Topiramate


  Issues for Surgery


For treatment of epilepsy – precipitation of rebound seizures or status epilepticus if omitted.

For migraine prophylaxis [unlicensed] – risk of acute migraine attack if omitted.

Risk of metabolic acidosis if continued (see Further Information).

Risk of nephrolithiasis if continued without adequate hydration (see Further Information).


  Advice in the Perioperative period


Elective and Emergency Surgery


Continue.

Epilepsy
Patients should be advised to take their regular medications on the day of surgery1, 2, 3.

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).

Post-operative Advice

Regular dosing of the patient’s usual oral medication should be re-established as early as possible post-operatively2, 3.

Topiramate is only available as oral preparations. If patients with epilepsy cannot resume their usual oral medication post-operatively, the advice of a Neurologist should be sought to determine the most appropriate antiepileptic preparation, dose, route and frequency to be used.

Monitor renal and hepatic function post-operatively since any impairment may lead to reduced clearance and the need to alter the dose of topiramate1, 4. Consult relevant product literature where necessary.


  Interaction(s) with Common Anaesthetic Agents


For general information regarding the use of anaesthetic agents in patients with epilepsy – see Antiepileptics – A General Overview.

Ketamine

One study suggests that topiramate might attenuate the effects of ketamine, whereas another did not find an interaction5.

Diazepam

The manufacturer of topiramate predicts that it will inhibit the metabolism of diazepam (by cytochrome P450 enzyme CYP2C19). Bear the possibility in mind should any unexpected increase in diazepam adverse effects occur5.

Central Nervous System (CNS) Depressants

Concomitant administration of topiramate and CNS depressants has not been evaluated in clinical studies6. There may be potential for additive CNS depressant effects with administration of other CNS depressant medicines e.g. benzodiazepines, inhalational and intravenous anaesthetics, local anaesthetics, opioids and some antiemetics.


  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.

CNS Depressants – see Interaction(s) with Common Anaesthetic Agents

Proton Pump Inhibitors (PPIs)

The manufacturer of topiramate predicts that it will inhibit the metabolism of some PPIs by the cytochrome P450 enzyme CYP2C19 (lansoprazole, omeprazole, rabeprazole). Bear this in mind should any unexpected increase in PPI adverse effects occur5.


  Further Information


MHRA/CHM Advice: Antiepileptic Drugs: updated advice on switching between different manufacturer’s products (November 2017)1

Epilepsy
Topiramate is a category 2 antiepileptic, hence the need for continued supply of a particular manufacturer’s product should be based on clinical judgement and consultation with the patient and / or carer taking into account factors such as seizure frequency and treatment history. (For more information see Antiepileptics – A General Overview).

Other Indications
There is no specific advice available for maintaining patients on a specific manufacturer’s product for indications other than epilepsy.

Hydration

Ensure adequate hydration throughout the perioperative period to maintain a good urine output, to try to reduce the risk of developing renal calculi, especially in predisposed patients1, 4, 6.

Metabolic acidosis

Hyperchloremic, non-anion gap, metabolic acidosis (i.e. decreased serum bicarbonate below the normal reference range in the absence of respiratory alkalosis) is associated with topiramate treatment1, 4, 6. This decrease in serum bicarbonate is due to the inhibitory effect of topiramate on renal carbonic anhydrase4, 5. Surgery can predispose to acidosis and this may be additive to the bicarbonate lowering effects of topiramateIf there are signs or symptoms indicative of metabolic acidosis, measurement of serum bicarbonate is recommended6. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing topiramate (using dose tapering)4, 6 – discuss with a Neurologist where appropriate.


  References


  1. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press http://www.medicinescomplete.com [Accessed 30th June 2019]
  2. Perks A, Cheema S, Mohanraj R. Anaesthesia and epilepsy. BJA: British Journal of Anaesthesia. 2012; 108(4):562-571
  3. Carter EL, Adapa RM. Adult epilepsy and anaesthesia. BJA Education, 2015; 15(3):111-117
  4. Topiramate. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 9th July 2019]
  5. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 30th June 2019]
  6. Summary of Product Characteristics – Topamax® (topiramate) 200mg. Janssen-Cilag Ltd. Accessed via www.medicines.org.uk 09/07/2019 [date of revision of the text March 2019]