ERYTHROMYCIN ETHYLSUCCINATE
Clinical safety rating: safe
Inhibits CYP3A4 increasing levels of many drugs (eg statins carbamazepine) May cause QT prolongation and subsequent arrhythmias.
Erythromycin ethylsuccinate is a macrolide antibiotic that binds to the 50S subunit of the bacterial ribosome, inhibiting protein synthesis by blocking translocation of peptidyl-tRNA. It may also have anti-inflammatory and immunomodulatory effects.
| Metabolism | Primarily hepatic metabolism via cytochrome P450 isoenzyme 3A4 (CYP3A4). Major metabolites include N-demethylerythromycin and other inactive metabolites. Excretion mainly in bile with some renal elimination. |
| Excretion | Primarily hepatic metabolism and biliary excretion (80-90% as unchanged drug and metabolites into bile); renal excretion accounts for 5-15% of unchanged drug; fecal elimination of unabsorbed drug. |
| Half-life | Terminal elimination half-life: 1.5-2 hours in adults with normal renal function; extended to 5-6 hours in patients with severe hepatic impairment; not significantly altered by renal failure. |
| Protein binding | Approximately 70-80% bound to serum albumin (primarily) and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.6-0.9 L/kg; indicates distribution into total body water and some tissue binding. |
| Bioavailability | Oral (ethylsuccinate): 35-45% due to first-pass metabolism; intramuscular: approximately 100% (well absorbed but slower); intravenous: 100%. |
| Onset of Action | Oral: 1-2 hours; intramuscular: 30 minutes; intravenous: within minutes; topical: slow onset over several days. |
| Duration of Action | Oral: 6-8 hours; IM: 8-12 hours; IV: 6-8 hours; topical: continuous with regular application. |
400-800 mg orally every 6 hours or 4 times daily; maximum 4 g/day. Intravenous form available but ethylester is oral only.
| Dosage form | TABLET |
| Renal impairment | No adjustment necessary for mild to moderate renal impairment. In severe renal impairment (CrCl <10 mL/min), consider decreasing dose or increasing interval to every 8-12 hours due to reduced clearance. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% or extend interval. Child-Pugh C: avoid use or reduce dose by 75% and monitor liver function. |
| Pediatric use | 30-50 mg/kg/day orally divided every 6-8 hours; maximum 2 g/day. For severe infections, up to 60-100 mg/kg/day divided every 6 hours. |
| Geriatric use | Use lower end of dosing range (400 mg every 6 hours) due to age-related decline in hepatic clearance; monitor for ototoxicity and QT prolongation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Inhibits CYP3A4 increasing levels of many drugs (eg statins carbamazepine) May cause QT prolongation and subsequent arrhythmias.
| FDA category | Human |
| Breastfeeding | Compatible with breastfeeding. Erythromycin is excreted into breast milk in small amounts (M/P ratio approximately 0.3). No adverse effects reported in nursing infants; monitor for gastrointestinal disturbances and rash. Use caution in infants with hepatic impairment or pyloric stenosis risk. |
| Teratogenic Risk |
■ FDA Black Box Warning
None.
| Common Effects | Nausea |
| Serious Effects |
["Hypersensitivity to erythromycin or any macrolide antibiotic","Concurrent use with ergotamine or dihydroergotamine (risk of ergot toxicity)","Concurrent use with cisapride, pimozide, or certain statins (e.g., lovastatin, simvastatin) due to increased risk of serious cardiac events","Hepatic disease","QTc interval prolongation or family history of Long QT syndrome","Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia)","History of cholestatic jaundice associated with prior erythromycin use"]
| Precautions | ["Prolongation of QT interval and risk of torsades de pointes, especially in patients with pre-existing cardiac conditions, electrolyte disturbances, or concurrent use of other QT-prolonging drugs","Potent CYP3A4 inhibitor: increased risk of adverse effects with drugs metabolized by CYP3A4 (e.g., statins, warfarin, ergotamines)","Infantile hypertrophic pyloric stenosis (IHPS) in neonates exposed to erythromycin","Clostridium difficile-associated diarrhea (CDAD)","Hepatic dysfunction, including cholestatic hepatitis","Exacerbation of myasthenia gravis","Ototoxicity (especially with high doses or renal impairment)","Allergic reactions, including anaphylaxis","Pseudomembranous colitis"] |
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| FDA pregnancy category B. No evidence of teratogenicity in animal studies; inadequate human data. Theoretical risk of pyloric stenosis with erythromycin exposure in the first trimester; generally considered low risk. Avoid in second and third trimesters for maternal infections due to increased risk of infantile hypertrophic pyloric stenosis (IHPS) when used late in pregnancy or during labor. |
| Fetal Monitoring | Monitor maternal liver function tests (especially with high doses or prolonged therapy). Fetal heart rate monitoring is not required but consider if used near term due to association with pyloric stenosis. In neonates, observe for signs of pyloric stenosis (projectile vomiting) if exposed late in pregnancy. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment of fertility. |