Pioglitazone

  Issues for Surgery

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

Combination product containing metformin – risk of lactic acidosis if continued (see Interaction(s) with other Common Medicines used in the Perioperative Period and Further Information).

Potential for hypoglycaemia when taken concomitantly with other blood glucose lowering medicines and continued during nil by mouth (NBM) period.

  Advice in the Perioperative period

Elective and Emergency Surgery
Pioglitazone should be taken as normal the day prior to surgery (including combination products)¹.

Morning or Afternoon Surgery.
Continue^{1, 2}.

EXCEPT:

• Competact^® – contains metformin (see Metformin monograph).

Consideration should be given to prescribing the components of combination products as separate medicines perioperatively.

Patients having Surgery for Bladder Cancer
Pioglitazone containing medications are contraindicated in previous or active bladder cancer (see Further Information).

Patients undergoing Bariatric Surgery
Patients with type 2 diabetes mellitus commencing liver reduction diet (LRD): Although pioglitazone increases insulin sensitivity, it can still be continued during the LRD as it does not cause hypoglycaemia providing other oral hypoglycaemics are reviewed (see Further Information).

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

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

Ensure emergency treatment of hypoglycaemia is prescribed i.e. Glucogel^® and 20% dextrose. Rapid acting insulin should also be prescribed^{1, 2}.

Post-operative Advice
If withheld due to use of VRIII, restart once VRIII discontinued and patient eating and drinking normally¹.

For combination product containing metformin – follow advice on restarting in Metformin monograph.

Patients undergoing Bariatric Surgery
Improved glycaemic control is expected because of reduced calorie intake, early satiety and weight loss following bariatric surgery, therefore discontinuation of pioglitazone should be considered 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^{2, 3, 5, 6}.

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

None for pioglitazone alone^{2, 3, 4}

Iodinated Contrast Agents
Caution with combination products containing metformin and concomitant use of iodinated contrast agents⁶ – see Metformin monograph.

Non-Steroidal Anti-inflammatory Drugs (NSAIDs)
Caution with combination products containing metformin and concomitant use of NSAIDs⁶ – see Metformin monograph.

  Further Information

Lactic Acidosis
Risk of lactic acidosis with combination products containing metformin⁶ – see Metformin monograph.

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 with type 2 diabetes who are expected to miss more than one meal should have VRIII if they develop hyperglycaemia (capillary blood glucose (CBG) >12mmol/L)¹.

Bladder Cancer
Pioglitazone is contraindicated in patients with active or previous bladder cancer and should be used with caution in patients with risk factors for bladder cancer as the European Medicines Agency have advised that there is a small increased risk of bladder cancer in patients treated with pioglitazone^{2, 4, 6}.

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. Whilst pioglitazone does not cause hypoglycaemia, the reduction in dietary intake means it is unlikely to have any benefit during the LRD.

  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. Busetto L, Dicker D, Aznar C et al. Practical Recommendations of the Obesity Management Task Force of the European Association for the Study of Obesity for the Post-Bariatric Surgery Medical Management. Obesity Facts 2017;10:597 – 632. DOI: 10.1159/000481825
4. Summary of Product Characteristics – Actos^® (pioglitazone) Tablets. Takeda UK Ltd. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text June 2019]
5. Pioglitazone Hydrochloride. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. Electronic version. Truven Health Analytics, Greenwood Village, Colorado, USA. http://www.micromedexsolutions.com [Accessed 1^st March 2021]
6.  Summary of Product Characteristics – Competact^® (pioglitazone + metformin) 15mg/850mg film-coated Tablets. Takeda UK Ltd. Accessed via www.medicines.org.uk 27/02/2021 [date of revision of the text October 2018]