Divalproex dosage

Lamotrigine is effective for the maintenance treatment of bipolar disorder. It is more effective for depression relapse prevention than for mania relapse. Its primary limitation as an acute treatment is the time required for titration to an effective dosage. In addition to maintenance monotherapy, it is sometimes used in combination with lithium or divalproex, although combination with divalproex increases the risk of rash, and lamotrigine dosage adjustment is required.37... 

Usual dose When used as monotherapy or adjunct therapy (with lithium or divalproex), initiate quetiapine in twice-daily doses totaling 100 mg/day on day 1, increased to 400 mg/day on day 4 in increments of up to 100 mg/day in twice-daily divided doses. Further dosage adjustments up to 800 mg/day by day 6 should be in increments of no more than 200 mg/day. The safety of doses above 800 mg/day has not been evaluated in clinical trials. 

Adjunctive therapy - Divalproex sodium or valproic acid may be added to the patient s regimen at a dosage of 10 to 15 mg/kg/day. The dosage may be increased by 5 to 10 mg/kg/wk to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses less than 60 mg/kg/day. If satisfactory clinical response has not been achieved, measure plasma levels to determine whether they are in the usually accepted therapeutic range (50 to 100 mcg/mL). If the total daily dose exceeds 250 mg, administer in divided doses. 

Mania (divalproex sodium delayed-release tablets) 750 mg/day in divided doses increase as rapidly as possible to achieve the lowest therapeutic dose that produces the desired clinical effect or the desired range of plasma concentrations (trough plasma concentrations 50 to 125 mcg/mL). Maximum concentrations generally were achieved within 14 days. Maximum recommended dosage is 60 mg/kg/day. 

Pharmacology This group includes valproic acid, sodium valproate (the sodium salt), and divalproex sodium (a compound containing equal proportions of valproic acid and sodium valproate). Regardless of form, dosage is expressed as valproic acid equivalents. 

The sodium salt of valproate is marketed in Europe as a tablet and is quite hygroscopic. In Central and South America, the magnesium salt is available, which is considerably less hygroscopic. The free acid of valproate was first marketed in the USA in a capsule containing corn oil the sodium salt is also available in syrup, primarily for pediatric use. An enteric-coated tablet of divalproex sodium is also marketed in the USA. This improved product, a 1 1 coordination compound of valproic acid and sodium valproate, is as bioavailable as the capsule but is absorbed much more slowly and is preferred by many patients. Peak concentrations following administration of the enteric-coated tablets are seen in 3-4 hours. Various extended-release preparations are available not all are bioequivalent and may require dosage adjustment. 

Landy SH, McGinnis J. Divalproex sodium— review of prophylactic migraine efficacy, safety and dosage, with recommendations. Tenn Med. 1999 92 135-6. 

Extended-release (ER) divalproex (valproate semisodium) is not bioequivalent to delayed-release (DR) divalproex. In a randomized, crossover study in 36 healthy volunteers the bioequivalence of divalproex ER once a day and divalproex DR at 14% and 20% lower daily doses given twice a day were compared (122). The two formulations gave equivalent exposure (AUC) with lower peak and higher trough concentrations, that is less fluctuation during the dosage interval, with divalproex DR. 

KM is a 20-year-old woman with a history of epilepsy and scoliosis. Her seizures have been controlled on a maintenance dosage of divalproex sodium. She is scheduled to undergo a spinal fusion, and will not be taking anything by mouth (NPO) for several days. Which factor should be taken into consideration for her postsurgical care ... 

Valproic Acid. Valproic acid (VPA), is available in several chemical forms, including valproic acid, sodium valproate, and divalproex sodium, a stable coordination compound containing equal proportions of valproic acid and sodium valproate. In either of these forms, the dosage is expressed as valproic acid equivalents (Table 6.1) (18).Oral valproic acid derivatives are rapidly absorbed the absolute bioavailability of divalproex extended-release (ER) tablets was about 90% relative to that of the intravenous infusion. The ER form had an average bioavailability of 81 -89%compared to that of divalproex delayed-release tablets given twice daily. The relationship between plasma concentration and clinical response is not clear. This may be attributed to the nonlinear concentration-dependent protein binding of valproic acid, which in turn affects the clearance of the agent (18). 

Pharmacokinetics. Valproic acid appears to be absorbed completely from available oral dosage forms when administered on an empty stomach. However, the rate of absorption differs among preparations. Peak concentrations occur in 0.5 to 1 hour with the syrup, 1 to 3 hours with the capsule, and 2 to 6 hours with the enteric-coated tablet. The extended-release formulation (Depakote-ER) is FDA approved for use in both patients with migraine headache and epilepsy. It should be noted, however, that the bioavailability of this formulation is approximately 15% less than that of enteric-coated divalproex sodium (Depakote). 

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