Antimuscarinics for Urinary Disorders

  Issues for Surgery

Risk of increased urinary frequency, urgency and urge incontinence if omitted.

Solifenacin and tolterodine – risk of QT-interval prolongation if continued (see Interaction(s) with Common Anaesthetic Agents and Interaction(s) with other Common Medicines used in the Perioperative Period)

Combination product containing tamsulosin – risk of hypotension if continued (see Alpha-adrenoceptor Blockers monograph).

Combination product containing tamsulosin – risk of Intraoperative Floppy Iris Syndrome (IFIS) if continued prior to cataract surgery (see Alpha-adrenoceptor Blockers monograph).

  Advice in the Perioperative period

Elective and Emergency Surgery
Continue – including the following combination product:

• Solifenacin and tamsulosin (also see Alpha-adrenoceptor Blockers monograph)

Patients undergoing Cataract Surgery
For combination product containing tamsulosin – ensure the Ophthalmologist / Cataract Surgeon is aware the patient is taking an alpha-adrenoceptor blocker (see Further Information)¹.

Post-operative Advice
Restart post-operatively when next dose due.

Review if patient develops reduced gastrointestinal motility (e.g. ileus) post-operatively^{1, 2, 3, 4, 5, 6, 7, 8, 9, 10}.

Review appropriateness of continuing treatment if patient develops post-operative delirium².

Patients undergoing Overactive Bladder Surgery
Review the need for antimuscarinic post-operatively.

  Interaction(s) with Common Anaesthetic Agents

Antimuscarinic action
Antimuscarinic action may be additive with agents that also have antimuscarinic effects such as atropine and glycopyrronium^{2, 11}. 

Hypotension
For combination product containing tamsulosin see Alpha-adrenoceptor Blockers monograph.

QT-Interval Prolongation

Tolterodine prolongs the QT-interval and post-marketing reports indicate solifenacin may also prolong the QT-interval¹¹.  Co-administration with other medicines known to prolong the QT-interval must be based on careful assessment of the potential risks and benefits for each patient.

Anaesthetic agents that may be used in the perioperative period that are known to, or predicted to, prolong the QT-interval include^{2, 11}: -

• desflurane, isoflurane, sevoflurane – avoid for tolterodine; for solifenacin*
• thiopental (theoretical)**

*monitor ECG if concurrent use unavoidable; if risk factors for QT-prolongation are also present (increasing age, female sex, cardiac disease, and some metabolic disturbances e.g. hypokalaemia) use greater caution

**monitor ECG with concurrent use if risk factors for QT-prolongation are also present (increasing age, female sex, cardiac disease, and some metabolic disturbances e.g. hypokalaemia).

Whilst QT-interval prolongation has not been observed in patients taking fesoterodine the manufacturers advise caution with concomitant administration of medicines known to prolong the QT-interval⁴.

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

Prokinetics
Due to the effect of antimuscarinics on gastro-intestinal motility the effectiveness of prokinetic agents e.g. metoclopramide may be reduced^{4, 5, 6, 7, 8, 9, 12}. 

Antimuscarinic action
Antiemetics (for solifenacin and tolterodine also see QT-interval prolongation below)
Antimuscarinic action may be additive with antiemetics that also have antimuscarinic effects such as cyclizine, haloperidol, levomepromazine or prochlorperazine^{2, 11}.

Nefopam
Antimuscarinic action may be additive with nefopam which also has antimuscarinic effects^{2, 11}.

Antimicrobials (for solifenacin and tolterodine also see QT-interval prolongation below)
Clarithromycin (and to a lesser extent erythromycin) is predicted to increase the exposure of darifenacin, fesoterodine, oxybutynin, solifenacin and tolterodine^{2, 11}.  Whilst single surgical prophylactic doses should not pose a problem, consult product literature if continued post-operative treatment necessary as depending on the antimuscarinic concomitant use may be contraindicated or require dose reduction or monitoring for adverse effects.

Hypokalaemia
Dexamethasone and hydrocortisone may cause hypokalaemia (potentially increasing the risk of torsades de pointes with solifenacin or tolterodine)² – monitor potassium levels.  If hypokalaemia occurs, corrective action should be taken and QT-interval monitored.

