Sulfonylureas

Glibenclamide, Gliclazide, Glimepiride, Glipizide, Tolbutamide

[Wockhardt, the only UK manufacturer of glibenclamide, have discontinued production.  At the current time, this preparation remains in the British National Formulary and has been included in this monograph as unlicensed imports are available for patients in whom a switch to an alternative is inappropriate] 

  Issues for Surgery

Hypoglycaemia if continued during nil by mouth (NBM) period / during liver reduction (LRD) diet for patients undergoing Bariatric Surgery.

Increased risk of post-operative infection and delayed wound healing due to poor glycaemic control if omitted.

  Advice in the Perioperative period

Elective Surgery
Sulfonylureas should be taken as normal the day prior to surgery¹ – EXCEPT for patients undergoing Bariatric Surgery, see below.

Morning Surgery
Once daily dosing (in the morning) – omit the dose on day of surgery¹

Twice daily dosing – omit the morning dose on day of surgery¹

Afternoon Surgery
Once daily dosing (in the morning) – omit the dose of day of surgery¹

Twice daily dosing – omit both doses on day of surgery¹

Patients undergoing Bariatric Surgery
Patients with type 2 diabetes mellitus commencing liver reduction diet (LRD): Patients taking sulfonylureas are at increased risk of hypoglycaemia during the LRD and they should be discontinued when the LRD commences² (see Further Information).

Patients with type 2 diabetes mellitus not following a LRD: Follow the advice above for Elective Surgery.

Emergency Surgery
In the event of emergency surgery and the patient has already taken their sulfonylurea dose(s) monitor blood glucose levels closely and treat any hypoglycaemia accordingly.

Perioperative Considerations
Commence variable rate intravenous insulin infusion (VRIII) perioperatively where indicated (see Further Information) and omit sulfonylurea during VRIII treatment¹..

Ensure emergency treatment of hypoglycaemia is prescribed i.e. Glucogel^® and 20% dextrose. Rapid acting insulin should also be prescribed^{1, 3}.

Post-operative Advice
Restart once eating and drinking normally and VRIII (where applicable) has been stopped^{1, 3}. Due to the risk of hypoglycaemia with sulfonylureas, capillary blood glucose (CBG) should be monitored post-operatively and consideration should be given to omitting or reducing the dose if reduced food intake. Monitor renal function – dose reduction may be necessary if decline in renal function post-operatively.

NB: Patients undergoing afternoon surgery and taking twice daily sulfonylurea will restart their medication the day after surgery, once they are eating and drinking normally and VRIII (where applicable) has been stopped.

Patients undergoing Bariatric Surgery
Improved glycaemic control is expected because of reduced calorie intake, early satiety and weight loss following bariatric surgery, therefore sulfonylureas should be discontinued post-operatively³. Blood glucose should be monitored until eating habits and food intake stabilises³. Patients should have their need for ongoing pharmacological management of their diabetes reviewed by their General Practitioner and / or Bariatric Surgical Team.

  Interaction(s) with Common Anaesthetic Agents

None^{3, 4, 5, 6, 7, 8}.

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

Non-Steroidal Anti-inflammatory Drugs (NSAIDs)

Caution with concomitant use of NSAIDs as they may cause hypoglycaemia^{3, 4, 5, 6, 7}.

Antibiotics

Clarithromycin slightly increases, and sulfamethoxazole (found in co-trimoxazole) increases, sulfonylurea exposure which may cause hypoglycaemia^{2, 3, 4, 5, 6, 7}. Case reports of hypoglycaemia have been noted with concomitant use of glibenclamide and ciprofloxacin⁷. Increase CBG monitoring with concomitant use and adjust dose of sulfonylurea if necessary⁷.

  Further Information

VRIII

Patients with a planned short starvation period (no more than one missed meal in total) should be managed by modification of their usual diabetes medication, avoiding VRIII wherever possible (although VRIII may be necessary if emergency surgery or in people with poorly controlled diabetes (HbA1c >69mmol/mol))¹. Patients expected to miss more than one meal should have VRIII if they develop hyperglycaemia (CBG >12mmol/L)¹.

Liver Reduction Diet (LRD)
Most people needing bariatric surgery have a large, fatty liver which can cause difficulty for laparoscopic surgery, as the stomach cannot be easily accessed. The LRD typically start 10 – 15 days prior to bariatric surgery and is based on low calories, in particular low carbohydrate, and fat. This forces stored glycogen to be released from the liver (plus some water), making it softer, more flexible and easier to move. Due to the reduced calorie and carbohydrate intake, CBG levels will most likely be reduced. Since sulfonylureas cause hypoglycaemia, the risk is increased due to the reduction in dietary intake and they should be stopped at the start of the LRD³.

  References

1. Centre for Perioperative Care. Guideline for Perioperative Care for People with Diabetes Mellitus Undergoing Elective and Emergency Surgery (March 2021). Available at: https://cpoc.org.uk/guidelines-resources/guidelines [Accessed on 8^th March 2021]
2. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 27^th February 2021]
3. Summary of Product Characteristics – Diamicron^® (gliclazide) 80mg Tablets. Servier Laboratories Limited. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text February 2020]
4. Summary of Product Characteristics – Gliclazide Accord-UK 30mg Prolonged-release Tablets. Accord-UK Ltd. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text February 2021]
5. Summary of Product Characteristics – Glimepiride 1mg Tablets. Accord Healthcare Ltd. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text December 2020]
6. Summary of Product Characteristics – Glipizide 5mg Tablets. Mylan. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text May 2017]
7. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 27^th February 2021]