Adult Dosing
Mania associated with bipolar disorder
- Extended Release
- Start dose: 25 mg/kg/day PO daily; increase rapidly to achieve the lowest therapeutic dose
- Max: 60 mg/kg/day
- Delayed Release
- Start dose: 750 mg/day PO in divided doses; increase rapidly to achieve the lowest therapeutic dose
- Max: 60 mg/kg/day
Complex Partial Seizures
Monotherapy
- Extended Release
- Initial dose: 10-15 mg/kg/day PO daily; increase by 5-10 mg/kg qwk to achieve optimal clinical response and plasma level of 50 to 100 mcg/mL
- Max: 60 mg/kg/day
- Delayed release
- Initial dose: 10-15 mg/kg/day in divided doses; increase by 5-10 mg/kg qwk to achieve optimal clinical response and plasma level of 50 to 100 mcg/mL
- Max: 60 mg/kg/day
Conversion to Monotherapy
- Extended Release
- Initial dose: 10-15 mg/kg/day PO daily; increase by 5-10 mg/kg qwk to achieve optimal clinical response and plasma level of 50 to 100 mcg/mL
- Max: 60 mg/kg/day
- Reduce concomitant antiepilepsy drug dosage by 25% q2 wks, at the initiation of divalproex sodium
- Delayed release
- Initial dose: 10-15 mg/kg/day PO in divided doses; increase by 5-10 mg/kg qwk to achieve optimal clinical response and plasma level of 50 to 100 mcg/mL
- Max: 60 mg/kg/day
- Reduce concomitant antiepilepsy drug dosage by 25% q2 wks, at the initiation of divalproex sodium
Adjunctive Therapy
- Extended Release
- Initial dose: 10-15 mg/kg/day PO daily; increase by 5-10 mg/kg qwk to achieve optimal clinical response and plasma level of 50 to 100 mcg/mL
- Max: 60 mg/kg/day
- Delayed release
- Initial dose: 10-15 mg/kg/day PO in divided doses; increase by 5-10 mg/kg qwk to achieve optimal clinical response and plasma level of 50 to 100 mcg/mL
- Max: 60 mg/kg/day
Simple and Complex Absence Seizures
- Extended Release
- Initial dose: 15 mg/kg/day PO daily; increase by 5-10 mg/kg/day qwk
- Max: 60 mg/kg/day
- Delayed release
- Initial dose: 15 mg/kg/day PO in divided doses; increase by 5-10 mg/kg/day qwk
- Max: 60 mg/kg/day
Prophylaxis of migraine
- Extended Release
- Initial dose: 500 mg PO daily x 1 wk, then increase to 1000 mg PO qd
- Max: 1000 mg/day
- Delayed release
- Initial dose: 250 mg PO bid
- Max: 1000 mg/day
Notes:- When converting from delayed release tablet to extended release tablet, administer ETABS once daily at a dose 8-20% higher than the total daily dose of delayed release tablet
- Use lower starting dose in elderly patients
Pediatric Dosing
Complex Partial Seizures (>10 yrs)
Monotherapy
- Extended Release
- Initial dose: 10-15 mg/kg/day PO daily; increase by 5-10 mg/kg qwk to achieve optimal clinical response and plasma level of 50 to 100 mcg/mL
- Max: 60 mg/kg/day
- Delayed release
- Initial dose: 10-15 mg/kg/day in divided doses; increase by 5-10 mg/kg qwk to achieve optimal clinical response and plasma level of 50 to 100 mcg/mL
- Max: 60 mg/kg/day
Conversion to Monotherapy
- Extended Release
- Initial dose: 10-15 mg/kg/day PO daily; increase by 5-10 mg/kg qwk to achieve optimal clinical response and plasma level of 50 to 100 mcg/mL
- Max: 60 mg/kg/day
- Reduce concomitant antiepilepsy drug dosage by 25% q2 wks at the initiation of divalproex sodium
- Delayed release
- Initial dose: 10-15 mg/kg/day PO in divided doses; increase by 5-10 mg/kg qwk to achieve optimal clinical response and plasma level of 50 to 100 mcg/mL
- Max: 60 mg/kg/day
- Reduce concomitant antiepilepsy drug dosage by 25% q2 wks at the initiation of divalproex sodium
Adjunctive Therapy
- Extended Release
- Initial dose: 10-15 mg/kg/day PO daily; increase by 5-10 mg/kg qwk to achieve optimal clinical response and plasma level of 50 to 100 mcg/mL
- Max: 60 mg/kg/day
- Delayed release
- Initial dose: 10-15 mg/kg/day PO in divided doses; increase by 5-10 mg/kg qwk to achieve optimal clinical response and plasma level of 50 to 100 mcg/mL
- Max: 60 mg/kg/day
Simple and Complex Absence Seizures (>10 yrs)
- Extended Release
- Initial dose: 15 mg/kg/day PO daily; increase by 5-10 mg/kg/day qwk
- Max: 60 mg/kg/day
- Delayed release
