Brands of salmeterol
This list is not intended to be exhaustive.
Inhaled: Salmeterol: Serevent®
Inhaled (combination products, with corticosteroid): AirFluSal®, Avenor®, Combisal®, Fixkoh®, Fusacomb®, Sereflo®, Seretide®, Sirdupla®, Soltel®, Stalpex®
Issues for surgery
For asthma and chronic obstructive pulmonary disease (COPD) – increased risk of exacerbation if omitted.
For combination products containing corticosteroids – potential increased risk of acute adrenal insufficiency (e.g. severe hypotension, tiredness and weakness, confusion, psychosis, tachycardia) if omitted – see Further information.
Advice in the perioperative period
Elective and emergency surgery
Continue (including combination products).
There are numerous inhaled preparations which contain salmeterol, either as a single agent or in combination products with corticosteroids – all of these can be continued pre-operatively. Check active ingredients of currently available preparations in British National Formulary.
Advise patients who are prescribed regular salmeterol inhaled preparations 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.
Interactions with common anaesthetic agents
Halogenated anaesthetics
Salmeterol may cause hypokalaemia. Concomitant use with medications that prolong the QT-interval (e.g. desflurane, isoflurane, sevoflurane and possibly thiopental) increases the risk of torsades de pointes. This risk may be greater with inhaled combination products also containing a corticosteroid. Monitor serum potassium and QT-interval with concomitant treatment.
Interactions with other common medicines used in the perioperative period
Corticosteroids
Dexamethasone and hydrocortisone may cause hypokalaemia which would potentiate any salmeterol-mediated hypokalaemia. This risk may be greater with inhaled combination products also containing a corticosteroid. Hypokalaemia increases the risk of torsades de pointes with medications which prolong the QT-interval e.g. antiemetics (domperidone, droperidol, granisetron, haloperidol, ondansetron and possibly prochlorperazine), antimicrobials (ciprofloxacin, clarithromycin, erythromycin) and loperamide.
Macrolides
See also Corticosteroids above.
Clarithromycin, a potent CYP3A4 inhibitor, is expected to markedly increase the exposure to inhaled salmeterol. Erythromycin, however, is not expected to interact with salmeterol to a clinically significant extent. The manufacturer of salmeterol advises avoid concomitant treatment with potent CYP3A4 inhibitors due to the risk of QT-interval prolongation; 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
Products containing corticosteroids
Systemic absorption
Although not intended it is possible that inhaled administration of corticosteroids may result in systemic absorption, particularly if high doses are used or with prolonged treatment.
Adrenal suppression, perioperative stress and corticosteroid replacement
Whilst adrenal insufficiency is most common in patients taking systemic corticosteroids there is evidence that this can occur with chronic corticosteroid administration via other routes. High doses and prolonged treatment duration results in increased systemic absorption and therefore risk of adrenal insufficiency; however, there is no dose, administration route or treatment duration for which the risk of adrenal insufficiency can safely be excluded. Meta-analysis indicates incidence of adrenal insufficiency is lower in patients prescribed intranasal (4.2%) and inhaled (7.8%) corticosteroids compared to oral (48.7%) and intra-articular (52.2%) corticosteroids, although this incidence is likely to be higher in individuals receiving corticosteroids by multiple routes.
The possibility of adrenal insufficiency should be considered in individuals taking inhaled or intranasal corticosteroids who fail to improve as anticipated post-operatively. Current evidence on the necessity of administering perioperative stress-dose steroids for patients with suspected secondary adrenal insufficiency is inadequate to either support or refute this practice; however, if adrenal insufficiency is suspected, corticosteroid replacement appears to carry minimal risk compared with the risk of adrenal crisis.
References
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://about.medicinescomplete.com [Accessed on 27th June 2021]
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://about.medicinescomplete.com [Accessed on 27th June 2021]
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]