Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
E.E.S. 400 vs AZITHROMYCIN
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Erythromycin, a macrolide antibiotic, binds to the 50S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis. At high concentrations, it may also inhibit RNA synthesis.
Binds to the 50S ribosomal subunit of susceptible bacteria, inhibiting m RNA translation and thus protein synthesis. Exhibits concentration-dependent bactericidal activity.
Treatment of infections caused by susceptible strains of microorganisms: respiratory tract infections (including Legionnaires disease, pertussis), skin and soft tissue infections, diphtheria, syphilis, chlamydial infections, and ocular infections in neonates.,Prophylaxis of recurrent rheumatic fever.,Off-label: gastrointestinal motility disorder (as a motilin agonist).
Acute bacterial exacerbations of chronic obstructive pulmonary disease due to H. influenzae, M. catarrhalis, or S. pneumoniae,Acute bacterial sinusitis due to H. influenzae, M. catarrhalis, or S. pneumoniae,Community-acquired pneumonia due to C. pneumoniae, H. influenzae, M. pneumoniae, or S. pneumoniae,Pharyngitis/tonsillitis due to S. pyogenes,Uncomplicated skin and skin structure infections due to S. aureus, S. pyogenes, or S. agalactiae,Urethritis/cervicitis due to C. trachomatis or N. gonorrhoeae,Genital ulcer disease due to H. ducreyi,Acute otitis media due to H. influenzae, M. catarrhalis, or S. pneumoniae,Prevention of disseminated M. avium complex disease in advanced HIV infection,Pertussis (off-label)
Erythromycin ethylsuccinate 400 mg orally every 6 hours. For severe infections, up to 4 g/day in divided doses.
500 mg orally once daily for 3 days, or 500 mg IV once daily for at least 2 days followed by 500 mg orally to complete 7-10 days of therapy for community-acquired pneumonia. For other indications, typical adult dose is 500 mg orally on day 1 then 250 mg orally once daily on days 2-5.
1.5-2.0 hours in adults with normal renal function; may be prolonged in hepatic impairment (up to 5-6 hours) but not significantly changed in renal disease.
Terminal half-life of approximately 68 hours (range 35–96 h) after multiple doses, allowing once-daily dosing and a prolonged post-antibiotic effect.
Primarily metabolized in the liver via demethylation by CYP3A4; undergoes N-demethylation and hydroxylation.
Primarily hepatic, not via cytochrome P450 system. Partially metabolized to inactive metabolites. Eliminated via biliary excretion and renal excretion (<15% unchanged).
Primarily hepatic (biliary) excretion of unchanged drug and metabolites; approximately 2-5% renal excretion of unchanged drug; 5-15% fecal elimination.
Primarily biliary/fecal (approx. 50% unchanged); renal excretion accounts for about 12% of the dose.
70-80% bound to albumin; binding is reversible and saturable at high concentrations.
7–51% (concentration-dependent); primarily binds to albumin.
Approximately 0.7 L/kg (range 0.5-0.9 L/kg); indicates extensive tissue penetration including intracellular and inflammatory fluids.
31.1 L/kg (range 23–50 L/kg), indicating extensive tissue penetration and sequestration (e.g., WBCs, liver, lung).
Oral (as erythromycin ethylsuccinate): approximately 30-65% (variable, reduced by food); intravenous: 100%.
Oral: 37–40% (fasting); food may decrease absorption by ~50%.
No specific dose adjustment required for renal impairment; caution with high doses in severe renal failure (Cr Cl <10 m L/min) due to potential ototoxicity.
No dose adjustment required for GFR ≥10 m L/min. For GFR <10 m L/min, caution advised; no specific dose recommendation, consider alternative agent.
In hepatic impairment, reduce dose by 50-75% depending on severity. Child-Pugh Class A: no adjustment; Class B: reduce to 50% of normal dose; Class C: avoid or use with extreme caution, maximum 1 g per day.
No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh class A and B). Contraindicated in severe hepatic impairment (Child-Pugh class C).
30-50 mg/kg/day in 4 divided doses. For severe infections, up to 60-100 mg/kg/day. Maximum 2 g/day.
