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Valproic Acid Dosage

Applies to the following strength(s): 100 mg/mL ; 250 mg ; 250 mg/5 mL ; 125 mg ; 500 mg

The information at Drugs.com is not a substitute for medical advice. Always consult your doctor or pharmacist.

Usual Adult Dose for:

Usual Pediatric Dose for:

Additional dosage information:

Usual Adult Dose for Epilepsy

Complex partial seizures:
Initial dose: 10 to 15 mg/kg orally or IV daily; increase by 5 to 10 mg/kg per week if necessary according to clinical response
Maintenance dose: 10 to 60 mg/kg daily
Maximum dose: 60 mg/kg daily

Simple and complex absence seizures:
Initial dose: 15 mg/kg orally or IV daily; increase by 5 to 10 mg/kg per week if necessary according to clinical response
Maintenance dose: 10 to 60 mg/kg daily
Maximum dose: 60 mg/kg daily

Comments:
-If the total daily dose exceeds 250 mg, it should be given in divided doses.
-When converting to monotherapy, concomitant antiepilepsy drug (AED) dosage can ordinarily be reduced by approximately 25% every 2 weeks. This reduction may be started at initiation of this drug, or delayed by 1 to 2 weeks if there is a concern that seizures are likely to occur with a reduction. The speed and duration of withdrawal of the concomitant AED can be highly variable.
-Optimal clinical response is usually achieved at daily doses below 60 mg/kg/day; if satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). There is no recommendation regarding the safety of this drug at doses above 60 mg/kg/day.
-If a dose is missed it should be taken as soon as possible, unless it is almost time for the next dose. If a dose is skipped, the patient should not double the next dose.
-AEDs should not be abruptly discontinued because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life.

Comments:
-The IV formulation should be administered as a 60-minute infusion (but not more than 20 mg/min) with the same frequency as the oral products, although plasma concentration monitoring and dosage adjustments may be necessary.
-Use of the IV formulation for periods longer than 14 days has not been studied.
-Patients on the IV formulation should be switched to the oral formulation as soon as it is clinically feasible.

Uses: Monotherapy and adjunctive therapy of complex partial seizures and simple and complex absence seizures; adjunctive therapy in patients with multiple seizure types that include absence seizures

Usual Pediatric Dose for Epilepsy

10 years or older:
Complex partial seizures:
Initial dose: 10 to 15 mg/kg orally or IV daily; increase by 5 to 10 mg/kg per week if necessary according to clinical response
Maintenance dose: 10 to 60 mg/kg daily
Maximum dose: 60 mg/kg daily

Simple and complex absence seizures:
Initial dose: 15 mg/kg orally or IV daily; increase by 5 to 10 mg/kg per week if necessary according to clinical response
Maintenance dose: 10 to 60 mg/kg daily
Maximum dose: 60 mg/kg daily

Comments:
-If the total daily dose exceeds 250 mg, it should be given in divided doses.
-When converting to monotherapy, concomitant antiepilepsy drug (AED) dosage can ordinarily be reduced by approximately 25% every 2 weeks. This reduction may be started at initiation of this drug, or delayed by 1 to 2 weeks if there is a concern that seizures are likely to occur with a reduction. The speed and duration of withdrawal of the concomitant AED can be highly variable.
-Optimal clinical response is usually achieved at daily doses below 60 mg/kg/day; if satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). There is no recommendation regarding the safety of this drug at doses above 60 mg/kg/day.
-If a dose is missed it should be taken as soon as possible, unless it is almost time for the next dose. If a dose is skipped, the patient should not double the next dose.
-AEDs should not be abruptly discontinued because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life.

Comments:
-The IV formulation should be administered as a 60-minute infusion (but not more than 20 mg/min) with the same frequency as the oral products, although plasma concentration monitoring and dosage adjustments may be necessary.
-Use of the IV formulation for periods longer than 14 days has not been studied.
-Patients on the IV formulation should be switched to the oral formulation as soon as it is clinically feasible.

Uses: Monotherapy and adjunctive therapy of complex partial seizures and simple and complex absence seizures; adjunctive therapy in patients with multiple seizure types that include absence seizures

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

Hepatic disease or significant hepatic dysfunction: Contraindicated

Dose Adjustments

-When switching from oral formulations to IV, the total daily dose of the IV formulation should be equivalent to the total daily dose of the oral formulation and should be administered as a 60-minute infusion (but not more than 20 mg/min) with the same frequency as the oral formulation, although plasma concentration monitoring and dosage adjustments may be necessary.
-Geriatric patients: Reduce starting dose and increase dosage more slowly
-Dose reduction should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence.
-Thrombocytopenia: The probability of thrombocytopenia increases significantly at total valproate concentrations of 110 mcg/mL (females) or 135 mcg/mL (males) or more.
-Patients stabilized on rufinamide before being prescribed this drug should begin this drug at a low dose, and titrate to a clinically effective dose

