ERYTHROMYCIN
Clinical safety rating: safe
Inhibits CYP3A4 increasing levels of many drugs (eg statins carbamazepine) May cause QT prolongation and subsequent arrhythmias.
Binds to the 50S ribosomal subunit, inhibiting bacterial protein synthesis by blocking the translocation step.
| Metabolism | Primarily hepatic via cytochrome P450 3A4 (CYP3A4); inhibits CYP3A4. |
| Excretion | Primarily hepatic (biliary) elimination; approximately 2-5% excreted unchanged in urine, 30-60% excreted in feces via bile. |
| Half-life | Terminal half-life is 1.4-2 hours in adults with normal renal function; may be prolonged to 5-6 hours in anuria. |
| Protein binding | 70-80% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.6-1.2 L/kg; high Vd indicates extensive tissue penetration. |
| Bioavailability | Oral (base/estearate): 20-35%; Oral (ethylsuccinate): 25-40%; Intravenous: 100%. |
| Onset of Action | Oral: 1-2 hours; IV: immediate; Topical: several days to weeks for clinical effect in acne. |
| Duration of Action | Oral: 6-12 hours; IV: 6-12 hours; Topical: continuous with regular application. |
| Molecular Weight | 733.93 |
250-500 mg orally every 6 hours or 500-1000 mg intravenously every 6 hours; maximum 4 g/day.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment necessary for mild to moderate renal impairment. For severe renal impairment (CrCl <10 mL/min), reduce dose by 50% or extend interval to every 8-12 hours. |
| Liver impairment | In severe hepatic impairment (Child-Pugh class C), reduce dose by 50% or extend dosing interval. Avoid use in patients with pre-existing liver disease if possible. |
| Pediatric use | Oral: 30-50 mg/kg/day divided every 6 hours. Intravenous: 15-20 mg/kg/day divided every 6 hours; maximum 4 g/day. |
| Geriatric use | Use with caution due to increased risk of QT prolongation and hearing loss. Start at lower end of dosing range; monitor renal function and hearing. |
| 1st trimester | Erythromycin is generally considered safe in the first trimester; however, use only if clearly needed. No increased risk of major malformations has been observed in large epidemiological studies. |
| 2nd trimester | Erythromycin is generally considered safe in the second trimester; no known fetal risk. |
| 3rd trimester | Erythromycin is generally considered safe in the third trimester; however, rare cases of infantile hypertrophic pyloric stenosis have been associated with late pregnancy exposure. |
Clinical note
Inhibits CYP3A4 increasing levels of many drugs (eg statins carbamazepine) May cause QT prolongation and subsequent arrhythmias.
| FDA category | Human |
| Placental transfer | Erythromycin crosses the placenta; fetal serum levels are approximately 1-20% of maternal serum levels. |
■ FDA Black Box Warning
Increased risk of infantile hypertrophic pyloric stenosis (IHPS) when used in neonates; also, QT prolongation and Torsades de Pointes, especially with IV administration or in patients with risk factors.
| Common Effects | Nausea |
| Serious Effects |
Hypersensitivity to erythromycin or any macrolide antibioticPatients receiving terfenadine, astemizole, cisapride, pimozide, ergotamine, or dihydroergotamine (due to risk of QT prolongation and torsades de pointes)Hepatic dysfunction in combination with certain drugs (e.g., statins metabolized by CYP3A4)
| Precautions | QT prolongation and risk of cardiac arrhythmias; avoid with other QT-prolonging drugs., Hepatotoxicity (especially with estolate salt)., Exacerbation of myasthenia gravis., Clostridium difficile-associated diarrhea., Potential for drug interactions due to CYP3A4 inhibition. |
| Food/Dietary |
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| Breastfeeding |
| Erythromycin is excreted into breast milk in small amounts, but it is generally considered compatible with breastfeeding. Monitor the infant for potential adverse effects such as gastrointestinal disturbances and rash. No evidence of harm to nursing infants. |
| Lactation Rating | L1 (Compatible) |
| Teratogenic Risk | FDA Category B. No evidence of teratogenicity in animal studies. Limited human data: no increased risk of major malformations reported. Use during pregnancy only if clearly needed. |
| Fetal Monitoring | Monitor maternal liver function tests, hearing (especially with high doses or renal impairment), and signs of QT prolongation (ECG if risk factors). Fetal monitoring not routinely required. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies show no impairment. |
| Grapefruit and grapefruit juice should be avoided as they inhibit CYP3A4 metabolism, increasing erythromycin plasma concentrations and risk of QT prolongation and other toxicities. High-fat meals may delay absorption but do not significantly alter overall bioavailability. Alcohol does not directly interact but may exacerbate gastrointestinal side effects. |
| Clinical Pearls | Erythromycin is a macrolide antibiotic that also acts as a motilin receptor agonist, causing prokinetic effects. It is commonly used for gastrointestinal dysmotility. It is a potent inhibitor of CYP3A4, leading to significant drug interactions, especially with statins and warfarin. Intravenous administration carries risk of QT prolongation and sudden cardiac death, particularly in patients with preexisting heart disease or electrolyte abnormalities. Consider alternative agents in patients on QT-prolonging drugs or with prolonged QTc. |
| Patient Advice | Take erythromycin exactly as prescribed and for the full duration, even if you feel better. · Do not crush or chew enteric-coated tablets; swallow them whole with a full glass of water. · Avoid grapefruit juice while taking this medication as it can increase blood levels and risk of side effects. · If you miss a dose, take it as soon as you remember unless it is almost time for the next dose; do not double the dose. · Common side effects include nausea, vomiting, abdominal cramps, and diarrhea; if severe or bloody diarrhea occurs, contact your doctor immediately. · Inform your doctor of all medications you are taking, especially blood thinners, statins, and other antibiotics. · Seek emergency care if you experience chest pain, palpitations, fainting, or severe dizziness, as this drug can affect heart rhythm. |