Divalproex sodium is the sodium salt of valproic acid. It is primarily used to treat epilepsy and bipolar disorder and to prevent migraine headaches. They are useful for the prevention of seizures in those with absence seizures, partial seizures, and generalized seizures.

● Use as monotherapy or adjunctive therapy in the management of complex partial seizures and simple or complex absence seizures.
● Adjunctive therapy in the management of multiple seizure types that include absence seizures.
● Prophylaxis of migraine headaches.
● Acute management of mania associated with bipolar disorder.
Off-label uses include:
● Maintenance therapy for bipolar disorder.
● Treatment for acute bipolar depression.
● Emergency treatment of status epilepticus.


Mechanism of Action:
Valproate is known to inhibit succinic semialdehyde dehydrogenase. This inhibition results in an increase in succinic semialdehyde which acts as an inhibitor of GABA transaminase ultimately reducing GABA metabolism and increasing GABAergic neurotransmission. As GABA is an inhibitory neurotransmitter, this increase results in increased inhibitory activity. A possible secondary contributor to cortical inhibition is a direct suppression of voltage gated sodium channel activity and indirect suppression through effects on GABA.


Absorption: The oral delayed-release tablet formulation has a Tmax of 4 hours
Volume of distribution: 11 L/1.73m2
Protein binding: Protein binding is linear at low concentrations, 10% bound at 4 mcg/mL, but becomes non-linear at higher concentrations, increasing up to 18.5% bound at 135 mcg/Ml
Most of the drug is metabolized to glucuronide conjugates (30-50%) of the parent drug or of metabolites. 
Another large portion is metabolized through mitochondrial β-oxidation (40%).
The remainder of metabolism (15-20%) occurs through oxidation, hydroxylation, and dehydrogenation.
Route of elimination:
Most of the drug is eliminated through hepatic metabolism, about 30-50%. 
The other major contributing pathway is mitochondrial β-oxidation, about 40%.
Other oxidative pathways make up an additional 15-20%.
Less than 3% is excreted unchanged in the urine.
Half-life is 13-19 hours.

Side Effects
Common side effects include:
● Nausea
● Vomiting
● Sleepiness
● Dry mouth
Immediately discontinue the use if any severe side effects are observed and consult your physician.

Some products that may interact with this drug include:
● Antidepressants (e.g., amitriptyline, nortriptyline, phenelzine)
● Certain antibiotics (carbapenems such as doripenem, imipenem)
● Irinotecan
● Mefloquine
● Orlistat
● Other medications for seizure (e.g., ethosuximide, lamotrigine, phenytoin, rufinamide, topiramate)
● Rifampin
● Vorinostat
● Warfarin
● Zidovudine.

This medication should not be consumed in following conditions:
● High amount of ammonium in the blood
● Low amount of albumin proteins in the blood
● Porphyria
● Decreased blood platelets
● Depression
● Organic mental disorder
● Liver problems
● Pregnancy
● Urea cycle disorder

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