Erythromycin (Systemic)

Brand names: E.E.S., ERYC, EryPed, Ery-Tab, Erythrocin, PCE
Drug class: Erythromycins
VA class: AM200
CAS number: 114-07-8

Medically reviewed by Drugs.com on Jun 21, 2022. Written by ASHP.

Introduction

Antibacterial; macrolide antibiotic produced by Saccharopolyspora erythraeus.

Uses for Erythromycin (Systemic)

Acute Otitis Media (AOM)

Treatment of AOM in children caused by susceptible Haemophilus influenzae. The fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole acetyl must be used; erythromycin is not effective when used alone for treatment of H. influenzae infections.

The fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole acetyl is an alternative (not a preferred agent) for treatment of AOM. The drug is recommended as an alternative in patients with type I penicillin hypersensitivity. May not be effective for treatment of AOM that fails to respond to amoxicillin since a high incidence of S. pneumoniae resistant to the fixed-combination drug has been reported.

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci). Generally effective in eradicating S. pyogenes from the nasopharynx, but efficacy in prevention of subsequent rheumatic fever has not been established to date.

CDC, AAP, IDSA, AHA, and others recommend oral penicillin V or IM penicillin G benzathine as treatments of choice; oral cephalosporins and oral macrolides considered alternatives. Amoxicillin sometimes used instead of penicillin V, especially for young children.

Erythromycin usually the preferred alternative for treatment of streptococcal pharyngitis in patients hypersensitive to penicillin. Although S. pyogenes resistant to erythromycin and other macrolides have been reported and may be prevalent in some areas of the world (e.g., Japan, Finland), the incidence of these resistant S. pyogenes in the US has been relatively low to date.

Respiratory Tract Infections

Treatment of respiratory tract infections caused by susceptible S. pneumoniae.

Treatment of respiratory tract infections caused by Mycoplasma pneumoniae or C. pneumoniae.

Erythromycin usually not effective when used alone for treatment of respiratory tract infections caused by H. influenzae.

Skin and Skin StructureInfections

Treatment of mild to moderate skin and skin structure infections caused by S. pyogenes or Staphylococcus aureus. Consider that erythromycin-resistant Staphylococci may develop during treatment.

Treatment of erythrasma caused by Corynbacterium minutissimum.

Acne

Treatment of acne^{† [off-label]}.

Amebiasis

Has been used for treatment of intestinal amebiasis caused by Entamoeba histolytica. Erythromycin generally not recommended for treatment of amebiasis; regimen of choice for intestinal amebiasis is metronidazole or tinidazole followed by a luminal amebicide such as iodoquinol or paromomycin.

Anthrax

Alternative for treatment of anthrax^{† [off-label]}.

Multiple-drug parenteral regimens recommended for treatment of inhalational anthrax that occurs as the result of exposure to B. anthracis spores in the context of biologic warfare or bioterrorism. Initiate treatment with IV ciprofloxacin or doxycycline and 1 or 2 other anti-infective agents predicted to be effective (e.g., chloramphenicol, clindamycin, rifampin, vancomycin, clarithromycin, imipenem, penicillin, ampicillin); if meningitis is established or suspected, use IV ciprofloxacin (rather than doxycycline) and chloramphenicol, rifampin, or penicillin.

Bartonella Infections

Has been used in conjunction with IM or IV ceftriaxone for treatment of bacteremia caused by Bartonella quintana^{† [off-label]} (formerly Rochalimaea quintana).

Optimum regimens for treatment of infections caused by B. quintana or for treatment of cat scratch disease or other B. henselae infections have not been identified.

USPHS/IDSA suggests that long-term suppression with erythromycin or doxycycline be considered to prevent recurrence of Bartonella infection in HIV-infected patients^{† [off-label]}.

Campylobacter Infections

Treatment of symptomatic enteric infections caused by Campylobacter jejuni^{† [off-label]}. Recommended by CDC, IDSA, and AAP as a treatment of choice.

Chancroid

Treatment of chancroid^† (genital ulcers caused by H. ducreyi).

CDC and others recommend azithromycin, ceftriaxone, ciprofloxacin or erythromycin as drugs of choice for treatment of chancroid. HIV-infected patients and uncircumcised patients may not respond to treatment as well as those who are HIV-negative or circumcised. Some experts prefer the 7-day erythromycin regimen instead of single-dose azithromycin or ceftriaxone regimens in HIV-infected individuals.