For otitis media and community-acquired pneumonia: 10 mg/kg orally or IV on day 1 (max 500 mg), then 5 mg/kg (max 250 mg) once daily on days 2-5. For pharyngitis/tonsillitis: 12 mg/kg orally once daily for 5 days (max 500 mg/day).
No specific dose adjustment; monitor for QT prolongation and hearing loss. Consider lower end of dosing range due to age-related decline in hepatic function.
No specific dose adjustment required; use same dosing as younger adults. Monitor renal function due to age-related decline, but no modification needed unless severe renal impairment (Cr Cl <10 m L/min).
Increased risk of infantile hypertrophic pyloric stenosis (IHPS) when given to neonates. Erythromycin has also been associated with prolongation of the QT interval and risk of cardiac arrhythmias, including torsades de pointes.
None.
Hepatic dysfunction, QT prolongation (risk of arrhythmia), exacerbation of myasthenia gravis, Clostridioides difficile-associated diarrhea, ototoxicity (especially with high doses or renal impairment), potential for drug interactions (CYP3A4 inhibitors/inducers).
Hepatotoxicity: hepatitis, cholestatic jaundice, hepatic necrosis, hepatic failure,QT prolongation and torsades de pointes (especially with concurrent use of other QT-prolonging agents, electrolyte abnormalities, bradycardia, or structural heart disease),Clostridioides difficile-associated diarrhea (CDAD),Aggravation of myasthenia gravis,Severe allergic reactions (angioedema, anaphylaxis, Stevens-Johnson syndrome),Infantile hypertrophic pyloric stenosis (IHPS) in neonates following oral azithromycin,Use in pregnancy: category B; avoid during breastfeeding due to potential for disruption of infant gut flora
Hypersensitivity to erythromycin or any macrolide antibiotic, concomitant use with terfenadine, astemizole, cisapride, pimozide, ergotamine, or dihydroergotamine (risk of cardiac arrhythmias).
Hypersensitivity to azithromycin, erythromycin, or any macrolide antibiotic,History of cholestatic jaundice or hepatic dysfunction associated with prior azithromycin use,Concurrent use with ergotamine or dihydroergotamine (possible ergot toxicity)
Take with food to minimize gastrointestinal upset. Avoid grapefruit juice as it can increase erythromycin concentrations via CYP3A4 inhibition. No other significant food interactions.
Food does not significantly affect absorption; can be taken with or without food. However, avoiding high-fat meals may reduce minor GI side effects. No known specific food interactions.
FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; inadequate human studies in first trimester. No known risk of major birth defects or miscarriage. Avoid in maternal myasthenia gravis due to potential neonatal hypotonia.
FDA Category B. No evidence of teratogenicity in animal studies; limited human data show no increased risk of major malformations. First trimester: No significant association with birth defects. Second/third trimester: No reported fetal harm from short-term use for infections like chorioamnionitis. Use only if clearly needed.
Compatible with breastfeeding. Erythromycin is excreted into breast milk in small amounts (M/P ratio approximately 0.5). No adverse effects reported in infants. Monitor infant for gastrointestinal disturbances or rash.
Azithromycin is excreted into breast milk in low amounts. M/P ratio approximately 0.2-0.6. Relative infant dose estimated at 2-6% of maternal weight-adjusted dose. Generally considered compatible with breastfeeding; monitor infant for diarrhea or rash.
No dose adjustment required. Physiologic changes in pregnancy (increased volume of distribution, renal clearance) do not necessitate dose changes for erythromycin. Standard adult dosing applies.
No dose adjustment required for pregnancy. Standard adult dosing (500 mg on day 1, then 250 mg daily for 4 days) is appropriate. Note: Pregnancy may increase volume of distribution, but pharmacokinetic studies suggest no significant decrease in AUC; no need for dose increase.
E. E. S. 400 (erythromycin ethylsuccinate) is a macrolide antibiotic with bacteriostatic activity. It is a prodrug hydrolyzed to erythromycin base. Use with caution in patients with hepatic impairment or preexisting hearing loss. Monitor for QT prolongation, especially with concurrent use of other QT-prolonging drugs. Commonly used as an alternative in penicillin-allergic patients for respiratory tract infections. It also has prokinetic effects on the GI tract, which can be utilized in gastroparesis but may cause abdominal cramping.
