Zonisamide


  Issues for Surgery


Precipitation of rebound seizures or status epilepticus if omitted.

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

Risk of renal calculi with dehydration if continued (see Further Information).


  Advice in the Perioperative period


Elective and Emergency Surgery

Continue.

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.

Zonisamide is only available as an oral preparation. If patients 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 function – there is limited information on the use of zonisamide in renal impairment. It should be discontinued in patients who develop acute renal failure or where a clinically significant sustained increase in serum creatinine is observed6. A Neurologist should be consulted to ensure an appropriate management plan is in place.


  Interaction(s) with Common Anaesthetic Agents


None1, 4, 5, 6.

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


  Interaction(s) with other Common Medicines used in the Perioperative Period


None1, 4, 5, 6.

For general information regarding the use of antiemetics in patients with epilepsy – see ‘Antiepileptics – A General Overview’.


  Further Information


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

Zonisamide 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).

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 patients5.

Metabolic Acidosis 

Hyperchloraemic, non-anion gap, metabolic acidosis (i.e. decreased serum bicarbonate below the normal reference range in the absence of respiratory alkalosis) is associated with zonisamide treatment. This is caused by renal bicarbonate loss due to the inhibitory effect of zonisamide on carbonic anhydrase. Surgery can predispose patients to acidosis and may have an additive effect to the bicarbonate lowering effects of zonisamide6. It appears to be more frequent and severe in younger patients. Appropriate monitoring of bicarbonate levels should take place in patients undergoing surgery. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing zonisamide (by gradual withdrawal)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. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 20th July 2019]
  5. Zonisamide. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 20th July 2019]
  6. Summary of Product Characteristics – Zonisamide Accord 100mg Hard Capsules. Accord-UK Ltd. Accessed via www.medicines.org.uk 20/07/2019 [date of revision of the text April 2019]