Semisodium valproate

Common Name Divalproex sodium Natrii hydrogenii valproas Semisodium valproate Sodium hydrogen valproate Valproate semisodium... 

The availability of anticonvulsant mood stabilizers has led to comparative studies with lithium. A review of the comparative efficacy and tolerability of drug treatments for bipolar disorder included tolerability comparisons of lithium versus carbamazepine, lithium versus valproate semisodium, and lithium versus other medications (47). 

Valproic acid is available as sodium, magnesium, and calcium salts, as the free acid, and as a coordination compound, valproate semisodium (divalproex sodium), which comprises the sodium salt of valproic acid and free valproic acid in a 1 1 molar ratio. AH share the same active principle (valproic acid) and have virtually identical tolerability, although the formulation influences the incidence of gastrointestinal adverse effects. Valpromide (rINN) is a prodrug of valproate, to which it is converted with a half-hfe of less than 1 hour. Valnoctamide (rINN) is an isomer of valpromide. 

In a retrospective survey, gastrointestinal adverse effects were less common in 150 patients taking valproate semisodium than in an equal number taking valproic acid (15 versus 29%), despite the fact that serum valproic acid concentrations were comparable in the two groups (73). Patients taking valproate semisodium were less likely to discontinue medication because of gastrointestinal adverse effects (4 versus 13%). The difference was ascribed to the enteric-coated formulation of valproate semisodium. 

The suggestion that divalproex (valproate semisodium) causes fewer gastrointestinal adverse reactions than valproate (SEDA-23, 94) (58) has been challenged (74). In other cited studies divalproex was associated with a higher risk of gastrointestinal effects. 

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. 

I Available in different formulations. Valproate semisodium (divalproex sodirnn in the USA) is a mixture of sodium valproate and valproic acid and is now hcensed in the UK for the treatment of acute mania. 

I Valproate semisodium and other valproate preparations do not have the same dose equivalence (higher bioavailability with v proate semisodium). 

In the UK the National Institute for Clinical Excellence (NICE) has given guidance supporting the use of olanzapine and valproate semisodium in acute mania. NICE guidelines on the treatment of bipolar disorder are expected in June 2006. 

National Institute for Clinical Excellence Technology Appraisal Guidance 66. Olanzapine and valproate semisodium in the treatment of acute mania associated with bipolar 1 disorder, 2003. http //WWW. nice, org. uk/... 

An isolated report describes a 28% reduction in valproate clearance in a patient taking valproate semisodium with propranolol 40 mg, and a 35% reduction with propranolol 80 mg. However, 12 other patients taking valproate had no changes in clearance, serum levels or half-life when given propranolol 60 or 120 mg daily for 3 weeks. This interaction would therefore not appear to be of general importance. No special precautions would seem necessary. 

Aripiprazole 30 mg daily was given to 6 healthy subjects for 5 weeks, with valproate semisodium (divalproex sodium) daily in doses to achieve a serum valproate level of 50 to 125 mg/L, for weeks 3 to 5 of the study. The mean AUC and maximum plasma concentrations of aripiprazole were found to decrease by 24% and 26%, respectively, and the time to maximum aripiprazole levels was extended by 2 hours. Since aripiprazole and valproate share the same protein binding sites, it was considered likely that the valproate displaced bound aripiprazole leading to increased... 

In healthy subjects, lorazepam 1 mg every 12 hours for 3 days had no effect on the pharmacokinetics of valproate semisodium 500 mg every 12 hours. However, valproate semisodium increased the AUC and maximum serum levels of lorazepam by 20% and 8%, respectively. Sedation scores were not affected by concurrent treatment, suggesting that the interaction is not clinically significant. ... 

A randomised, placebo-controlled study in 191 patients found that quetiapine, combined with either lithium or valproate semisodium (divalproex sodium), was superior to lithium or valproate semisodium alone for treating bipolar mania. The incidence of extrapyramidal symptoms in patients receiving quetiapine with lithium or valproate semisodium was similar to those receiving placebo with lithium or valproate semisodium. No special precautions would therefore appear to be necessary on concurrent use. 

Analysis of plasma quetiapine levels of 94 patients, 9 of whom were also taking valproate, found a 77% increase in the concentration dose ratio compared with those patients not taking valproate. The US manufacturers report that valproate semisodium (divalproex sodium) increases the maximum plasma levels of quetiapine by 17%, and the UK manufacturers state that these changes are not clinically relevant. ... 

Depakote (Valproate semisodium). Sanofi-Aventis. UK Summary of product characteristics, September 2005. 

Sodium valproate and valproate semisodium do not appear to alter the efficacy of combined oral contraceptives. In one study, sodium valproate increased ethinylestradiol levels. Ethinylestradiol may reduce valproate levels but there appears to be only one case where this resulted in a loss of seizure control. 

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