ILOSONE SULFA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ILOSONE SULFA (ILOSONE SULFA).
Ilosone (erythromycin) is a macrolide antibiotic that inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit. Sulfa (sulfisoxazole) is a sulfonamide that inhibits dihydropteroate synthase, blocking folate synthesis. The combination provides synergistic bacteriostatic activity.
| Metabolism | Erythromycin is primarily metabolized by CYP3A4; sulfisoxazole is acetylated and glucuronidated in the liver, with metabolites excreted renally. |
| Excretion | Renal: 70-80% as unchanged drug and active metabolite (sulfisoxazole); Biliary: 10-15% as metabolites; Fecal: <5% |
| Half-life | Erythromycin: 1.5-2 hours; Sulfisoxazole: 4-7 hours; clinical context: dose adjustment in renal impairment (CrCl <50 mL/min) needed for sulfisoxazole |
| Protein binding | Erythromycin: 65-90% bound to albumin and alpha-1-acid glycoprotein; Sulfisoxazole: 50-60% bound to albumin |
| Volume of Distribution | Erythromycin: 0.6-0.9 L/kg; Sulfisoxazole: 0.15-0.3 L/kg; clinical meaning: erythromycin distributes into tissues (e.g., prostate, lung), sulfisoxazole remains largely in extracellular fluid |
| Bioavailability | Oral: 30-65% (erythromycin base), variability due to gastric acid degradation; enteric-coated formulation 30-40% |
| Onset of Action | Oral: 1-2 hours (therapeutic concentrations); time to clinical effect: 24-48 hours for symptom improvement |
| Duration of Action | Dosing interval every 6 hours; clinical notes: sustained concentration for 6 hours with typical dosing, longer in renal impairment |
| Molecular Weight | Erythromycin estolate: 1056.4 Da; Trisulfapyrimidines: ~214.2 Da each |
Each 5 mL suspension contains 250 mg erythromycin base and 600 mg sulfisoxazole; typical adult dose is 10 mL (2 tsp) every 6 hours, not to exceed 40 mL/day.
| Dosage form | SUSPENSION |
| Renal impairment | Contraindicated in severe renal impairment (CrCl <15 mL/min); for CrCl 15-50 mL/min, reduce dose by 50% and give every 12-24 hours; monitor for sulfonamide toxicity. |
| Liver impairment | Child-Pugh A: No adjustment; Child-Pugh B: Caution, reduce dose by 50%; Child-Pugh C: Avoid use due to risk of erythromycin hepatotoxicity and sulfonamide accumulation. |
| Pediatric use | For children >2 months: based on sulfisoxazole component (50 mg/kg/day) or erythromycin component (30-50 mg/kg/day) divided every 6 hours, maximum 2 g/day sulfisoxazole. Weight-based: <8 kg: 10 mg/kg erythromycin every 6 hours; 8-16 kg: 1/2 tsp every 6 hours; >16 kg: 1 tsp every 6 hours. |
| Geriatric use | Lower initial dose due to age-related renal and hepatic decline; start at 5 mL every 6 hours, titrate carefully; monitor renal function and serum levels of sulfisoxazole, as increased risk of adverse effects (renal, hepatic, skin reactions). |
| 1st trimester | Avoid due to sulfonamide component which may cause kernicterus and teratogenic effects like cleft palate; erythromycin estolate is contraindicated in pregnancy due to hepatotoxicity risk. |
| 2nd trimester | Avoid; risk of hepatotoxicity from erythromycin estolate and kernicterus from sulfonamide. |
| 3rd trimester | Avoid; sulfonamide increases risk of kernicterus in neonates; erythromycin estolate may cause maternal hepatotoxicity. |
Clinical note
Comprehensive clinical and safety monograph for ILOSONE SULFA (ILOSONE SULFA).
| Placental transfer | Both erythromycin and sulfonamide cross the placenta; sulfonamide reaches fetal concentrations 50-90% of maternal levels. |
| Breastfeeding | Contraindicated during breastfeeding due to sulfonamide excretion into breast milk which may cause kernicterus in infants with G6PD deficiency or hyperbilirubinemia; erythromycin estolate is associated with infantile hypertrophic pyloric stenosis. |
■ FDA Black Box Warning
WARNING: HEPATIC DYSFUNCTION — Erythromycin has been associated with severe hepatic toxicity, including jaundice and hepatitis, especially when used in combination with sulfonamides. Discontinue immediately if signs of hepatic injury occur.
| Serious Effects |
Hypersensitivity to erythromycin, sulfonamides, or any componentPreexisting liver disease or hepatic impairmentPatients receiving concomitant cisapride, pimozide, or ergotamine/dihydroergotamine (risk of QT prolongation with erythromycin)Infants less than 2 months of age (risk of kernicterus from sulfonamide)Pregnancy (especially near term) and breastfeeding
| Precautions | Hepatotoxicity: Monitor liver function tests; avoid in patients with pre-existing liver disease, Sulfonamide hypersensitivity reactions (including Stevens-Johnson syndrome), QT prolongation and risk of cardiac arrhythmias (erythromycin), Renal impairment: Dose adjustment may be necessary for sulfisoxazole, Crystalluria: Ensure adequate fluid intake to prevent sulfonamide crystal formation |
| Food/Dietary | Avoid alcohol due to disulfiram-like reaction with erythromycin. Take on an empty stomach (1 hour before or 2 hours after meals) with a full glass of water. May reduce absorption of some foods; no specific dietary restrictions. Maintain adequate hydration. |
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| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Pregnancy Category D (erythromycin estolate) and C (trisulfapyrimidines). First trimester: Sulfonamides cross placenta; risk of neural tube defects, cardiovascular anomalies, oral clefts. Later trimesters: Sulfonamides displace bilirubin, risk of kernicterus in fetus; erythromycin estolate associated with hepatotoxicity in mother. Avoid in pregnancy unless no alternative. |
| Fetal Monitoring | Monitor maternal liver function tests (LFTs) due to erythromycin estolate hepatotoxicity risk; baseline and periodic LFTs. Fetal monitoring: Ultrasound for congenital anomalies if exposure in first trimester. Monitor neonate for jaundice and kernicterus after delivery. |
| Fertility Effects | No known clinically significant effects on fertility. Erythromycin and sulfonamides do not impair gametogenesis or reproductive function in animal studies. |
| Clinical Pearls | Ilosone Sulfa is a fixed-dose combination of erythromycin (a macrolide antibiotic) and sulfisoxazole (a sulfonamide). Use is limited to acute otitis media in children with susceptible strains. Monitor for hypersensitivity reactions, especially to sulfa component. Erythromycin can prolong QTc interval; coadministration with QTc-prolonging drugs increases arrhythmia risk. Sulfisoxazole may cause crystalluria; ensure adequate hydration. Avoid in infants <2 months due to sulfonamide-induced kernicterus. |
| Patient Advice | Take exactly as prescribed; complete full course even if feeling better. · Drink plenty of fluids to prevent kidney stones from sulfa component. · Avoid sun exposure; use sunscreen as sulfonamides increase photosensitivity. · Report rash, fever, sore throat, or unusual bleeding/bruising immediately. · May cause diarrhea; contact provider if severe or bloody. · Do not take with antacids; separate by at least 2 hours. |