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. |
| Molecular Weight | 862.09 |
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 | Generally considered safe; no increased risk of major malformations in human studies. Used for treating infections. |
| 2nd trimester | Safe; no known fetal risks. |
| 3rd trimester | Safe; avoid in neonates due to risk of infantile hypertrophic pyloric stenosis (IHPS) if used near term. |
Clinical note
Inhibits CYP3A4 increasing levels of many drugs (eg statins carbamazepine) May cause QT prolongation and subsequent arrhythmias.
| FDA category | Human |
| Placental transfer | Crosses placenta to a limited extent; fetal serum levels about 20% of maternal levels. |
| Breastfeeding | Compatible with breastfeeding; minimal amounts excreted into breast milk; risk of gastrointestinal disturbance or rash in infant. Avoid if infant has jaundice or hepatic impairment. |
■ FDA Black Box Warning
None.
| Common Effects | Nausea |
| Serious Effects |
Hypersensitivity to erythromycin or any macrolideConcurrent use with ergotamine or dihydroergotamineHepatic dysfunction associated with prior erythromycin useUse in neonates with pyloric stenosis or at risk for IHPS
| 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 |
Loading safety data…
| Lactation Rating | L1 (Safe) |
| Teratogenic Risk | 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. |
| Food/Dietary |
| Grapefruit and grapefruit juice may increase erythromycin levels and risk of toxicity. Avoid concurrent ingestion. Food does not significantly decrease absorption and may be taken to reduce GI upset. |
| Clinical Pearls | Erythromycin ethylsuccinate is a prodrug that is hydrolyzed to erythromycin base. It is less susceptible to acid degradation and may be taken without regard to meals. However, food may enhance absorption. Monitor for QT prolongation, especially in patients with electrolyte imbalances, bradycardia, or concurrent use of other QT-prolonging drugs. Erythromycin is a potent CYP3A4 inhibitor and can increase levels of statins, warfarin, and other drugs. Avoid concurrent use with pimozide, terfenadine, astemizole, or cisapride due to risk of cardiac arrhythmias. |
| Patient Advice | Take this medication exactly as prescribed, with or without food. If stomach upset occurs, taking with food may help. · Do not crush or chew tablets; swallow whole. · Complete the full course of therapy even if you feel better to prevent recurrence or resistance. · Report any signs of liver problems (yellowing eyes/skin, dark urine, severe stomach pain) or hearing loss (especially with high doses or renal impairment). · Avoid taking with grapefruit or grapefruit juice as it may increase side effects. · Inform your doctor about all medications you take, especially blood thinners, statins, or drugs for heart rhythm problems. · Seek immediate medical attention if you experience fainting, rapid or irregular heartbeat, or severe dizziness. |