrointestinal System
  Nausea 31% 10%
  Dyspepsia 13% 9%
  Diarrhea 12% 7%
  Vomiting 11% 1%
  Abdominal pain 9% 4%
  Increased appetite 6% 4%
Nervous System
  Asthenia 20% 9%
  Somnolence 17% 5%
  Dizziness 12% 6%
  Tremor 9% 0%
Other
  Weight gain 8% 2%
  Back pain 8% 6%
  Alopecia 7% 1%
1 The following adverse reactions occurred in greater than 5% of Depakote-treated patients and at a greater incidence for placebo than for Depakote: flu syndrome and pharyngitis.

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.

Read the entire FDA prescribing information for Depakote ER (Divalproex Sodium)

&Copy; Depakote ER Patient Information is supplied by Cerner Multum, Inc. and Depakote ER Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.