valproate
Table of Contents
sodium valproate (Epilim)
see also:
introduction
- sodium valproate is an anticonvulsant which is also used to Rx bipolar disorder, and is sometimes used to reduce incidence of migraine attacks
- it's actions are attributed to:
- the blockade of voltage dependent Na+ channels
- increased brain levels of gamma-aminobutyric acid (GABA)
- it does not have any significant hypnotic effect and has less sedative effects than some older anticonvulsants
- has been shown to be effective in the treatment of absence seizures (petit mal), tonic-clonic seizures (grand mal) and myoclonic seizures.
- it has similar efficacy to lithium carbonate in the Rx of mania
- serum levels are of limited utility but may be useful in assessing compliance
P/K
- rapidly absorbed after oral dose in fasting patients with peak blood levels at 1-4hrs
- absorption is delayed if taken with food with peak blood levels at 3-7hrs but abdorption is still almost complete
- gastric irritation is less likely to occur with the enteric coated tablets
- correlation between the daily dose per bodyweight and plasma levels of drug has been poor
- correlation between plasma levels of drug and CNS actions has been poor
- correlation between saliva levels and plasma levels of drug is poor
- CSF levels are 5-15% of plasma levels
- protein binding sites become saturated at plasma levels > 120 microgram/mL, or in patients with hypoalbuminaemia, causing free drug levels to rise dramatically with further dosage increase
- 40-60% metabolised by glucuronidation, most of remainder metabolised by oxidation
- 1-3% excreted unchanged in urine
- plasma half-life is variable but appears to be 8-12 hours
C/I
- pregnancy (category D) - if taken in 1st TM, 1-2% risk of neural tube defects, and may be associated with other fetal changes
- PH HS to valproate
- urea cycle disorders
- hepatic porphyria
precautions
- prenatal use in women who may become pregnant is not advised unless necessary or contraception is used
- lactation
- children - increased risk of pancreatitis, hepatitis; avoid concurrent salicylates or barbiturates
- liver or renal dysfunction
- ornithine transcarbamylase (OTC) deficiency
- surgery - prolonged bleeding time and/or thrombocytopenia may occur
- suicidality - may increase risk of suicidal thoughts or behaviour
- avoid abrupt withdrawal as risk of seizure
- weight gain may occur
- diabetes mellitus or dental caries as Epilim syrup contains sucrose 3.6 g/5 mL
- operating machinery or driving, particularly if high dose, rapid cessation, or other anticonvulsants or sedatives used
adverse effects
- fetal malformations
- dose-related cognitive deficits in children if taken during pregnancy
- may increase risk of autism spectrum disorder when taken prenatally (adjusted hazard ratio 2.9)
- fatigue
- nausea
- may cause some sedation, impaired memory, confusion, nystagmus
- very uncommonly may cause other CNS effects such as ataxia
- gastric irritation
- sleeping disorders
- flu-like illness
- suicidality risk
- alopecia
- HS reactions
- osteopenia / osteoporosis
- prolonged bleeding time
- deafness - reversible and irreversible
- other more rare adverse effects
usual dose
- dose is usually bd
- adults:
- start at 600mg/day and increase by 200mg/d every 3 days until control achieved or max. 2,500mg/day
- most require 1,000 to 2,000 mg/day (i.e. 20 to 30 mg/kg/day)
- it may be necessary to raise the dose by 5 to 10 mg/kg/day when used in combination with anticonvulsants which induce liver enzyme activity, e.g. phenytoin, phenobarbitone and carbamazepine.
- iv dose for severe acute migraine:
- requires further study but 900-1200mg iv valproate appeared to substantially reduce migraine headache pain within 60 minutes in ~75% of patients 1)
valproate.txt · Last modified: 2014/11/24 10:40 by 127.0.0.1