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divalproex sodium
generic
Black Box Warnings .
Hepatotoxicity
serious or fatal hepatic failure has occurred, usually during 1st 6mo of tx; patients <2 yo at incr. risk of fatal hepatotoxicity, especially if multiple anticonvulsant tx, congenital metabolic disorder, severe seizure disorder with intellectual disability, or organic brain disease; in patients <2 yo, weigh benefit vs. risk, use with extreme caution and as monotherapy; incidence of fatal hepatotoxicity decr. considerably in progressively older patient groups; hepatotoxicity may be preceded by malaise, weakness, lethargy, facial edema, anorexia, vomiting and loss of seizure control; monitor signs/symptoms including LFTs at baseline, then frequently, especially during 1st 6mo of tx
Increased Hepatotoxicity Risk in Mitochondrial Disease
incr. risk of acute liver failure and death in patients with hereditary neurometabolic syndromes caused by mitochondrial DNA polymerase gamma (POLG) gene mutations (e.g. Alpers Huttenlocher Syndrome); contraindicated in patients with POLG-related mitochondrial disorders and in patients <2 yo with suspected hereditary mitochondrial disease; in patients >2 yo with suspected mitochondrial disorder, use only if failed other anticonvulsant tx and monitor hepatotoxicity signs/symptoms including LFTs regularly; perform POLG mutation screening per current clinical practice
Fetal Risk
can cause major congenital malformations including neural tube defects, decr. IQ scores, neurodevelopmental disorders after in utero exposure; contraindicated for migraine prophylaxis use in pregnancy and patients of childbearing potential without effective contraception; should not be used for epilepsy or bipolar disorder use in pregnancy or patients planning to become pregnant unless other tx options have failed or are unacceptable; patients of childbearing potential should use effective contraception during tx
Pancreatitis
life-threatening pancreatitis, including hemorrhagic cases with rapid progression from initial symptoms to death reported in children and adults; cases reported shortly after initial use as well as after several years of use; advise patients to promptly report signs/symptoms including abdominal pain, nausea, vomiting, and/or anorexia; D/C tx if pancreatitis diagnosis and start alternative tx as clinically indicated
Adult Dosing .
Dosage forms: DR CAP: 125 mg; DR TAB: 125 mg, 250 mg, 500 mg; ER TAB: 250 mg, 500 mg
Special Note
- [equivalency or interchangeability info]
- Info: divalproex sodium ER and DR tabs not bioequivalent; incr. total daily dose by 8-20% if switching from DR tab to ER tab
partial seizures, complex
- [delayed-release form]
- Dose: 30-60 mg/kg/day PO divided bid-tid; Start: 10-15 mg/kg/day PO divided qd-tid, incr. by 5-10 mg/kg/day q7 days; Max: 60 mg/kg/day; Info: decr. start dose and titrate slowly in elderly patients; adjust dose based on tx response and serum levels; divide doses >250 mg/day; give with food; taper dose gradually to D/C
- [extended-release form]
- Dose: 30-60 mg/kg/dose ER PO qd; Start: 10-15 mg/kg/dose ER PO qd, incr. by 5-10 mg/kg/day q7 days; Max: 60 mg/kg/day ER; Info: decr. start dose and titrate slowly in elderly patients; adjust dose based on tx response and serum levels; give with food; do not cut/crush/chew ER tab; taper dose gradually to D/C
absence seizures, simple and complex
- [delayed-release form]
