ZMAX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZMAX (ZMAX).
Azithromycin, the active ingredient in ZMAX, is a macrolide antibiotic that binds to the 50S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis and bacterial growth.
| Metabolism | Azithromycin is primarily eliminated unchanged in bile (biliary excretion) and undergoes minimal hepatic metabolism via N-demethylation; it is not significantly metabolized by cytochrome P450 enzymes. |
| Excretion | Renal: ~20% unchanged; fecal: ~50% as metabolites; biliary: ~30% as metabolites and parent drug. |
| Half-life | Terminal half-life: 68 hours (range 40-80 h); prolonged in hepatic impairment (up to 120 h) and elderly; supports once-weekly dosing. |
| Protein binding | 70-80% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 3.5-4.0 L/kg indicating extensive tissue distribution; accumulates in lung tissue with tissue-to-plasma ratio of 5:1. |
| Bioavailability | Oral: 10-15% due to extensive first-pass metabolism; intramuscular: 25-30%. |
| Onset of Action | Oral: 1-2 hours (effect on sputum clearance); IV: 15-30 minutes. |
| Duration of Action | Approximately 24-36 hours after oral dose; sustained mucolytic effect for up to 24 hours after IV administration. |
500 mg orally once daily, administered as a single dose on an empty stomach.
| Dosage form | FOR SUSPENSION, EXTENDED RELEASE |
| Renal impairment | For CrCl 10-50 mL/min: 250 mg orally once daily. For CrCl <10 mL/min or hemodialysis: 250 mg orally once daily, administered after dialysis on dialysis days. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); use with caution. |
| Pediatric use | For children ≥6 months: 10 mg/kg (max 500 mg) orally once daily for 3 days. |
| Geriatric use | No specific dose adjustment beyond renal function assessment. Use lower end of dosing range due to potential decreased renal function and increased risk of adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZMAX (ZMAX).
| Breastfeeding | Excreted in breast milk. M/P ratio: 0.3 to 0.6. Concentrations considered low; use with caution in infants <4 weeks due to risk of kernicterus. Manufacturer recommends weighing benefit vs risk. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Limited human data; animal studies show fetal harm (skeletal anomalies, reduced fetal weight). Second/third trimester: No specific fetal risks in humans; potential neonatal effects: hemolytic anemia, gray baby syndrome if used near term. |
| Fetal Monitoring |
■ 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.
| Precautions | Hepatotoxicity (elevated liver enzymes, hepatitis, hepatocellular necrosis), QT prolongation (especially in patients with pre-existing conditions or concurrent use of other QT-prolonging drugs), Clostridioides difficile-associated diarrhea, severe allergic reactions (including anaphylaxis and angioedema), and exacerbation of myasthenia gravis. |
Loading safety data…
| Maternal: CBC with differential, renal function, hepatic function, serum drug levels (trough 15-20 mg/dL). Fetal: Ultrasound for growth restriction if used >3 weeks; neonatal monitoring for jaundice, hypoglycemia, electrolyte imbalances. |
| Fertility Effects | No human studies on fertility. Animal studies: reduced fertility at high doses (2x human dose). Possibly reversible impairment of spermatogenesis and ovulation in animal models. |