What are the potential side effects of Azithromycin (macrolide antibiotic)?

Azithromycin Side Effects

Azithromycin commonly causes gastrointestinal side effects including diarrhea, nausea, abdominal pain, and vomiting, but these are typically mild to moderate and rarely require discontinuation of treatment. 1, 2

Common Side Effects

Gastrointestinal Effects

• Diarrhea/loose stools (4-7% of adults, up to 5.8% in children) 2
• Nausea (3-5% of adults) 2
• Abdominal pain (2-5% of adults) 2
• Vomiting (2-7% of adults) 2
• Dyspepsia and flatulence (1%) 2
• Anorexia and constipation (less than 1%) 1

Nervous System Effects

• Dizziness (1%) 2
• Headache (less than 1%) 2
• Vertigo and somnolence (less than 1%) 2

Allergic Reactions

• Rash and pruritus (less than 1%) 2
• Photosensitivity (less than 1%) 2
• Angioedema (rare) 2

General Effects

• Fatigue and asthenia (less than 1%) 2
• Paresthesia and malaise (less than 1%) 1

Serious Side Effects

Cardiovascular Effects

• QT prolongation and risk of torsades de pointes (rare) 1
• Palpitations and chest pain (less than 1%) 2
• Arrhythmias (rare) 1

Hepatobiliary Effects

• Hepatic dysfunction (rare) 1
• Cholestatic jaundice (rare) 2, 3

Severe Skin Reactions

• Erythema multiforme (rare) 1
• Stevens-Johnson syndrome (rare) 1
• Toxic epidermal necrolysis (rare) 1

Other Serious Effects

• Pseudomembranous colitis (rare) 1
• Hearing loss, deafness, tinnitus (rare) 1
• Anaphylaxis (rare) 1

Special Considerations

Antimicrobial Resistance

• Long-term use may increase antimicrobial resistance to macrolides 1
• Resistance rates can reach 48.7% with prolonged use but may decrease after discontinuation 1

Drug Interactions

• Avoid concomitant use with aluminum or magnesium-containing antacids as they reduce azithromycin absorption 1
• Monitor patients when used with drugs metabolized by cytochrome P450 enzyme system 1
• Potential interactions with digoxin, triazolam, and ergot alkaloids 1

Contraindications

• Hypersensitivity to azithromycin, erythromycin, any macrolide, or ketolide 1
• History of cholestatic jaundice/hepatic dysfunction associated with previous azithromycin use 1

Risk Mitigation Strategies

Cardiac Risk Assessment

• Obtain ECG before initiating therapy in patients with cardiac risk factors 1
• Avoid in patients with known prolonged QT interval (>450ms for men, >470ms for women) 1
• Screen for concurrent QT-prolonging medications 1
• Consider repeat ECG one month after initiating therapy 1

Patient Monitoring

• Warn patients about potential gastrointestinal side effects 1
• Monitor liver function in patients with pre-existing liver disease 1
• Consider dose reduction if GI side effects are problematic 1

Population-Specific Considerations

Pediatric Patients

• Generally well-tolerated in children 4
• Side effect profile similar to adults but with different incidence rates 2
• Single high-dose regimens may have more side effects but are still well-tolerated 4

Pregnancy and Lactation

• FDA Pregnancy Category B 1
• Distributed into breast milk; use with caution in nursing women 1

Azithromycin has a favorable safety profile compared to other macrolides like erythromycin, with fewer gastrointestinal side effects and drug interactions 5, 6. Most adverse effects are mild and self-limiting, with discontinuation rates due to side effects being approximately 0.7% in clinical trials 2.