- Dose: 30-60 mg/kg/day PO divided bid-tid; Start: 15 mg/kg/day PO divided qd-tid, incr. by 5-10 mg/kg/day q7 days; Max: 60 mg/kg/day; Info: decr. start dose and titrate slowly in elderly patients; adjust dose based on tx response and serum levels; divide doses >250 mg/day; give with food; taper dose gradually to D/C
- [extended-release form]
- Dose: 30-60 mg/kg/dose ER PO qd; Start: 15 mg/kg/day ER PO qd, incr. by 5-10 mg/kg/day q7 days; Max: 60 mg/kg/day ER; Info: decr. start dose and titrate slowly in elderly patients; adjust dose based on tx response and serum levels; give with food; do not cut/crush/chew ER tab; taper dose gradually to D/C
bipolar disorder, acute manic
- [delayed-release form]
- Dose: 250-500 mg PO tid; Start: 250 mg PO tid, may incr. dose rapidly to lowest effective dose; Max: 60 mg/kg/day; Info: decr. start dose and titrate slowly in elderly patients; adjust dose based on tx response and serum levels; give with food; taper dose gradually to D/C
- [extended-release form]
- Dose: 25-60 mg/kg/dose ER PO qd; Start: 25 mg/kg/dose ER PO qd, may incr. dose rapidly to lowest effective dose; Max: 60 mg/kg/day ER; Info: decr. start dose and titrate slowly in elderly patients; adjust dose based on tx response and serum levels; give with food; do not cut/crush/chew ER tab; taper dose gradually to D/C
migraine prophylaxis
- [delayed-release form]
- Dose: 250-500 mg PO bid; Start: 250 mg PO bid; Info: decr. start dose and titrate slowly in elderly patients; give with food; taper dose gradually to D/C
- [extended-release form]
- Dose: 500-1000 mg ER PO qd; Start: 500 mg ER PO qd x1wk, then incr. to 1000 mg ER PO qd; Info: decr. start dose and titrate slowly in elderly patients; give with food; do not cut/crush/chew ER tab; taper dose gradually to D/C
renal dosing
- [no adjustment]
- renal impairment: no adjustment
- HD/PD: no adjustment; no supplement
hepatic dosing
- [see below]
- hepatic disease/significant impairment: contraindicated
Peds Dosing .
- Dosage forms: DR CAP: 125 mg; DR TAB: 125 mg, 250 mg, 500 mg; ER TAB: 250 mg, 500 mg
Special Note
- [equivalency or interchangeability info]
- Info: divalproex sodium ER and DR tabs not bioequivalent; incr. total daily dose by 8-20% if switching from DR tab to ER tab
partial seizures, complex
- [delayed-release form, 10 yo and older]
- Dose: 30-60 mg/kg/day PO divided bid-tid; Start: 10-15 mg/kg/day PO divided qd-tid, incr. by 5-10 mg/kg/day q7 days; Max: 60 mg/kg/day; Info: adjust dose based on tx response and serum levels; divide doses >250 mg/day; give with food; taper dose gradually to D/C
- [extended-release form, 10 yo and older]
- Dose: 30-60 mg/kg/dose ER PO qd; Start: 10-15 mg/kg/dose ER PO qd, incr. by 5-10 mg/kg/day q7 days; Max: 60 mg/kg/day ER; Info: adjust dose based on tx response and serum levels; give with food; do not cut/crush/chew ER tab; taper dose gradually to D/C
absence seizures, simple and complex
- [delayed-release form, 10 yo and older]
- Dose: 30-60 mg/kg/day PO divided bid-tid; Start: 15 mg/kg/day PO divided qd-tid, incr. by 5-10 mg/kg/day q7 days; Max: 60 mg/kg/day; Info: adjust dose based on tx response and serum levels; divide doses >250 mg/day; give with food; taper dose gradually to D/C
- [extended-release form, 10 yo and older]
- Dose: 30-60 mg/kg/dose ER PO qd; Start: 15 mg/kg/dose ER PO qd, incr. by 5-10 mg/kg/day q7 days; Max: 60 mg/kg/day ER; Info: adjust dose based on tx response and serum levels; give with food; do not cut/crush/chew ER tab; taper dose gradually to D/C
renal dosing
- [no adjustment]
- renal impairment: no adjustment
- HD/PD: no adjustment; no supplement
hepatic dosing
- [see below]
- hepatic disease/significant impairment: contraindicated