- Initial dose: 15 mg/kg/day PO in divided doses; increase by 5-10 mg/kg/day qwk
- Max: 60 mg/kg/day
Note:
- When converting from delayed release tablet to extended release tablet, administer ER TABS once daily at a dose 8-20% higher than the total daily dose of delayed release tablet
[Outline]
See Supplemental Patient Information
- Fatal hepatic failure has occurred in patients receiving valproic acid, especially in the first six months of treatment. Closely monitor the patients and perform LFT at base line and at frequent intervals during the treatment [US Black box warning]
- Valproate and any other antiepileptic drug may be teratogenic, eg causing neural tube defects. Use cautiously during pregnancy and in women of childbearing age, and only if potential benefit to mother outweighs the risk to the fetus . Therapy can also cause decreased IQ scores following in utero exposure [US Black box warning]
- Valproate causes clotting disorder. Use of valproate during pregnancy in women with low fibrinogen levels may cause afibrinogenemia in infants and lead to hemorrhagic death
- Maternal use of valproate during pregnancy causes hepatotoxicity in infants
- Do not discontinue the antiepileptic drug abruptly in patients with major seizures as it can precipitate status epilepticus with attendant hypoxia and threat to life
- Life-threatening pancreatitis has occurred in both children and adults receiving valproate [US Black box warning]
- Avoid use of valproic acid in patients with known urea cycle disorders, as it causes hyperammonemic encephalopathy in such patients
- Before starting valproic acid therapy evaluate for urea cycle disorder (UCD) in patients with a history of unexplained encephalopathy or coma, pregnancy-related or postpartum encephalopathy, unexplained mental retardation, or history of elevated plasma ammonia or glutamine, cyclical vomiting and lethargy, episodic extreme irritability, ataxia, low BUN, or protein avoidance, family history of UCD or a family history of unexplained infant deaths. Immediately discontinue the drug if patient develops unexplained hyperammonemic encephalopathy and provide prompt treatment
- Monitor the patient receiving any antiepileptic drug including valproate for the signs of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior, as antiepileptic drugs increase the risk of suicidal tendencies in the patients
- Thrombocytopenia occurs with total valproate concentrations of
110 mcg/mL (female) - 135 mcg/mL (male). Monitor platelet counts and coagulation before starting the treatment and periodically thereafter - Hyperammonemia has been reported with valproate therapy. Patients developing unexplained lethargy and vomiting or changes in mental status, hyperammonemic encephalopathy, hypothermia should be evaluated for hyperammonemia. Discontinue the drug if high ammonia level is observed and initiate appropriate treatment for hyperammonemia
- Concomitant use of topiramate and valproic acid causes hyperammonemia with or without encephalopathy. Patients with inborn errors of metabolism or reduced hepatic mitochondrial activity are at higher risk
- Valproate causes hypothermia; discontinue the drug on development of hypothermia manifested by lethargy, confusion, coma, and significant alterations in other major organ systems such as the cardiovascular and respiratory systems. Monitor blood ammonia levels
- Multi-organ hypersensitivity reactions with variable sign and symptoms resulting in to hospitalization or death have occurred with valproate therapy in adult and pediatric patients. Discontinue the drug if this reaction is suspected and start an alternative treatment
- Concomitant use of carbapenem antibiotic with valproate reduce serum valproic acid concentrations to subtherapeutic levels, resulting in loss of seizure control
- Valproic acid causes somnolence in elderly patients and also dehydration and weight loss. Use valproic acid cautiously in elderly patients and increase dosage slowly, with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse events. Consider dose reduction or discontinuation of valproate in patients with decreased food or fluid intake and excessive somnolence
