Erythromycin Estolate
Erythromycin estolate is a macrolide antibiotic.
Dosage and Administration
Administration
Erythromycin estolate is administered orally.
Dosage
Dosage of erythromycin estolate is expressed in terms of erythromycin. The usual adult oral dosage of erythromycin as the estolate is 250 mg every 6 hours. In severe infections, dosage may be increased to 4 g or more daily. The usual oral dosage of erythromycin as the estolate in children is 30-50 mg/kg daily in 4 equally divided doses. For more severe infections, this dosage may be doubled.
Alternatively, a pediatric dosage of 0.9-3 g/m2 daily in 4 equally divided doses has been recommended. The manufacturers state that adults and children may receive one-half the total daily dose every 12 hours as an alternative dosage schedule, but some clinicians believe this schedule is inadequate for all but minor infections caused by highly susceptible organisms.
Pharyngitis and Tonsillitis
The usual dosage of erythromycin as the estolate for the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A b-hemolytic streptococci) is 20-50 mg/kg daily (maximum 1 g daily) given in 2-4 divided doses for 10 days or longer.
Prophylaxis of Recurrent Rheumatic Fever
For continuous prophylaxis to prevent recurrences in patients with a history of rheumatic heart disease, the usual oral dosage of erythromycin is 250 mg twice daily. When selecting anti-infectives for prophylaxis of recurrent rheumatic fever, the current recommendations published by the American Heart Association (AHA) should be consulted.
Syphilis
Although penicillin G is the drug of choice for all stages of syphilis, the manufacturers state that erythromycin as the estolate may be given in a dosage of 20 g over 10 days for the treatment of primary syphilis.
Erythromycin is no longer included in US Centers for Disease Control and Prevention (CDC) recommendations for the treatment of any form of syphilis in adults or adolescents (including primary, secondary, latent, or tertiary syphilis or neurosyphilis) and is not recommended for the treatment of congenital syphilis or syphilis in older infants and children. In addition, erythromycin is no longer recommended by the CDC or American Academy of Pediatrics (AAP) for the treatment of syphilis in pregnant women who are hypersensitive to penicillin since numerous treatment failures (including in the fetus) have been reported with the drug.
Gonorrhea and Associated Infections
The AAP currently recommends that all children beyond the neonatal period being treated for uncomplicated vulvovaginal, urethral, or pharyngeal gonorrhea, epididymitis, proctitis, or disseminated gonococcal infections including meningitis or endocarditis receive presumptive treatment for possible coexisting chlamydial infections. If oral erythromycin is used for presumptive treatment of chlamydial infection in children who weigh less than 45 kg, the AAP recommends a dosage of 50 mg/kg daily (maximum 2 g daily) given in 4 divided doses for 7 days.
Chlamydial Infections
For the treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis in nonpregnant adults and adolescents in whom tetracyclines and azithromycin are contraindicated or not tolerated, the CDC and others recommended oral erythromycin in a dosage of 500 mg 4 times daily for 7 days. The dosage of oral erythromycin recommended by CDC for the treatment of these infections in children weighing 45 kg or less is 50 mg/kg daily given in 4 divided doses for 14 days.
For the treatment of chlamydial urogenital infections during pregnancy, the manufacturers recommend an oral erythromycin dosage of 500 mg 4 times daily for at least 7 days; for women who cannot tolerate this regimen, the manufacturers recommend an oral erythromycin dosage of 250 mg 4 times daily for at least 14 days. However, the CDC and other clinicians do not recommend use of erythromycin estolate in pregnant women because of the drug’s potential for hepatotoxicity.
For the treatment of pneumonia caused by C. trachomatis in infants, the recommended dosage of oral erythromycin is 50 mg/kg daily given in 4 divided doses for 14 days; follow-up is recommended and a second course of therapy may be necessary. For the treatment of ophthalmia neonatorum caused by C. trachomatis, the recommended dosage of oral erythromycin is 50 mg/kg daily given in 4 divided doses for 14 days; follow-up is recommended and a second course of therapy may be necessary.
For the treatment of trachoma in children, oral erythromycin has been given for 40 days in conjunction with topical anti-infective therapy; however, optimum therapy has not been established, and treatment may be difficult.
Intestinal Amebiasis
Although erythromycin is not considered a drug of choice for the treatment of intestinal amebiasis caused by Entamoeba histolytica, the manufacturers state that adults may receive 250 mg of erythromycin 4 times daily for 10-14 days and that children may be given 30-50 mg/kg daily in divided doses for 10-14 days.
Pertussis
Although the optimum dosage and duration of erythromycin for the treatment of pertussis or prevention in susceptible contacts have not been established, a dosage of 40-50 mg/kg daily (maximum 2 g daily) given in divided doses for 14 days usually is recommended.
While a shorter duration of erythromycin therapy (e.g., 7 or 10 days) may be effective in some patients, 100, 114 prophylaxis failures and bacteriologic relapse of pertussis have been reported with erythromycin regimens shorter than 14 days. Therefore, the CDC, US Public Health Service Advisory Committee on Immunization Practices (ACIP), AAP, and some clinicians recommend that a 14-day course of erythromycin therapy be used for treatment or prevention of pertussis.
Although data from controlled studies are lacking, the CDC recommends that all household and other close contacts of individuals with pertussis receive a 14-day regimen of prophylaxis (regardless of age and vaccination status) since this may prevent or minimize transmission of the disease.
In addition, all close contacts younger than 7 years of age who are not fully immunized against pertussis should receive the remaining required doses of a preparation containing pertussis vaccine (using minimal intervals between doses) and those who are fully immunized but have not received a vaccine dose within the last 3 years should receive a booster dose of a pertussis vaccine preparation.
Legionnaires’ Disease
Although the optimum dosage and duration of erythromycin for the treatment of Legionnaires’ disease have not been established, dosages of 1-4 g daily in divided doses have been given alone or in combination with rifampin. A parenteral regimen usually is necessary for the initial treatment of severe Legionnaires’ disease and the addition of rifampin is recommended during the first 3-5 days of therapy in severely ill and/or immunocompromised patients; after a response is obtained, rifampin can be discontinued and therapy changed to oral erythromycin.
The duration of therapy in patients with Legionnaires’s disease usually is 10-21 days; some clinicians recommend 14 days of therapy for patients with mild disease and 21 days for those who are immunocompromised or have severe disease.
Cautions
Erythromycin estolate shares the toxic potentials of the erythromycins, and the usual precautions of erythromycin therapy should be observed. (See Cautions in the Erythromycins General Statement 8:12.12.04.)
Hepatic Effects
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 is contraindicated in patients with hepatic dysfunction or preexisting liver disease.
Chemistry and Stability
Chemistry
Erythromycin estolate, the sodium lauryl sulfate salt of the propionate ester of erythromycin, occurs as a white, odorless or practically odorless, practically tasteless, crystalline powder. The drug is practically insoluble in water and has a solubility of approximately 50 mg/mL in alcohol at 25°C.
Stability
Commercially available preparations of erythromycin estolate should be protected from light and have expiration dates of 2-5 years following the date of manufacture, depending on the dosage form. The manufacturers recommend that commercially available oral suspensions of the drug be refrigerated to retain palatability. For further information on chemistry, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of erythromycin estolate, see the Erythromycins General Statement 8:12.12.04.
Preparations
Erythromycin Estolate Oral Capsules 250 mg (of erythromycin) Erythromycin Estolate Capsules , Barr Suspension 125 mg (of erythromycin) per Erythromycin Estolate 5 mL Suspension, Alpharma 250 mg (of erythromycin) per Erythromycin Estolate 5 mL Suspension, Alpharma