Azithromycin
1. Drug Name
Generic Name: Azithromycin
Brand Names: Zithromax, Zmax, Azithral, Azithro, and others.
2. Drug Classification
Class: Antibiotic, Macrolide
Subclass: None (macrolide class)
3. Mechanism of Action
Primary Action: Azithromycin works by inhibiting bacterial protein synthesis. It binds to the 50S ribosomal subunit of bacteria, specifically the peptidyl transferase center, thereby preventing the elongation of the polypeptide chain. This halts protein synthesis, leading to bacterial cell death or inhibition of bacterial growth (bacteriostatic or bactericidal depending on the organism and concentration).
Spectrum of Activity: Azithromycin is effective against a wide range of gram-positive, gram-negative, and atypical organisms. This includes:
Gram-positive bacteria like Streptococcus pneumoniae and Staphylococcus aureus (non-MRSA strains).
Gram-negative bacteria such as Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae.
Atypical organisms like Chlamydia trachomatis, Mycoplasma pneumoniae, and Legionella pneumophila.
Resistance: Azithromycin resistance can develop through alterations in the bacterial ribosomal binding site or efflux pump activity. Resistance is most commonly seen with Streptococcus pneumoniae and Haemophilus influenzae, and azithromycin should not be used indiscriminately to prevent resistance development.
4. Pharmacokinetics
Absorption: Azithromycin is well absorbed following oral administration, with a bioavailability of approximately 37%. Its absorption is not significantly affected by food, although taking it on an empty stomach may increase absorption. It has a long half-life, which allows for once-daily dosing.
Distribution: Azithromycin is widely distributed throughout the body and achieves high concentrations in tissues, particularly in the lungs, tonsils, and prostate. It has a relatively low concentration in the blood compared to tissues.
Metabolism: Azithromycin is primarily metabolized by the liver via the cytochrome P450 system (CYP3A4). However, it has a low potential for drug-drug interactions via this pathway compared to other macrolides.
Excretion: Azithromycin is excreted unchanged in the bile (approximately 50%–70%) and to a lesser extent in the urine (approximately 6%). The drug has a long elimination half-life of 68 hours, allowing for a shorter treatment course.
Special Considerations: Dose adjustments are not required in mild to moderate renal dysfunction, but caution should be used in severe renal impairment. Hepatic adjustment is also advised in patients with liver dysfunction.
5. Indications
Primary Indications:
Respiratory Tract Infections: Including community-acquired pneumonia, acute bronchitis, and sinusitis.
Otitis Media: Acute middle ear infections, particularly in children.
Skin and Soft Tissue Infections: For infections caused by susceptible organisms, such as Streptococcus pyogenes.
Genital Infections: Treatment of Chlamydia trachomatis and Neisseria gonorrhoeae, as well as urethritis and cervicitis.
Pharyngitis/Tonsillitis: Caused by Streptococcus pyogenes.
Off-label Uses:
Legionella pneumonia (in combination with other agents).
Mycobacterial infections (e.g., Mycobacterium avium complex).
Traveler’s diarrhea (due to Campylobacter jejuni or Shigella).
Specific Populations: Azithromycin is commonly used in pediatric patients for respiratory tract infections, ear infections, and chlamydial infections.
6. Dosage and Administration
Adult Dosing:
Respiratory Infections (e.g., pneumonia, bronchitis): 500 mg once daily for 3–5 days.
Genital Infections (e.g., chlamydia): 1 gram as a single dose.
Skin Infections: 500 mg once daily for 3–7 days.
Surgical Prophylaxis: 1 gram as a single dose, typically given 1–2 hours before the procedure.
Pediatric Dosing:
Otitis Media (Middle Ear Infection): 10 mg/kg once daily for 3 days (maximum dose: 500 mg per day).
Community-Acquired Pneumonia: 10 mg/kg once daily for 5 days.
Renal/Hepatic Adjustments: Dose adjustments are not typically required in patients with renal impairment unless they have severe renal dysfunction. Hepatic dysfunction should be considered when dosing, and patients should be monitored closely for adverse effects.
Route of Administration: Azithromycin is typically administered orally, but it is also available as an intravenous formulation for hospital settings or when oral administration is not feasible.
7. Contraindications
Absolute Contraindications:
Known hypersensitivity to azithromycin, other macrolide antibiotics, or any excipients in the formulation.
Relative Contraindications:
Liver Dysfunction: Use with caution in patients with hepatic impairment, as azithromycin is metabolized by the liver.
QT Prolongation: Azithromycin should be used with caution in patients with a history of QT prolongation or those taking medications that prolong the QT interval (e.g., antiarrhythmic drugs, certain antipsychotics).
8. Warnings and Precautions
QT Interval Prolongation: Azithromycin has been associated with prolongation of the QT interval, which may increase the risk of torsades de pointes, especially in patients with existing heart conditions, electrolyte abnormalities, or those on other QT-prolonging drugs.