Monitor for QTc prolongation especially in patients with preexisting cardiac conditions or those on other QT-prolonging drugs. Azithromycin has a long half-life (68 hours) allowing for shorter treatment courses. Use with caution in hepatic impairment; consider alternative in severe liver disease. Not recommended for pneumonia in patients with bacteremia due to increased mortality risk. Administer on an empty stomach or with food if GI upset occurs; however, absorption is unaffected by food.
Take this medication exactly as prescribed, usually every 6 hours or as directed.,Complete the full course even if you feel better to prevent resistance.,May cause stomach upset; taking with food can reduce GI irritation.,Avoid grapefruit juice as it may affect drug levels.,Report symptoms of liver problems (yellowing skin/eyes, dark urine) or hearing loss immediately.,Do not take with certain medications like statins or warfarin without consulting your doctor.,Use effective contraception if applicable, as erythromycin may reduce birth control pill efficacy.
Take exactly as prescribed; do not skip doses or stop early even if you feel better.,Do not take antacids containing aluminum or magnesium within 2 hours before or after this medication.,Report any signs of liver problems (nausea, vomiting, dark urine, jaundice) or severe diarrhea (watery or bloody) immediately.,Azithromycin may cause dizziness; avoid driving or operating machinery until you know how it affects you.,Inform your doctor if you have a history of QT prolongation, heart rhythm problems, or electrolyte imbalances.,Store at room temperature away from moisture and heat; discard any unused liquid after 10 days.
No interactions on record
"Azithromycin, a macrolide antibiotic, is known to prolong the QT interval by blocking cardiac potassium channels (specifically IKr), which can lead to torsades de pointes. Mifepristone also poses a risk of QT prolongation, likely via similar mechanisms. Coadministration may result in additive QTc prolongation, increasing the risk of life-threatening ventricular arrhythmias, especially in patients with preexisting cardiac conditions or electrolyte disturbances."
"Lumiracoxib is a selective COX-2 inhibitor primarily metabolized by CYP2C9 and to a lesser extent by CYP3A4. Azithromycin, a macrolide antibiotic, is a known inhibitor of CYP3A4. Concomitant use may decrease the metabolism of azithromycin, leading to increased plasma concentrations and potential toxicity, such as QT prolongation and hepatotoxicity. Elevated azithromycin levels can also enhance its antibacterial effects but raise safety concerns."
"Azithromycin, a macrolide antibiotic, inhibits the cardiac potassium channel encoded by hERG (human Ether-à-go-go-Related Gene), leading to prolonged cardiac repolarization and increased risk of QTc interval prolongation. Arformoterol, a long-acting beta-2 agonist, can also prolong the QTc interval via beta-adrenergic receptor-mediated effects on cardiac ion channels. Concurrent use may result in additive QTc prolongation, predisposing patients to potentially fatal ventricular arrhythmias such as torsades de pointes."
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about E.E.S. 400 vs AZITHROMYCIN, answered by our medical review team.
E.E.S. 400 is a Macrolide Antibiotic that works by Erythromycin, a macrolide antibiotic, binds to the 50S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis. At high concentrations, it may also inhibit RNA synthesis.. AZITHROMYCIN is a Macrolide Antibiotic that works by Binds to the 50S ribosomal subunit of susceptible bacteria, inhibiting m RNA translation and thus protein synthesis. Exhibits concentration-dependent bactericidal activity.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between E.E.S. 400 and AZITHROMYCIN depend on the specific clinical indication. These are both Macrolide Antibiotic agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of E.E.S. 400 is: Erythromycin ethylsuccinate 400 mg orally every 6 hours. For severe infections, up to 4 g/day in divided doses.. The standard adult dose of AZITHROMYCIN is: 500 mg orally once daily for 3 days, or 500 mg IV once daily for at least 2 days followed by 500 mg orally to complete 7-10 days of therapy for community-acquired pneumonia. For other indications, typical adult dose is 500 mg orally on day 1 then 250 mg orally once daily on days 2-5.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between E.E.S. 400 and AZITHROMYCIN in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. E.E.S. 400 is classified as Category C. FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; inadequate human studies in first trimester. No known risk of major birth defects or miscarriage. Avoid i. AZITHROMYCIN is classified as Category A/B. FDA Category B. No evidence of teratogenicity in animal studies; limited human data show no increased risk of major malformations. First trimester: No significant association with . Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.