|•||Monotherapy and adjunctive therapy for simple and complex absence seizures.|
|•||Monotherapy and adjunctive therapy for complex partial seizures.|
|•||Adjunctive therapy for patients with multiple seizure types, including absence seizures.|
Divalproex sodium only:
Regular-release and delayed-release formulations usually given in 2–4 divided doses daily; extended-release formulation (Depakote ER) usually given once daily
|•||PO (Adults and Children >10 yr): Single-agent therapy (complex partial seizures) — Initial dose of 10–15 mg/kg/day in 1–4 divided doses; by 5–10 mg/kg/day weekly until therapeutic response achieved (not to exceed 60 mg/kg/day); when daily dosage exceeds 250 mg, give in divided doses. Polytherapy (complex partial seizures) — Initial dose of 10–15 mg/kg/day; by 5–10 mg/kg/day weekly until therapeutic response achieved (not to exceed 60 mg/kg/day); when daily dosage exceeds 250 mg, give in divided doses .|
|•||PO (Adults and Children >2 yr [>10 yr for Depakote ER]): Simple and complex absence seizures-Initial dose of 15 mg/kg/day in 1–4 divided doses; by 5–10 mg/kg/day weekly until therapeutic response achieved (not to exceed 60 mg/kg/day); when daily dosage exceeds 250 mg, give in divided doses.|
|•||IV (Adults and Children): Give same daily dose and at same frequency as was given orally; switch to oral formulation as soon as possible .|
|•||Rect (Adults and Children): Dilute syrup 1:1 with water for use as a retention enema. Give 17–20 mg/kg load, maintenance 10–15 mg/kg/dose q 8 hr.|
|•||PO (Adults): Depakote — Initial dose of 750 mg/day in divided doses initially, titrated rapidly to desired clinical effect or trough plasma levels of 50–125 mcg/ml (not to exceed 60 mg/kg/day). Depakote ER– Initial dose of 25 mg/kg once daily; titrated rapidly to desired clinical effect of trough plasma levels of 85–125 mcg/ml (not to exceed 60 mg/kg/day) .|
|•||PO (Adults and Children 16 yr): Depakote — 250 mg twice daily (up to 1000 mg/day). Depakote ER — 500 mg once daily for 1 wk, then to 1000 mg once daily .|
Hepatic disease or dysfunction; known urea cycle disorders; hypersensitivity to the drug.
Use Cautiously in:
|•||History of liver disease.|
|•||Organic brain disease.|
|•||Bone marrow depression.|
|•||Geri: risk of adverse effects.|
|•||OB: Use during pregnancy is linked to congenital anomalies, neural tube defects, clotting abnormalities, and hepatic dysfunction in the neonate. Use with extreme caution. Lactation: Valproates pass into breast milk. Consider discontinuing nursing when valproates are administered to the nursing mother.|
|•||Pedi: Children, especially <2 yr (at risk for potentially fatal hepatotoxicity).|
CV: Arrythmia, hypertension, hypotension, palpitation, postural hypotension, tachycardia, vasodilation (more than 1% and less than 5%); bradycardia (postmarketing).
CNS: Tremor (57%); headache (31%); somnolence (30%); asthenia (27%); dizziness (25%); insomnia (15%); nervousness (11%); ataxia (8%); amnesia (7%); abnormal thinking, emotional lability (6%); depression (5%); abnormal dreams, abnormal gait, agitation, anxiety, catatonic reaction, confusion, dysarthria, hallucinations, hypertonia, hypokinesia, incoordination, increased reflexes, paresthesia, personality disorder, speech disorder, tardive dyskinesia, vertigo (more than 1% and less than 5%); aggression, behavioral deterioration, cerebral atrophy, dementia, emotional upset, encephalopathy, hostility, hyperactivity, hypesthesia, parkinsonism, psychosis (postmarketing).
DERM: Alopecia (24%); rash (6%); discoid lupus erythematosus, dry skin, furunculosis, maculopapular rash, petechiae, pruritus, seborrhea (more than 1% and less than 5%); bruising, cutaneous vasculitis, erythema multiforme, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (postmarketing).
EENT: Diplopia (16%); amblyopia, blurred vision (12%); nystagmus, pharyngitis (8%); tinnitus (7%); abnormal vision, conjunctivitis, deafness, dry eyes, ear pain/disorder, epistaxis, eye pain, otitis media, photophobia, taste perversion (more than 1% and less than 5%); hearing loss, spots before eyes (postmarketing).
