Divalproex

Mechanism :

The drug's anticonvulsant activity may be related to increased brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. Valproic Acid may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. It is also a histone deacetylase inhibitor.

Indication :

• Complex partial seizures
• Simple and complex absence seizures
• Mania
• Migraine Prophylaxis

Contraindications :

Hypersensitivity, Liver disease, significant hepatic impairment, Urea cycle disorders.

Mitochondrial disorders caused by mutations in mitochondrial DNA polymerase-gamma (POLG; e.g., Alpers-Huttenlocher Syndrome) and children <2 years of age who are suspected of having a POLG-related disorder.

Migraine headache prevention in women who are pregnant or plan to become pregnant.

Dosing :

Adverse Effect :

Transient dose-dependent elevations of serum amylase, liver transaminases, and ammonia; ataxia, drowsiness, hand tremors, reversible sensorineural hearing loss associated with valproate, encephalopathy, nausea, vomiting, pancreatitis respiratory failure, edema, vasodilation, rash.

Interaction :

Acetylsalicylic acid: Increases the effect of valproic acid.
Carbamazepine: Decreases the effect of valproic acid.
Clarithromycin: The macrolide antibiotic, Erythromycin, may increase the serum concentration of Valproic acid. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Clarithromycin is initiated, discontinued or dose changed.
Eltrombopag: Affects hepatic CYP2C9/10 metabolism, will increase effect/level of eltrombopag.
Erythromycin: The macrolide antibiotic, Erythromycin, may increase the serum concentration of Valproic acid. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Erythromycin is initiated, discontinued or dose changed.
Felbamate: Felbamate, a CYP2C19 inhibitor, may decrease the metabolism of Valproic acid, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Felbamate is initiated, discontinued or dose changed.
Glycerol Phenylbutyrate: Valproic acid may induce hyperammonemia. Monitor ammonia levels closely when use of valproic acid is necessary in UCD patients.
Lacosamide: Valproic acid toxicity may occur at any time during the treatment course and should be considered in patients with acute changes in mentation, especially if there has been a recent change in antiepileptic therapy.
Lamotrigine: Valproic acid may increase the adverse effects of Lamotrigine by increasing Lamotrigine serum concentration. The Lamotrigine dose should be reduced by 50% during concomitant therapy. Monitor for changes in Lamotrigine therapeutic and adverse effects if Valproic acid is initiated, discontinued or dose changed.
Lorazepam: Valproic acid may increase the serum concentration of Lorazepam by reducing Lorazepam metabolism. The Lorazepam dose should be reduced by 50% during concomitant therapy. Monitor for increased Lorazepam effects and toxicity.
Nimodipine: Valproic acid increases the effect of nimodipine.
Rifampicin: Rifampin may reduce the serum concentration of Valproic acid by increasing Valproic acid metabolism. Valproic acid dose adjustments may be required during concomitant therapy. Monitor Valproic acid serum concentrations, efficacy and toxicity if Rifampin is initiated, discontinued or dose changed.

Rufinamide: Valproic acid may increase the therapeutic/toxic effects of Rufinamide. Consider alternate therapy or monitor for changes in Rufinamide serum concentrations, therapeutic and adverse effects if Valproic acid is initiated, discontinued or dose changed. Decreases clearance of rufinamide and is a selective inhibitor of human carboxylesterase thus increasing serum concentrations.

Hepatic Dose :