Sodium Valproate, Valproic Acid [as Semisodium Salt]
Issues for Surgery
For treatment of epilepsy – precipitation of rebound seizures or status epilepticus if omitted.
For treatment of manic episodes associated with bipolar disorder – risk of mania if omitted.
For migraine prophylaxis [unlicensed] – risk of acute migraine attack if omitted.
Advice in the Perioperative period
Elective and Emergency Surgery
Check full blood count and ensure no undue potential for bleeding pre-operatively1, 2, 3 (see Further Information).
Abrupt withdrawal of any anticonvulsant drug should be avoided1.
Confirm with the patient if they need to be maintained on a specific manufacturer’s product (see Further Information).
Regular dosing of the patient’s usual oral medication should be re-established as early as possible post-operatively4, 5.
If it is anticipated that patients will be immobilised for a prolonged period post-operatively, consider commencing vitamin D supplementation1 (see Further Information).
Interaction(s) with Common Anaesthetic Agents
For general information regarding the use of anaesthetic agents in patients with epilepsy – see ‘Antiepileptics – A General Overview’.
Cautious dosing of propofol is advised as valproate potentially increases the concentration of propofol in the plasma2, 6, 7
Sodium valproate has been reported to displace diazepam from plasma-protein binding sites leading to increased diazepam concentrations and increased sedative effects7, 8. Use of valproate semisodium with lorazepam has resulted in raised concentrations of lorazepam due to inhibition of glucuronidation of lorazepam leading to a possible increase in sedative effects7, 8. This interaction may occur with other benzodiazepines2, 7.
Interaction(s) with other Common Medicines used in the Perioperative Period
For general information regarding the use of antiemetics in patients with epilepsy – see ‘Antiepileptics – A General Overview’.
With the exception of carbapenems (see above), whilst single surgical prophylactic doses should not pose a problem, continued post-operative treatment may require close monitoring. Consult current product literature.
Salicylates (e.g. aspirin) should not be used concomitantly with valproate since they use the same metabolic pathway2, 3.
Concomitant use of valproate and paracetamol may increase the risk of hepatotoxicity1.
MHRA/CHM Advice: Antiepileptic Drugs: updated advice on switching between different manufacturer’s products (November 2017)1
To ensure the correct medication is prescribed for the patient's condition, care must be taken not to confuse Depakote® with Epilim® or sodium valproate. Patients with bipolar disorder and epilepsy are distinct populations. These differences are reflected in the patient information leaflets, which clearly indicate specific indications for these differing medications1.
Plasma-valproate concentrations are not a useful index of efficacy; therefore, routine monitoring is unhelpful and not recommended1.
Liver dysfunction (including fatal hepatic failure) has occurred in association with valproate, usually within the first 6 months of treatment and usually involving multiple antiepileptic therapy. Raised liver enzymes are common and usually transient but patients should be reassessed clinically and liver function (including prothrombin time) monitored until return to normal. Discontinue if abnormally prolonged prothrombin time (particularly in association with other relevant abnormalities e.g. significant decrease in fibrinogen and coagulation factors; increased bilirubin level and raised transaminases)1, 2, 3 – seek advice from Neurologist / Psychiatrist on alternative treatment plan.
Rarely, valproate treatment has been associated with a decrease in bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term therapy. The mechanism by which valproate affects bone metabolism has not been identified1, 2, 3.