HHE Respiratory 2019 | Page 23

(Note: This is not an exhaustive list – consult the BNF or Summary of Product Characteristics for more in-depth information on adverse effects). Quote here kpkp pk pkpk pk ppkp pk pkpk pkpk pk kpkp pk pkpk pk ppkp pk pkpk pkpk pk kpkp pk pkpk pk ppkp pk pkpk pkpk pk kpkp pk pkpk pk ppkp pk pkpk pkpk pk kpkp Implementation of guidance The BTS macrolide guidelines should be used in conjunction with the relevant disease guideline (for example, with BTS bronchiectasis guide). Holistic care (both pharmacological and non- pharmacological) should be optimised first, ensuring that patients are being treated appropriate to disease stage/severity and that individual circumstances have been taken into account. This includes comorbidities, polypharmacy, addressing non-adherence, and ensuring smoking cessation before considering macrolides. Prior to macrolide initiation, in-depth patient consultation and counselling are required to present treatment risks and benefits, discuss side effects, review potential or actual interactions (especially during exacerbation) and to manage expectations of therapy. Azithromycin is principally cleared by the liver so should be used with caution in significant liver disease. It can be taken with or without food at any time of day but indigestion remedies should be avoided for two hours before the azithromycin dose and if taking as a coated tablet, must be swallowed whole not chewed or crushed. Electrolyte disturbances and medicines such as amiodarone, fluoroquinolones and some antidepressants/antipsychotics may potentiate QT prolongation. 7 Practical considerations The guideline will be published with an associated generic patient information leaflet that can be locally adapted and which will include the basic information to cover during counselling. Close communication will be necessary across primary, secondary/tertiary care to ensure clear shared care and follow up plans are developed and followed, ensuring that prescribing and monitoring are ongoing. Close liaison with the healthcare team (in particular with pharmacists) is also necessary to ensure recognition of adverse effects and manifestation of any medicine interactions (recognition more so during an exacerbation where acute therapies may interact). This is especially important during the initial phase after starting therapy when patients may present to primary care providers or acute services. Increased discussion and rapport with patients will support the increased pharmacovigilance required and also for potential Medicines and Healthcare products Regulatory Authority ‘Yellow card’ reporting. Antimicrobial stewardship is also necessary. What we do not know The use of macrolides during disease exacerbation is unclear and evidence for this is lacking. It may be appropriate to hold the macrolide during exacerbation, for example, in bronchiectasis where the patient may require intravenous antibiotics. Some experts believe that patients should not be treated with full dose macrolide during an exacerbation if on prophylaxis, however some clinicians acutely increase the dose of the same agent. Current practice varies widely across the UK. Limitations of the available macrolide evidence mean we do not have any data on long term effect, not only in terms of safety and clinical effect but also antimicrobial resistance and the microbiome. There is no long-term data on use beyond one year or head-to-head comparison between the different macrolides to show superiority of one over another. The guidelines raise relevant research questions such as: which disease phenotypes/ subgroups would gain most benefit from macrolides? Is seasonal use of macrolides or rotation with other antibiotics beneficial? What is the potential for use in a younger population (study populations were older)? Also, is the threshold for use that has been suggested appropriate? Would this need to be tightened or relaxed? Further research will inform these questions. Conclusions The new BTS macrolide guidelines will provide much needed guidance for the use of macrolides as immunomodulatory agents across various respiratory disease areas. However, guidelines are a guide and common sense applies – practitioners should ‘use clinical judgment, knowledge and expertise’ before initiation, taking into account individual patient needs and choice. Macrolides appear to reduce inflammation, bronchial hyperreactivity and exacerbations and may affect other parameters too. They are not a magic bullet – all other treatments should be optimised first and they should be avoided in current smokers (ineffective). 23 HHE 2019 | hospitalhealthcare.com References 1 National Institutes of Health. Drug Record. Macrolide antibiotics. https://livertox.nih. gov/MacrolideAntibiotics.htm (accessed August 2019). 2 National Institute for Health and Care Excellence. Cystic fibrosis: long-term azithromycin. Evidence summary ESOUM37. www.nice.org.uk/advice/ esuom37/chapter/Key-points- from-the-evidence (accessed August 2019). 3 British Thoracic Society. Long-term macrolide guideline 2019. www.brit-thoracic.org. uk/quality-improvement/ guidelines/long-term-macrolide- use/ (accessed August 2019). 4 Gibson PG et al. Effects of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES) a randomised, double blind, placebo- controlled trial. Lancet. 2017;390(10095):659–68. 5 Albert RK et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med 2011;365:689–98. 6 National Institute for Health and Care Excellence. NG115. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. December 2018 www.nice.org.uk/guidance/ ng115 (accessed August 2019). 7 British National Formulary https://bnf.nice.org.uk/ (accessed August 2019).