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

Azithromycin Side Effects

The most common side effects of azithromycin are gastrointestinal disturbances including diarrhea (4-5%), nausea (3%), abdominal pain (2-3%), and vomiting (2%), which are generally mild to moderate and rarely lead to discontinuation of therapy. 1

Common Side Effects

Gastrointestinal Effects

• Diarrhea/loose stools (4-5% in adults, up to 7% with single 1g dose)
• Nausea (3% in adults, up to 5% with single 1g dose)
• Abdominal pain (2-3% in adults, up to 5% with single 1g dose)
• Vomiting (less than 2% in adults)
• Dyspepsia (1%)
• Flatulence (<1%)

These gastrointestinal side effects are more frequent with azithromycin than with placebo but occur less frequently than with erythromycin 2, 1.

Other Common Side Effects (occurring in <1% of patients)

• Headache
• Dizziness
• Fatigue
• Rash/pruritus

Serious but Rare Side Effects

Cardiac Effects

• QT interval prolongation
• Torsades de pointes (rare but potentially fatal)

Patients at increased risk for cardiac side effects include:

• Elderly patients (>80 years)
• Patients with existing heart disease
• Those taking other QT-prolonging medications
• Patients with electrolyte abnormalities (particularly hypokalemia)
• Patients with bradycardia
• Those with genetic predisposition to QT prolongation 2

Hepatic Effects

• Elevated liver enzymes (ALT/AST increases in approximately 1.5-1.7% of patients)
• Cholestatic jaundice (rare)
• Hepatotoxicity (rare) 1, 3

Allergic Reactions

• Rash
• Angioedema (rare)
• Anaphylaxis (very rare but potentially fatal) 1

Other Serious Side Effects

• Infantile hypertrophic pyloric stenosis (in infants <1 month, though azithromycin has lower risk than erythromycin) 2
• Ototoxicity (hearing loss, tinnitus) - reported in long-term use 2, 1
• Pseudomembranous colitis/C. difficile-associated diarrhea 1

Drug Interactions

Azithromycin has fewer drug interactions than other macrolides due to its limited metabolism by the cytochrome P450 system, but important interactions include:

• Antacids containing aluminum or magnesium: Reduce absorption of azithromycin (separate administration times) 2
• Drugs metabolized by cytochrome P450: Potential interactions requiring monitoring (e.g., digoxin, triazolam, ergot alkaloids) 2
• QT-prolonging medications: Increased risk of cardiac arrhythmias when combined 2

Special Populations

Pediatric Patients

• Side effect profile similar to adults but with different incidence rates
• Most common side effects in children: diarrhea (1.8-5.8%), abdominal pain (1.2-3.4%), vomiting (1.1-5.6%), nausea (0.4-1.9%), and rash (0.4-1.6%) 1, 4

Pregnancy

• FDA Pregnancy Category B drug 2

Hepatic Impairment

• Use with caution in patients with impaired hepatic function 2, 1

Antimicrobial Resistance Concerns

Long-term azithromycin use may increase antimicrobial resistance to macrolides. Studies have shown up to 48.7% of patients receiving azithromycin developed macrolide-resistant streptococci, compared to 28.6% receiving placebo 2.

Clinical Recommendations

1. Monitor patients for gastrointestinal side effects, which are usually mild and self-limiting
2. Perform ECG before initiating therapy in patients with cardiac risk factors
3. Consider ECG monitoring one month after starting long-term therapy to check for QT prolongation
4. Use caution when prescribing to patients with hepatic impairment
5. Avoid co-administration with aluminum or magnesium-containing antacids
6. Monitor for signs of superinfection during therapy

Azithromycin generally has a better safety profile than erythromycin, with fewer gastrointestinal side effects and drug interactions, making it a preferred macrolide for many indications 3.