Valproate
Medication used for epilepsy, bipolar disorder and migraine / From Wikipedia, the free encyclopedia
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Valproate (valproic acid, VPA, sodium valproate, and valproate semisodium forms) are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches.[6] They are useful for the prevention of seizures in those with absence seizures, partial seizures, and generalized seizures.[6] They can be given intravenously or by mouth, and the tablet forms exist in both long- and short-acting formulations.[6]
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Trade names | Depakote, Epilim, Convulex, others |
Other names | VPA; valproic acid; sodium valproate (sodium); valproate semisodium (semisodium); 2-propylvaleric acid |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682412 |
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Routes of administration | By mouth, intravenous |
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Bioavailability | Rapid absorption |
Protein binding | 80–90%[5] |
Metabolism | Liver—glucuronide conjugation 30–50%, mitochondrial β-oxidation over 40% |
Elimination half-life | 9–16 hours[5] |
Excretion | Urine (30–50%)[5] |
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ECHA InfoCard | 100.002.525 |
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Formula | C8H16O2 |
Molar mass | 144.214 g·mol−1 |
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Common side effects of valproate include nausea, vomiting, somnolence, and dry mouth.[6] Serious side effects can include liver failure, and regular monitoring of liver function tests is therefore recommended.[6] Other serious risks include pancreatitis and an increased suicide risk.[6] Valproate is known to cause serious abnormalities in fetuses if taken during pregnancy,[6][7] and is contra-indicated for women of childbearing age unless the drug is essential to their medical condition and the recipient is also prescribed a contraceptive.[6][8][3] The United States Food and Drug Administration has indicated a black box warning given the frequency and severity of the side effects and teratogenicity.[3] As of 2022 the drug was still prescribed in the UK to potentially pregnant women, but use declined by 51% from 2018–19 to 2020–21.[9]
Valproate's precise mechanism of action is unclear.[6][10] Proposed mechanisms include affecting GABA levels, blocking voltage-gated sodium channels, inhibiting histone deacetylases, and increasing LEF1.[11][12][13] Valproic acid is a branched short-chain fatty acid (SCFA), a derivative of valeric acid.[11]
Valproate was originally synthesized in 1881 and came into medical use in 1962.[14] It is on the World Health Organization's List of Essential Medicines[15][16] and is available as a generic medication.[6] In 2021, it was the 155th most commonly prescribed medication in the United States, with more than 3 million prescriptions.[17][18]