Chlamydial Infections

Alternative for treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis when tetracyclines and azithromycin are contraindicated or not tolerated. Erythromycin is less effective than either azithromycin or doxycycline and GI effects associated with the drug may discourage patient compliance with the regimen; CDC recommends that the first dose be taken under supervision.

A drug of choice for treatment of urogenital chlamydial infections in pregnant women and in young children.

Alternative for presumptive treatment of coexisting chlamydial infections in patients receiving treatment for gonorrhea. Preferred drugs are azithromycin or doxycycline; erythromycin may be preferred in young children.

Treatment of urethritis caused by Ureaplasma urealyticum.

Treatment of chlamydial pneumonia in infants.

Treatment of initial episodes and recurrences of chlamydial conjunctivitis in neonates.

Alternative to doxycycline for treatment of lymphogranuloma venereum^† caused by invasive serotypes of C. trachomatis (serovars L1, L2, L3). Erythromycin may be the preferred regimen for pregnant and lactating women.

Alternative for treatment of psittacosis when tetracyclines are contraindicated (e.g., in pregnant women, children younger than 9 years of age).

Diphtheria

Adjunct to diphtheria antitoxin for treatment of diphtheria caused by Corynebacterium diphtheria. Diphtheria antitoxin is the most important aspect of treatment of respiratory diphtheria. Anti-infectives may eliminate C. diphtheriae from infected sites, prevent spread of the organism and further toxin production, and prevent or terminate the diphtheria carrier state, but appear to be of no value in neutralizing diphtheria toxin and should not be considered a substitute for antitoxin therapy.

Because diphtheria infection often does not confer immunity, active immunization with a diphtheria toxoid preparation should be initiated or completed during convalescence.

Prevention of diphtheria in close contacts of patients with diphtheria. Prophylaxis is indicated in all household or other close contacts of individuals with suspected or proven diphtheria, regardless of vaccination status; prophylaxis should be initiated promptly and should not be delayed pending culture results. An age-appropriate diphtheria toxoid preparation also may be necessary depending on immunization status.

Elimination of diphtheria carrier state in individuals known to carry toxigenic strains of C. diphtheriae.

Granuloma Inguinale (Donovanosis)

Alternative for treatment of granuloma inguinale^† (donovanosis) caused by Calymmatobacterium granulomatis.

CDC recommends doxycycline or co-trimoxazole as drugs of choice; ciprofloxacin, erythromycin, and azithromycin are alternatives. Erythromycin may be preferred in pregnant and lactating women.

Legionnaires’ Disease

Treatment of Legionnaires’ disease caused by Legionella pneumophila; used with or without rifampin.

Lyme Disease

Alternative for treatment of early Lyme disease^†. IDSA, AAP, and others recommend doxycycline, amoxicillin, or cefuroxime as first-line agents; macrolides may be less effective.

Nongonococcal Urethritis

Treatment of nongonococcal urethritis (NGU).

CDC and others recommend azithromycin or doxycycline as drugs of choice for treatment of NGU; erythromycin (erythromycin base or ethylsuccinate) or fluoroquinolones (levofloxacin, ofloxacin) are alternatives. A regimen of erythromycin and metronidazole is recommended by CDC for treatment of recurrent and persistent urethritis in patients who were compliant with their initial regimen and have not been re-exposed.

Pelvic Inflammatory Disease (PID)

IV erythromycin lactobionate followed by oral erythromycin has been used for treatment of PID) caused by N. gonorrhoeae, but erythromycins are not included in current CDC recommendations for treatment of PID.

Pertussis

Treatment of Bordetella pertussis infection (pertussis, whooping cough); a drug of choice.

Prevention of pertussis in contacts of patients with the disease; drug of choice.

CDC, AAP, and other clinicians recommend anti-infective prophylaxis for all household and other close contacts (e.g., those in childcare) of individuals with pertussis, regardless of age or vaccination status. Close contacts <7 years of age who are not fully immunized against pertussis also 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.

Syphilis

Has been used as an alternative for treatment of primary syphilis in penicillin-allergic individuals.

Penicillin G is drug of choice for treatment of all stages of syphilis. Erythromycin is less effective than other possible penicillin alternatives and is not included in CDC recommendations for treatment of any form of syphilis in adults or adolescents (including primary, secondary, latent, or tertiary syphilis or neurosyphilis).

