Adult Dosing

Acute mania, Bipolar disorder [Stavzor]

• 750 mg qd in divided doses; [Max: 60 mg/kg/day]

Complex Partial Seizures

Monotherapy

• Initial: 10-15 mg/kg/day PO
• Titer: Increase 5-10 mg/kg/wk PO to achieve optimal response; [Max: 60 mg/kg/day]

Conversion to Monotherapy

• Initial: 10-15 mg/kg/day PO
• Titer: Increase 5-10 mg/kg/wk PO to achieve optimal response; [Max: 60 mg/kg/day]
• Reduce concomitant antiepilepsy drug (AED) dosage by approx 25% q2 wks

Adjunctive Therapy

• Start: 10-15 mg/kg/day PO
• Titer: Increase 5-10 mg/kg/wk PO to achieve optimal response; [Max: 60 mg/kg/day]

Simple and Complex Absence Seizures

• Initial: 15 mg/kg/day PO
• Titer: Increase 5-10 mg/kg/day PO qwk until seizures are controlled; [Max: 60 mg/kg/day]

Migraine [Stavzor]

• 250 mg PO bid

Note:

• Do not cut/crush/chew/open the capsule
• Dose >250 mg/day should be divided in 2-3 times a day

Pediatric Dosing

Complex Partial Seizures (10 yrs)

Monotherapy

• Initial: 10-15 mg/kg/day PO
• Titer: Increase 5-10 mg/kg/wk PO to achieve optimal response; [Max: 60 mg/kg/day]

Conversion to Monotherapy (10 yrs)

• Initial: 10-15 mg/kg/day PO
• Titer: Increase 5-10 mg/kg/wk PO to achieve optimal response; [Max: 60 mg/kg/day]
• Reduce concomitant antiepilepsy drug (AED) dosage by approx 25% q2 wks

Adjunctive Therapy (10 yrs)

• Start: 10-15 mg/kg/day PO
• Titer: Increase 5-10 mg/kg/wk PO to achieve optimal response; [Max: 60 mg/kg/day]

Simple and Complex Absence Seizures (10 yrs)

• Initial: 15 mg/kg/day PO
• Titer: Increase 5-10 mg/kg/day PO qwk until seizures are controlled; [Max: 60 mg/kg/day]

Note:

• Do not cut/crush/chew/open the capsule
• Dose >250 mg/day should be divided

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment of acute mania associated with bipolar disorder [safety and efficacy for >3 weeks has not been established (Stavzor)]
• Monotherapy and adjunctive therapy in the treatment of complex partial seizures
• Sole and adjunctive therapy in the treatment of simple and complex absence seizures
• Adjunctive therapy multiple seizure
• Prophylaxis of migraine (Stavzor)

Note:

• Do not use in women of childbearing age unless the drug is essential for disease management; as it may cause decreased IQ, neural tube defects and other congenital malformations

• Hypersensitivity to any of the ingredients of the product
• Hepatic disease or significant hepatic dysfunction
• Urea cycle disorders

• Fatal hepatic failure have occurred in patients receiving valporic acid usually during the first six month of treatment
• Children under 2 years of age and on multiple anticonvulsants or have congenital metabolic disorder, severe seizure disorders accompanied by mental retardation and organic brain disease are at higher risk of developing hepatotoxicity. Use with extreme caution in these patients and only if potential benefit outweighed against risk
• Incidence of hepatotoxicity decreases in progressively older patients
• Patients should be closely monitor for appearance of any of these symptoms of fatal liver diseases such as malaise, weakness, lethargy, anorexia, vomiting facial edema, and loss of seizure control in epilepsy patients. Liver function test should be performed at the baseline and at frequent interval during the treatment especially in first 6 months
• Teratogenicity such as neural tube defect have occurred with the therapy, hence use valproate product in women of child bearing age only if potential benefit outweighed against risk to the fetus or other antiseizure medications have failed to control the symptoms. Therapy can also cause lower cognitive test scores following in utero exposure
• Women of childbearing potential should use effective contraception while taking valproate products
• Life threatening pancreatitis, hemorrhagic with rapid progression from initial symptoms to death has occurred in both children and adults receiving valproate. Monitor the patients for symptoms of pancreatitis such as abdominal pain, nausea, vomiting, anorexia if pancreatitis is diagnosed, immediately discontinue the drug and provide treatment for underlying medical condition

