BOX WARNING
HEPATOTOXICITY
HEPATIC FAILURE RESULTING IN FATALITIES HAS OCCURRED IN PATIENTS RECEIVING VALPROIC ACID AND ITS DERIVATIVES. EXPERIENCE HAS INDICATED THAT CHILDREN UNDER THE AGE OF TWO YEARS ARE AT A CONSIDERABLY INCREASED RISK OF DEVELOPING FATAL HEPATOTOXICITY, ESPECIALLY THOSE ON MULTIPLE ANTICONVULSANTS, THOSE WITH CONGENITAL METABOLIC DISORDERS, THOSE WITH SEVERE SEIZURE DISORDERS ACCOMPANIED BY MENTAL RETARDATION, AND THOSE WITH ORGANIC BRAIN DISEASE. WHEN DEPACON IS USED IN THIS PATIENT GROUP, IT SHOULD BE USED WITH EXTREME CAUTION AND AS A SOLE AGENT. THE BENEFITS OF THERAPY SHOULD BE WEIGHED AGAINST THE RISKS. ABOVE THIS AGE GROUP, EXPERIENCE IN EPILEPSY HAS INDICATED THAT THE INCIDENCE OF FATAL HEPATOTOXICITY DECREASES CONSIDERABLY IN PROGRESSIVELY OLDER PATIENT GROUPS.
THESE INCIDENTS USUALLY HAVE OCCURRED DURING THE FIRST SIX MONTHS OF TREATMENT. SERIOUS OR FATAL HEPATOTOXICITY MAY BE PRECEDED BY NON-SPECIFIC SYMPTOMS SUCH AS MALAISE, WEAKNESS, LETHARGY, FACIAL EDEMA, ANOREXIA, AND VOMITING. IN PATIENTS WITH EPILEPSY, A LOSS OF SEIZURE CONTROL MAY ALSO OCCUR. PATIENTS SHOULD BE MONITORED CLOSELY FOR APPEARANCE OF THESE SYMPTOMS. LIVER FUNCTION TESTS SHOULD BE PERFORMED PRIOR TO THERAPY AND AT FREQUENT INTERVALS THEREAFTER, ESPECIALLY DURING THE FIRST SIX MONTHS.
TERATOGENICITY
VALPROATE CAN PRODUCE TERATOGENIC EFFECTS SUCH AS NEURAL TUBE DEFECTS (E.G., SPINA BIFIDA). ACCORDINGLY, THE USE OF VALPROATE PRODUCTS IN WOMEN OF CHILDBEARING POTENTIAL REQUIRES THAT THE BENEFITS OF ITS USE BE WEIGHED AGAINST THE RISK OF INJURY TO THE FETUS. THIS IS ESPECIALLY IMPORTANT WHEN THE TREATMENT OF A SPONTANEOUSLY REVERSIBLE CONDITION NOT ORDINARILY ASSOCIATED WITH PERMANENT INJURY OR RISK OF DEATH (E.G., MIGRAINE) IS CONTEMPLATED. SEE WARNINGS, INFORMATION FOR PATIENTS.
PANCREATITIS
CASES OF LIFE-THREATENING PANCREATITIS HAVE BEEN REPORTED IN BOTH CHILDREN AND ADULTS RECEIVING VALPROATE. SOME OF THE CASES HAVE BEEN DESCRIBED AS HEMORRHAGIC WITH A RAPID PROGRESSION FROM INITIAL SYMPTOMS TO DEATH. CASES HAVE BEEN REPORTED SHORTLY AFTER INITIAL USE AS WELL AS AFTER SEVERAL YEARS OF USE. PATIENTS AND GUARDIANS SHOULD BE WARNED THAT ABDOMINAL PAIN, NAUSEA, VOMITING, AND/OR ANOREXIA CAN BE SYMPTOMS OF PANCREATITIS THAT REQUIRE PROMPT MEDICAL EVALUATION. IF PANCREATITIS IS DIAGNOSED, VALPROATE SHOULD ORDINARILY BE DISCONTINUED. ALTERNATIVE TREATMENT FOR THE UNDERLYING MEDICAL CONDITION SHOULD BE INITIATED AS CLINICALLY INDICATED. (See WARNINGS and PRECAUTIONS.)
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DEPACON SUMMARY
Valproate sodium is the sodium salt of valproic acid designated as sodium 2-propylpentanoate.
DEPACON is indicated as an intravenous alternative in patients for whom oral administration of valproate products is temporarily not feasible in the following conditions:
DEPACON 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. DEPACON is also indicated for use as sole and adjunctive therapy in the treatment of patients with 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.
SEE WARNINGS FOR STATEMENT REGARDING FATAL HEPATIC DYSFUNCTION.
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NEWS HIGHLIGHTS
Published Studies Related to Depacon (Valproate)
Valproate preparations for agitation in dementia. [2009.07.08]
CONCLUSIONS: The updated review corroborates the earlier findings that valproate preparations are ineffective in treating agitation among demented patients, and that valproate therapy is associated with an unacceptable rate of adverse effects. More research on the use of valproate preparations for agitation of people with dementia is needed. On the basis of current evidence, valproate therapy cannot be recommended for management of agitation in dementia.
