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Erythromycin Ethylsuccinate / Sulfisoxazole Acetyl

Pronunciation: e-RITH-roe-MYE-sin ETH-il-SUX-i-nate/SUL-fi-SOX-a-zole a-SEET-il
Class: Antibiotic combination

Trade Names

Erythromycin and Sulfisoxazole
- Granules for suspension, oral Erythromycin 200 mg/sulfisoxazole 600 mg per 5 mL


Erythromycin suppresses bacterial protein synthesis; sulfonamides interfere with bacterial folic acid synthesis.

Indications and Usage

Treatment of acute otitis media in children caused by susceptible strains of Haemophilus influenzae .

Unlabeled Uses

Sinusitis in children/adolescents.


Hypersensitivity to either erythromycin or sulfisoxazole; children younger than 2 mo; pregnant women at term; mothers breast-feeding infants younger than 2 mo; concomitant use with terfenadine.

Dosage and Administration

Children 2 mo and older

PO Erythromycin 50 mg/kg/day or sulfisoxazole 150 mg/kg/day (max, sulfisoxazole 6 g/day) in equally divided doses 3 or 4 times daily for 10 days.

General Advice

  • May be administered with or without food.
  • Shake suspension well before administrating dose.


Store granules at room temperature. Store reconstituted suspension between 26° and 46°F. Do not freeze. Discard any unused suspension after 14 days.

Drug Interactions

Anticoagulants (eg, warfarin)

The anticoagulant effect of warfarin may be increased by erythromycin and sulfisoxazole. Monitor anticoagulant activity and adjust the warfarin dose as needed.

Azole antifungal agents (eg, ketoconazole)

Erythromycin plasma concentrations may be elevated, increasing the risk of erythromycin adverse reactions, including sudden death from cardiac causes. Avoid coadministration.

Benzodiazepines (eg, midazolam, triazolam)

Erythromycin may decrease Cl of benzodiazepines undergoing oxidative metabolism, increasing the pharmacologic effects and risk of adverse reactions (eg, sedation, prolonged sedation). Monitor for increased or prolonged sedation. Adjust the benzodiazepine dose as needed. Benzodiazepines undergoing conjugative metabolism (eg, temazepam) may be a safer alternative.


Bromocriptine serum concentrations may be elevated, increasing the pharmacologic effects and risk of toxicity.


The antiplatelet effect of clopidogrel may be inhibited. Closely monitor platelet function when starting or stopping erythromycin. Because azithromycin does not inhibit CYP3A4, it may be a safer alternative.


Colchicine concentrations may be elevated because of CYP3A4 inhibition by erythromycin, increasing the pharmacologic effects and risk of adverse reactions. Coadminister with caution and monitor for colchicine-related toxicity. The recommended colchicine dose for the treatment of a gout flare in patients receiving erythromycin is 1.2 mg for 1 dose. A 3-day lapse should occur before subsequent colchicine administration. The recommended maximum colchicine dosage for treatment of familial Mediterranean fever in patients receiving erythromycin is 1.2 mg daily.

CYP3A4 substrates (eg, alfentanil, atorvastatin, bromocriptine, buspirone, cabergoline, carbamazepine, cilostazol, cinacalcet, cisapride, cyclosporine, disopyramide, eletriptan, eplerenone, eszopiclone, everolimus, felodipine, fentanyl, fesoterodine, imatinib, lovastatin, lurasidone, maraviroc, meglitinides [eg, nateglinide, repaglinide], phenytoin, phosphodiesterase type 5 inhibitors [eg, sildenafil, tadalafil, vardenafil], protease inhibitors [eg, ritonavir], quetiapine, ranolazine, roflumilast, serotonin reuptake inhibitors [eg, sertraline], simvastatin, sirolimus, tacrolimus, tolterodine, tolvaptan)

Serum concentrations of these drugs may be elevated because of CYP3A4 inhibition by erythromycin, increasing the pharmacologic effects and risk of adverse reactions. Close clinical and laboratory monitoring of these agents is warranted. Rhabdomyolysis with or without renal impairment has been reported in seriously ill patients receiving erythromycin concurrently with lovastatin. Adjust the dose of these drugs as needed. In certain instances, avoid coadministration (eg, simvastatin, tolvaptan).


