E.E.S. 400
Clinical safety rating: caution
Comprehensive clinical and safety monograph for E.E.S. 400 (E.E.S. 400).
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.
| Metabolism | Primarily metabolized in the liver via demethylation by CYP3A4; undergoes N-demethylation and hydroxylation. |
| Excretion | Primarily hepatic (biliary) excretion of unchanged drug and metabolites; approximately 2-5% renal excretion of unchanged drug; 5-15% fecal elimination. |
| Half-life | 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. |
| Protein binding | 70-80% bound to albumin; binding is reversible and saturable at high concentrations. |
| Volume of Distribution | Approximately 0.7 L/kg (range 0.5-0.9 L/kg); indicates extensive tissue penetration including intracellular and inflammatory fluids. |
| Bioavailability | Oral (as erythromycin ethylsuccinate): approximately 30-65% (variable, reduced by food); intravenous: 100%. |
| Onset of Action | Oral: 1-2 hours (bacteriostatic effect); intravenous: rapid (within 30 minutes) for serum concentrations. |
| Duration of Action | 6-12 hours for bacteriostatic effect; clinical duration varies with infection site and pathogen; post-antibiotic effect of 2-6 hours for susceptible organisms. |
| Molecular Weight | 733.93 |
Erythromycin ethylsuccinate 400 mg orally every 6 hours. For severe infections, up to 4 g/day in divided doses.
| Dosage form | SUSPENSION |
| Renal impairment | No specific dose adjustment required for renal impairment; caution with high doses in severe renal failure (CrCl <10 mL/min) due to potential ototoxicity. |
| Liver impairment | 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. |
| Pediatric use | 30-50 mg/kg/day in 4 divided doses. For severe infections, up to 60-100 mg/kg/day. Maximum 2 g/day. |
| Geriatric use | 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. |
| 1st trimester | Crosses placenta; use only if clearly needed. No adequate well-controlled studies in pregnant women. Animal studies show no fetal risk. |
| 2nd trimester | Generally considered safe; no known teratogenic effects. |
| 3rd trimester | Use near term may cause gray baby syndrome in neonates; avoid if possible. |
Clinical note
Comprehensive clinical and safety monograph for E.E.S. 400 (E.E.S. 400).
| Placental transfer | Crosses placenta; fetal serum levels are 2-3% of maternal serum levels. |
| Breastfeeding | Enters breast milk in small amounts; usually compatible with breastfeeding. Monitor infant for gastrointestinal disturbances or rash. |
| Lactation Rating |
■ FDA Black Box Warning
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.
| Serious Effects |
Hypersensitivity to erythromycin or any macrolide antibioticConcurrent use with cisapride, pimozide, or ergotamine due to risk of QT prolongation and cardiac arrhythmias
| Precautions | 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). |
| Food/Dietary | Take with food to minimize gastrointestinal upset. Avoid grapefruit juice as it can increase erythromycin concentrations via CYP3A4 inhibition. No other significant food interactions. |
Loading safety data…
| L1 (Safe) |
| Teratogenic Risk | 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. |
| Fetal Monitoring | Monitor maternal liver function tests (AST, ALT) and hearing (especially with high doses or prolonged use). No specific fetal monitoring required. Observe for maternal QT prolongation if concurrent risk factors. |
| Fertility Effects | No known effects on fertility. Erythromycin does not impair spermatogenesis or oogenesis. |
| Clinical Pearls | 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. |
| Patient Advice | 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. |