Valproate (VPA), and its valproic acidsodium valproate, and valproate semisodium forms, are medications primarily used to treat epilepsy and bipolar disorder and to prevent migraine headaches. It is useful for the prevention of seizures in those with absence seizures, partial seizures, and generalized seizures. It can be given intravenously or by mouth. Long and short acting formulation of tablets exist.

Common side effects can include nausea, vomiting, sleepiness, and a dry mouth.  Serious side effects can include liver problems and regular monitoring of liver function tests is therefore recommended. Other serious risks include pancreatitis and an increased suicide risk.  It is known to cause serious abnormalities in the baby if taken during pregnancy. Because of this it is not typically recommended in women of childbearing age who have migraines. Valproic acid has a black box warning for hepatotoxicity, pancreatitis, and fetal abnormalities. Valproate in elderly people with dementia caused increased sleepiness. More people stopped the medication for this reason. Additional side effects of weight loss and decreased food intake was also associated in one half of people who become sleepy.

Valproate was first made in 1881 and it came into medical use in 1962. Valproate is included in the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world is between 0.14 and 0.52 USD per day. In the United States, it costs roughly $0.90 USD per day as of 2015.  It is marketed under the brand names Depakote and Epilim among others.

History[edit | edit source]

Valproic acid was first synthesized in 1882 by Beverly S. Burton as an analogue of valeric acid, found naturally in valerian. Valproic acid is a carboxylic acid, a clear liquid at room temperature. For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity. He found it prevented pentylenetetrazol-induced convulsions in laboratory rats. It was approved as an antiepileptic drug in 1967 in France and has become the most widely prescribed antiepileptic drug worldwide. Valproic acid has also been used for migraine prophylaxis and bipolar disorder.



Contraindications[edit | edit source]

Contraindications are conditions that you should discuss with your doctor that generally prevent this medication from being prescribed. If any of these conditions occur while you are taking the medication, inform your doctor immediately. Always discuss your concerns about your medications with your doctor's office or a qualified medical practitioner before discontinuing any medication. Contraindications include:

  • Pre-existing acute or chronic liver dysfunction or family history of severe liver inflammation (hepatitis), particularly medicine related.
  • Known hypersensitivity to valproate or any of the ingredients used in the preparation
  • Urea cycle disorders
  • Hepatic porphyria
  • Hepatotoxicity
  • Mitochondrial disease
  • Pancreatitis
  • Porphyria

Known drug interactions[edit | edit source]

Depakote is known to have interactions (which increase or decrease the effectiveness or potency of the drug) with the following medications:

Aspirin: may increase valproate concentrations. May also interfere with valproate's metabolism.

Benzodiazepines: may cause CNS depression and there are possible pharmacokinetic interactions.

Carbapenem antibiotics: reduces valproate levels, potentially leading to seizures.

Cimetidine: inhibits valproate's metabolism in the liver, leading to increased valproate concentrations.

Erythromycin: inhibits valproate's metabolism in the liver, leading to increased valproate concentrations.

Ethosuximide: may increase ethosuximide concentrations and lead to toxicity.

Felbamate: may increase plasma concentrations of valproate.

Mefloquine: may increase valproate metabolism combined with the direct epileptogenic effects of mefloquine.

Oral contraceptives: may reduce plasma concentrations of valproate.

Primidone: may accelerate metabolism of valproate, leading to a decline of serum levels and potential breakthrough seizure.

Rifampin: increases the clearance of valproate, leading to decreased valproate concentrations

Warfarin: may increase warfarin concentration and prolong bleeding time.

Zidovudine: may increase zidovudine serum concentration and lead to toxicity.

Always make sure your doctor knows of all the medications, including over the counter medications and supplements, that you are taking.



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