Long-acting Beta2 Adrenoreceptor Agonists (Oral and Inhaled)



Bambuterol (Bambec®), Formoterol (Oxis®), Indacaterol (Onbrez®), Olodaterol (Striverdi®), Salmeterol (Serevent®), Vilanterol (only available as combination product)

 Combination products include AirFluSal®, Anoro®, Atectura®, Bevespi®, ] Duaklir®, DuoResp®, Enerzair®, Fobumix®, Flutiform®, Fostair®, Luforbec®, Relvar®, Seretide®, Spiolto®, Symbicort®, Trelegy®, Trimbow®, Trixeo®, Ultibro® but this list is not intended to be exhaustive

  Issues for Surgery


For asthma and chronic obstructive pulmonary disease (COPD) – increased risk of exacerbation if omitted.


  Advice in the Perioperative period


Elective and Emergency Surgery
Continue (including combination products). 

There are numerous inhaled preparations which contain long acting beta2 adrenoceptor agonists, either as single agents or in combination products with corticosteroids and / or antimuscarinics – all of these can be continued pre-operatively.  Check active ingredients of currently available preparations in British National Formulary and see also Corticosteroids (Inhaled, Nebulised and Intranasal) monograph and Inhaled Antimuscarinics monograph if applicable.

Advise patients who are prescribed regular long acting beta2 adrenoceptor agonists but do not usually take them regularly to do so pre-operatively to optimise disease control prior to anaesthesia.

Confirm the inhaler brand, strength and device with the patient.


Post-operative Advice
Restart post-operatively as soon as next dose is due.

For patients taking bambuterol tablets
Monitor renal function – dose reduction may be necessary if renal function is impaired post-operatively1 (consult current product literature).

If swallowing difficulties or unreliable oral absorption post-operatively consider inhaled administration of long-acting beta2 adrenoceptor agonist, or rescue doses of short-acting beta2 adrenoceptor agonist.


  Interaction(s) with Common Anaesthetic Agents


Halogenated Anaesthetics
Long-acting beta2 adrenoceptor agonists may cause hypokalaemia1, 2, 3, 4, 5, 6, 7. Concomitant use with medications that prolong the QT-interval (e.g. desflurane, isoflurane, sevoflurane and possibly thiopental) increases the risk of torsades de pointes1, 2, 3, 4, 5.  Monitor serum potassium and QT-interval with concomitant treatment. 

Neuromuscular Blocking Drugs (NMBDs)
Bambuterol, but not other long-acting beta2 adrenoceptor agonists, can prolong the recovery time from neuromuscular blockade with suxamethonium and mivacurium1, 2, 3.  The effect appears to be related to both the dose and the timing of bambuterol administration2; the manufacturer suggests this interaction should be considered for other NMBDs metabolised by plasma cholinesterase3.  However, the interaction is thought to only be clinically significant in patients with abnormal plasma cholinesterase activity2


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


Corticosteroids
Dexamethasone and hydrocortisone may cause hypokalaemia which would potentiate any long acting betaadrenoceptor agonist mediated hypokalaemia1, 2, 3, 4, 5, 6, 7. Hypokalaemia increases the risk of torsades de pointes with medications which prolong the QT-interval e.g. antiemetics (domperidone, droperdiol, granisetron, haloperidol, ondansetron and possibly prochlorperazine), antimicrobials (ciprofloxacin, clarithromycin, erythromycin) and loperamide1, 2.

Macrolides (see also Corticosteroids above)
Clarithromycin, a potent CYP3A4 inhibitor, is expected to markedly increase the exposure to inhaled salmeterol but not other long-acting beta2 adrenoceptor agonists1, 2, 7.  Erythromycin, however, is not expected to interact with salmeterol to a clinically significant extent2.  The manufacturer of salmeterol advises avoid concomitant treatment with potent CYP3A4 inhibitors due to the risk of QT-interval prolongation2, 7; however, as clarithromycin is an appropriate treatment for COPD exacerbations the combination is likely to be commonly used. Bear the interaction in mind if QT-interval prolongation is noted on an electrocardiogram (ECG)


  Further Information


None relevant.

 

  References



  1. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://about.medicinescomplete.com [Accessed on 27th June 2021]
  2. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://about.medicinescomplete.com [Accessed on 27th June 2021]
  3. Summary of Product Characteristics – Bambec® (bambuterol) Tablets 10mg. AstraZeneca UK Limited. Accessed via www.medicines.org.uk 27/06/2021 [date of revision of the text January 2017]
  4. Summary of Product Characteristics – Oxis® (formoterol) Turbohaler 6, inhalation powder. AstraZeneca UK Limited. Accessed via www.medicines.org.uk 27/06/2021 [date of revision of the text March 2020]
  5. Summary of Product Characteristics – Striverdi® (olodaterol) Respimat 2.5 microgram, solution for inhalation. Boehringer Ingelheim Limited. Accessed via www.medicines.org.uk 27/06/2021 [date of revision of the text January 2021]
  6. Summary of Product Characteristics – Onbrez® (indacaterol) Breezhaler 150 microgram inhalation powder, hard capsules. Novartis Pharmaceuticals UK Limited. Accessed via www.medicines.org.uk 27/06/2021 [date of revision of the text January 2021]
  7. Summary of Product Characteristics – Serevent® (salmeterol) Accuhaler. GlaxoSmithKline UK. Accessed via www.medicines.org.uk 27/06/2021 [date of revision of the text November 2019]