E.E.S. 400

Clinical safety rating: caution

Comprehensive clinical and safety monograph for E.E.S. 400 (E.E.S. 400).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for E.E.S. 400 (E.E.S. 400).

Breastfeeding	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.
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

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to erythromycin or any macrolide antibiotic, concomitant use with terfenadine, astemizole, cisapride, pimozide, ergotamine, or dihydroergotamine (risk of cardiac arrhythmias).

Clinical Precautions

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).

Clinical Tips & Counseling

Drug interactions

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E.E.S. 400

Clinical safety rating: caution

Comprehensive clinical and safety monograph for E.E.S. 400 (E.E.S. 400).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for E.E.S. 400 (E.E.S. 400).

Breastfeeding	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.
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

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to erythromycin or any macrolide antibiotic, concomitant use with terfenadine, astemizole, cisapride, pimozide, ergotamine, or dihydroergotamine (risk of cardiac arrhythmias).