Preoperative Intestinal Antisepsis

Adjunct to mechanical cleansing of the large intestine for intestinal antisepsis prior to elective colorectal surgery; used in conjunction with neomycin.

Prevention of Bacterial Endocarditis

Has been used as an alternative to penicillins for prevention of bacterial endocarditis in penicillin-allergic patients undergoing certain dental, oral, respiratory tract, or esophageal procedures who have cardiac conditions that put them at high or moderate risk. AHA no longer recommends erythromycin for this use, but states that practitioners who have successfully used an erythromycin (i.e., erythromycin ethylsuccinate, erythromycin stearate) for prophylaxis in individual patients may choose to continue using these agents.

Erythromycins are not appropriate for prevention of bacterial endocarditis in patients undergoing GI, biliary, or genitourinary tract procedures because causative organisms are likely to be erythromycin-resistant.

Consult most recent AHA recommendations for specific information on which cardiac conditions are associated with high or moderate risk of endocarditis and which procedures require prophylaxis.

Prevention of Rheumatic Fever Recurrence

Alternative to IM penicillin G benzathine, oral penicillin V potassium, and oral sulfadiazine for prevention of recurrence of rheumatic fever (secondary prophylaxis) in patients hypersensitive to penicillins and sulfonamides.

Continuous prophylaxis recommended following treatment of documented rheumatic fever (even if manifested solely by Sydenham chorea) and in those with evidence of rheumatic heart disease.

Prevention of Perinatal Group B Streptococcal Disease

Alternative to penicillin G or ampicillin for prevention of perinatal group B streptococcal (GBS) disease^† in penicillin-allergic pregnant women at risk for anaphylaxis with a β-lactam anti-infective.

Intrapartum anti-infective prophylaxis to prevent early-onset neonatal GBS disease is administered to women identified as GBS carriers during routine prenatal GBS screening performed at 35–37 weeks during the current pregnancy and to women who have GBS bacteriuria during the current pregnancy, a previous infant with invasive GBS disease, unknown GBS status with delivery at <37 weeks gestation, amniotic membrane rupture for ≥18 hours, or intrapartum temperature of ≥38°C.

Penicillin G is the regimen of choice and ampicillin is the preferred alternative. Cefazolin can be used in penicillin-allergic women who do not have immediate-type penicillin hypersensitivity, but clindamycin or erythromycin should be used in penicillin-allergic women at high risk for anaphylaxis.

Consider that S. agalactiae (group B streptococci) with in vitro resistance to clindamycin and erythromycin has been reported with increasing frequency; perform in vitro susceptibility tests of clinical isolates obtained during GBS prenatal screening. GBS resistant to erythromycin often are resistant to clindamycin, although this may not be evident in results of in vitro testing. If in vitro susceptibility testing is not possible, results are unknown, or isolates are found to be resistant to erythromycin or clindamycin, vancomycin is recommended for intrapartum prophylaxis in penicillin-allergic women at high risk for anaphylaxis with β-lactams.

Erythromycin (Systemic) Dosage and Administration

Administration

Administer orally as erythromycin base, stearate, ethylsuccinate, or estolate. Administer erythromycin lactobionate by IV infusion.

Oral route usually preferred and should replace parenteral route as soon as possible.

Oral Administration

Erthromycin delayed-release tablets (PCE Dispertab, Ery-Tab) may be given without regard to meals, but optimal absorption of PCE Dispertab occurs when the tablets are given in the fasting state (at least 30 minutes and, preferably, 2 hours before meals). Erythromycin film-coated tablets should be administered in the fasting state (at least 30 minutes and, preferably, 2 hours before or after meals).

Erythromycin delayed-release capsules containing enteric-coated pellets of erythromycin (ERYC) may be swallowed intact or the entire contents of a capsule(s) may be sprinkled on a small amount of applesauce immediately prior to administration; subdividing the contents of a capsule is not recommended. The enteric-coated pellets contained in the capsules should not be chewed or crushed. If the capsule contents are administered by sprinkling on applesauce, the patient should drink some water after swallowing the applesauce to ensure that the pellets are swallowed. If the pellets are accidentally spilled, the dose preparation should be started over with a new capsule.

Erythromycin ethylsuccinate oral suspensions, chewable tablets, and film-coated tablets (E.E.S., EryPed) are given without regard to meals. Chewable tablets should not be swallowed whole.

