ERYTHROMYCIN ETHYLSUCCINATE AND SULFISOXAZOLE ACETYL
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 inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit, blocking peptide chain elongation. Sulfisoxazole acetyl is a sulfonamide that inhibits dihydropteroate synthase, blocking folic acid synthesis.
| Metabolism | Erythromycin ethylsuccinate is metabolized by CYP3A4; sulfisoxazole acetyl is metabolized by N-acetylation and glucuronidation. |
| Excretion | Erythromycin ethylsuccinate is primarily excreted in bile (up to 80% as unchanged drug), with about 12-15% eliminated renally. Sulfisoxazole acetyl is renally excreted, with approximately 85% of the dose appearing in urine as acetylated and deacetylated metabolites. Fecal elimination accounts for less than 10% of sulfisoxazole. |
| Half-life | Erythromycin: terminal half-life of 1.4-2.0 hours in adults; prolonged to 4-6 hours in anuria. Sulfisoxazole: half-life 4.5-7 hours in adults; increased in renal impairment. The combination's clinical context warrants dosing interval adjustments in renal dysfunction. |
| Protein binding | Erythromycin: 70-90% bound to albumin. Sulfisoxazole: approximately 85% bound to albumin. Binding is concentration-dependent and may be displaced by other highly bound drugs. |
| Volume of Distribution | Erythromycin: Vd approximately 0.6-0.8 L/kg, indicating extensive tissue distribution. Sulfisoxazole: Vd 0.15-0.3 L/kg, primarily confined to extracellular fluid. Clinical: higher Vd of erythromycin supports its use in intracellular infections. |
| Bioavailability | Erythromycin ethylsuccinate: oral bioavailability is 30-65% due to first-pass metabolism; food may increase absorption. Sulfisoxazole acetyl: well absorbed orally, bioavailability >90%. |
| Onset of Action | Oral administration: clinical effect (e.g., fever reduction, symptom improvement) typically begins within 24-48 hours for susceptible infections; peak serum concentrations achieved by 1-4 hours. |
| Duration of Action | Erythromycin: bacteriostatic levels persist for 6-8 hours after a single dose. Sulfisoxazole: therapeutic levels maintained for 8-12 hours. The combination is usually dosed every 6-8 hours. Note: duration may be shorter for highly susceptible pathogens. |
Erythromycin ethylsuccinate (400 mg) and sulfisoxazole acetyl (600 mg) per 5 mL suspension: 2-3 teaspoonfuls (10-15 mL) orally every 6 hours for 10-14 days. Maximum daily dose: 6 g sulfisoxazole.
| Dosage form | GRANULE |
| Renal impairment | GFR >50 mL/min: no adjustment. GFR 10-50 mL/min: administer every 8-12 hours. GFR <10 mL/min: administer every 12-24 hours. Avoid in severe renal impairment (CrCl <10 mL/min) due to sulfonamide accumulation. |
| 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 for toxicity. |
| Pediatric use | Children 2 months to 12 years: based on sulfisoxazole component: initial dose 75 mg/kg, then 150 mg/kg/day divided every 6 hours (max 6 g/day). Use weight-based dosing: erythromycin ethylsuccinate 50 mg/kg/day and sulfisoxazole acetyl 150 mg/kg/day divided every 6 hours. |
| Geriatric use | Elderly patients are more susceptible to sulfonamide adverse effects (e.g., severe skin reactions, hematologic toxicity). Monitor renal function closely; adjust dose for GFR. Caution with potassium- and magnesium-sparing diuretics (hyperkalemia, sulfonamide potentiation). Standard adult dose may be reduced by 25-50% if GFR <60 mL/min. |
| 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 | Both erythromycin and sulfisoxazole are excreted into breast milk in small amounts. Erythromycin M/P ratio not well defined; estimated milk-plasma ratio ~0.4-0.5. Sulfisoxazole M/P ratio ~0.1-0.3. Risk of infant kernicterus from sulfisoxazole due to bilirubin displacement; contraindicated in nursing infants with G6PD deficiency, hyperbilirubinemia, or prematurity. American Academy of Pediatrics considers sulfonamides as maternal medication usually compatible with breastfeeding if infant is healthy and full-term. Use only if benefit outweighs risk. |
■ FDA Black Box Warning
None
| Common Effects | Nausea |
| Serious Effects |
["Hypersensitivity to erythromycin, sulfonamides, or any component","Concomitant use with cisapride, pimozide, ergotamine, or dihydroergotamine","History of cholestatic jaundice or hepatic dysfunction with erythromycin","Infants less than 2 months of age (sulfonamide risk of kernicterus)","Porphyria"]
| Precautions | ["Hepatic toxicity including jaundice and hepatitis","QT interval prolongation and risk of cardiac arrhythmias (especially with CYP3A4 inhibitors)","Clostridioides difficile-associated diarrhea","Severe cutaneous adverse reactions (e.g., Stevens-Johnson syndrome) with sulfonamide component","Hypersensitivity reactions","Hematologic changes (agranulocytosis, aplastic anemia) with sulfonamides"] |
Loading safety data…
| Teratogenic Risk | Pregnancy Category C (original FDA). First trimester: Sulfisoxazole, a sulfonamide, competes with bilirubin for protein binding, increasing risk of kernicterus if used near term. Erythromycin ethylsuccinate not associated with major malformations but limited data. Second and third trimesters: Sulfisoxazole risk of neonatal jaundice and hemolytic anemia in G6PD-deficient infants; avoid after 32 weeks. Overall risk appears low but caution advised. |
| Fetal Monitoring | Monitor maternal liver function, renal function, and CBC with differential due to sulfonamide adverse effects. Monitor infant for jaundice, hemolytic anemia, and kernicterus signs if used near term or during nursing. Assess fetal growth and well-being via ultrasound if prolonged use. Baseline G6PD screening in infant if breastfed. |
| Fertility Effects | No known adverse effects on fertility from erythromycin ethylsuccinate or sulfisoxazole. No human studies indicating impaired fertility. Animal studies limited but no evidence of reproductive toxicity at therapeutic doses. |