What is this medication?
Valproate (Divalproex/Valproic Acid), Depakene/Depacon/Depakote
Anticonvulsant; Antimanic; Histone Deacetylase Inhibitor
Brand Name US: Depakene/Depacon/Depakote
Canadian Equivalent: Epival
“ALERT: US Boxed Warning
Hepatic failure resulting in fatalities has occurred in patients receiving valproate. These incidents usually have occurred during the first 6 months of treatment. Serious or fatal hepatotoxicity may be preceded by nonspecific 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. Serum liver tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first 6 months.
Children <2 years of age 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 these products are used in this patient group, they should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. The incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups.
Patients with mitochondrial disease:
There is an increased risk of valproate-induced acute liver failure and resultant deaths in patients with hereditary neurometabolic syndromes caused by DNA mutations of the mitochondrial DNA polymerase gamma (POLG) gene (eg, Alpers-Huttenlocher syndrome). Valproate is contraindicated in patients known to have mitochondrial disorders caused by POLG mutations and children younger than 2 years who are clinically suspected of having a mitochondrial disorder. In patients >2 years of age who are clinically suspected of having a hereditary mitochondrial disease, only use after other anticonvulsants have failed. This older group of patients should be closely monitored during treatment with valproate for the development of acute liver injury with regular clinical assessments and serum liver testing. POLG mutation screening should be performed in accordance with current clinical practice.
Valproate can cause major congenital malformations, particularly neural tube defects (eg, spina bifida). In addition, valproate can cause decreased IQ scores and neurodevelopmental disorders following in utero exposure. Valproate is therefore contraindicated for prophylaxis of migraine headaches in pregnant women and in women of childbearing potential who are not using effective contraception. Valproate should not be used to treat women with epilepsy or bipolar disorder who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. Valproate should not be administered to a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. In such situations, effective contraception should be used.
A Medication Guide describing the risks of valproate is available for patients.
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.”
How does this medication work?
Valproate (Divalproex/Valproic Acid), Depakene/Depacon/Depakote increases the effects/availability of gamma-aminobutyric acid (GABA) which is an inhibitory neurotransmitter. Also blocks sodium-dependent sodium channels which usually are responsible for high frequency repetitive neuronal firing, essentially calming overactive nerves. Divalproex is a compound consisting of both valproic acid and sodium valproate and breaks down in the gastrointestinal tract to valproate.
How should I take this medication?
250-3000mg daily divided into one to four doses depending on dosage form, the condition it is used for, efficacy and patient tolerance to side effects
How to Take: Follow instructions provided by physician/pharmacy label, swallow whole, take consistently at same times each day with food unless otherwise directed, store at room temperature
You Need to Avoid: May cause significant sedation so care should be taken if consuming alcohol. Caution should be taken when operating heavy machinery on this medication due to sedative effects and decrease mental alertness.
What should I watch for while using this medication?
Before starting Valproate (Divalproex/Valproic Acid), Depakene/Depacon/Depakote make sure your physician is aware of any allergies or medications you currently take, if you have liver disease, mitochondrial disease, a recent head trauma, or are pregnant or breastfeeding
Valproate and other antiepileptics can rarely cause suicidal ideation regardless of condition they are prescribed for. Valproate can also rarely cause pancreatitis; liver failure and other serious adverse reactions so patients must be monitored regularly by their physician while on this medication.
What if I miss a dose?
If you miss a dose of medication, try to take it as soon as possible. However, if it is almost time for your next dose, take only that scheduled dose. Do not take double or extra doses.
How should I store this medication?
Keep out of the reach of children at all times. Store at room temperature, 59 to 86° F (15 to 30° C). Protect from light. Keep the container tightly closed. Properly dispose of any unused medication after the expiration date.
What are the possible side effects of using this medication?
Headache, drowsiness, dizziness, insomnia, alopecia (hair loss), nausea, diarrhea, upset stomach, thrombocytopenia, tremor, asthenia (weakness), visual disturbances, infection
Note this is not a complete list of side effects, only common ones, most of which are dosage dependent.
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