- Valproic acid is partially eliminated as ketometabolite in the urine and lead to false interpretation of urine ketone test and also alters the thyroid function test
- Consider periodic determinations of valproate and concomitant drugs during the early course of therapy, as valproic acid may interact with concurrently administered drugs which are capable of enzyme induction
- Increased risk of lower cognitive function has been reported in children born to mothers exposed to valproate sodium or related products throughout their pregnancy, as compared to the children born to mothers exposed to other anti-seizure medications
- If patient experiences medication residue in feces , then monitor plasma valproate levels and consider alternative therapy if clinically indicated
Cautions: Use cautiously in
- Renal impairment
- History of liver disease
- Pediatric patients
- Organic brain disease
- Head injury
- History of depression
- Mental retardation with seizure disorder
- Congenital metabolic disorders
- Multiple anticonvulsants use
- Myelosuppression
- Bleeding tendencies
Supplemental Patient Information
- As valproate causes CNS depression patients are advised not to drive an automobile or operate dangerous machinery
- Women those who are planning to become pregnant or have become pregnant should inform their doctors as valproate is known to cause teratogenic effect in fetus
- Patients should immediately report to the physician if there is fever associated with other organ system involvement (rash, lymphadenopathy, etc.) during the treatment
Depakote interacts with :
Pregnancy Category:D
Breastfeeding: Divalproex results in valproic acid in the maternal bloodstream. Low level of valproic acid is excreted in breastmilk; no unquestionable adverse reactions to valproic acid have been reported during breastfeeding. Monitor infant serum valproate levels, platelets and liver enzymes during maternal therapy as breastfed infants are at risk for valproate induced hepatotoxicity and thrombocytopenia. Monitor infants for jaundice and other signs of liver damage, unusual bruising or bleeding. Combination therapy with sedating anticonvulsants or psychotropics may result in infant sedation or withdrawal reactions. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 20 May 2011). Valproate is excreted in breast milk 1-10% of serum concentrations. Manufacturer advises to discontinue nursing when valproate is administered to a nursing woman.
US Trade Name(s)
US Availability
divalproex sodium (generic)
- Delayed Release TABS: 125, 250, 500 mg
- CAPS (Sprinkles): 125 mg
- ETABS: 250, 500 mg
Depakote
- Delayed Release TABS: 125, 250, 500 mg
- CAPS (Sprinkles): 125 mg
Depakote ER
Canadian Trade Name(s)
Canadian Availability
divalproex sodium (generic)
Epival
UK Trade Name(s)
UK Availability
Australian Trade Name(s)
Australian Availability
[Outline]
Pricing data from www.DrugStore.com in U.S.A.
- Depakote 125 MG TBEC [Bottle] (ABBOTT)
60 mg = $70.99
180 mg = $200.97 - Divalproex Sodium 125 MG CPSP [Bottle] (ZYDUS PHARMACEUTICALS (USA))
30 mg = $25.99
90 mg = $65.97 - Divalproex Sodium 500 MG TBEC [Bottle] (UPSHER-SMITH)
100 mg = $49.99
300 mg = $129.96 - Divalproex Sodium 250 MG TB24 [Bottle] (MYLAN)
100 mg = $139.99
300 mg = $389.99 - Divalproex Sodium 125 MG TBEC [Bottle] (UPSHER-SMITH)
100 mg = $24.99
300 mg = $59.97 - Depakote ER 500 MG TB24 [Bottle] (ABBOTT)
30 mg = $111.99
90 mg = $307.97 - Depakote 250 MG TBEC [Bottle] (ABBOTT)
60 mg = $136.99
180 mg = $385.98 - Depakote Sprinkles 125 MG CPSP [Bottle] (ABBOTT)
60 mg = $71.99
180 mg = $199.96 - Divalproex Sodium 500 MG TB24 [Bottle] (MYLAN)
100 mg = $59.99
300 mg = $179.96 - Divalproex Sodium 250 MG TBEC [Bottle] (UPSHER-SMITH)
100 mg = $29.99
300 mg = $69.96 - Depakote ER 250 MG TB24 [Bottle] (ABBOTT)
30 mg = $67.99
90 mg = $180.96
Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.