Therapeutic drug monitoring:
-The relationship between plasma concentration and clinical response is not well documented.
-Epilepsy: The therapeutic range is commonly considered to be 50 to 100 mcg/mL of total valproate, although some patients may be controlled with lower or higher plasma concentrations.
-Mania: Patients have been dosed (in clinical trials) to clinical response with trough plasma concentrations between 50 and 125 mcg/mL
-Monitoring of valproate and concomitant drug concentrations should be increased whenever enzyme inducing drugs are introduced or withdrawn
-Monitoring of total concentrations may be misleading in patients with liver disease since free concentrations may be substantially elevated in these patients whereas total concentrations may appear to be normal.
-Protein binding is substantially reduced in renal failure; monitoring of total concentrations may be misleading in these patients.

Precautions

US BOXED WARNINGS:
HEPATOTOXICITY:
-Hepatic failure resulting in fatalities has occurred in patients taking this drug and its derivatives. This usually occurs during the first 6 months of treatment and may be preceded by nonspecific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting.
-In patients with epilepsy, a loss of seizure control may occur.
-Children younger than 2 years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, or with congenital metabolic disorders, or with severe seizure disorders accompanied by mental retardation, or with organic brain disease. Use this drug with extreme caution and only as monotherapy in this patient group. Fatal hepatotoxicity decreases considerably in older patients.
-Liver function tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first 6 months.
MITOCHONDRIAL DISEASE:
-There is an increased risk of drug-induced acute liver failure and death in patients with hereditary neurometabolic syndromes caused by DNA mutations of the mitochondrial DNA Polymerase gamma (POLG) gene (e.g., Alpers Huttenlocher Syndrome). This drug is contraindicated in patients known to have mitochondrial disorders caused by POLG mutations and children under 2 years of age who are clinically suspected of having a mitochondrial disorder.
-This drug should only be used in patients over 2 years of age who are clinically suspected of having a hereditary mitochondrial disease after other anticonvulsants have failed. These patients should be closely monitored during treatment for the development of acute liver injury with regular clinical assessments and serum liver testing. POLG mutation screening should be performed in accordance with current clinical practice.
FETAL RISK:
-This drug can cause major congenital malformations, particularly neural tube defects (e.g., spina bifida). It can also cause decreased IQ scores following in utero exposure.
-This drug should only be used to treat pregnant women with epilepsy if other medications have failed to control their symptoms or are otherwise unacceptable.
-This drug should not be administered to a woman of childbearing potential unless the drug is essential to the management of her medical condition; this is especially important when its use is considered for a condition not usually associated with permanent injury or death (e.g., migraine).
-Women should use effective contraception while taking this drug.
PANCREATITIS:
-Cases of life-threatening pancreatitis have been reported in patients receiving valproate; some cases were hemorrhagic with a rapid progression from initial symptoms to death. Cases have been reported initially and after prolonged use. Abdominal pain, nausea, vomiting and/or anorexia can be symptoms of pancreatitis. If pancreatitis is diagnosed, treatment should be discontinued and alternative treatment initiated as clinically indicated.

Use of valproate sodium injection has not been studied in children below the age of 10 years.

Consult WARNINGS for additional precautions

Dialysis

Hemodialysis: Hemodialysis reduces valproate concentrations by about 20%; no adjustment recommended.
Peritoneal dialysis: Data not available

Other Comments

Administration advice:
-This drug should be taken with food.
-Uncoated tablets: Doses may be swallowed whole or crushed and swallowed with water.
-Enteric-coated tablets: Doses should be swallowed whole, if necessary with a little water.
-Oral controlled release tablets: Doses should be swallowed whole and not crushed or chewed.
-Oral modified release granules: Should not be crushed or chewed, but either poured into the mouth and washed down with a cold drink, or sprinkled on a small amount of soft food or in drinks that are cold or at room temperature (e.g., yogurt, mousse, jam, ice cream, milkshake, orange juice, or something similar), then swallowed immediately. The granules should not be sprinkled on warm or hot foods and drinks (e.g., soup, coffee, tea).
-IV: Administer as an IV infusion over at least 60 minutes but not more than 20 mg/min

IV compatibility: Normal saline, glucose 5% or glucose saline

Monitoring:
-General: Patients receiving doses near the maximum recommended daily dose should be monitored more closely.
-Hematologic: Platelet counts
-Hepatic: Liver function tests
-Nervous system: Seizures
-Psychiatric: Emergence or worsening of depression, suicidal thoughts or behavior, and/or unusual changes in mood or behavior

Patient advice:
-Antiepileptic drugs, including valproate, may increase the risk of suicidal thoughts and behavior. Be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Report any behavior of concern to your healthcare provider as soon as possible.
-Valproate may cause drowsiness and dizziness; do not drive a car or operate dangerous machinery until you know how this drug affects you.

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