Sodium valproate

Question 1

What is sodium valproate?

Answer 1

fatty acid with anticonvulsant properties

Question 2

What class of drugs does sodium valproate belong to?

Answer 2

anticonvulsants

other drugs: primidone, benzodiazepines,
diazepam, gabapengin, topiramate, phenytoin, acetazolamide, clobazam, lamotrigine,

Question 3

What is the mechanism of action of sodium valproate?

Answer 3

• dissocaites to valproate ion in GIT
• inhibits GABA transaminase to increase GABA activity
• supresses reptitive neuronal firing by inhibiting V sensitive Na channels
• inhibits histone deacetylase for HIV therapy potential

Question 4

What is sodium valproate indicated for?

Answer 4

epilepsy
treatment/recurrence prevention of mania bipolar disorder
migraine prophylaxis [unapproved on NZF]

Question 5

What are the relevant PK/PD parameters of sodium valproate?

Answer 5

• non linear concentration dependent protine binding afects clearance
• rapidly absorbed from the GIT although rate can vary with formulation administered
• 90% protein binding if given at 40ug/ml, 82.5% protein binding if gien at 130ug/mL
• metabolised almost entirely by liver

Question 6

What are the cautions associated with sodium valproate use?

Answer 6

• monitor LFT before therapy and during first 6 months esp. in risk patients
• meausre full blood count/ensure no undue potential bleeding
• lupus
• false positive urine tests for ketones
• avoid abrupt withdrawal
• Vitamin D supplementation for patients immoblised for long periods
• heaptic toxicity
• pancreatitis should be warned

Question 7

What are the contraindications with sodium valproate use?

Answer 7

family history of severe hepatic dysfunction,
acute porphyria
pregnancy class D but compatible with breastfeeding

Question 8

What are the adverse effects with sodium valproate use?

Answer 8

nausa, GI irritation, diarrhoea, weight gain, hyperammonaemia, thrombocytopenia, transiet hair loss (regrowth can be curly)

Question 9

What are the drug interactions associated with sodium valproate use?

Answer 9

Colestyramine causes small reduction in sodium valproate absorption

Increases lorazepam exposure, may increase its sedative effects

serum phenobarbital elvels may be increased with cc use of sodium valproate

Question 10

What are the alarm bells with sodium valproate use?

Answer 10

Do not stop or change dose without consulting doctor
may cause drowsiness
avoid alcohol
don ot take Ca, Fe within 2 hours of dse,
report symptoms of hepaottoxicity or pancreaitis (malaise, weakness, lethargy, facial oedema, anorexia, nausea, vomiting, abdominal pain, jaundice.

report immediately if depression/suicidality.

women of childbearing age MUST use effective contraception.