Azithromycin
Azithromycin
Generic Name
Azithromycin
Drug Class
** Macrolide
Mechanism
Azithromycin inhibits bacterial protein synthesis by reversible binding to the 50S ribosomal subunit.
• Blocks translocation, stalling the elongation step.
• Broadly active against Gram‑positive cocci (*Streptococcus pyogenes*, *Staphylococcus aureus*) and many Gram‑negative and atypical organisms (*Mycoplasma pneumoniae*, *Chlamydia trachomatis*, *Legionella pneumophila*).
• A post‑antibiotic effect (PAE) of ~2–4 h contributes to its prolonged efficacy.
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Pharmacokinetics
| Parameter | Value |
| Absorption | Oral bioavailability ~37 % (food reduces absorption by ~30 %). |
| Distribution | Highly tissue‑penetrant; achieved concentrations up to 10–100× plasma in lungs, macrophages, and epithelial cells. |
| Half‑life | Terminal half‑life ~68 h (due to intracellular release). |
| Metabolism | Minimal hepatic metabolism; primarily unchanged. |
| Elimination | Renal excretion (~30 % of dose). |
| Special Populations | Renal function <10 mL/min: dosing interval extends to 7 days/1 month; hepatic dysfunction has minimal impact on clearance. |
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Indications
- Upper & lower respiratory tract infections: community‑acquired pneumonia, sinusitis, pharyngitis (except severe strep).
- Skin & soft‑tissue infections: acute bacterial skin infections, folliculitis, acne vulgaris.
- Sexually transmitted infections: *Chlamydia trachomatis* (1 g single dose), *Neisseria gonorrhoeae* (when amenable to macrolide‑based therapy).
- Pulmonary tuberculosis (as adjunct): short‑course azithro–rifampin regimens.
- Others: pertussis, dog and cat lick dermatitis, atypical infections (Legionella, Mycoplasma).
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Contraindications
| Category | Key Points |
| Contraindications | Severe penicillin/macrolide hypersensitivity, active severe hepatic disease (e.g., fulminant hepatic failure). |
| Warnings |
• QT‑interval prolongation – caution in patients with congenital long QT, arrhythmias, or on concomitant QT‑prolonging drugs. • Drug–drug interactions – inhibit CYP3A4; can elevate levels of simvastatin, carbamazepine, digoxin. • Hepatotoxicity – rare cholestatic injury; monitor LFTs in high‑dose regimens. • C. difficile infection risk – not first‑line for colonic disease. |
| Precautions |
• Adjust dose/interval in renal impairment. • Avoid in patients on life‑supporting drugs (e.g., digoxin) unless monitoring. |
| Pregnancy/Nursing | Category B. Use only if benefits outweigh risks; avoid prolonged therapy during pregnancy. |
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Dosing
| Situation | Regimen | Comments |
| Adults & Adolescents |
• Infectious diseases: 500 mg oral once daily × 3 days, or 500 mg day 1 then 250 mg days 2‑5. • Acne: 500 mg PO once daily for 3–4 weeks. | 1‑day single dose (750 mg) for *Chlamydia trachomatis*. |
| Children (<11 yrs) | 10 mg/kg/day PO (max 500 mg) for 5 days or 15 mg/kg on day 1 then 10 mg/kg days 2‑5. | Weight‑based; not routinely used for infants <6 mo. |
| Renal impairment |
• CrCl 30–49 mL/min: twice weekly dosing. • CrCl <30 mL/min: 2 weeks/1 month dosing. | Do not use for CrCl <10 mL/min. |
| Hepatic impairment | No dosage adjustment required, but monitor LFTs. | Monitor for jaundice or cholestasis. |
| IV route | 2 mg/kg loading, then 1 mg/kg daily in 4–6 h infusion. | Remains well tolerated; used in severe infections or non‑compliant patients. |
Note: Avoid food rich in calcium or magnesium on the same day due to reduced absorption.
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Monitoring
| Parameter | Frequency | Rationale |
| Serum creatinine & CrCl | Prior to therapy; repeat if renal function changes | Dose adjustment needed. |
| Liver function tests (ALT, AST, bilirubin) | Baseline; repeat after 7–10 days in high‑dose/long‑term regimens | Detect hepatotoxicity. |
| ECG (QTc) | Baseline in patients with cardiac disease or on QT‑prolonging drugs | Ensure safe dosing. |
| Adverse event | Daily during inpatient stays or if patient reports symptoms | Monitor GI, rash, signs of infection. |
| Pregnancy tests | Female of childbearing potential | Avoid inadvertent pregnancy exposure. |
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Clinical Pearls
1. Three‑day “z” regimen: The 500 mg/250 mg day 2‑5 schedule exploits azithromycin’s long half‑life to treat pneumonia with excellent adherence, superior to shorter courses of other macrolides.
2. Single‑dose therapy for chlamydia: A one‑time 1 g dose simplifies treatment, improves compliance, and is as effective as multi‑day regimens.
3. Avoid calcium‑rich foods on dosing day: Calcium, magnesium, iron, or zinc chelate the drug, reducing oral bioavailability by ~30 %; recommend a 2‑hour separation from meals.
4. Caution with digoxin: Azithromycin may raise digoxin serum levels. Monitor trough concentrations if concurrent use inevitable.
5. Use in severe hepatic disease? Not recommended in patients with acute liver failure or severe cirrhosis; mild elevations in hepatic enzymes are common, but serious hepatotoxicity is possible.
6. Resistance considerations: Overuse contributes to macrolide‑resistant *S. pneumoniae* and *H. pylori*; reserve azithromycin for documented susceptibility or for pathogens lacking alternative agents.
7. Real‑world dosing in TB: Rescue regimens in drug‑resistant TB (e.g., azithromycin 500 mg daily + rifampin) have shown improved outcomes but require close monitoring for drug‑drug interactions.
8. Pregnancy and lactation: Category B; breast‑feeding is generally considered safe for short courses, but avoid prolonged exposure in toddlers.
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