ZITHROMAX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZITHROMAX (ZITHROMAX).
Azithromycin is a macrolide antibiotic that binds to the 50S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis by preventing translocation of peptides. It also has immunomodulatory and anti-inflammatory effects.
| Metabolism | Azithromycin is primarily metabolized in the liver via demethylation; however, it is not extensively metabolized. It is a substrate of CYP3A4, but does not significantly inhibit or induce CYP enzymes. Elimination occurs mainly via biliary excretion as unchanged drug. |
| Excretion | Primarily eliminated via biliary/fecal route (∼50-60% as unchanged drug); renal excretion accounts for ∼12% of the dose; minimal metabolism. |
| Half-life | Terminal elimination half-life of approximately 68 hours (range 35-96 hours), allowing once-weekly dosing for some indications. |
| Protein binding | 7-50% (concentration-dependent; lower at therapeutic concentrations); binds primarily to albumin. |
| Volume of Distribution | Approximately 23-31 L/kg; extensive tissue distribution (concentrations in tissues 10-100 times serum levels). |
| Bioavailability | Oral bioavailability: 37-38% (variable due to first-pass metabolism); absolute bioavailability not determined for IV route (100% intravenously). |
| Onset of Action | Oral: 2.5-4 hours (time to peak serum concentration); IV infusion: near end of 1-hour infusion; clinical effect may be delayed 24-48 hours. |
| Duration of Action | Concentration-dependent; bactericidal levels persist for 5-7 days after single oral dose (due to extensive tissue accumulation and long half-life). |
| Action Class | Macrolides |
| Brand Substitutes | Azax 500 Tablet, Zady 500 Tablet, Trulimax 500mg Tablet, Azifast 500 Tablet, Zithrox 500 Tablet, Azicip 250 Tablet, Azikem 250mg Tablet, Fitzee 250 Tablet, Azax 250 Tablet, Zerox 250 Tablet |
500 mg orally once daily for 3 days, or 2 g orally as a single dose for certain infections.
| Dosage form | CAPSULE |
| Renal impairment | No adjustment required for mild to moderate renal impairment (CrCl >10 mL/min). For severe impairment (CrCl <10 mL/min), caution advised; specific dosing guidelines not established. |
| Liver impairment | Contraindicated in patients with Child-Pugh Class C cirrhosis. For Child-Pugh Class A or B, no dose adjustment recommended but monitor for hepatotoxicity. |
| Pediatric use | 10 mg/kg orally once daily on day 1, followed by 5 mg/kg orally once daily on days 2-5 (maximum 500 mg/day). For acute otitis media: 30 mg/kg as a single dose. |
| Geriatric use | No specific dose adjustment required; monitor for QT prolongation and hearing loss, especially in those with pre-existing conditions or receiving concomitant ototoxic or cardiotoxic drugs. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZITHROMAX (ZITHROMAX).
| Breastfeeding | Azithromycin is excreted into human breast milk. The milk-to-plasma (M/P) ratio is approximately 0.7–1.5. Limited data suggest low infant exposure (relative infant dose <2% of maternal weight-adjusted dose). It is considered compatible with breastfeeding by the American Academy of Pediatrics. However, monitor infant for diarrhea, rash, and feeding intolerance. |
| Teratogenic Risk | Azithromycin (Zithromax) is FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, but adequate human studies in pregnant women are lacking. There is no evidence of teratogenicity in first trimester exposure from registry data. In second and third trimesters, no increased risk of major malformations or adverse fetal outcomes has been reported. However, use only if clearly needed. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to azithromycin, erythromycin, or any macrolide antibiotic.","History of cholestatic jaundice or hepatic dysfunction associated with prior azithromycin use.","Concomitant use with ergotamine or dihydroergotamine (potential for ergot toxicity)."]
| Precautions | ["Hepatotoxicity: severe liver injury may occur; discontinue if signs of hepatitis occur.","Cardiovascular: QT prolongation and risk of torsades de pointes, especially in patients with known QT prolongation, electrolyte disturbances, or on other QT-prolonging drugs.","Infantile hypertrophic pyloric stenosis (IHPS): reported in neonates following azithromycin use; monitor for vomiting or feeding intolerance.","Clostridioides difficile-associated diarrhea: may occur; treat if suspected.","Allergic reactions: serious hypersensitivity including anaphylaxis, Stevens-Johnson syndrome, and drug reaction with eosinophilia and systemic symptoms (DRESS).","Myasthenia gravis: may exacerbate weakness.","Superinfection: prolonged use may result in overgrowth of nonsusceptible organisms."] |
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| Fetal Monitoring | No specific fetal monitoring required. Routine prenatal care is sufficient. Monitor maternal liver function tests if prolonged therapy. In neonates, observe for hypertrophic pyloric stenosis (increased risk when exposed in first 2 weeks of life via breast milk or direct administration). |
| Fertility Effects | No known adverse effects on fertility in animal studies or human data. Azithromycin does not impair female or male reproductive function. |