Long-term Macrolide Antibiotics

In respiratory conditions other than cystic fibrosis (CF) or non-CF bronchiectasis

Evidence supporting use of long-term macrolide antibiotics for the management of respiratory conditions other than CF or non-CF bronchiectasis (such as Chronic Obstructive Pulmonary Disease (COPD)) is relatively weak; however it is unlikely further large scale studies will be undertaken.

The following criteria has been agreed between local Respiratory specialists and the NHS Tayside Antimicrobial Management Group (AMG):

The decision to commence long-term macrolides should be made by secondary care respiratory specialists. A 3 month trial will be overseen by a respiratory specialist. The decision to continue the macrolide antibiotic beyond 3 months will be taken on a case by case basis and the patient will undergo a full assessment including monitoring of exacerbation frequency, exercise tolerance, pulmonary function testing, acute antibiotic prescriptions, and quality of life.

Clarithromycin 250mg daily is the macrolide antibiotic usually used and if it is to be continued after the initial 3 month trial period, this is most often to be indefinitely. After the 3 month trial and full patient assessment there is no routine review of patients by secondary care, unless other aspects of the patient’s condition require this.

Drug interactions with macrolide antibiotics

When secondary care respiratory specialists are initiating long-term macrolides, consideration should be given to the patient’s existing medication and whether any drug interactions may occur. Specialists should provide advice to GPs where this is an issue and a decision has been made to commence a long-term macrolide antibiotic. Most macrolides inhibit the cytochrome P450 isoenzyme CYP3A4, common interactions with macrolides include (but not exclusively):

Atorvastatin and simvastatin (increased plasma concentration of statin and increased risk of serious adverse reactions such as myopathy or rhabdomyolysis). Pravastatin and rosuvastatin do not appear to be metabolised by the cytochrome P450 system, and are alternatives in patients on clarithromycin. Erythromycin reduces the plasma concentration of rosuvastatin. See Tayside Prescriber, Issue 102, May 2009 for further information on statin interactions. Calcium channel blockers (possible increased plasma levels of calcium channel blockers). Coumarins (anticoagulant effect may be enhanced). Digoxin (increased plasma concentration of digoxin and increased risk of toxicity). Drugs that prolong the QT interval (erythromycin has a high risk of causing QT prolongation and clarithromycin has some risk). Concurrent use of more than one drug that prolongs the QT interval increases the risk of torsade de pointes, which may lead to life-threatening ventricular arrhythmias. Proton pump inhibitors (increased levels of esomeprazole, lansoprazole and omeprazole with clarithromycin. Erythromycin may raise omeprazole levels. Proton pump inhibitors may also increase serum levels of clarithromycin). Theophylline (increased plasma concentration of theophylline). Erythromycin levels may be reduced by theophylline.

For further information on drug interactions see BNF.

In cystic fibrosis (CF) or non-CF bronchiectasis

For information on the role of long-term antibiotics in non-CF bronchiectasis see BTS guideline. For further information on antibiotic treatment in cystic fibrosis see Adult CF Antibiotic Guideline.