Hepatotoxicity: Azithromycin may cause hepatotoxicity, particularly in those with preexisting liver disease. Regular monitoring of liver enzymes may be warranted during prolonged therapy.
Clostridium difficile Infection: As with other antibiotics, azithromycin can lead to an overgrowth of C. difficile in the colon, potentially leading to colitis.
9. Adverse Effects
Common Adverse Effects (≥10%):
Gastrointestinal symptoms such as diarrhea, nausea, and abdominal pain.
Headache.
Dizziness.
Less Common but Clinically Significant:
Cardiovascular: Prolonged QT interval, arrhythmias, and torsades de pointes (rare).
Hepatic: Elevations in liver enzymes (ALT, AST), hepatitis (rare).
Hematologic: Eosinophilia, neutropenia, thrombocytopenia (rare).
Serious Adverse Reactions:
Anaphylaxis, angioedema, and Stevens-Johnson syndrome.
Liver failure (rare but serious in those with preexisting liver disease).
Acute kidney injury (rare).
10. Drug Interactions
Major Drug Interactions:
Antacids (e.g., magnesium/aluminum hydroxide): Can reduce the absorption of azithromycin. Azithromycin should be taken at least 1 hour before or 2 hours after antacids.
QT-Prolonging Drugs: Azithromycin may potentiate the effects of drugs that prolong the QT interval, such as antiarrhythmic agents, antipsychotics, and some antidepressants.
CYP3A4 Inhibitors: Azithromycin is metabolized by CYP3A4, and drugs that inhibit this enzyme (e.g., ketoconazole, erythromycin) may increase azithromycin concentrations, potentially increasing the risk of adverse effects.
Food-Drug Interactions: Azithromycin absorption is not significantly affected by food, but taking it with food may help reduce gastrointestinal discomfort.
Lab Test Interference: Azithromycin may interfere with liver function tests (transaminases, bilirubin) and urine glucose testing (non-reducing sugar method).
11. Clinical Pharmacology
Pharmacodynamics: Azithromycin’s bactericidal or bacteriostatic action is dose-dependent. It exhibits concentration-dependent killing against most susceptible bacteria, particularly in tissues.
Additional Effects: Azithromycin may have anti-inflammatory effects, which could contribute to its efficacy in conditions like chronic obstructive pulmonary disease (COPD) and acute bacterial sinusitis.
12. Special Populations
Pregnancy: Azithromycin is categorized as Pregnancy Category B. It is generally considered safe during pregnancy but should be used only when clearly needed.
Lactation: Azithromycin is excreted in breast milk, but its concentration is low, and it is generally considered safe for use during breastfeeding.
Pediatrics: Azithromycin is commonly prescribed to children for respiratory infections, otitis media, and genital infections. It is generally well-tolerated in this population.
Renal/Hepatic Dysfunction: Azithromycin should be used with caution in patients with hepatic dysfunction. No dose adjustment is typically required for renal dysfunction unless severe.
13. Therapeutic Uses
First-line Therapy: Azithromycin is often used as a first-line treatment for community-acquired pneumonia, otitis media, chlamydia, and acute bacterial sinusitis.
Second-line Therapy: For conditions like strep throat (when penicillin cannot be used), or in the treatment of certain mycobacterial infections.
Combination Therapy: Azithromycin may be used in combination with other antibiotics (e.g., ceftriaxone) for conditions like gonorrhea and pneumonia caused by multi-drug-resistant organisms.
Clinical Trials: Multiple studies support the efficacy of azithromycin in treating respiratory and genital tract infections.
14. Monitoring and Follow-Up
Lab Tests: Liver function tests and renal function tests should be monitored periodically, especially in prolonged therapy.
Symptom Monitoring: Watch for any allergic reactions, gastrointestinal symptoms, or cardiovascular events (e.g., palpitations, dizziness).
Toxicity Monitoring: Observe for signs of hepatotoxicity, QT prolongation, and superinfections (e.g., Clostridium difficile).
15. Overdose Management
Symptoms of Overdose: Overdose symptoms may include nausea, vomiting, diarrhea, and abdominal pain. In severe cases, cardiac arrhythmias and hypotension may occur.
Treatment Protocols: There is no specific antidote for azithromycin overdose. Management involves symptomatic treatment, such as gastric lavage, activated charcoal, and fluid resuscitation.
Supportive Measures: Continuous monitoring of vital signs, ECG monitoring for arrhythmias, and hydration are recommended.
16. Patient Counseling Information
Key Points to Discuss with Patients:
Complete the full course of treatment as prescribed, even if you feel better before finishing the medication.
Take azithromycin with or without food, as directed by your healthcare provider.
Notify your healthcare provider if you develop any new or unusual symptoms, particularly signs of an allergic reaction, liver issues, or prolonged diarrhea.
Signs/Symptoms to Watch For:
Severe abdominal pain, diarrhea with blood, or new onset of dark urine, which could indicate liver problems.
Irregular heartbeats, dizziness, or fainting, especially in those with a history of heart disease.