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Erythromycin

Hazardous Substances DataBank Number
3074
Related PubChem Records
Related CIDs

1 Human Health Effects

1.1 Human Toxicity Excerpts (Complete)

/SIGNS AND SYMPTOMS/ Initiation of erythromycin therapy in some patients stabilized on warfarin has resulted in prolongation of prothrombin time and bleeding. Increased anticoagulant effect may be more pronounced in geriatric patients. The exact mechanism(s) of this interaction has not been clearly established, but erythromycin may inhibit hepatic metabolism of warfarin. Prothrombin time should be monitored more closely than usual in patients receiving warfarin when erythromycin therapy is initiated, and warfarin dosage should be adjusted as necessary
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 233
Prolongation of the QT interval and development of ventricular arrhythmias, including atypical ventricular tachycardia (torsades de pointes), have been reported rarely with oral or IV erythromycin. Most reported cases have involved IV administration of the drug; limited data suggest that these adverse cardiac effects may depend on serum concentrations and/or rate of infusion of the drug. Erythromycin has exhibited concentration-dependent, reversible effects on cardiac conduction in electrophysiologic studies in humans and in Purkinje fibers isolated from dogs similar to those exhibited by class IA antiarrhythmic agents such as quinidine. Erythromycin prolongs the QT interval and blocks the potassium channel encoded by the human ether-a-gogo-related gene (HERG). It has been suggested that erythromycins be used with caution in patients at risk for QT prolongation and/or accumulation of the anti-infective, particularly when the drug is administered IV. Some clinicians suggest that decreasing the rate of IV infusion of erythromycin may reduce the risk of cardiac toxicity; however, decreasing the rate may not eliminate the risk, and discontinuance of the drug may be necessary. Additional study and experience are needed to elucidate further the mechanisms and possible risk factors for the development of this toxicity.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 232
In a population-based study, concomitant use of oral erythromycin and drugs that inhibit CYP3A (i.e., diltiazem, verapamil) was associated with an increased incidence of sudden death from cardiac causes. There was no increase in sudden cardiac death when oral erythromycin was used with calcium-channel blocking agents that do not inhibit CYP3A to a clinically important extent (e.g., nifedipine). Concomitant use of erythromycin and diltiazem or verapamil presumably increased plasma erythromycin concentrations resulting in an increased risk of QT prolongation (a dose-associated effect of erythromycin) and serious ventricular arrhythmias. In addition, erythromycin (a CYP3A inhibitor) is likely to increase plasma concentrations of diltiazem or verapamil leading to an increased risk of adverse effects associated with these drugs. Concomitant use of erythromycin and diltiazem or verapamil should be avoided.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 233
Concomitant use of erythromycin and digoxin has resulted in increased serum concentrations of digoxin, and initiation of erythromycin therapy in several patients receiving disopyramide reportedly has been associated with elevated serum disopyramide concentrations, QT-interval prolongation, and polymorphic ventricular tachycardia. In at least one patient, concomitant administration of oral quinidine sulfate and IV erythromycin lactobionate resulted in increased serum quinidine concentrations and possible quinidine toxicity including asymptomatic, nonsustained ventricular tachycardia. It has been suggested that quinidine concentrations and ECGs be monitored closely if erythromycin is used concomitantly with quinidine.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 233
/HUMAN EXPOSURE STUDIES/ To evaluate the risk for infantile hypertrophic pyloric stenosis among infants prescribed systemic erythromycin, infants prescribed a course of erythromycin ophthalmic ointment, and infants whose mothers were prescribed a macrolide antibiotic during pregnancy. ... Of 14,876 eligible infants, 43 (0.29%) developed infantile hypertrophic pyloric stenosis. Infants prescribed systemic erythromycin had increased risk of infantile hypertrophic pyloric stenosis, with the highest risk in the first 2 weeks of age (relative risk = 10.51 for erythromycin in first 2 weeks, 95% CI 4.48, 24.66). Erythromycin ophthalmic ointment for conjunctivitis was not associated with increased risk of infantile hypertrophic pyloric stenosis. Maternal macrolide antibiotics within 10 weeks of delivery may have been associated with higher risk of infantile hypertrophic pyloric stenosis but the data were not conclusive. This study confirms an association between systemic erythromycin in infants and subsequent infantile hypertrophic pyloric stenosis, with the highest risk in the first 2 weeks of age. No association was found with erythromycin ophthalmic ointment. A possible association with maternal macrolide therapy in late pregnancy requires further study. Systemic erythromycin should be used with prudence in early infancy.
Mahon BE et al; J Pediatr 139 (3): 380-4 (2001).
/CASE REPORTS/ A case of intravenous precipitation of erythromycin is reported along with the patient history, pathologic findings, and a description of the analytical methods and results. The patient was a 75-year-old woman with a history of myocardial infarction, deep venous thrombosis, and diabetes mellitus who underwent aortic valve replacement. She developed endocarditis and recurrent episodes of urosepsis, with multiple organ failure including severe gastric retention, for which she was treated with erythromycin intravenously. She died because of refractory septic shock. Autopsy revealed aortic valve endocarditis, thrombi in the right femoral vein, arterial (nonfungal) thromboemboli in the celiac trunk, and coarse material in the right femoral vein where the tip of the central venous catheter had been located. Microscopical examination of the coarse material showed that it was birefringent crystalline material. Part of the postmortem material was analyzed in the laboratory of the department of clinical pharmacy and revealed the presence of erythromycin. Erythromycin was detected using Fourier transform infrared spectroscopy. An additional specific color test and thin-layer chromatography confirmed this finding. On the basis of the postmortem findings, patient history, and analytical-toxicologic results, we conclude that erythromycin precipitation can occur in vivo after intravenous administration in patients with impaired blood flow.
Buiter HJ et al; Ther Drug Monit 30 (1): 125-9 (2008).
/CASE REPORTS/ Two cases of severe hearing loss due to intravenous administration of erythromycin lactobionate are described. Documented, bilateral sensorineuronal hearing loss developed in both patients and gradually improved when the dose of erythromycin was decreased. Neither patient had severe renal dysfunction (documented clearances of 25 to 30 mL/min), but both had hepatic dysfunction with elevated bilirubin levels. Additionally, both were receiving other ototoxic drugs concurrently. Both patients also had an acute psychotic reaction that was temporally related to the ototoxicity and high-dose erythromycin therapy. /Erythromycin lactobionate/
Umstead GS, Neumann KH; Arch Intern Med 146 (5): 897-9 (1986).
/CASE REPORTS/ ... A 15-year-old girl presented for care because of severe epigastric pain after an overdose of 5.3 g (16 x 333 mg tablets) of erythromycin base. Her physical examination was normal except for epigastric tenderness. Her serum lipase was 2024 U/L (normal, <60). She was treated with intravenous fluids and an opiate analgesic. Her serum lipase declined to 1834 and 73 U/L at 17 and 36 hours, respectively, after the initial measurement at which time she was asymptomatic. /This/ case supports transient pancreatitis as a potential consequence of erythromycin overdose.
Tenenbein MS, Tenenbein M; Pediatr Emerg Care 21 (10): 675-6 (2005).
/CASE REPORTS/ Bilateral sensorineural hearing loss developed in a 64-year-old woman treated with intravenous erythromycin lactobionate for bacteremic pneumococcal pneumonia. Discontinuance of the antibiotic led to prompt correction of the hearing deficit. Reversible hearing loss is an infrequently described adverse effect attributed to high-dose erythromycin therapy. Possible risk factors, including age, gender, and hepatic and renal function, may contribute to the development of erythromycin ototoxicity. /Erythromycin lactobionate/
Whitener CJ et al; South Med J 84 (10): 1214-6 (1991).
/CASE REPORTS/ Erythromycin is a frequently used antibiotic in patients with atypical respiratory infection and/or an allergy to penicillin. We report the case of a young woman who developed severe cholestasis and jaundice following treatment with erythromycin stearate. Two years later her general practitioner prescribed erythromycin succinate for pharyngitis. She experienced a severe second episode of jaundice and malaise. Different esters of erythromycin have been introduced to reduce side effects such as allergic reactions to erythromycin. The findings in our patient underline the fact that hypersensitivity is caused by the erythromycin molecule, independent from the type of esterification. Because of these side effects newer makrolides should be given preference over erythromycin.
Horn S et al; Wien Klin Wochenschr 111 (2): 76-7 (1999).
/CASE REPORTS/ A 24-year-old man who presented 12 years ago a systemic allergic reaction to penicillin, confirmed by skin tests and detection of specific IgE (RAST) /is reported/. Since then he had tolerated erythromycin on several occasions. Nine months ago, his general practitioner prescribed erythromycin orally as treatment for a respiratory infection. Thirty minutes after taking the first dose, 500 mg, he developed an anaphylactic reaction. The episode subsided with treatment with high dose corticosteroids, antihistamines, and epinephrine. Skin prick tests and intradermal tests were performed with erythromycin at different concentrations. We also measured total IgE and specific IgE to erythromycin by CAP and Phadezym RAST (Pharmacia, Uppsala, Sweden), respectively. We also performed a Prausnitz-Kustner test (PK test), and oral challenge test. Skin testing to erythromycin was not helpful because of cutaneous hyperreactiviness. No significant levels of specific IgE to erythromycin were detected. The oral challenge and the Prausnitz-Kustner test were positive. The positive history and oral challenge test suggested an anaphylactic reaction to erythromycin. The positive Prausnitz-Kustner test demonstrated the presence of specific IgE to erythromycin.
Jorro G et al; Ann Allergy Asthma Immunol 77 (6): 456-8 (1996).
/CASE REPORTS/ Cholestatic hepatitis developed in two patients while they were receiving erythromycin ethylsuccinate. Both patients had received the drug without apparent problem within two months of the episode of drug-related cholestatic injury. In both, there was complete resolution of the hepatic injury upon withdrawal of the drug. /Erythromycin ethylsuccinate/
Diehl AM et al; Am J Med 76 (5): 931-4 (1984).
/CASE REPORTS/ ... A 15-year-old girl presented for care because of severe epigastric pain after an overdose of 5.3 g (16 x 333 mg tablets) of erythromycin base. Her physical examination was normal except for epigastric tenderness. Her serum lipase was 2024 U/L (normal, <60). She was treated with intravenous fluids and an opiate analgesic. Her serum lipase declined to 1834 and 73 U/L at 17 and 36 hours, respectively, after the initial measurement at which time she was asymptomatic.
Pediatr Emerg Care 21 (10): 675-6 (2005).
/CASE REPORTS/ Two patients experienced hepatotoxicity associated with erythromycin estolate (Ilosone) usage, followed 13 and 15 years later by an hepatotoxic reaction with administration of erythromycin ethylsuccinate. These cases provide further evidence for erythromycin ethylsuccinate-associated hepatotoxicity and demonstrate erythromycin cross-sensitivity after previous erythromycin estolate liver injury. Hepatotoxicity to both sensitivity after previous erythromycin estolate liver injury. Hepatotoxicity to both estolate and ethylsuccinate preparations of erythromycin stimulates speculation regarding the potentially hepatotoxic moiety of the erythromycin molecule. Furthermore, these cases suggest that all erythromycin preparations should be avoided or used only with careful monitoring in patients with previous erythromycin-associated liver injury. /Erythromycin ethylsucciante, erythromycin estolate/
Keeffe EB et al; Dig Dis Sci 27 (8): 701-4 (1982).
/EPIDEMIOLOGY STUDIES/ ... A prospective, nested case-control study of assessment of auditory function in patients receiving erythromycin versus other antibiotics (control group) for community-acquired pneumonia /was conducted/. Sequential audiograms were performed during antibiotic therapy for both cases and controls by an audiologist unaware of the identity of the therapy administered. Erythromycin serum concentrations were obtained for all patients receiving erythromycin. Symptomatic ototoxicity (tinnitus or hearing loss) confirmed by audiograms was documented in five of 30 patients receiving erythromycin and none of 15 receiving other antibiotics. Ototoxicity was significantly related to high peak concentration and high AUC 0-infinity as a function of decreased total systemic clearance. Ototoxicity occurred only in those patients who received 4 g/day versus 2 g/day or no erythromycin (p = 0.05). Ototoxicity resolved in all patients within 6 to 14 days after discontinuation of therapy. Erythromycin ototoxicity is dose- and serum concentration-dependent. Patients receiving erythromycin, especially at a total daily dose of 4 g, should be monitored regularly for subjective evidence of sensorineural hearing dysfunction. Ototoxicity is reversible if the diagnosis is made early in the course.
Swanson DJ et al; Am J Med 92 (1): 61-8 (1992).

