Valproate

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Information about Valproate

Valproate or valproic acid is a branched chain organic acid that is used as therapy of epilepsy, bipolar disorders and migraine headaches and is a well known cause of several distinctive forms of acute and chronic liver injury.

Mechanism of action of Valproate

Valproate (val proe' ate) is a carboxylic acid derivative that appears to act by increasing brain levels of gamma aminobutyric acid (GABA), the major inhibitory neurotransmitter in the human brain. 

FDA approval information for Valproate

Valproate has been shown to be effective in several forms of seizures.  Valproate was approved for therapy of epilepsy in adults and children in 1978 and is currently one of the major anticonvulsant medications used. 

Clinical use of Valproate

Current approved uses include both monotherapy and in combination with other anticonvulsants for complex absence seizures, complex partial seizures and mixed seizure types.  Valproate is also used for prevention of migraine headaches and for bipolar disorders.  The recommended dose of valproate varies by indication. 

Dosage and administration for Valproate

The initial recommended dose for therapy of seizures is 10 to 15 mg/kg/day, with increases of 5 to 10 mg/kg/day weekly to achieve an optimal clinical response.  Monitoring of drug levels is often recommended.  Valproate is available in multiple generic and brand formulations as capsules, tablets and syrups and in delayed release forms of 125, 250 and 500 mg.  Oral forms also include divalproex, which dissociates into valproate in the gastrointestinal tract and is available in capsules of 125 mg under the brand name Depakote.  Valproate sodium is also available in parenteral formulations. 

Side effects of Valproate

Valproate has multiple side effects and clinically significant drug interactions; common side effects include headache, insomnia, nervousness, somnolence, tremor, blurred vision, nausea, weight gain and rash.

Anticonvulsants

Generic Name / Brand Name Liver Toxicity Score Approval Year Major Indications
Brivaracetam / Briviact E 2016 Partial seizures
Carbamazepine / Tegretol A 1968 Partial, mixed and generalized seizures, trigeminal neuralgia
Clobazam / Onfi E 2011 Seizures assocated with Lennox-Gastaut syndrome
Clonazepam / Klonopin D 1975 Absence and myoclonic seizures, anxiety and panic disorders
Clorazepate / Tranxene E 1972 Partial seizures, anxiety disorders, and alcohol withdrawal
Diazepam / Valium E 1963 Convulsions, anxiety disorders, muscle spasms
Eslicarbazepine / Aptiom D 2013 Partial seizures
Ethosuximide / Zarontin E 1960 Absence seizures
Ezogabine / Potiga E 2011 Partial seizures
Felbamate / Febatol B 1993 Refractory or severe epilepsy
Fosphenytoin / Cerebyx A 1996 Tonic-clonic seizures, status epilepticus
Gabapentin / Neurontin C 1993 Partial seizures, post-herpetic neuralgia
Lacosamide / Vimpat D 2008 Partial seizures
Lamotrigine / Lamictal B 1994 Partial and generalized tonic-clonic seizures, bipolar disorder
Levetiracetam / Keppra C 1999 Partial, generalized tonic-clonic, and myoclonic seizures
Methsuximide / Celontin E 1957 Absence seizures
Oxcarbazepine / Trileptal D 2000 Partial seziures
Perampanel / Fycompa E 2012 Partial and generalized tonic-clonic seizures
Phenobarbital / Luminal A 1916 Partial and generalized seizures, anxiety, and irritable bowel syndrome
Phenytoin / Dilantin A 1938 Generalized tonic-clonic and partial onset seizures, status epilepticus
Pregabalin / Lyrica C 2004 Partial seizures, fibromyalgia, and neuropathic pain
Primidone / Mysoline E 1954 Partial and generalized tonic-clonic seizures
Rufinamide / Banzel E 2008 Seizures associated with Lennox-Gastaut syndrome
Tiagabine / Gabitril E 1997 Partial seizures
Topiramate / Topamax C 1996 Partial and generalized tonic-clonic seizures, migraine headaches
Valproate / Depakene A 1978 Absence and complex partial seizures
Vigabatrin / Sabril D 2009 Refractory, complex partial seizures, and infantile spasms
Zonisamide / Zonegran D 2000 Partial seizures

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