May increase digoxin levels, increasing the risk of toxicity. Clinical and laboratory monitoring of digoxin is warranted. Adjust the digoxin dose as needed.


Erythromycin plasma concentrations may be elevated, increasing the risk of erythromycin adverse reactions. Avoid coadministration.


Dronedarone CYP3A4 metabolism is inhibited by erythromycin, increasing dronedarone concentrations and risk of adverse reactions . In addition, possible additive QT prolongation may occur, increasing the risk of life-threatening cardiac arrhythmias. Coadministration is contraindicated.


Erythromycin plasma concentrations may be reduced. Azithromycin may be a suitable alternative.

Ergot derivative (eg, dihydroergotamine, ergotamine)

Coadministration of erythromycin and ergot derivatives has been associated with acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia. Coadministration is contraindicated.

Grapefruit juice

Erythromycin plasma concentrations may be increased by concurrent use of grapefruit juice. Avoid concomitant use because elevated concentrations of erythromycin have been associated with an increased risk of sudden death from cardiac causes.


Methenamine is contraindicated for use with sulfisoxazole because of the potential for formation of insoluble precipitates in the urine.


Sulfonamides can displace methotrexate from protein-binding sites and increase free methotrexate levels. The pharmacologic effects of methotrexate may be increased. Toxicity characterized by bone marrow suppression has been reported. If coadministration cannot be avoided, monitor hematologic status. Discontinue both drugs if an interaction is suspected.


Plasma concentrations and pharmacologic effects of pitavastatin may be increased by erythromycin. If coadministration of erythromycin cannot be avoided, the pitavastatin dosage should not exceed 1 mg daily.

QT-prolonging drugs (eg, antiarrhythmic agents [eg, amiodarone, bretylium, disopyramide, dofetilide, procainamide, quinidine, sotalol], arsenic trioxide, chlorpromazine, cisapride, dolasetron, droperidol, gatifloxacin, halofantrine, levomethadyl, mefloquine, mesoridazine, moxifloxacin, pentamidine, pimozide, probucol, sparfloxacin, tacrolimus, thioridazine, ziprasidone)

The risk of life-threatening cardiac arrhythmias, including torsades de pointes, is increased. Caution is advised when 2 drugs that are suspected to prolong the QT interval are given concurrently. If coadministration is not contraindicated in the respective product information, monitor patients for QT prolongation, especially when a new drug is added to a stable regimen of another QT-prolonging agent.

Rifamycins (eg, rifampin)

Pharmacologic and toxic effects of rifamycins may be increased. Plasma concentrations and pharmacologic effects of erythromycin may be decreased. Dosage reduction of rifamycins may be needed, while larger doses of erythromycin may be needed.

Sulfonylureas (eg, glipizide)

Sulfisoxazole may potentiate hypoglycemic effects. Monitor blood glucose concentrations and observe the patient for signs of hypoglycemia. Adjust the sulfonylurea dose as needed.


May increase theophylline plasma concentrations, increasing the risk of toxicity. Erythromycin concentrations may be reduced, decreasing the pharmacologic effect. Monitor theophylline concentrations when starting or stopping erythromycin. Adjust dosages as needed. Consider using an anti-infective agent that is unlikely to interact.


May enhance anesthetic effects of thiopental. Lower doses of thiopental may be needed. Monitor the clinical response and adjust the thiopental dose as needed.


Additive phototoxicity may occur. Avoid concomitant use.

Tyrosine kinase receptor inhibitors (eg, dasatinib, lapatinib, sorafenib)

Tyrosine kinase receptor inhibitor CYP3A4 metabolism is inhibited by erythromycin, increasing the concentrations and risk of adverse reactions. In addition, possible additive QT prolongation may occur, increasing the risk of life-threatening cardiac arrhythmias. If coadministration cannot be avoided, close clinical monitoring for signs of adverse effects due to the tyrosine kinase receptor inhibitors is warranted. Monitor for the occurrence of QT prolongation.


Erythromycin and verapamil plasma concentrations may be elevated, increasing the risk of sudden death from cardiac causes. Avoid concurrent use.