1.2 Skin, Eye, and Respiratory Irritations

Possible eye, skin, ... and/or respiratory tract irritation.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Erythromycin; Catalog Number: 1242000; (Revision Date: December 3, 2009)

1.3 Populations at Special Risk (Complete)

Erythromycin estolate is contraindicated in patients with hepatic dysfunction or preexisting liver disease. /Erythromycin estolate/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 238

2 Emergency Medical Treatment

2.1 Antidote and Emergency Treatment (Complete)

Decontamination: Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. /Antibacterial agents/
Olson, K.R. (Ed.); Poisoning & Drug Overdose. 5th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2007., p. 82
Emergency and supportive measures: Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, anaphylaxis, and hemolysis if they occur. Replace fluid losses resulting from gastroenteritis with intravenous crystalloids. ... /Antibacterial agents/
Olson, K.R. (Ed.); Poisoning & Drug Overdose. 5th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2007., p. 82
Enhanced elimination: Most antibiotics are excreted unchanged in the urine, so maintenance of adequate urine flow is important. The role of forced diuresis in unclear. Hemodialysis is not usually indicated, except perhaps in patients with renal dysfunction and a high level of a toxic agent. /Antibacterial agents/
Olson, K.R. (Ed.); Poisoning & Drug Overdose. 5th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2007., p. 82
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160-1

3 Animal Toxicity Studies

3.1 Non-Human Toxicity Excerpts (Complete)

/ALTERNATIVE and IN VITRO TESTS/ Hepatotoxicity was evaluated using lactate dehydrogenase leakage and morphometric analysis of representative populations of cells examined optically. Results of the two techniques provided parallel information: cells exposed to the higher concentrations of erythromycin estolate had significantly greater lactate dehydrogenase release and higher percentages of morphologically damaged cells. Planimetric analysis of a second set of hepatocytes showed increasing swelling of cells with increasing concentration of erythromycin estolate. Severe cellular swelling preceded disintegration, as hepatocytes became progressively more damaged by erythromycin estolate. /Erythromycin estolate/
Sorensen EM, Acosta D; Toxicol Lett 27 (1-3): 73-82 (1985)
/VETERINARY CASE REPORTS/ Erythromycin ethylsuccinate has been reported to induce severe colitis in horses which is associated with major changes of the intestinal microflora. The subsequent growth of Clostridium difficile has been demonstrated as a potential etiological agent in antibiotic-induced acute colitis. /Erythromycin ethylsuccinate/
Gupta, R. C. (ed.) Veterinary Toxicology: Basic and Clinical Principles. 1st ed. New York, NY, p.1101 (2007)

3.2 Ecotoxicity Excerpts (Complete)

/AQUATIC SPECIES/ ... A systematic mixture ecotoxicity study was performed with the aquaculture antibiotics oxytetracycline, oxolinic acid, erythromycin, florfenicol, and flumequine. Test organisms were freshwater algae (Pseudokirchneriella subcapitata), activated sludge microorganisms, and luminescent bacteria (Vibrio fischeri). Design and statistical analysis of test results were based on isobolographic analysis. Synergistic effects were observed when combinations of erythromycin and oxytetracycline were tested on activated sludge microorganisms, and in these cases model predictions indicate independent action on the different bacterial species in the sludge. As predicted from the modes of action, concentration addition was evident when flumequine and oxolinic acid were mixed and tested on sludge bacteria. In the algae test, the combined toxicity of antibiotics could not be predicted based on knowledge of the modes of action of the individual compounds. Independent of the test species, our results gave examples of combined effects that were higher than predicted based on the assumption of concentration addition. This result underlines the need to consider the effects of mixtures of antibiotics on environmental organisms. The isobolographic method appears to be a suitable tool for this purpose, particularly for well-defined mixtures with few substances.
Christensen AM et al; Environ Toxicol Chem 25 (8): 2208-15 (2006)
/AQUATIC SPECIES/ Recent evidence indicates that a variety of antibiotic residues may affect the integrity of streams located downstream from wastewater treatment plants. Aquatic communities comprising bacterial and fungal decomposers and invertebrate detritivores (shredders) play an important role in the decomposition of allochthonous leaf litter, which acts as a primary energy source for small running waters. The aim of the present study was to assess whether an antibiotic mixture consisting of sulfamethoxazole, trimethoprim, erythromycin-H2O, roxithromycin, and clarithromycin has an effect on such a decomposer-detritivore system. Leaf discs were exposed to these antibiotics (total concentration of 2 or 200 ug/L) for approximately 20 days before offering these discs and corresponding control discs to an amphipod shredder, Gammarus fossarum, in a food choice experiment. Gammarus preferred the leaf discs conditioned in the presence of the antibiotic mixture at 200 ug/L over the control discs (pair-wise t test; p = 0.006). A similar tendency, while not significant, was observed for leaves conditioned with antibiotics at a concentration of 2 ug/L. The number of bacteria associated with leaves did not differ between treatments at either antibiotic concentration (t test; p = 0.57). In contrast, fungal biomass (measured as ergosterol) was significantly higher in the 200 ug/L treatment (t test; p = 0.038), suggesting that the preference of Gammarus may be related to a shift in fungal communities. Overall these results indicate that mixtures of antibiotics may disrupt important ecosystem processes such as organic matter flow in stream ecosystems, although effects are likely to be weak at antibiotic concentrations typical of streams receiving wastewater treatment plant effluents.
Bundschuh M et al; Environ Toxicol Chem 28 (1): 197-203 (2009)

3.3 Non-Human Toxicity Values (Complete)

LD50 Rat oral 9272 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1596
LD50 Mouse ip 463 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1596
LD50 Mouse sc 1800 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1596
LD50 Mouse im 426 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1596
LD50 Guinea pig ip 413 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1596
LD50 Hamster oral 3018 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1596

3.4 Ecotoxicity Values (Complete)

EC50; Species: Penaeus vannamei (Whiteleg shrimp, 1st stage nauplii); Conditions: saltwater, static 25-29 °C; Concentration: 29200 ug/L for 24 hr; Effect: intoxication, immobilization /formulation/
Williams RR et al; J Aquat Anim Health 4 (4): 262-70 (1992) as cited in the ECOTOX database. Available from, as of January 20, 2010
EC50; Species: Penaeus vannamei (Whiteleg shrimp, 1st stage mysis); Conditions: saltwater, static 25-29 °C; Concentration: >50000 ug/L for 48 hr; Effect: intoxication, immobilization /formulation/
Williams RR et al; J Aquat Anim Health 4 (4): 262-70 (1992) as cited in the ECOTOX database. Available from, as of January 20, 2010
EC50; Species: Penaeus vannamei (Whiteleg shrimp, 1st stage post-larvae); Conditions: saltwater, static 25-29 °C; Concentration: >500000 ug/L for 48 hr; Effect: intoxication, immobilization /formulation/
Williams RR et al; J Aquat Anim Health 4 (4): 262-70 (1992) as cited in the ECOTOX database. Available from, as of January 20, 2010
EC50; Species: Penaeus vannamei (Whiteleg shrimp, post-larvae, post-larvaeIII-mysisI); Conditions: saltwater, static 25-29 °C; Concentration: 22700 ug/L for 48 hr; Effect: intoxication, immobilization /formulation/
Williams RR et al; J Aquat Anim Health 4 (4): 262-70 (1992) as cited in the ECOTOX database. Available from, as of January 20, 2010
EC50; Species: Penaeus vannamei (Whiteleg shrimp, 1st stage Protozoea); Conditions: saltwater, static 25-29 °C; Concentration: 37700 ug/L for 48 hr; Effect: intoxication, immobilization /formulation/
Williams RR et al; J Aquat Anim Health 4 (4): 262-70 (1992) as cited in the ECOTOX database. Available from, as of January 20, 2010
EC50; Species: Penaeus vannamei (Whiteleg shrimp, ProtozoeaIII-mysisI interface); Conditions: saltwater, static 25-29 °C; Concentration: 49800 ug/L for 48 hr; Effect: intoxication, immobilization /formulation/
Williams RR et al; J Aquat Anim Health 4 (4): 262-70 (1992) as cited in the ECOTOX database. Available from, as of January 20, 2010
LC50; Species: Penaeus vannamei (Whiteleg shrimp, 1st stage nauplii); Conditions: saltwater, static 25-29 °C; Concentration: 30800 ug/L for 24 hr /formulation/
Williams RR et al; J Aquat Anim Health 4 (4): 262-70 (1992) as cited in the ECOTOX database. Available from, as of January 20, 2010
LC50; Species: Penaeus vannamei (Whiteleg shrimp, 1st stage protozoea); Conditions: saltwater, static 25-29 °C; Concentration: >50000 ug/L for 48 hr /formulation/
Williams RR et al; J Aquat Anim Health 4 (4): 262-70 (1992) as cited in the ECOTOX database. Available from, as of January 20, 2010
LC50; Species: Penaeus vannamei (Whiteleg shrimp, 1st stage mysis); Conditions: saltwater, static 25-29 °C; Concentration: >50000 ug/L for 48 hr /formulation/
Williams RR et al; J Aquat Anim Health 4 (4): 262-70 (1992) as cited in the ECOTOX database. Available from, as of January 20, 2010
LC50; Species: Penaeus vannamei (Whiteleg shrimp, 1st stage post-larva); Conditions: saltwater, static 25-29 °C; Concentration: >50000 ug/L for 48 hr /formulation/
Williams RR et al; J Aquat Anim Health 4 (4): 262-70 (1992) as cited in the ECOTOX database. Available from, as of January 20, 2010
LC50; Species: Penaeus vannamei (Whiteleg shrimp, post-larvaIII-mysisI interface); Conditions: saltwater, static 25-29 °C; Concentration: 85000 ug/L for 48 hr /formulation/
Williams RR et al; J Aquat Anim Health 4 (4): 262-70 (1992) as cited in the ECOTOX database. Available from, as of January 20, 2010
LC50; Species: Morone saxatilis (Striped bass, fry, 1 g); Conditions: freshwater, static, 12 °C, hardness 40 mg/L CaCO3; Concentration: 349000 ug/L for 96 hr (95% confidence interval: 266000-457000 ug/L) /formulation/
Bills TD et al; USDI FWS Resour Publ 192: 11 (1993) as cited in the ECOTOX database. Available from, as of January 20, 2010

4 Metabolism / Pharmacokinetics

4.1 Metabolism / Metabolites (Complete)

Twenty hours after an oral administration of 10 mg erythromycin to rats, about 37-43% of the administered radioactivity was recovered in the intestinal tract plus feces, 27.2 to 36.1% in the urine, 21-29% in the expired air. It was rapidly metabolized in the liver, mainly through demethylation process, and excreted in the bile as des-N-methyl-erythromycin, the major metabolite present only in the bile and in the intestinal contents of rats. The isotropic methyl group was eliminated in the expired air as CO2.

4.2 Absorption, Distribution and Excretion (Complete)

Absorption of orally administered erythromycins occurs mainly in the duodenum. The bioavailability of the drugs is variable and depends on several factors including the particular erythromycin derivative, the formulation of the dosage form administered, acid stability of the derivative, presence of food in the GI tract, and gastric emptying time.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 234
Erythromycin is rather slowly absorbed after oral administration. peak serum concentrations ranged from 0.1 to 4.8 ug/mL according to the form and the coating of erythromycin administered. The oral absorption is less that 50% and erythromycin is degraded by gastric acid. It is absorbed in the small intestine (mainly in duodenum for humans) as erythromycin base.
Erythromycin diffuses readily into intracellular fluids, achieving antibacterial activity in essentially all sites except the brain and CSF. Erythromycin penetrates into prostatic fluid, achieving concentrations approximately 40% of those in plasma. Concentrations in middle ear exudate reach only 50% of serum concentrations and thus may be inadequate for the treatment of otitis media caused by H. influenzae. Protein binding is approximately 70% to 80% for erythromycin base and even higher, 96%, for the estolate. Erythromycin traverses the placenta, and drug concentrations in fetal plasma are about 5% to 20% of those in the maternal circulation. Concentrations in breast milk are 50% of those in serum.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill, 2006., p. 1184
In an in vitro model using human skin, erythromycin was absorbed into the stratum corneum following topical application of 10-20 mg of the drug in a vehicle containing dimethylacetamide and 95% alcohol. The drug does not appear to be absorbed systemically following twice daily application of a 2% solution of the drug in a vehicle containing 77% alcohol and polyethylene glycol and acetone. It is not known if erythromycin is absorbed from intact or denuded skin, wounds, or mucous membranes following topical application of an ointment containing the drug.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3512
...Some studies report a sex related difference in absorption of erythromycin, resulting in less drug absorbed by women after oral administration.
Gossel, T.A., J.D. Bricker. Principles of Clinical Toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 1994., p. 30
Peak serum concentrations are 0.3 to 0.5 g/mL, 4 hours after oral administration of 250 mg of the base, and 0.3 to 1.9 g/mL after a single dose of 500 mg. Esters of erythromycin base (e.g., stearate, estolate, and ethylsuccinate) have improved acid stability, and their absorption is less altered by food. A single, oral 250 mg dose of erythromycin estolate produces peak serum concentrations of approximately 1.5 g/mL after 2 hours, and a 500-mg dose produces peak concentrations of 4 g/mL. Peak serum concentrations of erythromycin ethylsuccinate are 1.5 g/mL (0.5 g/mL of base) 1 to 2 hours after administration of a 500 mg dose. These peak values include the inactive ester and the free base, the latter of which comprises 20% to 35% of the total. The concentration of microbiologically active erythromycin base in serum therefore is similar for the various preparations. Higher concentrations of erythromycin can be achieved by intravenous administration. Values are approximately 10 g/mL 1 hour after intravenous administration of 500 to 1000 mg of erythromycin lactobionate.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill, 2006., p. 1184
Only 2% to 5% of orally administered erythromycin is excreted in active form in the urine; this value is from 12% to 15% after intravenous infusion. The antibiotic is concentrated in the liver and is excreted in the bile, which may contain as much as 250 g/mL when serum concentrations are very high. The serum elimination half-life of erythromycin is approximately 1.6 hours. Although the half-life may be prolonged in patients with anuria, dosage reduction is not routinely recommended in renal-failure patients. The drug is not removed significantly by either peritoneal dialysis or hemodialysis.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill, 2006., p. 1184
Macrolides are lipid soluble and thus widely distributed, and they penetrate well into most tissues including bronchial, prostatic, middle ear, and bone. Therapeutic concn generally are not achievable in the CNS. /Macrolides/
American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 1447
Twenty hours after an oral administration of 10 mg erythromycin to rats, about 37-43% of the administered radioactivity was recovered in the intestinal tract plus feces, 27.2 to 36.1% in the urine, 21-29% in the expired air.
The aim of this investigation was to examine the pharmacokinetics and mammary excretion of erythromycin administered to lactating ewes (n = 6) by the intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes at a dosage of 10 mg/kg. Blood and milk samples were collected at pre-determined times, and a microbiological assay method was used to measure erythromycin concentrations in serum and milk. The concentration-time data were analysed by compartmental and non-compartmental kinetic methods. The serum concentration-time data of erythromycin were fit to a two-compartment model after i.v. administration and a one-compartment model with first-order absorption after i.m. and s.c. administration. The elimination half-life (t(1/2beta)) was 4.502 +/- 1.487 h after i.v. administration, 4.874 +/- 0.296 h after i.m. administration and 6.536 +/- 0.151 h after s.c. administration. The clearance value (Cl tot) after i.v. dosing was 1.292 +/- 0.121 l/h/kg. After i.m. and s.c. administration, observed peak erthyromycin concentrations (Cmax) of 0.918 +/- 0.092 microg/ml and 0.787 +/- 0.010 microg/ml were achieved at 0.75 and 1.0 h (Tmax) respectively. The bioavailability obtained after i.m. and s.c. administration was 91.178 +/- 10.232% and 104.573 +/- 9.028% respectively. Erythromycin penetration from blood to milk was quick for all the routes of administration, and the high AUC milk/AUC serum (1.186, 1.057 and 1.108) and Cmax-milk/Cmax-serum ratios reached following i.v., i.m. and s.c. administration, respectively, indicated an extensive penetration of erythromycin into the milk.
Goudah A et al; J Vet Med A Physiol Pathol Clin Med 54 (10): 607-11 (2007).
Erythromycin and azithromycin are concentrated in the liver, and high concn are normally excreted into the bile; some drug is demethylated. A considerable portion of an oral dose of both agents is eliminated int he feces. Only 2-5% of an oral dose of erythromycin ... is eliminated in the urine; after iv admin of erythromycin the percentage may approach 15%.
American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 1449
Topical application of erythromycin probably does not produce significant antibacterial concentrations in deep layers of the cornea or in the aqueous humor. It is not known if erythromycin is absorbed to any substantial extent from mucous membranes.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 2856
The pharmacokinetics of erythromycin was studied in five lactating dairy cows following single intramammary infusion of 300 mg erythromycin in each of two quarters per cow with specific mastitis. Levels of erythromycin in plasma and quarter milk samples were measured by agar plate diffusion assay using Micrococcus luteus (ATCC 9341) as the test organism. Erythromycin level in plasma reached a peak concentration value (C(max)) of 0.07 +/- 0.01 ug/mL at 30 min; thereafter, levels declined gradually to reach 0.05 +/- 0.00 ug/mL 12 hr post drug administration. The pharmacokinetic profile of the drug revealed mean absorption half life (t(1/2 ka)) as 0.26 +/- 0.05 hr. The drug was eliminated slowly with elimination half-life (t(1/2 beta)) of 13.75 +/- 0.35 hr and elimination rate constant (k(el)) of 0.04 +/- 0.00 h(-1). The volume of distribution based on the zero-time plasma concentration intercept of the least-squares regression line of the elimination phase (V(d(B))) was 0.032 L/kg. The drug crossed to untreated quarters also; mean drug levels of 0.20 +/- 0.07, 0.23 +/- 0.07, 0.17 +/- 0.04, and 0.17 +/- 0.04 ug/mL were found at 3, 6, 8 and 12 hr, respectively. The mean drug concentration for treated quarters was measured as 22.97 +/- 2.31 ug/mL milk at first milking (12 hr) following drug infusion.
Bajwa NS et al; Vet Res Commun 31 (5): 603-10 (2007).