Renal Dose Adjustment

• Renal impairment: No dose adjustments

Hepatic Dose Adjustment

• Significant hepatic impairment: Contraindicated

See Supplemental Patient Information

• Fatal hepatic failure has occurred in patients receiving valproic acid especially in the first six month of treatment. Closely monitor the patients and perform LFT at base line and at frequent interval during the treatment [US Black box warning]
• Valproate and any other antiepleptic drug causes teratogenic effect such as neural tube defect in fetus. Use cautiously in pregnancy and women with child bearing age only if potential benefit to mother outweighed against the risk to the fetus. Therapy can also cause decreased IQ scores following in utero exposure [US Black box warning]
• 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
• Valproate causes clotting disorder, low fibrinogen level. Use of valproate in pregnancy causes afribrinogenemia in infant leading to the death due to hemorrhage
• Maternal use of valproate during pregnancy causes hepatotoxicity in infants
• Life threatening pancreatitis have 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
• 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
• 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
• 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 have occurred with valproate therapy in adult and pediatric patients
• 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
• 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 and initiate hyperammonemia treatment
• Concomitant use of topiramate and valproic acid causes hyperammonemia with or without encephalopathy

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
• Taking multiple anticonvulsants
• Myelosuppression
• Bleeding tendencies
• Elderly patients
• Concomitant use of aspirin

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

Depakene, Stavzor interacts with :

	Acenocoumarol
	Coumadin
	Doribax
	Doripenem
	Ertapenem
	Imipenem
	Invanz
	Jantoven
	Lamictal
	Lamictal CD
	Lamictal ODT
	Lamictal XR
	Lamotrigine
	Meropenem
	Merrem
	Merrem IV
	Primaxin
	Qudexy XR
	Retrovir
	Topamax
	Topiramate
	Trokendi XR
	Warfarin
	Zidovudine

Depakote interacts with :

	Acenocoumarol
	Coumadin
	Jantoven
	Warfarin

Pregnancy Category:D

Breastfeeding: Low level of valproic acid is excreted in breastmilk, no unquestionable adverse reactions to valproic acid have been reported during breastfeeding. Monitoring 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 13th December 2010). However manufacturer advises to discontinue nursing when valproate is administered to a nursing woman.

• CNS: Somnolence, tremor, dizziness, ataxia, amnesia, insomnia, headache, hypothermia, encephalopathy, coma, paresthesia
• PSYCHIATRY: Suicidal thoughts, emotional liability, abnormal thinking, depression, hallucinations, psychosis, agitation, confusion
• CV: Peripheral edema, vasodilatation
• EENT: Visual disturbances, blurred vision, tinnitus, nystagmus, diplopia, amblyopia
• GI: hepatotoxicity, pancreatitis, abdominal pain, anorexia, dyspepsia, nausea, vomiting, constipation, diarrhea, appetite change, elevated ALT, AST
• DERM: Alopecia, rashes, erythema multiforme, stevens johnson syndrome, toxic epidermal necrolysis
• RESP: Flu syndrome, infection, bronchitis, rhinitis, pharyngitis, dyspnea, pneumonia
• GU: Congenital anomalies, congenital neural tube defects, PCOS
• HEMA: Leukopenia, thrombocytopenia, ecchymosis, myleosuppression, aplastic anemia, pancytopenia
• METABOLIC: Weight gain, hyperammonemia, hyponatremia
• MUSC: Abnormal gait, myalgia, back pain
• MISC: Asthenia, fever, influenza, multi organ hypersensitivity reaction, photosensitivity

• Anticonvulsant; It inhibits enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings, resulting in increased brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS
• Rapidly absorbed in GI tract
• Metabolized by liver
• Renally excreted 30-50% as a glucuronide conjugate, (<3% unchanged)
• Half-life: 9-16 hrs

US Trade Name(s)

• Depakene
• Stavzor[Discontinued]

US Availability

valproic acid (generic)

• CAPS: 250 mg
• SYRUP: 250 mg/5 mL

Depakene

• CAPS: 250 mg
• SYRUP: 250 mg/5 mL

Stavzor

• Delayed Release CAPS: 125, 250, 500 mg

Canadian Trade Name(s)