Erythromycin stearate preferably should be administered in the fasting state or immediately before a meal.

Fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole acetyl is given without regard to meals.

Reconstitution

Reconstitute erythromycin ethylsuccinate powders for oral suspension with water according to manufacturers’ directions.

IV Infusion

Administer erythromycin lactobionate by continuous or intermittent IV infusion. Do not administer by rapid or direct IV injection because of the local irritative effects of the drug.

Continuous IV infusion usually is preferred, but the drug may be administered by intermittent IV infusion every 6 hours.

Reconstitution

Reconstitute ADD-Vantage vials according to the manufacturer’s instructions using 0.9% sodium chloride or 5% dextrose injection. The ADD-Vantage vials are for single use only.

Rate of Administration

For intermittent IV infusion; one-fourth of the total daily dose is administered over 20–60 minutes at intervals no longer than every 6 hours.

Dosage

Available as erythromycin base, estolate, ethylsuccinate, stearate, or lactobionate; dosage expressed in terms of erythromycin. Dosage of the fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole acetyl is expressed in terms of the erythromycin or sulfisoxazole content.

Erythromycin ethylsuccinate has different absorption characteristics than other commercially available forms of oral erythromycin and higher doses of the ethylsuccinate may be needed to achieve therapeutic effects. For adults, 400 mg of erythromycin as the ethylsuccinate provides erythromycin activity similar to that provided by 250 mg of erythromycin as the base, estolate, or stearate.

Pediatric Patients

General Pediatric Dosage

Treatment of Infections

Oral

Erythromycin (base, estolate, ethylsuccinate, or stearate): 30–50 mg/kg daily in 2–4 equally divided doses.

Dosage may be doubled for severe infections.

Erythromycin (lactobionate): 15–20 mg/kg daily. Dosage up to 4 g daily may be used for severe infections.

Acute Otitis Media (AOM)

Oral

Children ≥2 months of age (fixed combination containing erythromycin ethylsuccinate and sulfisoxazole acetyl): 12.5 mg/kg (based on erythromycin content) every 6 hours or 17 mg/kg (based on erythromycin content) every 8 hours (up to 2 g daily). Alternatively, the following approximate dosages expressed in terms of volumes of the fixed-combination suspension can be used. (See Table 1 and Table 2.)

Pediazole Dosage (6-Hour Dosing) for AOM in Children ≥2 Months of Age
Weight (in kg)	Dose (repeated every 6 h for 10 days)
<8	Calculate dose by body weight
8–15.9	2.5 mL
16–23.9	5 mL
24–31.9	7.5 mL
>32	10 mL

Pediazole Dosage (8-Hour Dosing) for AOM in Children ≥2 Months of Age
Weight (in kg)	Dose (repeated every 8 h for 10 days)
<6	Calculate dose by body weight
6–11.9	2.5 mL
12–17.9	5 mL
18–23.9	7.5 mL
24–30	10 mL
>30	12.5 mL

Amebiasis

Entamoeba histolytica Infections

Oral

Erythromycin (base, estolate, ethylsuccinate, or stearate): 30–50 mg/kg daily in divided doses for 10–14 days.

Anthrax†

IV

Erythromycin (lactobionate): 20–40 mg/kg daily given in divided doses every 6 hours.

Must be used in multiple-drug regimens that initially include IV ciprofloxacin or IV doxycycline and 1 or 2 other anti-infectives predicted to be effective.

Duration of treatment is 60 days if anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.

Chlamydial Infections

Uncomplicated Urethral, Endocervical, or Rectal Infections in Children Weighing <45 kg

Oral

Erythromycin (base or ethylsuccinate): 50 mg/kg daily (maximum 2 g daily) given in 4 divided doses for 14 days.

Uncomplicated Urethral, Endocervical, or Rectal Infections in Adolescents

Oral

Erythromycin (base or stearate): 500 mg 4 times daily for 7 days. Alternatively, 666 mg every 8 hours for 7 days.

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.

Presumptive Treatment of Chlamydial Infections in Children Weighing <45 kg with Gonorrhea

Oral

Erythromycin (base or ethylsuccinate): 50 mg/kg daily (maximum 2 g daily) given in 4 divided doses for 7 days.

Presumptive Treatment of Chlamydial Infections in Adolescents with Gonorrhea

Oral

Erythromycin (base): 500 mg 4 times daily for 7 days.