4.3 Biological Half-Life (Complete)

... The serum elimination half-life of erythromycin is approximately 1.6 hours.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill, 2006., p. 1184
The serum half-life in normal subjects is 2 hours and in anuric subjects, 4-6 hours.
Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 360

4.4 Mechanism of Action (Complete)

Macrolide antibiotics are bacteriostatic agents that inhibit protein synthesis by binding reversibly to 50S ribosomal subunits of sensitive microorganisms, at or very near the site that binds chloramphenicol. Erythromycin does not inhibit peptide bond formation per se, but rather inhibits the translocation step wherein a newly synthesized peptidyl tRNA molecule moves from the acceptor site on the ribosome to the peptidyl donor site. Gram-positive bacteria accumulate about 100 times more erythromycin than do gram-negative bacteria. Cells are considerably more permeable to the un-ionized form of the drug, which probably explains the increased antimicrobial activity at alkaline pH.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill, 2006., p. 1183
... /Erythromycin/ inhibits the growth of susceptible organisms (principally Propionibacterium acnes) on the surface of the skin and reduces the concn of free fatty acids in sebum ... The reduction in free fatty acids in sebum may be an indirect result of the inhibition of lipase-producing organisms which convert triglycerides into free fatty acids or may be a direct result of interference with lipase production in these organisms. /In acne treatment regimens/
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 95. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1995 (Plus Supplements 1995)., p. 2378
Although stromal-derived factor-1 (SDF-1) via its cognate receptor CXCR4 is assumed to play a critical role in migration of endothelial cells during new vessel formation after tissue injury, CXCR4 expression on endothelial cells is strictly regulated. Erythromycin (EM), a 14-membered ring macrolide, has an anti-inflammatory effect that may account for its clinical benefit in the treatment of chronic inflammatory diseases. However, the effects of EM on endothelial cells and especially their expression of CXCR4 have not been fully evaluated. In this study, we demonstrated that EM markedly induced CXCR4 surface expression on microvascular endothelial cells in vitro and lung capillary endothelial cells in vivo. This ability to induce CXCR4 surface expression on endothelial cells was restricted to 14-membered ring macrolides and was not observed in other antibiotics including a 16-membered ring macrolide, josamycin. Furthermore, this EM-induced expression of CXCR4 on endothelial cells was functionally significant as demonstrated by chemotaxis assays in vitro. These findings suggest that EM-induced CXCR4 surface expression on endothelial cells may promote migration of CXCR4-expressing endothelial cells into sites of tissue injury, which may be associated with the known anti-inflammatory activity of this macrolide.
Takagi Y et al; Am J Physiol Lung Cell Mol Physiol 297 (3): L420-31 (2009).

5 Pharmacology

5.1 Therapeutic Uses (Complete)

Antibiotics, Macrolide; Gastrointestinal Agents; Protein Synthesis Inhibitors
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
MEDICATION (VET): In veterinary medicine, /erythromycin/ is used the treatment of clinical and subclinical mastitis in lactating cows, for the treatment of infectious diseases due to erythromycin-sensitive bacteria (cattle, sheep, swine, poultry) and for the treatment of chronic respiratory diseases due to mycoplasma in poultry.
Erythromycin is used as an alternative agent in the treatment of anthrax. Parenteral penicillins generally have been considered the drugs of choice for the treatment of naturally occurring or endemic anthrax caused by susceptible strains of Bacillus anthracis, including clinically apparent GI, inhalational, or meningeal anthrax and anthrax septicemia, although IV ciprofloxacin or IV doxycycline also are recommended. Erythromycin is suggested as an alternative to penicillin G for the treatment of naturally occurring or endemic anthrax in patients hypersensitive to penicillins. ./NOT included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 228
Erythromycin is used topically in the treatment of acne vulgaris. Therapy of acne vulgaris must be individualized and frequently modified depending on the types of acne lesions which predominate and the response to therapy. Topical anti-infectives, including erythromycin, are generally effective in the treatment of mild to moderate inflammatory acne. However, use of topical anti-infectives as monotherapy may lead to bacterial resistance; this resistance is associated with decreased clinical efficacy. Topical erythromycin is particularly useful when used with benzoyl peroxide or topical retinoids. Results of clinical studies indicate that combination therapy results in a reduction in total lesion counts of 50 to 70%. /Included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3511
Erythromycin or other macrolides (azithromycin, clarithromycin) are used in the treatment of community-acquired pneumonia (CAP). /Included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 227
Erythromycin or other macrolides (azithromycin, clarithromycin) are used for the treatment of respiratory tract infections caused by Mycoplasma pneumoniae. Erythromycin also is used in the treatment of respiratory tract infections caused by C. pneumoniae (see Uses: Chlamydial Infections). Erythromycin or tetracyclines appear to be equally effective in shortening the duration of clinical symptoms and hastening radiographic improvement in adults with mycoplasmal pneumonia, despite failure to eradicate the pathogen from nasopharyngeal or sputum cultures. Although data are limited regarding efficacy for treatment of mycoplasmal pneumonia in children, some clinicians suggest that erythromycin is preferred for treating children with the infection. /Included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 227
A fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole acetyl is used in children for the treatment of acute otitis media (AOM) caused by susceptible Haemophilus influenzae.Erythromycin is not effective when used alone for the treatment of H. influenzae infections/ /Erythromycin ethylsuccinate; Included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 227
Parenteral erythromycin is used as an alternative to parenteral penicillin G or ampicillin for prevention of perinatal group B streptococcal disease in women who are hypersensitive to penicillin. Pregnant women who are colonized with group B streptococcal in the genital or rectal areas can transmit group B streptococcal infection to their infants during labor and delivery resulting in invasive neonatal infection that can be associated with substantial morbidity and mortality. Intrapartum anti-infective prophylaxis for prevention of early-onset neonatal GBS disease is administered selectively to women at high risk for transmitting group B streptococcal infection to their neonates. /NOT included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 226
Oral erythromycin is used as an alternative to IM penicillin G benzathine, oral penicillin V potassium, and oral sulfadiazine or sulfisoxazole for prevention of recurrent attacks of rheumatic fever (secondary prophylaxis) in patients hypersensitive to penicillins and sulfonamides. /Included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 226
Erythromycin or other macrolides (azithromycin, clarithromycin) are used orally for the treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A beta-hemolytic streptococci). Although macrolides usually are effective in eradicating S. pyogenes from the nasopharynx, efficacy of the drugs in the subsequent prevention of rheumatic fever remains to be established. /Included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 226
Erythromycin is used topically for prophylaxis of gonococcal ophthalmia neonatorum. /Included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 2856
Erythromycin is used topically in the treatment of superficial infections of the eye involving the conjunctiva and/or cornea caused by susceptible bacteria. /Included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 2855
Oral erythromycin base is used in conjunction with oral neomycin sulfate as an adjunct to mechanical cleansing of the large intestine for intestinal antisepsis prior to elective colorectal surgery. /Iincluded in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 231
Erythromycin, azithromycin, or clarithromycin has been used in the treatment of early Lyme disease, a spirochetal disease caused by tick-borne Borrelia burgdorferi. However, some evidence in patients with early Lyme disease suggests that certain macrolides (e.g., azithromycin, erythromycin) may be less effective than penicillins or tetracyclines, and the IDSA, AAP, and other clinicians recommend that macrolide antibiotics not be used as first-line therapy for early Lyme disease. /NOT included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 231
Erythromycin is considered the drug of choice for the treatment of Bordetella pertussis infection (pertussis, whooping cough) and for prevention in contacts of patients with pertussis. /Included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 230
Erythromycin or azithromycin has been used orally in the treatment of donovanosis caused by Calymmatobacterium granulomatis. /NOT Included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 230
Erythromycin has been used as an alternative to the preferred regimens (e.g., a single dose of oral azithromycin or a 7-day regimen of oral doxycycline) for the treatment of coexisting chlamydial infections in adults and adolescents receiving treatment for gonorrhea. /Included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 230
Erythromycin is used as an adjunct to diphtheria antitoxin in the treatment of respiratory tract infection caused by Corynebacterium diphtheria (diphtheria). Erythromycin also is used for prevention of diphtheria in close contacts of patients with diphtheria and to eliminate the diphtheria carrier state. /Included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 229
Although oral erythromycin has not been evaluated extensively in culture-confirmed cases, the drug is used as an alternative to doxycycline for the treatment of genital, inguinal, or anorectal infections caused by lymphogranuloma venereum serotypes of C. trachomatis. /NOT included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 229
Oral erythromycin is used for the treatment of urethritis caused by Ureaplasma urealyticum in adult males and for the treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis in adults in whom tetracyclines and azithromycin are contraindicated or not tolerated. Oral erythromycin also is used for the treatment of chlamydial urogenital infections during pregnancy and for the treatment of chlamydial pneumonia in infants. The AAP, CDC, and other clinicians also recommend oral erythromycin for the treatment of initial episodes and recurrences of chlamydial conjunctivitis in neonates. /Included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 229
Oral erythromycin is used for the treatment of chancroid (genital ulcers caused by H. ducreyi). /NOT included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 228
Oral erythromycin or oral azithromycin has been used in conjunction with IM or IV ceftriaxone for the treatment of bacteremia caused by Bartonella quintana (formerly Rochalimaea quintana).460 B. quintana, a gram-negative bacilli, can cause cutaneous bacillary angiomatosis, trench fever, bacteremia, endocarditis, and chronic lymphadenopathy. /NOT included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 228
Erythromycin is used for the treatment of mild to moderately severe infections of the upper and lower respiratory tract, skin, and soft tissue caused by Streptococcus pyogenes (group A beta-hemolytic streptococci). Erythromycin also is used to treat mild to moderately severe infections of the upper and lower respiratory tract caused by Streptococcus pneumoniae. Other macrolides (azithromycin, clarithromycin) generally are used orally as alternatives to first-line therapy with a natural penicillin for the treatment of mild to moderate upper and lower respiratory tract infections caused by susceptible S. pyogenes or S. pneumoniae when oral therapy of such infections is considered appropriate and when therapy with erythromycin or other less expensive anti-infectives would likely be less effective and/or associated with GI intolerance or noncompliance. /Included in US product label/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 226

