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Name: Valproic acid

Pregnancy Category D

Drug classes

  • Antiepileptic

Therapeutic actions

Mechanism of action not understood: antiepileptic activity may be related to the metabolism of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA); divalproex sodium is a compound containing equal proportions of valproic acid and sodium valproate.

Indications

Sole and adjunctive therapy in simple (petit mal) and complex absence seizures
Adjunctive therapy in patients with multiple seizure types, including absence seizures

Unlabeled uses: sole and adjunctive therapy in atypical absence, myoclonic and grand mal seizures; possibly effective therapy in atonic, complex partial, elementary partial, and infantile spasm seizures; prophylaxis for recurrent febrile seizures in children

Contraindications/cautions

Contraindicated in the presence of hypersensitivity to valproic acid, hepatic disease or significant hepatic dysfunction.

Use caution in the presence of children younger than 18 mo; children younger than 2 y, especially those receiving multiple antiepileptic drugs, those with congenital metabolic disorders, those with severe seizures accompanied by severe mental retardation, those with organic
brain disorders (higher risk of developing fatal hepatotoxicity); pregnancy (incidence of neural tube defects in the fetus may be increased in mothers receiving valproic acid during the first trimester of pregnancy; do not discontinue antiepileptic therapy in pregnant women who are receiving such therapy to prevent major seizures; discontinuing medication is likely to precipitate status epilepticus, with attendant hypoxia and risk to both mother and unborn child); lactation.

Adverse effects

  • CNS: Sedation, tremor (may be dose-related), emotional upset, depression, psychosis, aggression, hyperactivity, behavioral deterioration, weakness
  • GI: Nausea, vomiting, indigestion, diarrhea, abdominal cramps, constipation, anorexia with weight loss, increased appetite with weight gain
  • Hematologic: Slight elevations in SGOT, SGPT, LDH; increases in serum bilirubin, abnormal changes in other liver function tests, hepatic failure, altered bleeding time; thrombocytopenia; bruising; hematoma formation; frank hemorrhage; relative lymphocytosis; hypofibrinogenemia;
    leukopenia, eosinophilia, anemia, bone marrow suppression
  • GU: Irregular menses, secondary amenorrhea
  • Dermatologic: Transient increases in hair loss, skin rash, petechiae
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