Vinca alkaloids (eg, vinblastine, vinorelbine)

Vinca alkaloid plasma concentrations may be elevated, increasing the pharmacologic effects and risk of toxicity (eg, neutropenia). If coadministration of these agents cannot be avoided, closely monitor the patient and adjust the vinca alkaloid dose as needed.

Laboratory Test Interactions

Erythromycin interferes with the fluorometric determinations of urinary catecholamines.

Adverse Reactions


Cyanosis; palpitations; syncope; tachycardia; vasculitis; ventricular arrhythmias, including ventricular tachycardia and torsades de pointes in patients with prolonged QT intervals.


Anxiety; ataxia; convulsions; depression; disorientation; dizziness; drowsiness; fatigue; hallucinations; headache; insomnia; intracranial hypertension; lassitude; paresthesia; peripheral neuritis; psychosis; vertigo.


Diuresis, goiter, hypoglycemia (rare).


Abdominal pain; anorexia; diarrhea; emesis; flatulence; GI hemorrhage; glossitis; melena; nausea; pancreatitis; pseudomembranous colitis; salivary gland enlargement; stomatitis; vomiting.


Acute renal failure; crystalluria; hematuria; increased BUN and creatinine; nephritis; toxic nephrosis with oliguria and anuria; urinary retention.


Abnormal LFT results; hepatic dysfunction; hepatitis; hepatocellular necrosis; jaundice.


Agranulocytosis; anemia; aplastic anemia; clotting disorders, including hypoprothrombinemia and hypofibrinogenemia; eosinophilia; hemolytic anemia; leukopenia; methemoglobinemia; purpura; sulfhemoglobinemia; thrombocytopenia.


Allergic myocarditis; anaphylaxis; angioedema; arteritis; conjunctival and scleral injection; erythema multiforme (Stevens-Johnson syndrome); exfoliative dermatitis; photosensitivity; pruritus; rash; serum sickness; skin eruptions; TEN (Lydell syndrome); urticaria; vasculitis.


Cough; pneumonitis; pulmonary infiltrates; shortness of breath.


Edema (including periorbital); fever; flushing; hearing loss; periarteritis nodosum; reversible hearing loss; rigors; systemic lupus erythematosus; weakness.



Monitor CBC frequently. Perform urinalysis with microscopic examination and renal function tests, particularly in patients with impaired renal function. Monitor sulfisoxazole blood levels in patients with serious infections.


Category C . Use in pregnant women at term is contraindicated.


Excreted in breast milk.


Do not expose children younger than 2 mo (directly or through breast milk) to sulfonamides because of risk of kernicterus.

Renal Function

Use with caution in patients with renal impairment.

Hepatic Function

Use with caution in patients with hepatic impairment.

Special Risk Patients

May aggravate weakness in patients with myasthenia gravis. Use drug with caution in patients with severe allergies. Dose-related hemolytic anemia may occur in patients with G-6-PD deficiency.


Prolonged use may result in bacterial or fungal overgrowth of nonsusceptible microorganisms.


Rare fatalities from severe reactions including Stevens-Johnson syndrome, TEN, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias have been reported with sulfonamides.

Group A beta-hemolytic streptococci

Do not use sulfonamides for the treatment of group A beta-hemolytic streptococcal infections.

Hepatic effects

Hepatotoxicity has been associated with erythromycin.


May occur, especially in patients with renal insufficiency and with administration of large doses.

Pseudomembranous colitis

Consider possibility in patients with diarrhea.

Respiratory effects

Cough, shortness of breath, and pulmonary infiltrates are hypersensitivity reactions reported in association with sulfonamide treatment. Use with caution in patients with bronchial asthma.



Anorexia, blood dyscrasias, colic, crystalluria, diarrhea, dizziness, drowsiness, fever, headache, hematuria, jaundice, nausea, unconsciousness, vomiting.

Patient Information

  • Instruct patient/family to follow complete course of therapy.
  • Instruct patient to report these symptoms to health care provider: abdominal pain, bleeding, cyanosis, diarrhea, hallucinations, inability to void, palpitations, rash, seizures, shortness of breath, signs of superinfection, syncope, tachycardia, urticaria.
  • Caution patient to avoid exposure to sunlight and to use sunscreen or wear protective clothing to avoid photosensitivity reaction.
  • Instruct patient to maintain adequate fluid intake to prevent crystalluria and stone formation.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.