5.2 Drug Warnings (Complete)

Some commercially available formulations of erythromycin lactobionate powder for injection contain benzyl alcohol as a preservative. Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates. Toxicity appears to have resulted from administration of large amounts (i.e., about 100-400 mg/kg daily) of benzyl alcohol in these neonates. Although use of drugs preserved with benzyl alcohol should be avoided in neonates whenever possible, the American Academy of Pediatrics states that the presence of small amounts of the preservative in a commercially available injection should not proscribe its use when indicated in neonates. /Erythromycin lactobionate/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 240
In several neonates with infections caused by Ureaplasma urealyticum who received IV administration of erythromycin lactobionate, adverse cardiac effects (e.g., bradycardia, hypotension, cardiac arrest, arrhythmias) requiring cardiopulmonary resuscitation have been reported. Some clinicians state that these adverse effects may depend on serum concentration and/or infusion rate of the drug. It has been suggested that prolonged IV infusion of erythromycin lactobionate (e.g., over 60 minutes) may reduce such adverse cardiac effects. However, it has been suggested that certain individuals may be at increased risk of developing erythromycin-induced adverse cardiac effects and that decreasing the rate of IV infusion may decrease but not eliminate the risk of such effects. Further study is needed to determine the pharmacokinetics and safety of erythromycin lactobionate in neonates. /Erythromycin lactobionate/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 240
Maternal Medication usually Compatible with Breast-Feeding: Erythromycin: Reported Sign or Symptom in Infant or Effect on Lactation: None. /From Table 6/
Report of the American Academy of Pediatrics Committee on Drugs in Pediatrics 93 (1): 140 (1994)
POTENTIAL ADVERSE EFFECTS ON FETUS: None known. POTENTIAL SIDE EFFECTS ON BREAST-FED INFANT: None known, although theoretically could cause diarrhea in infant. COMMENTS: Crosses placenta in high doses to fetal level 24% of maternal; breast milk may exceed maternal serum concentration. FDA Category: B (B = Studies in laboratory animals have not demonstrated a fetal risk, but there are no controlled studies in pregnant women; or animal studies have shown an adverse effect (other than a decrease in fertility), but controlled studies in pregnant women have not demonstrated a risk to the fetus in the first trimester and there is no evidence of a risk in later trimesters.) /From Table II/
Stockton DL and AS Paller; J Am Acad Dermatol 23 (1): 87-103 (1990)
The most common adverse effects of oral erythromycins are GI and are dose related. Erythromycin stimulates smooth muscle and GI motility. Abdominal pain and cramping occur frequently. Nausea, vomiting, and diarrhea have also occurred, especially after large doses. Occasionally, stomatitis, heartburn, anorexia, melena, pruritus ani, and reversible mild acute pancreatitis have occurred. ...
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 231
Following prolonged or repeated erythromycin therapy, overgrowth of nonsusceptible bacteria or fungi may occur. Appropriate therapy should be instituted if such infection occurs. Because Clostridium difficile-associated diarrhea and colitis (also known as antibiotic-associated pseudomembranous colitis) caused by overgrowth of toxin-producing clostridia has been reported with the use of broad-spectrum anti-infective agents, it should be considered in the differential diagnosis of patients who develop diarrhea during anti-infective therapy. Colitis may range in severity from mild to life-threatening. Mild cases of colitis may respond to discontinuance of the drug alone, but diagnosis and management of moderate to severe cases should include sigmoidoscopy, appropriate bacteriologic studies, and treatment with fluid, electrolyte, and protein supplementation as indicated. If colitis is severe or is not relieved by discontinuance of the drug, appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) should be administered. Other causes of colitis also should be considered.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 232
Although a causal relationship to erythromycin lactobionate has not been established, nervous system effects including seizures, hallucinations, confusion, and vertigo have occurred rarely during therapy with the drug. /Erythromycin lactobioate/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 232
Ototoxicity consisting of bilateral hearing loss, in at least one case irreversible, has been reported rarely with erythromycin lactobionate, stearate, or ethylsuccinate. Tinnitus, alone or with vertigo, has also been reported rarely. Ototoxicity has generally occurred in patients with impaired renal or hepatic function and/or in those who were receiving high dosages of erythromycin (e.g., 4 g/day or more). Although hearing loss usually has been reversible following dosage reduction or discontinuance of the drug, sensorineural hearing loss that had not resolved after a follow-up period of at least 23 weeks also has been reported in a geriatric patient with underlying hepatic disease who received 2 g of IV erythromycin daily.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 232
Mild allergic reactions including urticaria, skin eruptions, and rash have occurred with erythromycin therapy. Serious allergic reactions including anaphylaxis have also been reported. Although a causal relationship was not definitely established, Stevens-Johnson syndrome occurred in at least one patient receiving oral erythromycin.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 232
Prolongation of the QT interval and development of ventricular arrhythmias, including atypical ventricular tachycardia (torsades de pointes), have been reported rarely with oral or IV erythromycin. Most reported cases have involved IV administration of the drug; limited data suggest that these adverse cardiac effects may depend on serum concentrations and/or rate of infusion of the drug. Erythromycin has exhibited concentration-dependent, reversible effects on cardiac conduction in electrophysiologic studies in humans and in Purkinje fibers isolated from dogs similar to those exhibited by class IA antiarrhythmic agents such as quinidine. Erythromycin prolongs the QT interval and blocks the potassium channel encoded by the human ether-a-gogo-related gene (HERG). It has been suggested that erythromycins be used with caution in patients at risk for QT prolongation and/or accumulation of the anti-infective, particularly when the drug is administered IV. Some clinicians suggest that decreasing the rate of IV infusion of erythromycin may reduce the risk of cardiac toxicity; however, decreasing the rate may not eliminate the risk, and discontinuance of the drug may be necessary. Additional study and experience are needed to elucidate further the mechanisms and possible risk factors for the development of this toxicity.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 232
Venous irritation and thrombophlebitis have occurred following IV administration of erythromycin lactobionate. The manufacturer states that pain and vessel trauma can be minimized if dilute solutions of the drug are administered by continuous infusion or by intermittent infusion slowly over 20-60 minutes. /Erythromycin lactobioate/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 232
Erythromycin estolate may rarely produce hepatotoxicity in the form of reversible cholestatic hepatitis. Symptoms of this toxicity resemble, and may be mistakenly diagnosed as, pancreatitis, biliary colic, cholecystitis, cholelithiasis, extrahepatic biliary obstruction or jaundice, viral hepatitis, perforated ulcer, an acute abdominal surgical problem, or hepatic disturbances due to phenothiazines. In a few patients, initial symptoms have developed after a few days, but onset generally follows 1-2 weeks of continuous therapy. A prodromal syndrome consisting of abdominal cramping, nausea, and vomiting may occur. Subsequent symptoms include severe upper abdominal pain or biliary colic, fever, anorexia, malaise, hepatic enlargement with or without jaundice, pale or acholic stools, dark urine, steatorrhea, pruritus, icterus, and occasionally rash. Leukocytosis and eosinophilia may occur, as well as elevations in serum bilirubin, altered liver function test results, and changes in hepatic enzymes. Liver biopsy may show periportal infiltration and a variable amount of liver cell necrosis. Although hepatotoxic effects are reversible upon discontinuance of the drug, symptoms may take several weeks to subside, and abnormal liver function tests may persist for 6 months. Erythromycin estolate-induced hepatotoxicity, which occurs primarily in adults, is most likely to appear in patients who receive the drug for longer than 10 days or in repeated courses of therapy. Therefore, use of the drug in these circumstances should be avoided. /Erythromycin estolate/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 237
Hepatic dysfunction, with or without jaundice, has occurred in patients receiving oral or parenteral erythromycin.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 231
Topical acne preparations containing peeling, desquamating, or abrasive agents (e.g., benzoyl peroxide, tretinoin, salicylic acid, sulfur) should be used cautiously in patients using topical anti-infectives /including erythromycin/ because a cumulative irritant effect could occur. In addition, information on the physical and/or chemical compatibility of topical anti-infectives and other topical acne preparations is not available. Concurrent use of abrasive or medicated soaps or cosmetic products containing alcohol (e.g., astringents, after-shave lotions) may also cause a cumulative irritant or drying effect in patients using topical anti-infectives.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3511
Topical use of erythromycin may result in overgrowth of nonsusceptible organisms including fungi. Gram-negative folliculitis has been reported rarely following topical use of erythromycin in the treatment of acne vulgaris. If superinfection or suprainfection occurs during erythromycin therapy, the drug should be discontinued and appropriate therapy instituted.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3511
Erythromycin has a low order of toxicity. Sensitivity reactions rarely occur following topical application of the drug. Generalized urticaria, which required treatment with systemic corticosteroids, has been reported in a few patients following topical use of erythromycin. The most frequent adverse reaction to erythromycin topical solutions is local dryness. Erythema, tenderness, burning, pruritus, oiliness, and desquamation have also been reported following topical application of erythromycin solutions or gel. Most of these reactions appear to be caused by the alcohol or other ingredients in commercially available solutions or gel of the drug rather than erythromycin. Irritation of the eye has been reported with topical erythromycin solutions or gel. Skin irritation, such as erythema and peeling, has occasionally been reported with topical application of erythromycin ointment for acne. At least one case of contact dermatitis has been reported following topical application of the ointment for acne, but a causal relationship to the ointment has not been established. A generalized urticarial reaction, which required systemic corticosteroid therapy and possibly was causally related to erythromycin, has been reported during topical use of the gel.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3511
Rarely, sensitivity reactions, ocular irritation, or redness occur following application of erythromycin ophthalmic ointment.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 2856