• Depakene
• Epival

Canadian Availability

valproic acid (generic)

• CAPS: 250, 500 mg
• Softgel CAPS: 250 mg
• SYRUP: 50 mg/mL

divalproex (generic )

• TABS: 125, 250, 500 mg
• ETABS: 125, 250, 500 mg
• SYRUP: 50 mg/mL

Depakene

• CAPS: 250 mg
• SYRUP: 50 mg/mL

Epival

• TABS: 125, 250, 500 mg

UK Trade Name(s)

• Depakote
• Epilim
• Episenta
• Epilim chrono
• Epilim chronosphere
• Orlept
• Orlept(SF)

UK Availability

Valpraote sodium (generic)

• TABS: 200, 500 mg
• ORAL LIQ: 200 mg/5 mL

Depakote

• TABS: 200, 500 mg

Epilim

• TABS: 100, 200, 500 mg
• LIQ: 200 mg/5 mL
• SYRUP: 200 mg/5 mL

Epilim chrono (sodium valproate/valproic acid)

• ETABS: 200mg (133.2 mg/58.0 mg)
• ETABS: 300 mg (199.8 mg/87.0 mg)
• ETABS: 500 mg (333 mg/145 mg)

Epilim chronosphere (sodium valproate/valproic acid)

• GRAN: 50 mg (33.33 mg/14.5 mg)/sachet
• GRAN: 100 mg (66.66 mg/29.03 mg)/sachet
• GRAN: 250 mg (166.76 mg/72.61 mg)/sachet
• GRAN: 500 mg (333 mg/145.14 mg)/sachet
• GRAN: 750 mg (500.06 mg/217.75 mg)/sachet
• GRAN: 1000 mg (666.60 mg/290.27 mg)/sachet

Episenta

• ECAPS: 150, 300 mg
• EGRAN: 500,1000 mg/sachet

Orlept

• TABS: 200, 500 mg

Orlept(SF)

• LIQ: 200 mg/5 mL

Australian Trade Name(s)

• Epilim
• Valprease
• Valpro

Australian Availability

valproate (generic)

• TABS: 200, 500 mg

Epilim

• TABS: 100, 200, 500 mg
• SYP: 200 mg/5 mL
• Sugar free LIQ: 200 mg/5 mL

Valprease

• TABS: 200, 500 mg

Valpro

• TABS: 200, 500 mg

[Outline]

Neurologic

Anticonvulsants

Pricing data from www.DrugStore.com in U.S.A.

• Valproic Acid 250 MG/5ML SYRP [Bottle] (QUALITEST)
  150 5ml = $21.99
  450 5ml = $55.97
• Valproic Acid 250 MG CAPS [Bottle] (TEVA PHARMACEUTICALS USA)
  30 mg = $19.99
  90 mg = $35.97
• Depakene 250 MG CAPS [Bottle] (ABBOTT)
  30 mg = $89.99
  90 mg = $255.97
• Depakene 250 MG/5ML SYRP [Bottle] (ABBOTT)
  150 5ml = $104.99
  450 5ml = $303.97

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.

• Depakene 250 MG Oral Capsule (Abbott Laboratories)
• Depakote 125 MG Enteric Coated Capsule (Abbott Laboratories)
• Depakote 125 MG Enteric Coated Tablet (Abbott Laboratories)
• Depakote 250 MG Enteric Coated Tablet (Abbott Laboratories)
• Depakote 500 MG Enteric Coated Tablet (Abbott Laboratories)
• Stavzor 125 MG Enteric Coated Capsule (Noven Therapeutics, LLC)
• Stavzor 250 MG Enteric Coated Capsule (Noven Therapeutics, LLC)
• Stavzor 500 MG Enteric Coated Capsule (Noven Therapeutics, LLC)
• Valproic acid 250 MG Oral Capsule (Banner Pharmacaps, Inc)
• Valproic acid 250 MG Oral Capsule (Contract Pharmacy Services-PA)
• Valproic acid 250 MG Oral Capsule (McKesson Packaging Services Business Unit of McKesson Corporation)
• Valproic acid 250 MG Oral Capsule (UDL Laboratories, Inc.)
• Valproic acid 250 MG Oral Capsule (Watson Laboratories, Inc.)