19. Adverse events across all studies.
| Study ID, drug, dose, schedule (weeks' duration) | Adverse events | ||
| Antibiotic (n) | Comparator (n) | Reporting of exacerbations as AEs | |
| Albert 2011, AZM, 250 mg once daily (52) | Discontinuation due to: audiogram‐confirmed hearing decrement (142), tinnitus (4), gastrointestinal tract (11), QTc prolongation (6), allergic reaction (5), abnormal laboratory test (4), other (10) | Discontinuation due to: audiogram‐confirmed hearing decrement, tinnitus (4), neoplasm (3), GI tract (6), QTc prolongation (4), allergic reaction (8), abnormal laboratory test (3), other (17) | Exacerbation was not reported as an AE |
| He 2010, ERY, 125 mg 3 times daily (26) | Discontinued due to: abdominal pain (1), complication of left heart failure (1) | Discontinued due to: respiratory insufficiency (2), other (1) | Exacerbation was not reported as an AE |
| Seemungal 2008 ERY, 250 mg twice daily (52) | Upper gastrointestinal (5), lower gastrointestinal (3), rash (3), other (3) | Upper gastrointestinal (5), lower gastrointestinal (3), rash (2), other (2) | Exacerbation was not reported as an AE |
| Sethi 2010, MOX, 400 mg once daily (5 days every 8 weeks) (48) | Cardiac disorders (3), gastrointestinal (diarrhoea, nausea, vomiting) (27), general disorders/administration site conditions (4), asthenia (3), immune system disorders (4), hypersensitivity (3), infections and infestations (5), musculoskeletal and connective tissue disorders (3), nervous system disorders (6), dizziness (3), respiratory, thoracic and mediastinal disorders (8), dyspnoea (4), skin and subcutaneous tissue disorders (5), AEs leading to discontinuation (26) | Cardiac disorders (1), gastrointestinal (diarrhoea, nausea, vomiting) (4), general disorders and administration site conditions (2), asthenia (0), hypersensitivity (0), infections and infestations (3), musculoskeletal and connective tissue disorders (1), nervous system disorders (4), dizziness (1), respiratory, thoracic, and mediastinal disorders (0), dyspnoea (0), skin and subcutaneous tissue disorders (5), AEs leading to discontinuation (16) | Exacerbation was not reported as an AE |
| Shafuddin 2015, ROX 300 mg once daily + DOX 100 mg once daily; or ROX 300 mg once daily (12) | Roxithromycin + doxycycline: nausea (12), diarrhoea (2), headache (4), abdominal pain (3), reflux (2), vomiting (1), abnormal liver function (1), abnormal ECG (1), rash (1), dyspnoea (0), dizziness (0), oral candidiasis (0), gastrointestinal upset (0) Roxithromycin alone: nausea (13), diarrhoea (3), headache (1), abdominal pain (1), reflux (1), vomiting (3), abnormal liver function (2), abnormal ECG (0), rash (1), dyspnoea (1), dizziness (4), oral candidiasis (2), gastrointestinal upset (2) |
Nausea (1), diarrhoea (1), headache (1), abdominal pain (1), reflux (0), vomiting (0), abnormal liver function (0), abnormal ECG (0), dyspnoea (2), dizziness (0), oral candidiasis (3), gastrointestinal upset (2) | Exacerbation was not reported as an AE |
| Simpson 2014, AZM, 250 mg once daily (12) | Diarrhoea (1), abdominal pain (0), nausea (0), vomiting (0), fever (0), headache (0), rash (0), hearing loss (0), other (10) | Diarrhoea (5), abdominal pain (0), nausea (0), vomiting (0), fever (0), headache (0), rash (0), hearing loss (0), other (9) | Exacerbation was not reported as an AE |
| Tan 2016, ERY, 125 mg 3 times daily (52) | Withdrawal due to: abdominal pain (1), left‐sided heart failure (1) | Withdrawal due to: respiratory insufficiency (2), unknown (1) | Exacerbation was not an outcome in the study |
| Uzun 2014, AZM, 500 mg once daily 3 times per week (52) | Diarrhoea (9), nausea/vomiting (3), other (4) | Diarrhoea (1), nausea/vomiting (2), other (7) | Exacerbaiton was not reported as an AE. 2 fatal SAEs occurred due to COPD respiratory failure, which were counted in the mortality outcome |
| Vermeersch 2019, AZM, 500 mg once daily (for first 3 days), AZM 250 mg every 2 days for rest of treatment duration (13) | Diarrhoea (20), nausea (12), anorexia (9), hearing loss (1), syncope (1) | Diarrhoea (15), nausea (11), anorexia (8), hearing loss (6), syncope (2) | Exacerbation was not reported as an AE |
Abbreviations
AE: adverse event;AZM: azithromycin; DOX: doxycyline; ECG: electrocardiogram; ERY: erythromycin; MOX: moxifloxacin; NR: not reported; QTc: corrected QT interval; ROX: roxithromycin; SAE: serious adverse event.