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Depakene (Valproic Acid) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

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 was generally well tolerated with most adverse events 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 2 lists treatment-emergent adverse events which were reported by ≥ 5% of DEPAKOTE-treated patients and for which the incidence was greater than in the placebo group, in a placebo-controlled trial of adjunctive therapy for the 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 events can be ascribed to DEPAKOTE alone, or the combination of DEPAKOTE and other antiepilepsy drugs.

Table 2. Adverse Events Reported by ≥ 5% of Patients Treated with DEPAKOTE During Placebo-Controlled Trial of Adjunctive Therapy for Complex Partial Seizures
Body System/Event Depakote (%)
(n = 77)
Placebo (%)
(n = 70)
Body as a Whole
    Headache3121
    Asthenia277
    Fever64
Gastrointestinal System
    Nausea4814
    Vomiting277
    Abdominal Pain236
    Diarrhea136
    Anorexia120
    Dyspepsia84
    Constipation51
Nervous System
    Somnolence2711
    Tremor256
    Dizziness2513
    Diplopia169
    Amblyopia/Blurred Vision129
    Ataxia81
    Nystagmus81
    Emotional Lability64
    Thinking Abnormal60
    Amnesia51
Respiratory System
    Flu Syndrome129
    Infection126
    Bronchitis51
    Rhinitis54
Other
    Alopecia61
    Weight Loss60

Table 3 lists treatment-emergent adverse events 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 events can be ascribed to DEPAKOTE alone, or the combination of DEPAKOTE and other antiepilepsy drugs.

Table 3. Adverse Events Reported by ≥ 5% of Patients in the High Dose Group in the Controlled Trial of DEPAKOTE Monotherapy for Complex Partial Seizures1
Body System/Event High Dose (%)
(n = 131)
Low Dose (%)
(n = 134)

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.

Body as a Whole
    Asthenia2110
Digestive System
    Nausea3426
     Diarrhea2319
    Vomiting2315
     Abdominal Pain129
    Anorexia114
    Dyspepsia1110
Hemic/Lymphatic System
    Thrombocytopenia241
    Ecchymosis54
Metabolic/Nutritional
     Weight Gain94
     Peripheral Edema83
Nervous System
    Tremor5719
    Somnolence3018
    Dizziness1813
    Insomnia159
    Nervousness117
    Amnesia74
    Nystagmus71
    Depression54
Respiratory System
    Infection2013
    Pharyngitis82
    Dyspnea51
Skin and Appendages
    Alopecia2413
Special Senses
    Amblyopia/Blurred Vision84
    Tinnitus71

The following additional adverse events 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.

Other Patient Populations

Adverse events that have been reported with all dosage forms of valproate from epilepsy trials, spontaneous reports, and other sources are listed below by body system.

Gastrointestinal

The most commonly reported side effects at the initiation of therapy are nausea, vomiting, and indigestion. These effects are usually transient and rarely require discontinuation of therapy. Diarrhea, abdominal cramps, and constipation have been reported. Both anorexia with some weight loss and increased appetite with weight gain have also been reported. The administration of delayed-release divalproex sodium may result in reduction of gastrointestinal side effects in some patients.

CNS Effects

Sedative effects have occurred in patients receiving valproate alone but occur most often in patients receiving combination therapy. Sedation usually abates upon reduction of other antiepileptic medication. Tremor (may be dose-related), hallucinations, ataxia, headache, nystagmus, diplopia, asterixis, "spots before eyes", dysarthria, dizziness, confusion, hypesthesia, vertigo, incoordination, and Parkinsonism have been reported with the use of valproate. Rare cases of coma have occurred in patients receiving valproate alone or in conjunction with phenobarbital. In rare instances encephalopathy with or without fever has developed shortly after the introduction of valproate monotherapy without evidence of hepatic dysfunction or inappropriately high plasma valproate levels. Although recovery has been described following drug withdrawal, there have been fatalities in patients with hyperammonemic encephalopathy, particularly in patients with underlying urea cycle disorders (see WARNINGS - Urea Cycle Disorders and PRECAUTIONS).

Several reports have noted reversible cerebral atrophy and dementia in association with valproate therapy.

Dermatologic

Transient hair loss, skin rash, photosensitivity, generalized pruritus, erythema multiforme, and Stevens-Johnson syndrome. Rare cases of toxic epidermal necrolysis have been reported including a fatal case in a 6 month old infant taking valproate and several other concomitant medications. An additional case of toxic epidermal necrosis resulting in death was reported in a 35 year old patient with AIDS taking several concomitant medications and with a history of multiple cutaneous drug reactions. Serious skin reactions have been reported with concomitant administration of lamotrigine and valproate (see PRECAUTIONS - Drug Interactions).