Valproate treatment and cocaine cue reactivity in cocaine dependent individuals. [2009.06.01]
Based on prior clinical trials indicating that gamma-aminobutyric acid (GABA)-based anticonvulsant medications reduce drug craving in cocaine dependent study participants, we tested the effects of valproate treatment on cue-induced cocaine craving. Crack cocaine dependent individuals (N=20) were tested in a randomized, placebo-controlled, within-subjects, crossover study design.
A double-blind randomized trial of mood stabilizer augmentation using lamotrigine and valproate for patients with schizophrenia who are stabilized and partially responsive. [2009.06]
CONCLUSIONS: Augmenting antipsychotics with the mood stabilizers of lamotrigine or divalproex sodium for most partially responsive patients with chronic schizophrenia did not seem to be a useful treatment strategy for improving the residual symptoms. The small sample size limits firm conclusions.
Lamotrigine and valproate pharmacokinetics interactions in epileptic patients. [2009.04]
Lamotrigine (LTG, 3,5-diamino-6- (2,3-dichlorphenyl)-,2,4-triazine) is an antiepileptic drug used mainly for partial and generalized seizures. The efficacy of LTG in treating resistant partial seizures was optimized when it was combined with valproate (VPA)...
Effects of valproate or lamotrigine monotherapy on the reproductive endocrine and insulin-related metabolic profile in Chinese adults with epilepsy: a prospective randomized study. [2009.04]
Cross-sectional studies have suggested that valproate treatment may be associated with hyperinsulinemia and hyperandrogenism in women. Few prospective data are available...
Clinical Trials Related to Depacon (Valproate)
Pediatric Switch Study for Children and Adolescent Patients With Epilepsy [Completed]
To assess the tolerability of switching from Depakote Sprinkle Capsules or Depakote tablets
to Depakote ER tablets in the pediatric population.
Valproate in Late Life Schizophrenia [Completed]
The purpose of this research study is to analyze the effectiveness and tolerability of a
medication, valproate ( Depakote and Depakote ER), in individuals age 50 years and older who
have schizophrenia.
An Open Label, Double Blind Study Using Consecutive Intravenous Depacon With Oral Depakote ER for the Treatment of Cluster Headaches. [Completed]
The purpose of this study is to collect and evaluate information on the use of Depakote
Extended Release (ER) and Depacon Intravenous (IV) in patients with cluster headaches.
Patients who are currently in a cluster cycle will be treated with 2 consecutive days of IV
Depacon followed by oral Depakote ER. Patients will receive a total of 1,000mg of Depacon
and 1,000mg of Depakote ER each day. Patients may have a 3rd day of IV Depacon followed by
oral Depakote ER if the primary investigator believes it to be beneficial. The patient is
then sent home on oral Depakote ER. The dose of Depakote ER can range from 500mg to 2,000mg
this dose is to be determined by the primary investigator. The patient will continue the
oral Depakote ER until the end of their cluster cycle or for a maximum of 6 weeks, which ever
comes first.
A Comparison Study of the Efficacy and Tolerability of Depakote ER and Depakote DR [Completed]
To compare the time to response, response rates, remission rates, and side effects in Bipolar
Disorder inpatients treated with Depakote ER or Depakote DR for acute mania or mixed mania.
Effects of Divalproex Sodium on Food Intake, Energy Expenditure, and Posture Allocation [Completed]
The purpose of the proposed study is to identify the mechanisms responsible for the weight
gain associated with Depakote treatment, and to identify methods to prevent and treat weight
gain in people taking Depakote. Both sides of the energy balance equation will be measured in
a sample of healthy lean and overweight adults. Energy intake will be measured in the
Pennington Center's Eating Laboratory, and total daily energy expenditure (TEE) and posture
allocation will be measured with the IDEEA™. Questionnaires that assess food cravings and
eating attitudes and behaviors will be used to determine if a behavioral phenotype is
associated with weight gain in response to Depakote treatment. It is hypothesized that
Depakote treatment will result in increased food intake. It is also hypothesized that the
time spent engaging in sedentary behavior will increase in response to Depakote treatment.
Time spent engaging in, and the energy expended during, physical activity is expected to
decrease significantly. Therefore, it is hypothesized that TEE is expected to decrease
significantly. The results will be used to identify specific behavioral targets to prevent
weight gain during treatment with Depakote. Potential targets include interventions to modify
food intake and physical activity. The degree to which each behavior (food intake or physical
activity) will be targeted is dependent on the results of this study. For instance, if the
majority of the weight gain associated with Depakote treatment is due to changes in food
intake, stronger dietary interventions will be suggested. Additionally, changes in endocrine
factors (hormones and peptides) will be evaluated during the study to determine if Depakote
is associated with an altered endocrine response that affects satiety, food intake, or energy
expenditure. If an altered endocrine response is found, these results will be used to
identify adjunctive medications or compounds to correct the endocrine response and reduce
weight gain. Genomic studies will also be possible, since gene sequencing and gene expression
can be analyzed from archived buffy coat samples.
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Page last updated: 2009-10-20
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