5.3 Interactions (Complete)

Erythromycin is metabolized by CYP3A and concomitant use with drugs that inhibit the CYP3A isoenzyme may result in increased erythromycin plasma concentrations. There is some evidence that concomitant use of oral erythromycin with drugs that inhibit CYP3A (i.e., fluconazole, ketoconazole, itraconazole, diltiazem, verapamil) is associated with an increased incidence of sudden death from cardiac causes, presumably because of increased plasma erythromycin concentrations resulting in an increased risk of QT prolongation (a dose-associated effect of erythromycin) and serious ventricular arrhythmias. Therefore, it has been suggested that concomitant use of erythromycin and drugs that are potent inhibitors of CYP3A should be avoided.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 232
Erythromycin may interact with astemizole and terfenadine (both drugs no longer commercially available in the US), resulting in potentially serious adverse cardiovascular effects. Some evidence indicates that erythromycin may alter the metabolism of astemizole and terfenadine, probably via inhibition of the cytochrome P-450 microsomal enzyme system. While erythromycin has been shown to decrease markedly the clearance of the active carboxylic acid metabolite of terfenadine, the effect of the macrolide on unchanged terfenadine concentrations has not been fully elucidated, but appears to show interindividual variation. In studies in extensive metabolizers of dextromethorphan or debrisoquin, erythromycin markedly impaired clearance of the active metabolite of terfenadine in all such individuals but produced measurable effects on unchanged terfenadine in only one-third of these individuals. In addition, erythromycin is known to inhibit the enzyme system responsible for astemizole's metabolism. Prolongation of the QT interval and ventricular tachycardia, including torsades de pointes, have been reported in some patients receiving astemizole or terfenadine concomitantly with erythromycin or the structurally related macrolide troleandomycin (no longer commercially available in the US). Rarely, cardiac arrest and death have been reported in patients receiving erythromycin and terfenadine concomitantly. Therefore, when terfenadine and astemizole were commercially available in the US, these antihistamines were contraindicated in patients receiving erythromycin, clarithromycin, or troleandomycin. In addition, concomitant administration of astemizole or terfenadine and azithromycin also was not recommended, although limited data suggested that azithromycin did not alter the metabolism of terfenadine.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 232
Although in vitro studies have shown varying degrees of additive or synergistic effects against some organisms when erythromycin was used in conjunction with penicillins, streptomycin, sulfonamides, rifampin, or chloramphenicol, the clinical importance of these reports has not been established. Antagonism of bactericidal activity has been observed between erythromycin and clindamycin in vitro. In addition, antagonism has been reported when a bacteriostatic drug was administered with a bactericidal drug, but antagonism has not been convincingly documented clinically.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 232
Concomitant use of erythromycin in patients receiving high dosage of theophylline has resulted in decreased clearance of theophylline, elevated serum theophylline concentrations, and a prolonged serum half-life of the bronchodilator. An interaction may be most likely to occur in patients receiving an erythromycin dosage greater than 1.5 g daily for more than 5 days. Patients receiving theophylline should be closely monitored for signs of theophylline toxicity when erythromycin is administered concomitantly; serum theophylline concentrations should be monitored and dosage of the bronchodilator reduced if indicated. Although further study is needed and the clinical importance has not been determined to date, there is some evidence that concomitant administration of erythromycin and theophylline can also result in decreased serum erythromycin concentrations and subtherapeutic concentrations of erythromycin may occur.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 233
Erythromycin administration does not appear to alter the pharmacokinetics of sufentanil.
Rice, S.A., K.J. Fish. Anesthetic Toxicity. New York, NY: Raven Press, Ltd., 1994., p. 209
Erythromycin, apparently through inhibition of cytochrome P-450 (CYP) microsomal enzyme systems, can reduce the hepatic metabolism of some drugs including carbamazepine, cyclosporine, using elimination and increasing serum concentrations of these drugs. In patients receiving concomitant erythromycin, serum concentrations of drugs metabolized by cytochrome P-450 microsomal enzyme systems should be monitored closely and dosage adjusted if necessary.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 232
Concomitant use of erythromycin and carbamazepine in adults or children has resulted in increased serum concentrations of carbamazepine and subsequent signs of carbamazepine toxicity (e.g., ataxia, dizziness, drowsiness, vomiting). Studies in adults indicate that erythromycin can substantially decrease serum clearance of carbamazepine, presumably by inhibiting hepatic metabolism of the drug. Patients receiving erythromycin and carbamazepine concomitantly should be monitored for evidence of carbamazepine toxicity; carbamazepine dosage should be reduced when necessary. Some clinicians suggest that use of an alternative anti-infective agent, instead of erythromycin, may be necessary in patients receiving carbamazepine.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 233
Concomitant use of erythromycin and digoxin has resulted in increased serum concentrations of digoxin, and initiation of erythromycin therapy in several patients receiving disopyramide reportedly has been associated with elevated serum disopyramide concentrations, QT-interval prolongation, and polymorphic ventricular tachycardia. In at least one patient, concomitant administration of oral quinidine sulfate and IV erythromycin lactobionate resulted in increased serum quinidine concentrations and possible quinidine toxicity including asymptomatic, nonsustained ventricular tachycardia. It has been suggested that quinidine concentrations and ECGs be monitored closely if erythromycin is used concomitantly with quinidine.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 233
Two men, aged 83 and 78 years, who received stable therapy with simvastatin 80 mg/day were hospitalized 1-2 weeks after completion of short-term treatment with erythromycin and clarithromycin, respectively. Both patients were admitted with myalgia, muscle weakness, functional disability (inability to raise arms and legs), and serum creatine kinase levels more than 60 times the upper limit of normal (ULN). Substantial elevations in aspartate aminotransferase (> 30 times the ULN) and alanine aminotransferase (> 7 times the ULN) levels were also observed. Rhabdomyolysis was diagnosed in both patients. Both recovered, but the combined events resulted in almost 40 days of hospitalization, the cost of which is considerable. According to the Naranjo adverse drug reaction probability scale, the likelihood that the rhabdomyolysis was secondary to a simvastatin-macrolide interaction was probable. Four cases of rhabdomyolysis after therapy with combined simvastatin and clarithromycin have been reported previously, but this is apparently the first report of rhabdomyolysis after coadministration of erythromycin. The interacting mechanism likely was inhibited cytochrome P450 (CYP) 3A4 metabolism and possibly P-glycoprotein transport of simvastatin as well. Previous reports of simvastatin-clarithromycin-related events involved additional drugs that inhibited CYP3A4 and P-glycoprotein. However, this was not the situation with our two patients. To prevent future events, it is crucial that clinicians recognize the interaction risk associated with concurrent use of simvastatin and clarithromycin or erythromycin. The risk could be managed by temporary interruption of simvastatin treatment or administration of a noninteracting antimicrobial agent.
Molden E, Andersson KS; Pharmacotherapy 27 (4): 603-7 (2007).
Initiation of erythromycin therapy in some patients stabilized on warfarin has resulted in prolongation of prothrombin time and bleeding. Increased anticoagulant effect may be more pronounced in geriatric patients. The exact mechanism(s) of this interaction has not been clearly established, but erythromycin may inhibit hepatic metabolism of warfarin. Prothrombin time should be monitored more closely than usual in patients receiving warfarin when erythromycin therapy is initiated, and warfarin dosage should be adjusted as necessary
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 233
Concomitant administration of erythromycin and ergotamine reportedly may induce ischemic reactions, dysesthesia, and peripheral vasospasm.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 233
A 79-year-old white woman was admitted to the hospital due to extreme fatigue and dizziness. On admission, heart rate was 40 beats/min and blood pressure was 80/40 mm Hg. An electrocardiogram showed complete atrioventricular (AV) block, escape rhythm of 50 beats/min, and QTc prolongation 583 msec. This event was attributed to concomitant treatment with verapamil 480 mg/d and erythromycin 2,000 mg/d, which was prescribed one week before admission. ... CYP3A4 is the main isoenzyme responsible for metabolism of erythromycin and verapamil. Both drugs are potent inhibitors of CYP3A4 and of P-glycoprotein; this may be the basis for the pharmacokinetic interaction between erythromycin and verapamil. In addition to being a woman, our patient had other risk factors for QT prolongation: slow baseline heart rate (probably induced by verapamil), left-ventricular hypertrophy, and possibly ischemic heart disease. ... This life-threatening arrhythmia was probably the result of a pharmacokinetic and/or pharmacodynamic interaction of high-dose verapamil and erythromycin.
Goldschmidt N et al; Ann Pharmacother 35 (11): 1396-9 (2001).
In a population-based study, concomitant use of oral erythromycin and drugs that inhibit CYP3A (i.e., diltiazem, verapamil) was associated with an increased incidence of sudden death from cardiac causes. There was no increase in sudden cardiac death when oral erythromycin was used with calcium-channel blocking agents that do not inhibit CYP3A to a clinically important extent (e.g., nifedipine). Concomitant use of erythromycin and diltiazem or verapamil presumably increased plasma erythromycin concentrations resulting in an increased risk of QT prolongation (a dose-associated effect of erythromycin) and serious ventricular arrhythmias. In addition, erythromycin (a CYP3A inhibitor) is likely to increase plasma concentrations of diltiazem or verapamil leading to an increased risk of adverse effects associated with these drugs. Concomitant use of erythromycin and diltiazem or verapamil should be avoided.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 233
Concomitant use of erythromycin and cyclosporine may result in substantial increases in blood or plasma concentrations of cyclosporine and subsequent signs of cyclosporine toxicity (e.g., nephrotoxicity). Studies in healthy adults indicate that erythromycin can substantially decrease plasma clearance of cyclosporine, presumably by inhibiting hepatic metabolism of the drug, although the exact mechanism remains to be clearly determined. Erythromycin and cyclosporine should be used concomitantly with caution, and patients should be monitored for evidence of cyclosporine toxicity. Renal function and blood or plasma concentrations of cyclosporine should be monitored when erythromycin therapy is administered or discontinued in patients receiving cyclosporine or vice versa, and cyclosporine dosage adjusted appropriately as necessary.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 233
In one patient stabilized on clozapine (800 mg daily), concomitant administration of oral erythromycin therapy (250 mg 4 times daily) appeared to precipitate a tonic-clonic seizure, possibly by interfering with metabolism of the drug.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 233
Oral or IV erythromycin markedly inhibit cytochrome P450 enzymes that metabolize cisapride (CYP3A4) and increase plasma cisapride concentrations, which may increase the potential for serious adverse effects (e.g., life-threatening cardiac arrhythmias) associated with the drug.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 233
Erythromycin may alter pharmacokinetics of midazolam. Following concomitant administration of erythromycin with oral midazolam (an oral dosage form of midazolam currently is not available in the US) in healthy individuals, oral bioavailability of midazolam increased, resulting in substantial increases in peak plasma concentrations and half-life and fourfold increases in the area under the plasma concentration-time curve (AUC) of midazolam. Pharmacokinetics of IV midazolam were not affected to the same extent by concomitant administration of erythromycin as were those of oral midazolam; however, clearance of IV midazolam was decreased by 54% and half-life and volume of distribution of IV midazolam were increased. Although the mechanism of these interactions is unknown, it has been suggested that erythromycin may decrease hepatic metabolism of midazolam. In these individuals, erythromycin potentiated the sedative effect of oral midazolam and, to a lesser extent, that of IV midazolam, and also altered substantially the psychomotor effects of midazolam. Some clinicians suggest that erythromycin not be used in patients receiving oral midazolam or, alternatively, dosage of oral midazolam be reduced by 50-75%. Patients should be observed carefully and dosage of IV midazolam should be adjusted in individuals receiving erythromycin concomitantly. Concomitant use of erythromycin apparently decreases clearance of triazolam and could increase the pharmacologic effects of the drug. A study in healthy adults indicates that peak serum concentration, elimination half-life, and area under the serum concentration time-curve (AUC) of triazolam are increased by about 50%, clearance of triazolam is decreased by about 50%, and the apparent volume of distribution of the drug is decreased by about 30% when erythromycin is given concomitantly. Patients receiving erythromycin and triazolam concomitantly should be monitored closely; a reduction in triazolam dosage may be necessary.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 233
This study examined in vitro interaction between domperidone and erythromycin. Both are prescribed for refractory gastroparesis. Domperidone is metabolized via human cytochrome P4503A4. Erythromycin is a CYP3A4 inhibitor. Incubations evaluated domperidone metabolite formation in human liver microsomes and recombinant CYP3A4. Concentration- and time-dependent inhibition of 500 microM domperidone was studied with 2.5-200 uM erythromycin over 10-40 min. Domperidone metabolite (5-hydroxy domperidone, M3) formation was inhibited by erythromycin in a concentration- and time-dependent manner. The K(I) estimate was 18.4 uM in human liver microsomes and 4.1 uM in CYP3A4. Using a model incorporating CYP3A4 hepatic and gut inhibition, in vitro estimates from human liver microsomes and CYP3A4 were used to predict in vivo AUCi/AUC ratios of 2.54 and 4.95, respectively. Significant inhibition of domperidone metabolism by erythromycin occurs. This predicts greater domperidone drug exposure when used with erythromycin.
Ung D et al; Xenobiotica 39 (10): 749-56 (2009).
Erythromycin, apparently through inhibition of cytochrome P-450 (CYP) microsomal enzyme systems, can reduce the hepatic metabolism of some drugs including carbamazepine, cyclosporine, hexobarbital, phenytoin, alfentanil, disopyramide, lovastatin, and bromocriptine, thereby decreasing elimination and increasing serum concentrations of these drugs. In patients receiving concomitant erythromycin, serum concentrations of drugs metabolized by cytochrome P-450 microsomal enzyme systems should be monitored closely and dosage adjusted if necessary.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 232
Oral erythromycin prolongs cardiac repolarization and is associated with case reports of torsades de pointes. Because erythromycin is extensively metabolized by cytochrome P-450 3A (CYP3A) isozymes, commonly used medications that inhibit the effects of CYP3A may increase plasma erythromycin concentrations, thereby increasing the risk of ventricular arrhythmias and sudden death. We studied the association between the use of erythromycin and the risk of sudden death from cardiac causes and whether this risk was increased with the concurrent use of strong inhibitors of CYP3A. ... A previously identified Tennessee Medicaid cohort that included 1,249,943 person-years of follow-up and 1476 cases of confirmed sudden death from cardiac causes /was studied/. The CYP3A inhibitors used in the study were nitroimidazole antifungal agents, diltiazem, verapamil, and troleandomycin; each doubles, at least, the area under the time-concentration curve for a CYP3A substrate. Amoxicillin, an antimicrobial agent with similar indications but which does not prolong cardiac repolarization, and former use of erythromycin also were studied, to assess possible confounding by indication. The multivariate adjusted rate of sudden death from cardiac causes among patients currently using erythromycin was twice as high (incidence-rate ratio, 2.01; 95 percent confidence interval, 1.08 to 3.75; P=0.03) as that among those who had not used any of the study antibiotic medications. There was no significant increase in the risk of sudden death among former users of erythromycin (incidence-rate ratio, 0.89; 95 percent confidence interval, 0.72 to 1.09; P=0.26) or among those who were currently using amoxicillin (incidence-rate ratio, 1.18; 95 percent confidence interval, 0.59 to 2.36; P=0.65). The adjusted rate of sudden death from cardiac causes was five times as high (incidence-rate ratio, 5.35; 95 percent confidence interval, 1.72 to 16.64; P=0.004) among those who concurrently used CYP3A inhibitors and erythromycin as that among those who had used neither CYP3A inhibitors nor any of the study antibiotic medications. In contrast, there was no increase in the risk of sudden death among those who concurrently used amoxicillin and CYP3A inhibitors or those currently using any of the study antibiotic medications who had formerly used CYP3A inhibitors. The concurrent use of erythromycin and strong inhibitors of CYP3A should be avoided.
Ray WA et al; N Engl J Med 351 (11): 1089-96 (2004).
The ability of erythromycin to inhibit the hepatic metabolism of carbamazepine causes carbamazepine toxicity. The severity of this drug interaction has been proposed to be related to the dose of erythromycin. The introduction of oral erythromycin produces a two- to fourfold increase in the carbamazepine serum concentration and the resultant toxic manifestations. Carbamazepine toxicity and a more marked increase in carbamazepine serum concentration were observed in a patient treated with intravenous erythromycin.
Mitsch RA; DICP 23 (11): 878-9 (1989).
A patient who had taken lovastatin for 7 years received erythromycin before dental procedures. Multiple organ toxicity developed, manifested as rhabdomyolysis, acute renal failure, pancreatitis, ileus, livedo reticularis, and elevated aminotransferase values, without liver injury. No previous reports have identified multiple organ injury of this magnitude. A computer literature search identified only three other reported instances of erythromycin and lovastatin interaction. Manifestations in these previous cases consisted of rhabdomyolysis in all three, as well as elevated aminotransferase values and acute renal failure in two cases. In all the cases, the clinical presentation of organ toxicity occurred after the cessation of erythromycin therapy between day 1 and day 5. Advanced age and chronic renal insufficiency were identified as potential risk factors for drug interaction. Health care professionals should be aware of the potential interaction between these two commonly prescribed drugs, which can mimic sepsis.
Wong PW et al; South Med J 91 (2): 202-5 (1998).

6 Environmental Fate & Exposure

6.1 Environmental Fate / Exposure Summary

Erythromycin's production and use as an antibiotic may result in its release to the environment through various waste streams. Erythromycin is produced by a strain of Streptomyces erythreus which is found in soil. If released to air, an estimated vapor pressure of 2.1X10-25 mm Hg at 25 °C indicates erythromycin will exist solely in the particulate phase in the atmosphere. Particulate-phase erythromycin will be removed from the atmosphere by wet or dry deposition. Erythromycin contains chromophores that absorb at wavelengths >290 nm and therefore may be susceptible to direct photolysis by sunlight. If released to soil, erythromycin is expected to have low mobility based upon an estimated Koc of 570. The pKa of erythromycin is 8.9, indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil is not expected because the base exists as an cation and cations do not volatilize. Erythromycin biodegradation in soil is dependent on both temperature and addition of a readily biodegradable source of organic carbon as suggested by 0, 75, 100% biodegradation in 30 days at 4, 20, and 30 °C, respectively, in a sandy loam soil plus cattle feces. If released into water, erythromycin is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Utilizing the Closed Bottle Test, -3% of the theoretical BOD was reported in 4 weeks, indicating that biodegradation is not an important environmental fate process in water. A pKa of 8.9 indicates erythromycin will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. An estimated BCF of 49 suggests the potential for bioconcentration in aquatic organisms is moderate. Hydrolysis is not expected to be an important environmental fate; however it may hydrolyze under basic conditions. Occupational exposure to erythromycin may occur through inhalation and dermal contact with this compound at workplaces where erythromycin is produced or used. Monitoring data indicate that the general population may be exposed to erythromycin via ingestion of contaminated drinking water, and dermal contact and ingestion of consumer products containing erythromycin. (SRC)

6.2 Probable Routes of Human Exposure (Complete)

NIOSH (NOES Survey 1981-1983) has statistically estimated that 44,142 workers (37,992 of these were female) were potentially exposed to erythromycin in the US(1). Occupational exposure to erythromycin may occur through inhalation and dermal contact with this compound at workplaces where erythromycin is produced or used. Monitoring data indicate that the general population may be exposed to erythromycin via ingestion of contaminated drinking water, and dermal contact and ingestion of consumer products containing erythromycin(SRC).
(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). Available from, as of Jan 10, 2010: https://www.cdc.gov/noes/
NIOSH (NOES Survey 1981-1983) has statistically estimated that 1,108 workers (615 of these were female) were potentially exposed to erythromycin stearate in the US(1). /Erythromycin stearate/
(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). Available from as of Jan 4, 2010: https://www.cdc.gov/noes/
NIOSH (NOES Survey 1981-1983) has statistically estimated that 3,065 workers (1,433 of these were female) were potentially exposed to erthyromycin ethylsuccinate in the US(1). /Erthyromycin ethylsuccinate/
(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). Available from as of Jan 4, 2010: https://www.cdc.gov/noes/

6.3 Natural Pollution Sources (Complete)

Antibiotic substance produced by strain of Streptomyces erythreus ... found in soil sample from Philippine Archipelago.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 630
... produced by a strain of Saccharopolyspora erthraea (formerly Streptomyces erythraeus)
Physicians Desk Reference 64th ed. PDR Network, LLC, Montvale, NJ. 2010, p. 435

6.4 Artificial Pollution Sources (Complete)

Erythromycin's production and use as an antibiotic(1) may result in its release to the environment through various waste streams(SRC).
(1) O'Neil MJ, ed; The Merck Index. 14th ed., Whitehouse Station, NJ: Merck and Co., Inc., p. 630 (2006)

