Valproate: Difference between revisions

No edit summary
No edit summary
Line 5: Line 5:


==Adult Dosing==
==Adult Dosing==
*Seizures
===[[Seizures]]===
** Oral (max 60mg/kg/d)
* Oral (max 60mg/kg/d)
*** Simple/complex absence: Initial 15mg/kg/d; increase 5-10mg/kg/d at weekly until therapeutic
** 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
** Complex partial: Initial 10-15mg/kg/d; increase 5-10mg/kg/d at weekly until therapeutic
**** Extended release formulation given once daily
*** Extended release formulation given once daily
**IV: same dose as oral, administered as 60min infusion
*IV: same dose as oral, administered as 60min infusion
* Status epilepticus, refractory
 
**IV: Loading 15-20mg/kg administered at 20mg/min
===[[Status epilepticus]], refractory===
***Maintenance: 1-5mg/kg/hr
*IV: Loading 15-20mg/kg administered at 20mg/min
*Mania
**Maintenance: 1-5mg/kg/hr
**Oral: Depakote Stavzor 750mg/d or Depakote ER 25mg/kg/d qday
 
*Migraine prophlyaxis
===[[Mania]]===
** Oral: Depakote, Stavzor 250mg BID or Depakote ER 500mg qday
*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
*Same as adult dosing
*Avoid extended release formulation in children <10yr
*Avoid extended release formulation in children <10yr
==Special Populations==
==Special Populations==
*[[Drug Ratings in Pregnancy|Pregnancy Rating]]: X
*[[Drug Ratings in Pregnancy|Pregnancy Rating]]: X
Line 32: Line 37:
*Allergy to class/drug
*Allergy to class/drug
*Severe hepatic impairment
*Severe hepatic impairment
*Pregnancy
*[[Pregnancy]]
*Urea cycle disorders
*Urea cycle disorders
*Mitochondrial disorders
*Mitochondrial disorders
==Adverse Reactions==
==Adverse Reactions==
===Serious===
===Serious===
Line 40: Line 46:
*Congenital malformation: neural tube defect  
*Congenital malformation: neural tube defect  
*Pancreatitis
*Pancreatitis
===Common===
===Common===
*Headache, drowsiness, dizziness, insomnia, nervousness, pain
*[[Headache]], drowsiness, dizziness, insomnia, nervousness, pain
*Alopecia
*[[Alopecia]]
*Nausea, vomiting, diarrhea, abdominal pain, anorexia
*[[Nausea]], [[vomiting]], [[diarrhea]], [[abdominal pain]], [[anorexia]]
*Thrombocytopenia
*[[Thrombocytopenia]]
*Infection
*Infection
*Tremor, weakness
*[[Tremor]], [[weakness]]
*Diplopia, visual disturbance
*[[Diplopia]], visual disturbance
*Flu-like symptoms
*[[Flu-like symptoms]]


==Toxicity==
==Toxicity==
Line 65: Line 72:
*[[Seizure]]
*[[Seizure]]


==Sources==
==References==
<references/>


<references/>
*UpToDate
[[Category:Drugs]]
[[Category:Drugs]]

Revision as of 15:39, 14 September 2015

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

Mania

  • 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

Toxicity

  • Potential use for early IV L-carnitine to reduce hepatotoxicity
  • 100 mg/kg IV once, followed by 50 mg/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

  1. 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.