AZITHROMYCIN
Clinical safety rating: safe
Nelfinavir increases azithromycin levels May potentiate the effects of warfarin and digoxin May cause QT prolongation and subsequent arrhythmias.
Binds to the 50S ribosomal subunit of susceptible bacteria, inhibiting mRNA translation and thus protein synthesis. Exhibits concentration-dependent bactericidal activity.
| Metabolism | Primarily hepatic, not via cytochrome P450 system. Partially metabolized to inactive metabolites. Eliminated via biliary excretion and renal excretion (<15% unchanged). |
| Excretion | Primarily biliary/fecal (approx. 50% unchanged); renal excretion accounts for about 12% of the dose. |
| Half-life | Terminal half-life of approximately 68 hours (range 35–96 h) after multiple doses, allowing once-daily dosing and a prolonged post-antibiotic effect. |
| Protein binding | 7–51% (concentration-dependent); primarily binds to albumin. |
| Volume of Distribution | 31.1 L/kg (range 23–50 L/kg), indicating extensive tissue penetration and sequestration (e.g., WBCs, liver, lung). |
| Bioavailability | Oral: 37–40% (fasting); food may decrease absorption by ~50%. |
| Onset of Action | Oral: 2–4 hours for clinical effect; IV: within 1 hour. |
| Duration of Action | 24 hours for susceptible organisms; tissue concentrations persist for 4–5 days after a 5-day course, enabling short-course therapy. |
| Molecular Weight | 748.99 |
500 mg orally once daily for 3 days, or 500 mg IV once daily for at least 2 days followed by 500 mg orally to complete 7-10 days of therapy for community-acquired pneumonia. For other indications, typical adult dose is 500 mg orally on day 1 then 250 mg orally once daily on days 2-5.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for GFR ≥10 mL/min. For GFR <10 mL/min, caution advised; no specific dose recommendation, consider alternative agent. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh class A and B). Contraindicated in severe hepatic impairment (Child-Pugh class C). |
| Pediatric use | For otitis media and community-acquired pneumonia: 10 mg/kg orally or IV on day 1 (max 500 mg), then 5 mg/kg (max 250 mg) once daily on days 2-5. For pharyngitis/tonsillitis: 12 mg/kg orally once daily for 5 days (max 500 mg/day). |
| Geriatric use | No specific dose adjustment required; use same dosing as younger adults. Monitor renal function due to age-related decline, but no modification needed unless severe renal impairment (CrCl <10 mL/min). |
| 1st trimester | Azithromycin crosses the placenta. Limited human data do not show an increased risk of major birth defects or miscarriage. Use only if clearly needed. |
| 2nd trimester | Considered safe; no evidence of fetal harm in animal studies. Use when benefit outweighs risk. |
| 3rd trimester | Generally safe; no known adverse fetal effects. Use for indicated infections. |
Clinical note
Nelfinavir increases azithromycin levels May potentiate the effects of warfarin and digoxin May cause QT prolongation and subsequent arrhythmias.
| FDA category | Human |
| Placental transfer | Azithromycin crosses the placenta. Based on studies, cord blood concentrations are approximately 0.5-2% of maternal serum levels, indicating moderate transfer. |
| Breastfeeding |
■ FDA Black Box Warning
None.
| Common Effects | Diarrhea |
| Serious Effects |
Hypersensitivity to azithromycin, erythromycin, or any macrolide antibioticHistory of cholestatic jaundice or hepatic dysfunction associated with prior azithromycin use
| Precautions | Hepatotoxicity: hepatitis, cholestatic jaundice, hepatic necrosis, hepatic failure, QT prolongation and torsades de pointes (especially with concurrent use of other QT-prolonging agents, electrolyte abnormalities, bradycardia, or structural heart disease), Clostridioides difficile-associated diarrhea (CDAD), Aggravation of myasthenia gravis, Severe allergic reactions (angioedema, anaphylaxis, Stevens-Johnson syndrome), Infantile hypertrophic pyloric stenosis (IHPS) in neonates following oral azithromycin, Use in pregnancy: category B; avoid during breastfeeding due to potential for disruption of infant gut flora |
| Food/Dietary |
Loading safety data…
| Azithromycin is excreted into breast milk in low amounts. The relative infant dose is approximately 0.4-0.6% of maternal weight-adjusted dose. It is considered compatible with breastfeeding; however, monitor infant for diarrhea or rash. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | FDA Category B. No evidence of teratogenicity in animal studies; limited human data show no increased risk of major malformations. First trimester: No significant association with birth defects. Second/third trimester: No reported fetal harm from short-term use for infections like chorioamnionitis. Use only if clearly needed. |
| Fetal Monitoring | No specific routine monitoring required. For prolonged therapy, consider liver function tests and ECG monitoring due to risk of QT prolongation (rare). In pregnancy, monitor for signs of maternal infection resolution and fetal heart rate if used for intra-amniotic infection. |
| Fertility Effects | No known adverse effects on fertility in animal or human studies. May be used for sexually transmitted infections that could impair fertility (e.g., chlamydia), potentially improving reproductive outcomes. |
| Food does not significantly affect absorption; can be taken with or without food. However, avoiding high-fat meals may reduce minor GI side effects. No known specific food interactions. |
| Clinical Pearls | Monitor for QTc prolongation especially in patients with preexisting cardiac conditions or those on other QT-prolonging drugs. Azithromycin has a long half-life (68 hours) allowing for shorter treatment courses. Use with caution in hepatic impairment; consider alternative in severe liver disease. Not recommended for pneumonia in patients with bacteremia due to increased mortality risk. Administer on an empty stomach or with food if GI upset occurs; however, absorption is unaffected by food. |
| Patient Advice | Take exactly as prescribed; do not skip doses or stop early even if you feel better. · Do not take antacids containing aluminum or magnesium within 2 hours before or after this medication. · Report any signs of liver problems (nausea, vomiting, dark urine, jaundice) or severe diarrhea (watery or bloody) immediately. · Azithromycin may cause dizziness; avoid driving or operating machinery until you know how it affects you. · Inform your doctor if you have a history of QT prolongation, heart rhythm problems, or electrolyte imbalances. · Store at room temperature away from moisture and heat; discard any unused liquid after 10 days. |