6.5 Environmental Fate (Complete)

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 570(SRC), determined from a log Kow of 3.06(2) and a regression-derived equation(3), indicates that erythromycin is expected to have low mobility in soil(SRC). The pKa of erythromycin is 8.9(2), indicating that this compound will almost entirely exist in the cation and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the base exists as an cation and cations do not volatilize. Erythromycin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.1X10-25 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Erythromycin biodegradation in soil is dependent on both temperature and addition of a readily biodegradable source of organic carbon(SRC) as suggested by 0, 75, 100% biodegradation in 30 days at 4, 20, and 30 °C, respectively, in a sandy loam soil plus cattle feces(6).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) McFarland JW et al; J Med Chem 40: 1340-6 (1997)
(3) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm as of Jan 8, 2010.
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(5) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(6) Sarmah AK et al; Chemosphere 65: 725-59 (2006)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 570(SRC), determined from a log Kow of 3.06(2) and a regression-derived equation(3), indicates that erythromycin is expected to adsorb to suspended solids and sediment(SRC). A pKa of 8.9(2) indicates erythromycin will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(4). According to a classification scheme(5), an estimated BCF of 49(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Utilizing the Closed Bottle Test, -3% of the theoretical BOD was reported in 4 weeks(7), indicating that biodegradation is not an important environmental fate process in water(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) McFarland JW et al; J Med Chem 40: 1340-6 (1997)
(3) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm as of Jan 8, 2010.
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds, Boca Raton, FL: Lewis Publ (2000)
(5) Franke C et al; Chemosphere 29: 1501-14 (1994)
(6) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(7) Alexy R et al; Chemosphere 57: 505-512 (2004)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), erythromycin, which has an estimated vapor pressure of 2.3X10-25 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase erythromycin may be removed from the air by wet or dry deposition(SRC). Erythromycin contains chromophores that absorb at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)

6.6 Environmental Biodegradation (Complete)

AEROBIC: Erythromycin was 0, 75, 100% degraded at 4, 20, and 30 °C, respectively, in sandy loam soil plus cattle feces in 30 days; a half-life of 11 days was reported in feces-amended soil at 20 °C(1). Degradation of erythromycin has been reported at 25% in 30 days using a sandy loam mixed with manure(2). Using the closed bottle test, erythromycin, present at 3 ug/L and 2.46 mg/L exhibited theoretical BODs of -3 and -3% after 14 and 28 days incubation, respectively, using an inoculum of municipal sewage treatment plant effluent and maintained at 20 °C(3). Addition of a readily biodegradable source of organic carbon such as sodium acetate increased the theoretical BOD to 23.1% after 28 days(3). Using a sandy loam soil (pH 6.0-6.3, clay 16.3%; sand 60.0%; silt 23.7%) amended with chicken feces, 3% and 75% activity was lost in 30 days at 4 and 20 °C, respectively, corresponding to a half-life of 11 days; 100% activity was observed at 30 °C after 18 days, corresponding to a half-life of 8.5 days(4).
(1) Sarmah AK et al; Chemosphere 65: 725-59 (2006)
(2) Thiele-Bruhn S; J Plant Nutr Soil Sci 166: 145-167 (2003)
(3) Alexy R et al; Chemosphere 57: 505-512 (2004)
(4) Gavalchin J, Katz SE; J AOAC Int 77: 481-5 (1994)
ANAEROBIC: Using a laboratory-scale anaerobic sequencing batch reactor representing pharmaceutical wastewater treatment at an organic loading rate of 2.9 g COD/L-day, adding erythromycin at 1 mg/L resulted in a 5% reduction in biogas production(1).
(1) Amin MH et al; Environ Sci Technol 40: 3971-3977 (2006)

6.7 Environmental Abiotic Degradation (Complete)

Erythromycin is not expected to undergo hydrolysis under environmental conditions(1); however, it may hydrolyze under basic conditions(SRC). Erythromycin contains chromophores that absorb at wavelengths >290 nm(1) and therefore may be susceptible to direct photolysis by sunlight(SRC).
(1) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990)

6.8 Environmental Bioconcentration (Complete)

An estimated BCF of 49 was calculated in fish for erythromycin(SRC), using a log Kow of 3.06(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).
(1) McFarland JW et al; J Med Chem 40: 1340-6 (1997)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm as of Jan 7, 2010.
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

6.9 Soil Adsorption / Mobility (Complete)

The Koc of erythromycin is estimated as 570(SRC), using a log Kow of 3.06(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that erythromycin is expected to have low mobility in soil. Freundlich adsorption coefficients for erythromycin A of 3.1X10-23, 0.86, 1.9X10-14, 2.0X10-5, 0.50, 2.57, 0.94 and 4.95 have been reported using HK, KK, CaK, FeK, HM, KM, CaM and FeM homoionic clays, respectively, at 25 °C(4). The pKa of erythromycin is 8.9(5), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(6).
(1) McFarland JW et al; J Med Chem 40: 1340-6 (1997)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm as of Jan 8, 2010.
(3) Swann RL et al; Res Rev 85: 17-28 (1983)
(4) Kim Y-H et al; J Environ Qual 33: 257-264 (2004)
(5) Jones OAH et al; Water Res 36: 5013-22 (2002)
(6) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)

6.10 Volatilization from Water / Soil (Complete)

A pKa of 8.9(1) indicates erythromycin will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water and moist soil surfaces is not expected to be an important fate process(2). Erythromycin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.1X10-25 mm Hg(SRC), determined from a fragment constant method(3).
(1) McFarland JW et al; J Med Chem 40: 1340-6 (1997)
(2) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds, Boca Raton, FL: Lewis Publ (2000)
(3) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)

6.11 Environmental Water Concentrations (Complete)

GROUNDWATER: Erythromycin was not detected in groundwater samples collected on September 6, 2000 downgradient of the Norman, OK Landfill Research site; reporting limit of 0.05 ug/L(1).
(1) Barnes KK et al; Ground Water Monit Remed 24: 119-126 (2004)
DRINKING WATER: It has been estimated that erythromycin is approximately 50% removed during drinking water treatment(1).
(1) Westerhoff P et al; Environ Sci Technol 39: 6649-6663 (2005)
SURFACE WATER: Erythromycin was detected in 10% of samples from 18 streams located in north-central and northwestern Arkansas sampled during March, April, and August, 2004; maximum concentration was 0.175 ug/L, minimum 0.154, detection limit of 0.10 in April and 0.005 ug/L in August(1). The compound showed a 21.5% frequency in a survey of 139 US streams sampled during 1999-2000, maximum concentration of 21.5 ug/L, minimum of 1.7 ug/L, detection limit 0.05 ug/L(2). Erythromycin was detected, not quantified in streams located in the vicinity of Iowa swine animal feeding operations as well as downstream from US waste water treatment plants(3). Streams sampled in Southern Ontario, Canada between May and November 2003 indicated a 5.6% frequency of detection for erythromycin with a concentration range of 0.9 to 51 ng/L, reporting limit of 0.9 ng/L(4). Erythromycin was detected at all 8 sampling sites from the River Po and River Lambro in Northern Italy at concentrations ranging from 1.40 to 15.90 ng/L, collected in October 2001(5). Samples from the River Elbe and its tributaries from the Czech Republic and Germany sampled in 1999 and 2000, contained erythromycin at concentrations ranging from 30 to 70 ng/L(6). It has been estimated that the concentration in surface water in Germany is a maximum of 1.70 ug/L(7).
(1) Haggard BE et al; J Environ Qual 35: 1078-1087 (2006)
(2) Kolpin DW et al; Environ Sci Technol 36: 1202-11 (2002)
(3) Meyer MT, Kolpin DW; in Amer Chem Soc, Div Environ Chem, Preprints Ext Abstr, 219th ACS Natl Meeting, 40: 106-7 (2000)
(4) Lissemore L et al; Chemosphere 64: 717-729 (2006)
(5) Calamari D et al; Environ Sci Technol 37: 1241-1248 (2003)
(6) Wiegel S et al; Chemosphere 57: 107-126 (2004)
(7) Zwiener C et al; pp. 81-89 in: Pharmaceuticals in the Environment., Kuemmerer K, ed., Berlin, Germany: Springer-Verlag (2001)

6.12 Effluent Concentrations (Complete)

Median and maximum concentrations of 0.080 and 0.838 ug/L, respectively, were reported for erythromycin, which was detected in the effluent of eight of eight waste water treatment plants in five Canadian cities sampled in 2002, detection limit = 0.001 ug/L(1). Erythromycin was not detected in groundwater samples collected on September 6, 2000 downgradient of the Norman, OK Landfill Research site; reporting limit of 0.05 ug/L(2). It has been estimated that the concentration in sewage water in Germany is a maximum of 6.00 ug/L(3).
(1) Miao X-S et al; Environ Sci Technol 38: 3533-3541 (2004)
(2) Barnes KK et al; Ground Water Monit Remed 24: 119-126 (2004)
(3) Zwiener C et al; pp. 81-89 in: Pharmaceuticals in the Environment., Kuemmerer K, ed., Berlin, Germany: Springer-Verlag (2001)

6.13 Other Environmental Concentrations (Complete)

Erythromycin, a top 25 prescription drug in the UK with 26,483.78 kg used per year, was detected in sludge samples at 2.21X10-5 ug/kg in 2000(1).
(1) Jones OAH et al; Water Res 36: 5013-22 (2002)

7 Environmental Standards & Regulations

7.1 Allowable Tolerances (Complete)

Tolerances for residues of erythromycin in food are established as follows: (a) 0.1 part per million in uncooked edible tissues of beef cattle and swine. (b) Zero in milk. (c) 0.025 part per million in uncooked eggs. (d) 0.125 part per million (negligible residue) in uncooked edible tissues of chickens and turkeys.
21 CFR 556.230 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 11, 2010: https://www.ecfr.gov

7.2 FDA Requirements (Complete)

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including erythromycin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 11, 2010: https://www.accessdata.fda.gov/scripts/cder/ob/docs/queryai.cfm
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including erythromycin ethyl succinate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Erythromycin ethyl succinate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 11, 2010: https://www.accessdata.fda.gov/scripts/cder/ob/docs/queryai.cfm
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including erythromycin lactobionate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Erythromycin lactobionate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 11, 2010: https://www.accessdata.fda.gov/scripts/cder/ob/docs/queryai.cfm
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including erythromycin stearate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Erythromycin stearate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 11, 2010: https://www.accessdata.fda.gov/scripts/cder/ob/docs/queryai.cfm
The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Erythromycin is included on this list.
US FDA/Center for Veterinary Medicine; The Green Book - On Line, Active Ingredients. Erythromycin (114-07-8). Available from, as of March 10, 2010: https://www.fda.gov/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/default.htm
The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Erythromycin phosphate is included on this list. /Erythromycin phosphate/
US FDA/Center for Veterinary Medicine; The Green Book - On Line, Active Ingredients. Erythromycin Phosphate (4501-00-2). Available from, as of March 10, 2010: https://www.fda.gov/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/default.htm
The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Erythromycin thiocyanate is included on this list. /Erythromycin thiocyanate/
US FDA/Center for Veterinary Medicine; The Green Book - On Line, Active Ingredients. Erythromycin Thiocyanate (7704-67-8). Available from, as of March 10, 2010: https://www.fda.gov/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/default.htm
Erythromycin. (1) Dog - For the treatment of bacterial pneumonia, upper respiratory infections (tonsillitis, bronchitis, tracheitis, pharyngitis, pleurisy), endometritis and metritis, and bacterial wound infections caused by Staphylococcus spp., Streptococcus spp., and Corynebacterium spp., sensitive to erythromycin. ... (2) Cats - For the treatment of bacterial pneumonia, upper respiratory infections (rhinitis, bronchitis), secondary infections associated with panleukopenia, and bacterial wound infections caused by Staphylococcus spp. and Streptococcus spp., susceptible to erythromycin. ... (3) Cattle - For the treatment of bovine respiratory disease (shipping fever complex and bacterial pneumonia) associated with Pasteurella multocida susceptible to erythromycin.
21 CFR 522.820 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 11, 2010: https://www.ecfr.gov
Erythromycin. Treatment of mastitis due to Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysgalactiae, and Streptococcus uberis in lactating or dry cows.
21 CFR 526.820 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 11, 2010: https://www.ecfr.gov
Tolerances for residues of erythromycin in food are established as follows: (a) 0.1 part per million in uncooked edible tissues of beef cattle and swine. (b) Zero in milk. (c) 0.025 part per million in uncooked eggs. (d) 0.125 part per million (negligible residue) in uncooked edible tissues of chickens and turkeys.
21 CFR 556.230 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 11, 2010: https://www.ecfr.gov
New animal drugs for use in animal feeds. Erythromycin thiocyanate. /Erythromycin thiocyanate/
Erythromycin thiocyanate in grams per ton
4.6 to 18.5
Indications for use
Chickens; growth promotion and feed efficiency
Erythromycin thiocyanate in grams per ton
9.25 to 18.5
Indications for use
Turkeys; growth promotion and feed efficiency
Limitations
For turkeys not over 12 weeks of age
Erythromycin thiocyanate in grams per ton
9.25 to 64.75
Indications for use
Swine; increase in weight gain, improved feed efficiency in starter pigs (9.25 to 64.75) and grower-finishing pigs (9.25)
Limitations
Starter ration for animals up to 35 lb body weight
Erythromycin thiocyanate in grams per ton
18.5
Indications for use
Laying chickens; aids in increasing egg production
Erythromycin thiocyanate in grams per ton
92.5
Indications for use
1. Chickens; as an aid in the prevention of chronic respiratory disease during periods of stress
Limitations
Feed for 2 day before stress and 3 to 6 day after stress; withdraw 24 hours before slaughter
Indications for use
2. Chickens; as an aid in the prevention of infectious coryza
Limitations
Feed for 7 to 14 days; withdraw 24 hours before slaughter
Indications for use
3. Turkeys; as an aid in the prevention of chronic respiratory disease during periods of stress
Limitations
Feed for 2 days before stress and 3 to 6 days after stress
Erythromycin thiocyanate in grams per ton
185
Indications for use
1. Chickens; as an aid in the prevention and reduction of lesions and in lowering severity of chronic respiratory disease
Limitations
Feed for 5 to 8 days; do not use in birds producing eggs for food purposes; withdraw 48 hours before slaughter
Indications for use
2. Turkeys; as an aid in the prevention and reduction of lesions and in lowering severity of chronic respiratory disease
Limitations
Feed for 5 to 8 days; do not use in birds producing eggs for food purposes
21 CFR 558.248 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 3, 2010: https://www.ecfr.gov
Erythromycin phosphate ... (1) Broiler and replacement chickens - As an aid in the control of chronic respiratory disease due to Mycoplasma gallisepticum susceptible to erythromycin. ... (2) Replacement chickens and chicken breeders - As an aid in the control of infectious coryza due to Hemophilus gallinarum susceptible to erythromycin. ... (3) Growing turkeys - As an aid in the control of blue comb (nonspecific infectious enteritis) caused by organisms susceptible to erythromycin. /Erythromycin phosphate/
21 CFR 520.823 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 11, 2010: https://www.ecfr.gov