QT-Interval Prolongation 
Tolterodine prolongs the QT-interval and post-marketing reports indicate solifenacin may also prolong the QT-interval¹¹.  Co-administration of solifenacin or tolterodine with medicines known to prolong the QT-interval must be based on a careful assessment of the potential risks and benefits for each patient since the risk of torsade de pointes may increase^{8, 11}. Whilst QT-interval prolongation has not been observed in patients taking fesoterodine the manufacturers advise caution with concomitant administration of medicines known to prolong the QT interval⁴.

Medicines that may be used in the perioperative period that are known to prolong the QT-interval include¹¹:-

• ciprofloxacin*
• clarithromycin – avoid with tolterodine, for solifenacin see Antimicrobials above
• domperidone – avoid
• droperidol – avoid with tolterodine, for solifenacin*
• erythromycin (particularly intravenous) – not recommended with tolterodine, for solifenacin see Antimicrobials above
• granisetron – avoid with tolterodine if risk factors, for solifenacin*
• haloperidol – avoid with tolterodine, for solifenacin if concurrent use unavoidable monitor ECG for all patients (risk further increased if risk factors present)
• loperamide*
• ondansetron – avoid with tolterodine, for solifenacin*
• prochlorperazine (theoretical risk)*

*monitor ECG with concurrent use if risk factors for QT-interval prolongation also present (increasing age, female sex, cardiac disease, and some metabolic disturbances e.g. hypokalaemia)

  Further Information

Intraoperative Floppy Iris Syndrome (IFIS)
For combination products containing tamsulosin see Alpha-adrenoceptor Blockers monograph.

  References

1. Summary of Product Characteristics – Vesomni® (solifenacin and tamsulosin) 6 mg/0.4 mg modified release tablets®. Astellas Pharma Ltd. Accessed via www.medicines.org.uk 03/02/2021 [date of revision of the text November 2019]
2. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://about.medicinescomplete.com [Accessed on 3^rd February 2021]
3. Summary of Product Characteristics – Emselex® (darifenacin) 7.5mg prolonged release tablets. Merus Labs Luxco II S.à R. L. Accessed via www.medicines.org.uk 06/11/2020 [date of revision of the text February 2019]
4. Summary of Product Characteristics – TOVIAZ® (fesoterodine) 4mg prolonged-release tablets. Pfizer Limited. Accessed via www.medicines.org.uk 06/11/2020 [date of revision of the text July 2019]
5. Summary of Product Characteristics – Kentera® (oxybutynin) transdermal patch. Orion Pharma (UK) Limited. Accessed via www.medicines.org.uk 06/11/2020 [date of revision of the text July 2014]
6. Summary of Product Characteristics – Lyrinel® (oxybutynin) XL 5mg prolonged release tablet. Janssen-Cilag Ltd Pharma (UK) Limited. Accessed via www.medicines.org.uk 06/11/2020 [date of revision of the text April 2020]
7. Summary of Product Characteristics – Solifenacin 5mg Film-Coated Tablets. Genus Pharmaceuticals. Accessed via www.medicines.org.uk 06/11/2020 [date of revision of the text July 2018]
8. Summary of Product Characteristics – Detrusitol® (tolterodine)XL 4mg. Upjohn UK Limited. Accessed via www.medicines.org.uk 06/11/2020 [date of revision of the text September 2020]
9. Summary of Product Characteristics – Detrunorm® (propiverine) 15mg Tablets. ADVANZ Pharma. Accessed via www.medicines.org.uk 03/02/2021 [date of revision of the text August 2014]
10. Summary of Product Characteristics – Urispas® (flavoxate) 200mg Film-coated Tablets. Recordati Pharmaceuticals Limited. Accessed via www.medicines.org.uk 03/02/2021 [date of revision of the text April 2020]
11. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://about.medicinescomplete.com [Accessed on 3^rd February 2021]
12.  Summary of Product Characteristics – Regurin® (trospium) 20mg Coated Tablets. Mylan. Accessed via www.medicines.org.uk 03/02/2021 [date of revision of the text January 2018]