Usage
Azithromycin is prescribed for a range of bacterial infections, including:
- Upper Respiratory Tract Infections: Pharyngitis/Tonsillitis, Sinusitis, Otitis Media.
- Lower Respiratory Tract Infections: Acute bacterial exacerbations of Chronic Bronchitis, Community-Acquired Pneumonia.
- Skin and Soft Tissue Infections: Impetigo, Erysipelas, Folliculitis.
- Sexually Transmitted Infections (STIs): Uncomplicated urethritis and cervicitis due to Chlamydia trachomatis and Neisseria gonorrhoeae.
Pharmacological Classification: Macrolide antibiotic
Mechanism of Action: Azithromycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit, thereby preventing the translocation of peptidyl tRNA from the A-site to the P-site. This ultimately stops bacterial growth and replication.
Alternate Names
- International Nonproprietary Name (INN): Azithromycin
- Brand Names: Zithromax, Zmax, AzaSite, Azasan
How It Works
Pharmacodynamics: Azithromycin exerts its bacteriostatic effect by inhibiting protein synthesis, as described above. High concentrations may also exhibit bactericidal activity.
Pharmacokinetics:
- Absorption: Oral absorption is variable and may be affected by food. Bioavailability is approximately 37%.
- Distribution: Azithromycin achieves high tissue concentrations, exceeding plasma concentrations, particularly in phagocytes.
- Metabolism: Hepatically metabolized to inactive metabolites.
- Elimination: Primarily eliminated via biliary excretion; some renal excretion occurs. The half-life is prolonged (2 to 4 days), allowing for once-daily dosing.
Mode of Action: Binds to the 50S ribosomal subunit.
Receptor Binding/Enzyme Inhibition: Inhibits protein synthesis by binding to the 50S ribosomal subunit.
Elimination Pathways: Primarily biliary excretion with some renal excretion.
Dosage
Standard Dosage
Adults:
- Most infections: 500 mg on Day 1, then 250 mg once daily on Days 2-5 OR 500 mg once daily for 3 days.
- Chlamydia trachomatis infection: 1 g as a single dose.
Children:
- Most infections: 10 mg/kg/day for 3 days OR 10 mg/kg on Day 1 followed by 5 mg/kg on Days 2-5.
Special Cases:
- Elderly Patients: No specific dose adjustments are typically necessary.
- Patients with Renal Impairment: Caution in severe renal impairment. Dose adjustments may be required in patients with GFR < 10 mL/min.
- Patients with Hepatic Dysfunction: Use with caution, dose adjustments may be required in patients with severe hepatic impairment.
- Patients with Comorbid Conditions: Consider potential drug interactions in patients with other underlying conditions.
Clinical Use Cases
Specific dosages in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations are not generally different from the standard dosages mentioned above. The choice of antibiotic and dosage would be based on the infection being treated and patient-specific factors.
Dosage Adjustments:
Dose adjustments are indicated in patients with severe renal or hepatic impairment. Consider genetic polymorphisms affecting drug metabolism.
Side Effects
Common Side Effects:
- Diarrhea
- Nausea
- Abdominal pain
- Vomiting
- Headache
- Dizziness
Rare but Serious Side Effects:
- Clostridium difficile-associated diarrhea
- Hepatotoxicity (including cholestatic jaundice)
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Angioedema
- Anaphylaxis
- QT interval prolongation
- Torsades de pointes
Long-Term Effects:
Long-term use can lead to antibiotic resistance and disruption of gut flora.
Adverse Drug Reactions (ADR):
As mentioned in “rare but serious side effects” above.
Contraindications
- Hypersensitivity to azithromycin, erythromycin, or any macrolide or ketolide antibiotic.
- History of cholestatic jaundice or hepatic dysfunction associated with prior azithromycin use.
- Concomitant use with pimozide.
Drug Interactions
Azithromycin has potentially clinically significant interactions with a number of drugs, including:
- CYP3A4 substrates: Increased concentrations of drugs metabolized by CYP3A4.
- P-glycoprotein substrates: Increased concentrations of drugs that are P-glycoprotein substrates.
- Warfarin: Increased risk of bleeding.
- Digoxin: Increased digoxin levels.
- Ergot alkaloids: Risk of ergotism.
- Statins: Increased risk of myopathy or rhabdomyolysis.
- Antacids: Reduced absorption of azithromycin.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B (Animal studies have not shown a risk to the fetus but there are no adequate and well-controlled studies in pregnant women. )
- Breastfeeding: Azithromycin is excreted in breast milk in low amounts and is considered compatible with breastfeeding. However, monitor infants for diarrhea, vomiting, or rash.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit.
- Side Effects: Diarrhea, nausea, abdominal pain, vomiting, headache, dizziness. Rare but serious: Hepatotoxicity, allergic reactions, QT prolongation, C. difficile-associated diarrhea.
- Contraindications: Hypersensitivity, history of cholestatic jaundice/hepatic dysfunction with prior use, concomitant pimozide.
- Drug Interactions: Warfarin, digoxin, ergot alkaloids, statins, antacids, CYP3A4 and P-glycoprotein substrates.
- Pregnancy & Breastfeeding: Generally safe; monitor infants for side effects during breastfeeding.
- Dosage: Adults: 500 mg on Day 1, then 250 mg on Days 2-5 OR 500 mg once daily for 3 days. Children: 10 mg/kg/day for 3 days OR 10 mg/kg on Day 1 followed by 5 mg/kg on Days 2-5.
- Monitoring Parameters: Liver function tests, ECG (in specific cases), resolution of infection symptoms.
Popular Combinations:
Azithromycin is not typically used in combination with other antibiotics except in specific cases like pelvic inflammatory disease where anaerobic coverage may be added.
Precautions
- General Precautions: Assess for hypersensitivity, hepatic and renal function before administration.
- Specific Populations: As described in the “Dosage” and “Pregnancy and Breastfeeding” sections.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Azithromycin?
A: Adults: 500 mg on Day 1, then 250 mg on Days 2-5 or 500 mg once daily for 3 days. Children: 10 mg/kg/day for 3 days or 10 mg/kg on Day 1 followed by 5 mg/kg on Days 2-5.
Q2: What are the common side effects of Azithromycin?
A: Diarrhea, nausea, abdominal pain, vomiting, and headache.
Q3: What are the serious side effects of Azithromycin?
A: C. difficile infection, hepatotoxicity, severe allergic reactions (including angioedema and anaphylaxis), QT prolongation, and Torsades de pointes.
Q4: Can Azithromycin be used in pregnancy?
A: Azithromycin is generally considered safe in pregnancy. Consult resources for the most up-to-date pregnancy category and recommendations.
Q5: Can Azithromycin be used during breastfeeding?
A: Yes, it is generally considered safe during breastfeeding, but monitor infants for adverse reactions.
Q6: What are the contraindications to using Azithromycin?
A: Hypersensitivity to azithromycin or related antibiotics, history of cholestatic jaundice/hepatic dysfunction with prior azithromycin use, and concomitant use of pimozide.
Q7: What are the significant drug interactions with Azithromycin?
A: Warfarin, digoxin, ergot alkaloids, statins, antacids, and drugs metabolized by CYP3A4 or those that are P-glycoprotein substrates.
Q8: How is Azithromycin eliminated from the body?
A: Primarily through biliary excretion with some renal excretion.
Q9: What is the mechanism of action of Azithromycin?
A: It inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit.
Q10: Is Azithromycin bacteriostatic or bactericidal?
A: Primarily bacteriostatic, but can be bactericidal at high concentrations.