8 Chemical / Physical Properties

8.1 Molecular Formula

C37-H67-N-O13

8.2 Molecular Weight

733.93
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 630

8.3 Color / Form (Complete)

Hydrated crystals from water
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 630
Crystals from water
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-230
White or slightly yellow crystals or powder
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 510

8.4 Odor

Odorless
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 510

8.5 Taste

Bitter
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 510

8.6 Melting Point

191 °C
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-230
After melting /at 135-140 °C, it/ resolidifies with second melting point 190-193 °C. ... Readily forms salts with acids
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 630
MP: 92 °C. Slightly soluble in ethanol, ethyl ether, chloroform; insoluble in water. /Erythromycin stearate/
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-230
Crystals from acetone aqueous. MP: 222 °C. MW: 862.05. /Erythromycin ethyl succinate/
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-230

8.7 LogP

log Kow = 3.06
McFarland JW et al; J Med Chem 40: 1340-6 (1997)

8.8 Dissociation Constants

pKa = 8.9
McFarland JW et al; J Med Chem 40: 1340-6 (1997)

8.9 Solubility (Complete)

WHITE OR SLIGHTLY YELLOW CRYSTALS OR POWDER, PRACTICALLY ODORLESS. SOLN IS ALKALINE TO LITMUS. SOL IN METHANOL, CHLOROFORM. /Erythromycin stearate/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1123
WHITE OR SLIGHTLY YELLOW, CRYSTALLINE POWDER. ODORLESS OR PRACTICALLY SO. PRACTICALLY TASTELESS. PKA 7. FREELY SOL IN ACETONE & CHLOROFORM; SOL IN 95% ETHANOL & BENZENE; SPARINGLY SOL IN ETHER; VERY SLIGHTLY SOL IN WATER. /Erythromycin ethyl succinate/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1123
FREELY SOLUBLE IN ALC, SOL IN POLYETHYLENE GLYCOL /Erythromycin ethyl succinate
American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984., p. 8: 12
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-230
Freely soluble in alcohols, acetone, chloroform, acetonitrile, ethyl acetate; moderately soluble in ether, ethylene dichloride, amyl acetate
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 690
Solubility in water: approx 2 mg/ML
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 690

8.10 Refractive Index

INDEX OF REFRACTION: 1.490 (ALPHA), 1.515 (BETA), 1.567 (GAMMA) /Erythromycin ethyl succinate/
Association of Official Analytical Chemists. Official Methods of Analysis. 10th ed. and supplements. Washington, DC: Association of Official Analytical Chemists, 1965. New editions through 13th ed. plus supplements, 1982., p. 13/966

8.11 Optical Rotation

Hydrated crystals from acetone + water, mp 106-110 °C. Specific optical rotation = -42.5 °C at 25 °C/D /Erythromycin ethyl succinate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 630
Specific optical rotation: -78 deg at 25 °C/D (c = 1.99 in ethanol)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 630

8.12 Other Experimental Properties (Complete)

Slightly hygroscopic
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 510
Erythromycins A and B contain the same sugar moieties, desosamine and cladinose (3-O-methylmycarose). They differ in position 12 of the aglycone, erythonolide, A having the hydrpxylsubstituent. Component C contains desoamine and the same aglycone present in A but differs by the presence of mycarose instead of cladinose.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 630
Crystals. Slightly bitter. MW 1018.40. /Erythromycin stearate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 631
ALCOHOLIC SOLN ARE LEVOROTATORY /Erythromycin stearate/
The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 483

9 Spectral Information

9.1 Mass Spectrometry

9.1.1 Other MS

Other MS
MASS: 3886 (National Bureau of Standards EPA-NIH Mass Spectra Data Base, NSRDS-NBS-63)

9.2 UV Spectra

UV max absorption (pH 6.3): 280 nm (epsilon = 50)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 630

9.3 IR Spectra

IR Spectra
IR: 2:363G (Aldrich Library of Infrared Spectra, Aldrich Chemical Co, Milwaukee, WI)

9.4 Other Spectra

Alcoholic solution is levorotatory
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 510

10 Chemical Safety & Handling

10.1 Fire Potential

This material is assumed to be combustible.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Erythromycin; Catalog Number: 1242000; (Revision Date: December 3, 2009)

10.2 Fire Fighting Procedures (Complete)

As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Erythromycin; Catalog Number: 1242000; (Revision Date: December 3, 2009)
Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and material.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Erythromycin; Catalog Number: 1242000; (Revision Date: December 3, 2009)

10.3 Firefighting Hazards (Complete)

This material is assumed to be combustible. As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential of static electricity.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Erythromycin; Catalog Number: 1242000; (Revision Date: December 3, 2009)

10.4 Personal Protective Equipment (PPE) (Complete)

For handling of laboratory scale quantities, a cloth lab coat is recommended. Where significant quantities are handled, work clothing may be necessary to prevent take-home contamination.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Erythromycin; Catalog Number: 1242000; (Revision Date: December 3, 2009)
Safety glasses with sideshields are recommended. Face shields or goggles may be required if splash potential exists or if corrosive materials are present. Approved eye protection (eg, bearing the ANSI Z87 OR CSA stamp) is preferred.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Erythromycin; Catalog Number: 1242000; (Revision Date: December 3, 2009)
Where respirators are deemed necessary to reduce or control occupational exposures, use NIOSH-approved respiratory protection and have an effective respirator program in place.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Erythromycin; Catalog Number: 1242000; (Revision Date: December 3, 2009)

10.5 Preventive Measures (Complete)

Airborne exposure should be controlled primarily by engineering controls such as general dilution ventilation, local exhaust ventilation, or process enclosure. Local exhaust ventilation is generally preferred to general exhaust because it can control the contaminant at its source, preventing dispersion into the work area. An industrial hygiene survey involving air monitoring may be sued to determine the effectiveness of engineering controls. Effectiveness of engineering controls intended for use with highly potent materials should be assessed by use of nontoxic surrogate materials.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Erythromycin; Catalog Number: 1242000; (Revision Date: December 3, 2009)
As a general rule, when handling USP Reference Standards, avoid all contact and inhalation of dust, mist, and/or vapors associated with this material. Clean equipment and work surfaces with suitable detergent or solvent after use. After removing gloves, wash hands and other exposed skin thoroughly.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Erythromycin; Catalog Number: 1242000; (Revision Date: December 3, 2009)
For handling solutions, ensure that the glove material is protective against the solvent being used. Use handling practices that minimize direct hand contact. Employees who are sensitive to natural rubber (latex) should use nitrile or other synthetic nonlatex gloves. Use of powdered latex gloves should be avoided due to the risk of latex allergy.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Erythromycin; Catalog Number: 1242000; (Revision Date: December 3, 2009)
Maintain eyewash facilities in the work area.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Erythromycin; Catalog Number: 1242000; (Revision Date: December 3, 2009)
SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.
SRP: Contaminated protective clothing should be segregated in a manner that results in no direct personal contact by personnel who handle, dispose of, or clean the clothing. Quality assurance procedures to confirm the efficacy of the cleaning procedures should be implemented prior to the decontaminated protective clothing being returned for reuse by the workers. Contaminated clothing (including shoes/socks) should not be taken home at end of shift, but should remain at employee's place of work for cleaning.

10.6 Storage Conditions (Complete)

Commercially available erythromycin topical solutions and gels should be stored at 15 - 30 °C; exposure to heat or open flames should be avoided. The topical ointment should be stored at a temperature less than 27 °C.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3512
Commercially available erythromycin stearate film-coated tablets should be stored in tight, light-resistant containers at 30 °C or lower. /Erythromycin stearate/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 242
Erythromycin lactobionate powder for injection should be stored at a temperature less than 40 °C, preferably between 15 - 30 °C. /erythromycin lactobionate/
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 240
Store in tight container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Erythromycin; Catalog Number: 1242000; (Revision Date: December 3, 2009)

10.7 Cleanup Methods (Complete)

Wear approved respiratory protection, chemically compatible gloves, and protective clothing. Wipe up spillage or collect spillage using a high-efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriate labeled container for disposal. Wash spill site.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Erythromycin; Catalog Number: 1242000; (Revision Date: December 3, 2009)

10.8 Disposal Methods (Complete)

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

11 Occupational Exposure Standards

11.1 Other Standards Regulations and Guidelines (Complete)

Workplace Environmental Exposure Level (WEEL): 8-hr Time-weighted Average (TWA) 3 mg/cu m.
American Industrial Hygiene Association; Emergency Response Planning Guidelines & Workplace Enviromental Exposure Levels. Fairfax, VA 2009, p. 41

12 Manufacturing / Use Information

12.1 Uses (Complete)

Antibiotic
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 630
THERAPEUTIC CATEGORY: Antibacterial /Erythromycin stearate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 631
THERAPEUTIC CATEGORY (VETERINARY): Antibacterial /Erythromycin stearate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 631
MEDICATION

12.2 Manufacturers

Abbott Fermentation Products De P.R., Inc., Km. 58, Carr. 2, Cruce Davila, P.O. Box 278, Barceloneta, PR 00617, (787) 846-3500; Production site: Barceloneta, Puerto Rico 00617
SRI Consulting. 2009 Directory of Chemical Producers. SRI Consulting. Menlo Park, CA 2009, p. 694
Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-3500, (847) 937-6100; Specialty Products Division; Production site: Abbott Park, IL 60064-3005 /Erythromycin and erythromycin stearate/
SRI Consulting. 2009 Directory of Chemical Producers. SRI Consulting. Menlo Park, CA 2009, p. 694
Abbott Laboratories, Pharmaceutical Products Division, North Chicago, IL 60065, (800) 255-5162 /Erythromycin ethyl succinate/
Physicians Desk Reference 64th ed. PDR Network, LLC, Montvale, NJ. 2010, p. 435
Eli Lilly and Company, Lilly Corporate Center, Mail Drop Code 1854, Indianapolis, IN 46285, (317) 276-2000; Production sites: Lafayette, IN 47902; Mayaguez, P.R. 00708
SRI Consulting. 2009 Directory of Chemical Producers. SRI Consulting. Menlo Park, CA 2009, p. 694

12.3 Methods of Manufacturing (Complete)

Elaborated during the growth of a strain of Streptomycees erythreus.
R. Hendrickson, et al. (eds.); Remington: The Science and Practice of Pharmacy 21th ed. Lippincott Williams and Wilkins, Baltimore, Maryalnd, p.1653 (2005)

12.4 General Manufacturing Information (Complete)

Isolation: McGuire et al, Antibiot & Chemother 2, 281 (1952); Bunch, McGuire, US Patent 2,653,899 (1953 to Lilly); Clark, Jr, US Patent 2,823,203 (1958 to Abbott).
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 630
There are three major erythromycins produced during fermentation, designated A, B, and C; A is the major and most important component.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 630
Antibiotic substance produced by strain of Streptomyces erythreus (Waksman) Waksman & Henrici, found in soil sample from Philippine Archipelago.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 630
... belongs to the macrolide group of antibiotics
Physicians Desk Reference 64th ed. PDR Network, LLC, Montvale, NJ. 2010, p. 435