Psychiatric

Emotional upset, depression, psychosis, aggression, hyperactivity, hostility, and behavioral deterioration.

Musculoskeletal

Weakness.

Hematologic

Thrombocytopenia and inhibition of the secondary phase of platelet aggregation may be reflected in altered bleeding time, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage (see PRECAUTIONS - General and Drug Interactions). Relative lymphocytosis, macrocytosis, hypofibrinogenemia, leukopenia, eosinophilia, anemia including macrocytic with or without folate deficiency, bone marrow suppression, pancytopenia, aplastic anemia, agranulocytosis, and acute intermittent porphyria.

Hepatic

Minor elevations of transaminases (e.g., SGOT and SGPT) and LDH are frequent and appear to be dose-related. Occasionally, laboratory test results include increases in serum bilirubin and abnormal changes in other liver function tests. These results may reflect potentially serious hepatotoxicity (see WARNINGS).

Endocrine

Irregular menses, secondary amenorrhea, breast enlargement, galactorrhea, and parotid gland swelling. Abnormal thyroid function tests (see PRECAUTIONS).

There have been rare spontaneous reports of polycystic ovary disease. A cause and effect relationship has not been established.

Pancreatic

Acute pancreatitis, including fatalities (see WARNINGS).

Metabolic

Hyperammonemia (see PRECAUTIONS), hyponatremia, and inappropriate ADH secretion.

There have been rare reports of Fanconi's syndrome occurring chiefly in children.

Decreased carnitine concentrations have been reported although the clinical relevance is undetermined.

Hyperglycinemia has occurred and was associated with a fatal outcome in a patient with preexistent nonketotic hyperglycinemia.

Genitourinary

Enuresis and urinary tract infection.

Special Senses

Hearing loss, either reversible or irreversible, has been reported; however, a cause and effect relationship has not been established. Ear pain has also been reported.

Other

Allergic reaction, anaphylaxis, edema of the extremities, lupus erythematosus, bone pain, cough increased, pneumonia, otitis media, bradycardia, cutaneous vasculitis, fever, and hypothermia.

Mania

Although DEPAKENE has not been evaluated for safety and efficacy in the treatment of manic episodes associated with bipolar disorder, the following adverse events not listed above were reported by 1% or more of patients from two placebo-controlled clinical trials of DEPAKOTE tablets.

Body as a Whole

Chills, neck pain, neck rigidity.

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 treatment of prophylaxis of migraine headaches, the following adverse events not listed above were reported by 1% or more of patients from two placebo-controlled clinical trials of DEPAKOTE tablets.

Body as a Whole

Face edema.

Digestive System

Dry mouth, stomatitis.

Urogenital System

Cystitis, metrorrhagia, and vaginal hemorrhage.



REPORTS OF SUSPECTED DEPAKENE SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Depakene. The information is not vetted and should not be considered as verified clinical evidence.

Possible Depakene side effects / adverse reactions in 48 year old female

Reported by a health professional (non-physician/pharmacist) from China on 2011-10-03

Patient: 48 year old female

Reactions: Contusion, Skin Discolouration, Petechiae, Autoimmune Thrombocytopenia

Suspect drug(s):
Depakene
    Administration route: Oral
    Indication: Mania

Depakene
    Dosage: daily
    Administration route: Oral
    Indication: Mental Disorder



Possible Depakene side effects / adverse reactions in 24 year old female

Reported by a pharmacist from Italy on 2011-10-03

Patient: 24 year old female

Reactions: Intentional Overdose, Suicide Attempt

Adverse event resulted in: hospitalization

Suspect drug(s):
Depakene
    Dosage: 15 grams total
    Administration route: Oral
    Indication: Suicide Attempt
    Start date: 2011-06-23
    End date: 2011-06-23

Acetaminophen
    Dosage: 5 mg total
    Administration route: Oral
    Indication: Intentional Self-Injury
    Start date: 2011-06-23
    End date: 2011-06-23



Possible Depakene side effects / adverse reactions in 74 year old female

Reported by a pharmacist from France on 2011-10-04

Patient: 74 year old female

Reactions: Thrombocytopenia

Suspect drug(s):
Depakene
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2009-04-21
    End date: 2009-07-08

Risperdal
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2009-04-23

Risperdal
    Administration route: Oral

Risperdal
    Administration route: Oral
    End date: 2009-06-26

Akineton
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2009-04-21
    End date: 2009-06-26

Urbanyl
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2009-04-29
    End date: 2009-06-23

Zolpidem
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2009-04-21
    End date: 2009-07-13

Tiapride Panpharma
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2009-06-08
    End date: 2009-06-23



See index of all Depakene side effect reports >>

Drug label data at the top of this Page last updated: 2009-05-07

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