(Note: This is not an exhaustive list – consult the BNF or
Summary of Product Characteristics for more in-depth
information on adverse effects).
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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
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
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
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
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
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).
HHE 2019 | hospitalhealthcare.com
1 National Institutes of Health.
Drug Record. Macrolide
(accessed August 2019).
2 National Institute for Health
and Care Excellence. Cystic
fibrosis: long-term azithromycin.
Evidence summary ESOUM37.
3 British Thoracic Society.
Long-term macrolide guideline
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.
5 Albert RK et al. Azithromycin
for prevention of exacerbations
of COPD. N Engl J Med
6 National Institute for Health
and Care Excellence. NG115.
Chronic obstructive pulmonary
disease in over 16s: diagnosis
and management. December
ng115 (accessed August 2019).
7 British National Formulary