Valproic acid divalproex sodium

Valproic acid/divalproex sodium 500-1,500 mg/day in divided doses... 

Valproic acid (divalproex sodium) 40-100 mcg/mL Trough Immediately prior to next dose Check 2-4 d after first dose or change in dose... 

McEvoy GK, Miller J, Snow EK, et al. Valproate sodium, valproic acid, divalproex sodium. AHFS Drug Information 2004. Bethesda, MD, American Society of Health-System Pharmacists, 2004 2152-2158. 

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. 

Valproic acid, valproate sodium, and (DVP) are carboxylic acid-derivative anticonvulsants. Divalproex sodium is a stable coordination compound consisting of valproic acid and valproate sodium in a 1 1 molar ratio (AHFS, 2000). It is a pro-drug of valproate, dissociating into valproate in the GI tract (AHFS, 2000), and a simple branched-chain carboxylic acid (w-dipropylacetic acid) with antiepileptic activity against a variety of types of seizures (Beydoun et al., 1997). Divalproex sodium has been approved for treating adults with simple and complex absence seizures (Mattson et al., 1992), and for mania. It has shown efficacy across a broad spectrum of BD subtypes (i.e., pure mania, mixed mania, and rapid cycling) (Pope et al., 1991 Bowden et al., 1994). 

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. 

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 most patients. Peak concentrations following administration of the enteric-coated tablets are seen in 3-4 hours. 

Depakote (divalproex sodium) is an enteric-coated stable compound containing both valproic acid and sodium valproate... 

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). 

Lithium Carbamazepine Oxcarbazepine Divalproex (DVPX) Sodium/Valproic Acid (VPA) Lamotrigine... 

Divalproex sodium is comprised of sodium valproate and valproic acid. The delayed-release and extended-release formulations are converted in the small intestine into valproic add, which is the systemically absorbed form. It was developed as an antiepileptic drug, but also has efficacy for mood stabilization and migraine headaches. It is FDA-approved for the treatment of the manic phase of bipolar disorder. It is generally equal in efficacy to lithium and some other drugs for bipolar mania. It has particular utility in bipolar disorder patients with rapid cycling, mixed mood features, and substance abuse comorbidity. Although not FDA-approved for relapse prevention, studies support this use, and it is widely prescribed for maintenance therapy. Divalproex can be used as monotherapy or in combination with lithium or an antipsychotic drug.31... 

The enteric-coated tablet divalproex sodium causes fewer GI side effects. It is metabolized in the gut to valproic acid. When switching from Depakote to Depakote-ER, the dose should be increased by 14% to 20%. Depakote ER may be given once daily. 

Valproic acid and divalproex sodium (a 1 1 molar combination of valproate sodium and valproic acid) can reduce the frequency, severity, and duration of headaches by at least 50% in up to 65% of migraineurs. 

Side effects of valproic acid and divalproex sodium include nausea (less common with divalproex sodium and gradual dosing titration), tremor,... 

Of the mood stabilizers, valproic acid (Depakene, Depakote) is the most widely used. Like the other mood stabilizers, its onset of action can be delayed by several days. Valproic acid is a reasonably well tolerated mood stabilizer. It does occasionally cause tremor, and it can on rare occasion lower platelet counts or cause liver problems. For this reason, blood monitoring is required when starting this medication. In addition, valproic acid can irritate the stomach lining, but this problem is largely overcome by using the buffered form sodium divalproex (Depakote or Depakote ER). Finally, valproic acid can also cause hair loss or drowsiness. 

Oral products Bedtime administration may minimize effects of CNS depression. Gl irritation may be minimized by taking with food or by slowly increasing the dose. Delayed-release divalproex sodium may reduce the incidence of irritative Gl effects. Swallow the extended-release tablets whole do not crush or chew. Swallow the valproic acid capsules without chewing to avoid local irritation of the mouth and throat. 

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. 

In epileptic patients previously receiving valproic acid therapy, initiate divalproex sodium at the same daily dose and dosing schedule. After the patient is stabilized on divalproex tablets, a dosing schedule of 2 or 3 times/day may be elected in selected patients. 

Absorption - /a pro c acid is rapidly and almost completely absorbed from the Gl tract. Absorption of the drug is delayed but not decreased by administration with meals administration of the drug with milk products does not affect the rate or degree of absorption. The bioavailability of valproate from divalproex sodium delayed-release tablets and capsules containing coated particles has been shown to be equivalent to that of valproic acid capsules. 

Divalproex sodium (Depakote, 125-, 250-, 500-mg tablets 125-mg sprinkle capsules) Valproate sodium injection (Depacon) Valproic acid (Depakene, 250-mg capsules ... 

Increase dose by 10%-20% when converting from valproate, divalproex, or valproic acid to tiie extended-release (ER) formulation of divalproex sodium. 

Several valproate preparations are available in the United States, including valproic acid, sodium valproate, divalproex sodium, and an extended-release preparation of divalproex sodium. Divalproex sodium is a dimer of sodium valproate and valproic acid with an enteric coating, and it is much better tolerated than other oral valproate preparations. An intravenous preparation also has become available, but it has not been well studied in patients with psychiatric disorders. The half-life of valproate is 9-16 hours. 

Carboxylic acid derivatives divalproex sodium valproic acid... 

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. 

Levine J, Chengappa KN, ParepaUy H. Side effect profile of enteric-coated divalproex sodium versus valproic acid. J Clin Psychiatry 2000 61(9) 680-1. 

Zarate CA Jr, Tohen M, Narendran R, Tomassini EC, McDonald J, Sederer M, Madrid AR. The adverse effect profile and efficacy of divalproex sodium compared with valproic acid a pharmacoepidemiology study. J Clin Psychiatry 1999 60(4) 232-6. 

Wagner PG, Welton SR, Hammond CM. Gastrointestinal adverse effects with divalproex sodium and valproic acid. J Clin Psychiatry 2000 61(4) 302-3. 

Case Conclusion Phenytoin was discontinued and JJ was started on valproic acid. She received an initial IV dose, followed by oral maintenance therapy of divalproex sodium. She was monitored closely for resolution of her reaction, which took several weeks. 

Drug Phenytoin (DPH) diibamazepine (CBZ) Valproic acid (VPA) and divalproex sodium Phenobarbital (PB)... 

Diuril chlorothiazide, divalproex sodium valproic acid, divaplon [inn] (RU 32698) is a methylimidazopyrimidine derivative, a BENZODIAZEPINE binding-site inverse agonist. 

A. Ahmad, E. D. Boudinot, and W. E. Barr, R. C. Reed, and W. R. Garnett, The use of Monte Carlo simulations to study the effect of poor compliance on the steady state concentrations of valproic acid following administration of enteric-coated and extended release divalproex sodium formulations. Biopharm Drug Disp 26 417 25 (2005). 

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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