12.5 Formulations / Preparations (Complete)

Table: Erythromycin Lactobionate Preparations
Route of Administration
Parenteral
Dosage Form
For injection, for IV infusion only
Strength
500 mg (of erythromycin)
Brand of Generic Name (Manufacturer)
Erythromycin Lactobionate-IV (Abbott)
Route of Administration
Parenteral
Dosage Form
For injection, for IV infusion only
Strength
500 mg (of erythromycin)
Brand of Generic Name (Manufacturer)
Erythromycin Lactobionate-IV ADD-Vantage (Abbott)
Route of Administration
Parenteral
Dosage Form
For injection, for IV infusion only
Strength
500 mg (of erythromycin)
Brand of Generic Name (Manufacturer)
Erythromycin Piggyback (Abbott)
Route of Administration
Parenteral
Dosage Form
For injection, for IV infusion only
Strength
1 g (of erythromycin)
Brand of Generic Name (Manufacturer)
Erythromycin Lactobionate-IV (Abbott)
Route of Administration
Parenteral
Dosage Form
For injection, for IV infusion only
Strength
1 g (of erythromycin)
Brand of Generic Name (Manufacturer)
Erythromycin Lactobinate-IV Add-Vantage (Abbott)
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 241
Table: Erythromycin Preparations
Route of Administration
Topical
Dosage Form
Gel
Strength
2%
Brand or Generic Name (Manufacturer)
Erythromycin Gel (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Administration
Topical
Dosage Form
Gel
Strength
2%
Brand or Generic Name (Manufacturer)
Erygel (Merz)
Route of Administration
Topical
Dosage Form
Ointment
Strength
2%
Brand or Generic Name (Manufacturer)
Akne-Mycin (Healthpoint)
Route of Administration
Topical
Dosage Form
Solution
Strength
2%
Brand or Generic Name (Manufacturer)
Erythromycin Solution (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Administration
Topical
Dosage Form
Solution
Strength
2%
Brand or Generic Name (Manufacturer)
Erythra-Derm (Paddock)
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3512
Table: Erythromycin Ethylsuccinate Preparations
Route of Adminstration
Oral
Dosage Form
For suspension
Strength
100 mg (of erythromycin) per 2.5 mL
Brand or Generic Name (Manufacturer)
EryPed Drops (Abbott)
Route of Adminstration
Oral
Dosage Form
For suspension
Strength
200 mg (of erythromycin) per 5 mL
Brand or Generic Name (Manufacturer)
E.E.S. Granules (Abbott)
Route of Adminstration
Oral
Dosage Form
For suspension
Strength
200 mg (of erythromycin) per 5 mL
Brand or Generic Name (Manufacturer)
EryPed (Abbott)
Route of Adminstration
Oral
Dosage Form
For suspension
Strength
400 mg (of erythromycin) per 5 mL
Brand or Generic Name (Manufacturer)
EryPed (Abbott)
Route of Adminstration
Oral
Dosage Form
Suspension
Strength
200 mg (of erythromycin) per 5 mL
Brand or Generic Name (Manufacturer)
E.E.S. Liquid (Abbott)
Route of Adminstration
Oral
Dosage Form
Suspension
Strength
200 mg (of erythromycin) per 5 mL
Brand or Generic Name (Manufacturer)
Erythromycin Ethylsuccinate Suspension (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Adminstration
Oral
Dosage Form
Suspension
Strength
400 mg (of erythromycin) per 5 mL
Brand or Generic Name (Manufacturer)
E.E.S. Liquid (Abbott)
Route of Adminstration
Oral
Dosage Form
Suspension
Strength
400 mg (of erythromycin) per 5 mL
Brand or Generic Name (Manufacturer)
Erythromycin Ethylsuccinate Suspension (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Adminstration
Oral
Dosage Form
Tablets, chewable
Strength
200 mg (of erythromycin)
Brand or Generic Name (Manufacturer)
EryPed, scored (Abbott)
Route of Adminstration
Oral
Dosage Form
Tablets, film-coated
Strength
400 mg (of erythromycin)
Brand or Generic Name (Manufacturer)
E.E.S. Filmtab (Abbott)
Route of Adminstration
Oral
Dosage Form
Tablets, film-coated
Strength
400 mg (of erythromycin)
Brand or Generic Name (Manufacturer)
Erythromycin Ethylsuccinate Film-coated Tablets (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 239
Table: Erythromycin Stearate Preparations
Route of Administration
Oral
Dosage Form
Tablets, film-coated
Strength
250 mg (of erythromycin)
Brand or Generic Name (Manufacturer)
Erythrocin Stearate Filmtab (Abbott)
Route of Administration
Oral
Dosage Form
Tablets, film-coated
Strength
250 mg (of erythromycin)
Brand or Generic Name (Manufacturer)
Erythromycin Stearate Tablets (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Administration
Oral
Dosage Form
Tablets, film-coated
Strength
500 mg (of erythromycin)
Brand or Generic Name (Manufacturer)
Erythrocin Stearate Filmtab (Abbott)
Route of Administration
Oral
Dosage Form
Tablets, film-coated
Strength
500 mg (of erythromycin)
Brand or Generic Name (Manufacturer)
Erythromycin Stearate Tablets (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 242
Table: Erythromycin Preparations
Route of Administration
Ophthalmic
Dosage Form
Ointment
Strength
0.5%
Brand or Generic Name (Manufacturer)
Erythromycin Ophthalmic Ointment (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Administration
Ophthalmic
Dosage Form
Ointment
Strength
0.5%
Brand or Generic Name (Manufacturer)
Romycin (OCuSOFT)
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 2856
Table: Erythromycin Estolate Preparations
Route of Administration
Oral
Dosage Form
Capsules
Strength
250 mg (of erythromycin)
Brand or Generic Name (Manufacturer)
Erythromycin Estolate Capsules (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Administration
Oral
Dosage Form
Suspension
Strength
125 mg (of erythromycin) per 5 mL
Brand or Generic Name (Manufacturer)
Erythromycin Estolate Suspension (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Administration
Oral
Dosage Form
Suspension
Strength
250 mg (of erythromycin) per 5 mL
Brand or Generic Name (Manufacturer)
Erythromycin Estolate Suspension (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 238

12.6 U.S. Production (Complete)

approx 1800 metric tons (1979) (estimate)
Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V9 879

13 Laboratory Methods

13.1 Clinical Laboratory Methods (Complete)

DETERMINATION OF ERYTHROMYCIN AFTER IN VITRO & IN VIVO ADMIN IN LIVER, LUNG, & KIDNEYS.
DETTA GE ET AL; ERYTHROMYCIN DETERMINATION IN ORGAN TISSUES; INFECTION (MUNICH) 7(SUPPL 2) 207-10 (1979)
FLUOROMETRIC METHOD FOR DETERMINING ERYTHROMYCIN IN WHOLE BLOOD OR PLASMA IS PROPOSED USING 1 ML SAMPLES. RESULTS ARE CORRELATED WITH MICROBIOLOGICAL ASSAY.
YI TSERNG K ET AL; FLUOROMETRIC DETERMINATION OF ERYTHROMYCIN AND ERTHROMYCIN PROPIONATE IN WHOLE BLOOD OR PLASMA AND CORRELATION OF RESULTS WITH MICROBIOLOGICAL ASSAY;. ANAL CHEM 48(FEB) 348-53 (1976)
FLUORIMETRIC DETERMINATION OF ERYTHROMYCIN ETHYLSUCCINATE IN SERUM BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC & EXTRACTION METHOD. METHOD CAPABLE OF DETECTING LESS THAN 0.01 UG/ML OF ERYTHROMYCIN AND ERYTHROMYCIN ETHYL SUCCINATE. /ERYTHROMYCIN ETHYL SUCCINATE/
TSUJI K; FLUORIMETRIC DETERMINATION OF ERYTHROMYCIN & ERYTHROMYCIN ETHYLSUCCINATE IN SERUM BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC POST-COLUMN, ON-STREAM DERIVATIZATION & EXTRACTION METHOD; J CHROMATOGR 158, 337 (1978)

13.2 Analytic Laboratory Methods (Complete)

Analyte: erythromycin; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2282 (2008)
Analyte: erythromycin; matrix: chemical purity; procedure: liquid chromatography with ultraviolet detection at 215 nm and comparison to standards
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.3185 (2008)
Analyte: erythromycin; matrix: pharmaceutical preparation (delayed-release capsule; delayed-release tablet; injection solution; intramammary infusion; ointment; ophthalmic ointment; tablet; topical gel; topical solution); procedure: thin-layer chromatography with comparison to standards (chemical identification)
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2284 (2008)
Analyte: erythromycin; matrix: pharmaceutical preparation (delayed-release capsule; delayed-release tablet; injection solution; intramammary infusion; pledget; tablet; topical gel; topical solution); procedure: microbial assay (cylinder-plate method) with comparison to standards (chemical purity)
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2284 (2008)
Analyte: erythromycin; matrix: pharmaceutical preparation (ointment); procedure: retention time of the peak in the liquid chromatogram with comparison to standards (chemical identification)
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2285 (2008)
Analyte: erythromycin; matrix: pharmaceutical preparation (ointment); procedure: liquid chromatography with electrochemical detection and comparison to standards (chemical purity)
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2285 (2008)
Analyte: erythromycin estolate; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards /erythromycin estolate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2288 (2008)
Analyte: erythromycin estolate; matrix: chemical purity; procedure: microbial assay (cylinder-plate method) with comparison to standards /erythromycin estolate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2288 (2008)
Analyte: erythromycin estolate; matrix: pharmaceutical preparation (capsule; dry mixture for oral suspension; oral suspension; tablet); procedure: thin-layer chromatography with comparison to standards (chemical identification) /erythromycin estolate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2289 (2008)
Analyte: erythromycin estolate; matrix: pharmaceutical preparation (capsule; dry mixture for oral suspension; oral suspension; tablet); procedure: microbial assay (cylinder-plate method) with comparison to standards (chemical purity) /erythromycin estolate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2289 (2008)
Analyte: erythromycin ethylsuccinate; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards /erythromycin ethylsuccinate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2291 (2008)
Analyte: erythromycin ethylsuccinate; matrix: chemical purity; procedure: liquid chromatography with ultraviolet detection at 215 nm and comparison to standards /erythromycin ethylsuccinate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2291 (2008)
Analyte: erythromycin ethylsuccinate; matrix: pharmaceutical preparation (dry mixture for oral suspension; injection solution; oral suspension; tablet); procedure: microbial assay (cylinder-plate method) with comparison to standards (chemical purity) /erythromycin ethylsuccinate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2292 (2008)
Analyte: erythromycin ethylsuccinate; matrix: pharmaceutical preparation (dry mixture for oral suspension; oral suspension; tablet); procedure: thin-layer chromatography with comparison to standards (chemical identification) /erythromycin ethylsuccinate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2292 (2008)
Analyte: erythromycin lactobionate; matrix: pharmaceutical preparation (dry mixture for injection solution; sterile solid); procedure: infrared absorption spectrophotometry with comparison to standards (chemical identification) /erythromycin lactobionate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2295 (2008)
Analyte: erythromycin lactobionate; matrix: pharmaceutical preparation (dry mixture for injection solution; sterile solid); procedure: microbial assay (cylinder-plate method) with comparison to standards (chemical purity)/erythromycin lactobionate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2295 (2008)
Analyte: erythromycin stearate; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards /erythromycin stearate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2296 (2008)
Analyte: erythromycin stearate; matrix: chemical purity; procedure: liquid chromatography with ultraviolet detection at 215 nm and comparison to standards /erythromycin stearate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2296 (2008)
Analyte: erythromycin stearate; matrix: pharmaceutical preparation (tablet); procedure: thin-layer chromatography with comparison to standards (chemical identification) /erythromycin stearate/
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2297 (2008)
Analyte: erythromycin; matrix: pharmaceutical preparation (tablet); procedure: microbial assay (cylinder-plate method) with comparison to standards (chemical purity)
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.2297 (2008)
Method: EPA-OW/OST 1694; Procedure: high performance liquid chromatography combined with tandem mass spectrometry; Analyte: thiabendazole; Matrix: water, soil, sediment, and biosolids; Detection Limit: 1 ng/L.
National Environmental Methods Index; Analytical, Test and Sampling Methods. Erythromycin (114-07-8). Available from, as of March 12, 2010: https://www.nemi.gov
Method: AOAC 971.48; Procedure: microbiological method; Analyte: erythromycin; Matrix: feeds; Detection Limit: not provided.
Official Methods of Analysis of AOAC International, 18th Edition Online. Erythromycin (114-07-8). Available from, as of March 15, 2010: https://www.aoac.org
Method: AOAC 988.08; Procedure: microbial receptor assay; Analyte: erythromycin; Matrix: milk; Detection Limit: 200 ng/mL.
Official Methods of Analysis of AOAC International, 18th Edition Online. Erythromycin (114-07-8). Available from, as of March 15, 2010: https://www.aoac.org
COLORIMETRIC METHOD FOR ESTIMATION OF ERYTHROMYCIN SALTS IS DESCRIBED.
SANGHAVI NM ET AL; COLORIMETRIC METHOD OF ESTIMATION OF ERYTHROMYCIN; CAN J PHARM SCI 10(2) 59-61 (1975)
VILIM A ET AL; J CHROMATOGR 133(1) 239 (1977)

14 Special References

14.1 Special Reports (Complete)

THE MECHANISM OF ACTION, SPECTRUM OF ACTIVITY, PHARMACOKINETICS, ADVERSE EFFECTS, THERAPEUTIC USES & CHOICE OF ERYTHROMYCIN PREPARATION TO USE ARE REVIEWED.[MEADE RH; DRUG THERAPY REVIEWS; ANTIMICROBIAL SPECTRUM, PHARMACOLOGY AND THERAPEUTIC USE OF ERYTHROMYCIN AND ITS DERIVATIVES; AM J HOSP PHARM 36(SEPT) 1185-89 (1979)]

15 Synonyms and Identifiers

Synonyms

114-07-8

Erythromycin

Dotycin

E-Base

EM

E-Mycin

Erythrocin

Erythrogran

Erythroguent

Erythromycin A

NCI-C55674

Oxacyclotetradecane-2,10-dione, 4-((2,6-dideoxy-3-c-methyl-3-o-methyl-alpha-L-ribo-hexopyranosyl)-oxy)-14-ethyl-7,12 ,13-tri-

Pantomicina

Pentadecanoic acid, 3-((2,6-dideoxy-3-c-methyl-3-o-methyl-alpha-L-ribo-hexopyranosyl)-oxy)-6,11,12,13-tetrahydroxy-2 ,4,6,8-

Propiocine

Robimycin

15.1 Substance Title

Erythromycin

15.2 Associated Chemicals (Complete)

16 Administrative Information

16.1 Hazardous Substances DataBank Number

3074

16.2 Last Revision Date

20100902

16.3 Last Review Date

Reviewed by SRP on 5/13/2010

16.4 Update History

Complete Update on 2010-09-02, 60 fields added/edited/deleted

Field Update on 2003-06-10, 0 fields added/edited/deleted

Complete Update on 02/14/2003, 1 field added/edited/deleted.

Complete Update on 01/14/2002, 1 field added/edited/deleted.

Complete Update on 03/28/2000, 1 field added/edited/deleted.

Complete Update on 02/02/2000, 1 field added/edited/deleted.

Complete Update on 09/21/1999, 1 field added/edited/deleted.

Complete Update on 08/26/1999, 1 field added/edited/deleted.

Complete Update on 05/12/1999, 2 fields added/edited/deleted.

Complete Update on 09/11/1998, 1 field added/edited/deleted.

Complete Update on 06/02/1998, 1 field added/edited/deleted.

Complete Update on 03/06/1998, 1 field added/edited/deleted.

Complete Update on 07/23/1996, 34 fields added/edited/deleted.

Field Update on 01/26/1996, 1 field added/edited/deleted.

Field Update on 08/21/1995, 1 field added/edited/deleted.

Complete Update on 03/24/1995, 1 field added/edited/deleted.

Complete Update on 12/30/1994, 1 field added/edited/deleted.

Complete Update on 08/23/1994, 1 field added/edited/deleted.

Complete Update on 11/01/1993, 1 field added/edited/deleted.

Field update on 12/28/1992, 1 field added/edited/deleted.

Complete Update on 10/10/1990, 1 field added/edited/deleted.

Field update on 05/18/1990, 1 field added/edited/deleted.

Complete Update on 04/16/1990, 1 field added/edited/deleted.

Field update on 12/29/1989, 1 field added/edited/deleted.

Complete Update on 12/31/1984

Created 19830315 by DS

CONTENTS