Erythromycin Ethylsuccinate

ERYTHROMYCIN ETHYLSUCCINATE- erythromycin ethylsuccinate granule, for suspension
ANI Pharmaceuticals, Inc.

DESCRIPTION

Erythromycin is produced by a strain of Saccharopolyspora erythraea (formerly Streptomyces erythraeus) and belongs to the macrolide group of antibiotics. It is basic and readily forms salts with acids. The base, the stearate salt, and the esters are poorly soluble in water. Erythromycin ethylsuccinate is an ester of erythromycin suitable for oral administration. Erythromycin ethylsuccinate is known chemically as erythromycin 2′-(ethylsuccinate). The molecular formula is C₄₃ H₇₅ NO₁₆ and the molecular weight is 862.06. The structural formula is:

The granules are intended for reconstitution with water. Each 5 mL teaspoonful of reconstituted palatable cherry-flavored suspension contains erythromycin ethylsuccinate equivalent to 200 mg of erythromycin.

Granules are intended primarily for pediatric use but can also be used in adults.

Inactive Ingredients: artificial cherry flavor, lactose anhydrous, methylparaben, polysorbate 80, povidone, simethicone, sodium citrate anhydrous, and sucrose.

CLINICAL PHARMACOLOGY

Orally administered erythromycin ethylsuccinate suspension is readily and reliably absorbed. Comparable serum levels of erythromycin are achieved in the fasting and nonfasting states.

Erythromycin diffuses readily into most body fluids. Only low concentrations are normally achieved in the spinal fluid, but passage of the drug across the blood-brain barrier increases in meningitis. In the presence of normal hepatic function, erythromycin is concentrated in the liver and excreted in the bile; the effect of hepatic dysfunction on excretion of erythromycin by the liver into the bile is not known. Less than 5 percent of the orally administered dose of erythromycin is excreted in active form in the urine.

Erythromycin crosses the placental barrier, but fetal plasma levels are low. The drug is excreted in human milk.

Microbiology

Mechanism of Action

Erythromycin acts by inhibition of protein synthesis by binding 50S ribosomal subunits of susceptible organisms. It does not affect nucleic acid synthesis.

Resistance

The major route of resistance is modification of the 23S rRNA in the 50S ribosomal subunit to insensitivity while efflux can also be significant.

Interactions with Other Antimicrobials

Antagonism exists in vitro between erythromycin and clindamycin, lincomycin, and chloramphenicol.

Antimicrobial Activity

Erythromycin has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections (See INDICATIONS AND USAGE).

Aerobic bacteria

Gram-positive bacteria:
Corynebacterium diphtheriae
Corynebacterium minutissimum
Listeria monocytogenes
Staphylococcus aureus (resistant organisms may emerge during treatment)
Streptococcus pneumoniae
Streptococcus pyogenes

Gram-negative bacteria:
Bordetella pertussis
Haemophilus influenzae
Legionella pneumophila
Neisseria gonorrhoeae

Other microorganisms

Chlamydia trachomatis
Entamoeba histolytica
Mycoplasma pneumoniae
Treponema pallidum
Ureaplasma urealyticum

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for erythromycin against isolates of similar genus or organism group. However, the efficacy of erythromycin in treating clinical infections caused by these bacteria has not been established in adequate and well controlled clinical trials.

Aerobic bacteria

Gram-positive bacteria:
Viridans group streptococci

Gram-negative bacteria:
Moraxella catarrhalis

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of erythromycin ethylsuccinate and other antibacterial drugs, erythromycin ethylsuccinate should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Erythromycin ethylsuccinate for oral suspension USP is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the diseases listed below:

Upper respiratory tract infections of mild to moderate degree caused by Streptococcus pyogenes, Streptococcus pneumoniae, or Haemophilus influenzae (when used concomitantly with adequate doses of sulfonamides, since many strains of H. influenzae are not susceptible to the erythromycin concentrations ordinarily achieved). (See appropriate sulfonamide labeling for prescribing information.)

Lower-respiratory tract infections of mild to moderate severity caused by Streptococcus pneumonia or Streptococcus pyogenes.

Listeriosis caused by Listeria monocytogenes.

Pertussis (whooping cough) caused by Bordetella pertussis. Erythromycin is effective in eliminating the organism from the nasopharynx of infected individuals rendering them noninfectious. Some clinical studies suggest that erythromycin may be helpful in the prophylaxis of pertussis in exposed susceptible individuals.

Respiratory tract infections due to Mycoplasma pneumoniae.

Skin and skin structure infections of mild to moderate severity caused by Streptococcus pyogenes or Staphylococcus aureus (resistant staphylococci may emerge during treatment).

Diphtheria: Infections due to Corynebacterium diphtheriae , as an adjunct to antitoxin, to prevent establishment of carriers and to eradicate the organism in carriers.

Erythrasma: In the treatment of infections due to Corynebacterium minutissimum.

Intestinal amebiasis caused by Entamoeba histolytica (oral erythromycins only). Extraenteric amebiasis requires treatment with other agents.

Acute pelvic inflammatory disease caused by Neisseria gonorrhoeae: As an alternative drug in treatment of acute pelvic inflammatory disease caused by N. gonorrhoeae in female patients with a history of sensitivity to penicillin. Patients should have a serologic test for syphilis before receiving erythromycin as treatment of gonorrhea and a follow-up serologic test for syphilis after 3 months.

Syphilis caused by Treponema pallidum: Erythromycin is an alternate choice of treatment for primary syphilis in patients allergic to the penicillins. In treatment of primary syphilis, spinal fluid examinations should be done before treatment and as part of follow-up after therapy.

Erythromycins are indicated for the treatment of the following infections caused by Chlamydia trachomatis: conjunctivitis of the newborn, pneumonia of infancy, and urogenital infections during pregnancy. When tetracyclines are contraindicated or not tolerated, erythromycin is indicated for the treatment of uncomplicated urethral, endocervical, or rectal infections in adults due to Chlamydia trachomatis.

When tetracyclines are contraindicated or not tolerated, erythromycin is indicated for the treatment of nongonococcal urethritis caused by Ureaplasma urealyticum.

Legionnaires’ Disease caused by Legionella pneumophila. Although no controlled clinical efficacy studies have been conducted, in vitro and limited preliminary clinical data suggest that erythromycin may be effective in treating Legionnaires’ Disease.

Prophylaxis

Prevention of Initial Attacks of Rheumatic Fever
Penicillin is considered by the American Heart Association to be the drug of choice in the prevention of initial attacks of rheumatic fever (treatment of Streptococcus pyogenes infections of the upper respiratory tract, e.g., tonsillitis or pharyngitis). Erythromycin is indicated for the treatment of penicillin-allergic patients.¹ The therapeutic dose should be administered for 10 days.

Prevention of Recurrent Attacks of Rheumatic Fever
Penicillin or sulfonamides are considered by the American Heart Association to be the drugs of choice in the prevention of recurrent attacks of rheumatic fever. In patients who are allergic to penicillin and sulfonamides, oral erythromycin is recommended by the American Heart Association in the long-term prophylaxis of streptococcal pharyngitis (for the prevention of recurrent attacks of rheumatic fever).¹