Valproic Acid Valproic acid - Encorate, Epilex, Epival, Valparin, Valtril Use: Management of simple and complex absence seizures; mixed seizure types; myoclonic and generalized tonic-clonic (grand mal) seizures; may be effective in partial seizures, infantile spasms, bipolar disorder; prevention of migraine headaches Pregnancy & Lactation : Risk Factor - D Warnings & Precautions: Hepatic failure resulting in fatalities has occurred in patients; children <2 years of age are at considerable risk; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause severe thrombocytopenia, bleeding; hepatotoxicity has been reported after 3 days to 6 months of therapy;tremors may indicate overdosage; use with caution in patients receiving other anticonvulsants Contraindication: Hypersensitivity to valproic acid or derivatives or any component; hepatic dysfunction Adverse Reactions : 1% to 10%: Endocrine & metabolic: Change in menstrual cycle Gastrointestinal: Abdominal cramps, anorexia, diarrhea, nausea, vomiting, weight gain.<1%: Drowsiness, ataxia, irritability, confusion, restlessness, hyperactivity, headache, malaise, alopecia, erythema multiforme, hyperammonemia, pancreatitis, thrombocytopenia, prolongation of bleeding time, transient increased liver enzymes, liver failure, tremor, nystagmus, spots before eyes Interactions : CYP2C19 enzyme substrate; CYP2C9 and 2D6 enzyme inhibitor, CYP3A3/4 enzyme inhibitor (weak) Decreased effects of phenytoin Decreased effects with carbamazepine, lamotrigine, possibly clonazepam (increased absence seizures have been reported) Increased effects/toxicity of diazepam, CNS depressants, alcohol Increased effects/toxicity with aspirin (increase valproic acid levels) Over Dose / Poisoning : Symptoms of overdose include coma, deep sleep, motor restlessness, visual hallucinations Supportive treatment is necessary; naloxone has been used to reverse CNS depressant effects, but may block action of other anticonvulsants Dosage : Children and Adults: Oral: Initial: 10-15 mg/kg/day in 1-3 divided doses; increase by 5-10 mg/kg/day at weekly intervals until therapeutic levels are achieved; maintenance: 30-60 mg/kg/day in 2-3 divided doses Children receiving more than 1 anticonvulsant (ie, polytherapy) may require doses up to 100 mg/kg/day in 3-4 divided doses I.V.:Administer as a 60 minute infusion (< or =20 mg/min) with the same frequency as oral products;switch patient to oral products as soon as possible Rectal: Dilute syrup 1:1 with water for use as a retention enema; loading dose: 17-20 mg/kg one time; maintenance: 10-15 mg/kg/dose every 8 hours Not dialyzable (0% to 5%) Dosing adjustment/comments in hepatic impairment: Reduce dose Patient Information : When used to treat generalized seizures, patient instructions are determined by patient’s condition and ability to understand. Oral: Take as directed; do not alter dose or timing of medication. Do not increase dose or take more than recommended. Do not crush or chew capsule or enteric-coated pill. While using this medication, do not use alcohol and other prescription or OTC medications (especially pain medications, sedatives, antihistamines, or hypnotics) without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). Diabetics should monitor serum glucose closely (valproic acid will alter results of urine ketones). Report alterations in menstrual cycle; abdominal cramps, unresolved diarrhea, vomiting, or constipation; skin rash; unusual bruising or bleeding; blood in urine, stool or vomitus; malaise; weakness; facial swelling; yellowing of skin or eyes; excessive sedation; or restlessness. Pregnancy precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures.