Divaldin®
Divalproex Sodium
tablet
Bipolar disorder: Treatment of mania (delayed release) or acute mania or acute episodes with mixed features with or without psychotic features (extended release) associated with bipolar disorder, as monotherapy or in combination with atypical antipsychotics.
Focal (partial) onset and generalized onset seizures: Monotherapy and adjunctive therapy in the treatment of patients with focal onset seizures with impairment of consciousness or awareness (complex partial) and generalized onset nonmotor seizures (absence), and as adjunctive therapy for multiple seizure types. May be used off-label as monotherapy for other seizure types.
Migraine prophylaxis: Prophylaxis of migraine headaches
Limitation of use: Do not administer to pregnant women, women who plan to become pregnant, or women of childbearing potential for the treatment of epilepsy or bipolar disorder unless essential for the management of her condition.
Mechanism of Action:
Method of Administration:
Causes increased availability of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, to brain neurons or may enhance the action of GABA or mimic its action at postsynaptic receptor sites. Also blocks voltage-dependent sodium channels, which results in suppression of high-frequency repetitive neuronal firing. Divalproex sodium is a compound of sodium valproate and valproic acid; divalproex dissociates to valproate in the GI tract.
Method of Administration:
Bipolar disorder:
Acute mania or acute episodes with mixed features (in combination with or as an alternative to an antipsychotic):
Initial: 500 to 750 mg/day; increase by 250 to 500 mg every 1 to 3 days to reach desired clinical effect and therapeutic serum concentration
Focal (partial) onset seizures and generalized onset seizures
Initial monotherapy or adjunctive therapy: 10 to 15 mg/kg/day for complex partial seizures or 15 mg/kg/day for absence seizures; increase by 5 to 10 mg/kg/day at weekly intervals until optimal clinical response and/or therapeutic levels are achieved; maximum recommended dose: 60 mg/kg/day
Migraine prophylaxis:
Initial: 500 mg once daily (ER) or in 2 divided doses (DR or ER); increase dose gradually based on response and tolerability in increments of 250 mg/day at intervals >3 days up to 1 g/day
Notes
Contraindications:
Hypersensitivity to valproic acid, divalproex, derivatives, or any component of the formulation; hepatic disease or significant impairment; urea cycle disorders; prevention of migraine in pregnant women and women of childbearing potential.
Interactions:
Some products that may interact with this drug include: certain antidepressants (such as amitriptyline, nortriptyline, phenelzine), certain antibiotics (carbapenems such as imipenem), irinotecan, mefloquine, orlistat, other medications for seizure (such as ethosuximide, lamotrigine, phenytoin, rufinamide, topiramate), rifampin, warfarin, vorinostat, zidovudine.
Low-dose aspirin, as prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually 81-162 milligrams a day), should be continued. Consult your doctor or pharmacist if you are using aspirin for any reason.
Tell your doctor or pharmacist if you are taking other products that cause drowsiness including alcohol, antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), and opioid pain relievers (such as codeine, hydrocodone).
Pregnancy and Lactation:
Neural tube defects, craniofacial defects (eg, oral clefts, craniosynostosis), cardiovascular malformations, hypospadias, and limb malformations (eg, clubfoot, polydactyly) have been reported, therefore it shouldn’t be used during pregnancy.
The decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Warning and Precaution:
- Acute head trauma: Not recommended for post-traumatic seizure prophylaxis in patients with acute head trauma; study results for this indication suggested increased mortality with IV valproate sodium use compared to IV phenytoin.
- Dementia: Not recommended for treatment of dementia-associated agitation or aggression; evidence suggests lack of efficacy for this indication, as well as, an increased risk of adverse effects.
- Hepatic impairment: Contraindicated for use in hepatic disease.
Adverse Reactions:
Dermatologic: Alopecia (6% to 24%)
Gastrointestinal: Abdominal pain (oral: 7% to 23%; IV: 1%), anorexia (4% to 12%), diarrhea (oral: 7% to 23%; IV: <1%), dyspepsia (7% to 23%), nausea (oral: 15% to 48%; IV: 3% to 6%), vomiting (oral: 7% to 27%; IV: 1%)
Hematologic & oncologic: Thrombocytopenia (1% to 27%; dose related)
Infection: Infection (12% to 20%)
Nervous system: Dizziness (oral: 12% to 25%; IV: 5% to 7%) (table 1), drowsiness (oral: 7% to 30%; IV: 2% to 11%) (table 2), headache (oral: 31%; IV: 3% to 4%), insomnia (9% to 15%), nervousness (oral: 7% to 11%; IV: <1%), pain (oral: 11%; IV: 1%)
Storage:
Store below 30 and protect from light and moisture.