Valproate: Difference between revisions
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==General== | ==General== | ||
*Type: [[Anticonvulsants]] | *Type: [[Anticonvulsants]] | ||
*Dosage Forms: | *Dosage Forms: 125mg; 250mg; 500mg; 100mg/mL; 250mg/5mL; 500mg/5mL | ||
*Common Trade Names: | *Common Trade Names: Depacon, Depakene, Depakote, Depakote ER. Depakote Sprinkles, Stavzor | ||
==Adult Dosing== | ==Adult Dosing== | ||
===[[Seizures]]=== | |||
*Oral (max 60mg/kg/d) | |||
**Simple/complex absence: Initial 15mg/kg/d; increase 5-10mg/kg/d at weekly until therapeutic | |||
**Complex partial: Initial 10-15mg/kg/d; increase 5-10mg/kg/d at weekly until therapeutic | |||
***Extended release formulation given once daily | |||
*IV: same dose as oral, administered as 60min infusion | |||
===[[Status epilepticus]], refractory=== | |||
*IV: Loading 15-20mg/kg administered at 20mg/min | |||
**Maintenance: 1-5mg/kg/hr | |||
===[[Bipolar disorder]], manic episode=== | |||
*Oral: Depakote Stavzor 750mg/d or Depakote ER 25mg/kg/d qday | |||
===[[Migraine]] prophlyaxis=== | |||
*Oral: Depakote, Stavzor 250mg BID or Depakote ER 500mg qday | |||
==Pediatric Dosing== | ==Pediatric Dosing== | ||
*Same as adult dosing | |||
*Avoid extended release formulation in children <10yr | |||
==Special Populations== | ==Special Populations== | ||
*[[Drug Ratings in Pregnancy|Pregnancy Rating]]: | *[[Drug Ratings in Pregnancy|Pregnancy Rating]]: X | ||
*Lactation: | *Lactation: Use with caution. Excreted in breast milk. | ||
*Renal Dosing | *Renal Dosing: No adjustment | ||
*Hepatic Dosing | *Hepatic Dosing | ||
** | **Mild-mod impairment: Not recommended | ||
** | **Severe impairment: Contraindicated | ||
==Contraindications== | ==Contraindications== | ||
*Allergy to class/drug | *Allergy to class/drug | ||
*Severe hepatic impairment | |||
*[[Pregnancy]] | |||
*Urea cycle disorders | |||
*Mitochondrial disorders | |||
==Adverse Reactions== | ==Adverse Reactions== | ||
===Serious=== | ===Serious=== | ||
*Hepatotoxicity | |||
*Congenital malformation: neural tube defect | |||
*[[Pancreatitis]] | |||
===Common=== | ===Common=== | ||
*[[Headache]], drowsiness, dizziness, insomnia, nervousness, pain | |||
*[[Alopecia]] | |||
*[[Nausea]], [[vomiting]], [[diarrhea]], [[abdominal pain]], anorexia | |||
*[[Thrombocytopenia]] | |||
*Infection | |||
*Tremor, [[weakness]] | |||
*[[Diplopia]], visual disturbance | |||
*[[Flu-like symptoms]] | |||
==Toxicity== | |||
*Potential use for early IV L-carnitine to reduce hepatotoxicity | |||
*100mg/kg IV once, followed by 50mg/kg (max 3 g per dose) q8hrs until ammonia levels normalize<ref>Perott J et al. L-carnitine for acute valproic acid overdose: a systematic review of published cases. Ann Pharmacother. 2010 Jul-Aug;44(7-8):1287-93. doi: 10.1345/aph.1P135. Epub 2010 Jun 29.</ref> | |||
==Pharmacology== | ==Pharmacology== | ||
*Half-life: | *Half-life: | ||
*Metabolism: | **Children >2mo: 7-13 hours | ||
*Excretion: | **Adult: 9-19 hours | ||
*Mechanism of Action: | *Metabolism: Hepatic glucuronide conjugation and mitochondrial beta-oxidation | ||
*Excretion: Urine | |||
*Mechanism of Action: Increases availability and enhances action of GABA | |||
==See Also== | ==See Also== | ||
*[[Seizure]] | |||
*[[Valproic acid toxicity]] | |||
*[[Valproic acid]] | |||
== | ==References== | ||
<references/> | |||
[[Category:Pharmacology]] | |||
[[Category: | [[Category:Neurology]] | ||
Latest revision as of 22:30, 22 February 2021
General
- Type: Anticonvulsants
- Dosage Forms: 125mg; 250mg; 500mg; 100mg/mL; 250mg/5mL; 500mg/5mL
- Common Trade Names: Depacon, Depakene, Depakote, Depakote ER. Depakote Sprinkles, Stavzor
Adult Dosing
Seizures
- Oral (max 60mg/kg/d)
- Simple/complex absence: Initial 15mg/kg/d; increase 5-10mg/kg/d at weekly until therapeutic
- Complex partial: Initial 10-15mg/kg/d; increase 5-10mg/kg/d at weekly until therapeutic
- Extended release formulation given once daily
- IV: same dose as oral, administered as 60min infusion
Status epilepticus, refractory
- IV: Loading 15-20mg/kg administered at 20mg/min
- Maintenance: 1-5mg/kg/hr
Bipolar disorder, manic episode
- Oral: Depakote Stavzor 750mg/d or Depakote ER 25mg/kg/d qday
Migraine prophlyaxis
- Oral: Depakote, Stavzor 250mg BID or Depakote ER 500mg qday
Pediatric Dosing
- Same as adult dosing
- Avoid extended release formulation in children <10yr
Special Populations
- Pregnancy Rating: X
- Lactation: Use with caution. Excreted in breast milk.
- Renal Dosing: No adjustment
- Hepatic Dosing
- Mild-mod impairment: Not recommended
- Severe impairment: Contraindicated
Contraindications
- Allergy to class/drug
- Severe hepatic impairment
- Pregnancy
- Urea cycle disorders
- Mitochondrial disorders
Adverse Reactions
Serious
- Hepatotoxicity
- Congenital malformation: neural tube defect
- Pancreatitis
Common
- Headache, drowsiness, dizziness, insomnia, nervousness, pain
- Alopecia
- Nausea, vomiting, diarrhea, abdominal pain, anorexia
- Thrombocytopenia
- Infection
- Tremor, weakness
- Diplopia, visual disturbance
- Flu-like symptoms
Toxicity
- Potential use for early IV L-carnitine to reduce hepatotoxicity
- 100mg/kg IV once, followed by 50mg/kg (max 3 g per dose) q8hrs until ammonia levels normalize[1]
Pharmacology
- Half-life:
- Children >2mo: 7-13 hours
- Adult: 9-19 hours
- Metabolism: Hepatic glucuronide conjugation and mitochondrial beta-oxidation
- Excretion: Urine
- Mechanism of Action: Increases availability and enhances action of GABA
See Also
References
- ↑ Perott J et al. L-carnitine for acute valproic acid overdose: a systematic review of published cases. Ann Pharmacother. 2010 Jul-Aug;44(7-8):1287-93. doi: 10.1345/aph.1P135. Epub 2010 Jun 29.