GI: Nausea (48%); vomiting (27%); abdominal pain, diarrhea (23%); dyspepsia (13%); anorexia (12%); increased appetite (6%); constipation (5%); dry mouth, eructation, fecal incontinence, flatulence, gastroenteritis, GI disorder, glossitis, hematemesis, increased appetite, pancreatitis, periodontal abscess, stomatitis, tooth disorder (more than 1% and less than 5%); abdominal cramps, acute pancreatitis (postmarketing).
GU: Amenorrhea, cystitis, dysmenorrhea, dysuria, metrorrhagia, urinary frequency, urinary incontinence, vaginal hemorrhage, vaginitis (more than 1% and less than 5%); breast enlargement, enuresis, galactorrhea, irregular menses, UTI (postmarketing).
HEMA/LYMPH: Thrombocytopenia (24% [high dose]); ecchymosis (5%); anemia, increased bleeding time, leukopenia (more than 1%); acute intermittent porphyria, agranulocytosis, aplastic anemia, bone marrow suppression, eosinophilia, frank hemorrhage, hematoma, hypofibrinogenemia, inhibition of platelet aggregation, macrocytosis, pancytopenia, relative lymphocytosis (postmarketing).
HEPA: Hepatotoxicity (postmarketing).
LABTESTABS: Increased ALT and AST (more than 1% and less than 5%); bilirubin, increased LDH (postmarketing).
LOCAL: Injection-site pain (3%); injection-site reaction (2%).
METAB: Weight gain (9%); peripheral edema (8%); weight loss (6%); edema, hypoproteinemia (more than 1% and less than 5%); Fanconi syndrome (primarily in children), hyperammonemia, hyperglycemia, hypernatremia, SIADH (postmarketing).
MUSC: Back pain (8%); neck pain, neck rigidity (1% or more); arthralgia, leg cramps, myalgia, myasthenia, twitching (more than 1% and less than 5%); bone pain, weakness (postmarketing).
RESP: Flu-like syndrome (12%); bronchitis, dyspnea, rhinitis (5%); hiccup, increased cough, pneumonia, sinusitis (more than 1% and less than 5%).
OTHER: Infection (20%); pain (11%); accidental injury, fever (6%); chest pain, chills, face edema, fungal infection, malaise, viral infection (more than 1% and less than 5%); abnormal thyroid function tests, anaphylaxis, coma, fever, hypothermia, lupus erythematosus, parotid gland swelling (postmarketing).
Alcohol, CNS depressants
Enhanced CNS depression.
Amitriptyline/Nortriptyline, barbiturates, diazepam, ethosuximide, hydantoins (eg, phenytoin), phenobarbital, primidone, zidovudine
Plasma levels of these drugs may be increased.
Carbamazepine plasma levels may be decreased while carbamazepine-10,11-epoxide levels may be increased; decreased valproic acid levels.
Carbapenem antibiotics (eg, ertapenem, imipenem, meropenem), charcoal, cholestyramine, rifampin
May decrease valproic acid levels.
Chlorpromazine, erythromycin, felbamate, fluoxetine, salicylates
May increase valproic acid levels.
Absence status may be induced in patients with a history of absence-type seizures.
Valproic acid plasma concentrations may be reduced, decreasing the efficacy.
Decreased valproic acid levels; increased lamotrigine levels.
Lorazepam plasma levels may be increased.
Risk of hepatic adverse reactions may be increased; olanzapine levels may be decreased.
May be displaced from binding site by valproate, transiently increasing tolbutamide levels. Clinical importance is not known.
Coadministration with valproic acid has been associated with hyperammonemia with and without encephalopathy. Plasma levels of both drugs may be decreased.
Warfarin may be displaced from its protein binding site, transiently increasing the anticoagulant effect.
Therapeutic Classification: anticonvulsants, vascular headache suppressants
Absorption: Well absorbed following oral administration; divalproex is enteric-coated, and absorption is delayed. ER form produces lower blood levels. IV administration results in complete bioavailability.
Distribution: Rapidly distributed into plasma and extracellular water. Cross blood-brain barrier and placenta; enters breast milk.
Protein Binding: 80–90%, decreased in neonates, elderly, renal impairment, or chronic hepatic disease.
Metabolism/Excretion: Mostly metabolized by the liver; minimal amounts excreted unchanged in urine.
Half-life: Adults: 9–16 hr.
|ORAL||2-4 DAYS||1-4 HOUR||6-24 HOUR|