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.

Treatment of Pneumonia Caused by C. trachomatis

Oral

Erythromycin (base, ethylsuccinate, or stearate): 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.

Treatment of Ophthalmia Neonatorum Caused by C. trachomatis

Oral

Erythromycin (base, ethylsuccinate, or stearate): 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.

Diphtheria

Treatment of Diphtheria

Oral

Erythromycin: 40–50 mg/kg daily (maximum 2 g daily) for 14 days. Patients usually are no longer contagious 48 hours after initiation of anti-infective therapy. Eradication of the organism should be confirmed by 2 consecutive negative cultures following completion of therapy.

Prevention of Diphtheria

Oral

Erythromycin: 40–50 mg/kg daily (maximum 2 g daily) for 7–10 days.

Elimination of Diphtheria Carrier State

Oral

Erythromycin: 40–50 mg/kg daily (maximum 2 g daily) for 7–10 days. Obtain follow-up cultures ≥2 weeks after completion of therapy; if cultures are positive, an additional 10-day course should be given and additional follow-up cultures obtained.

Lyme Disease†

Early Localized or Early Disseminated Lyme Disease†

Oral

Erythromycin: 12.5 mg/kg (up to 500 mg) 4 times daily for 14–21 days. Alternatively, 30 mg/kg daily in 3 divided doses (or 250 mg 3 times daily) for 14–21 days.

Nongonococcal Urethritis in Adolescents

Oral

Erythromycin (base): 500 mg 4 times daily for 7 days. Alternatively, 666 mg every 8 hours for ≥7 days. For recurrent and persistent urethritis, CDC recommends 500 mg 4 times daily for 7 days in conjunction with a single dose of oral metronidazole (2 g).

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days. For recurrent and persistent urethritis, CDC recommends 800 mg 4 times daily for 7 days in conjunction with a single dose of oral metronidazole (2 g).

Pertussis

Treatment or Prevention of Pertussis

Oral

Erthromycin (base or stearate): 40–50 mg/kg daily (maximum 2 g daily) in divided doses for 14 days.

Prevention of Bacterial Endocarditis†

Patients Undergoing Certain Dental, Oral, Respiratory Tract, or Esophageal Procedures†

Oral

Erythromycin (ethylsuccinate): 20 mg/kg 2 hours before the procedure and 10 mg/kg 6 hours later.

Erythromycin (stearate): 20 mg/kg 2 hours before the procedure and 10 mg/kg 6 hours later.

Adults

General Adult Dosage

Treatment of Infections

Oral

Erythromycin (base): 250 mg every 6 hours, 333 mg every 8 hours, or 500 mg every 12 hours. In severe infections, dosage may be increased up to 4 g daily; however, a twice-daily dosing schedule is not recommended when dosages exceeding 1 g daily are administered.

Erythromycin (estolate): 250 mg every 6 hours. In severe infections, dosage may be increased up to 4 g daily.

Erythromycin (ethylsuccinate): 400 mg every 6 hours. Dosage up to 4 g daily may be used for severe infections.

Erythromycin (stearate): 250 mg every 6 hours or 500 mg every 12 hours. In severe infections, dosage may be increased up to 4 g daily; however, a twice-daily dosing schedule is not recommended when dosage is >1 g daily.

Pharyngitis and Tonsillitis

Oral

Erythromycin (base): 250 mg every 6 hours, 333 mg every 8 hours, or 500 mg every 12 hours for 10 days.

Amebiasis

Entamoeba histolytica Infections

Oral

Erythromycin (base or stearate): 250 mg every 6 hours, 333 mg every 8 hours, or 500 mg every 12 hours for 10–14 days.

Erythromycin (estolate): 250 mg 4 times daily for 10–14 days.

Erythromycin (ethylsuccinate): 400 mg 4 times daily for 10–14 days.

Anthrax†

IV

Erythromycin (lactobionate): 15–20 mg/kg (up to 4 g) daily given in divided doses every 6 hours.

Must be used in multiple-drug regimens that initially include IV ciprofloxacin or IV doxycycline and 1 or 2 other anti-infectives predicted to be effective.

Duration of treatment is 60 days if anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.

Chancroid†

Oral

Erythromycin (base): 500 mg 3–4 times daily for 7 days.

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.

Chlamydial Infections

Uncomplicated Urethral, Endocervical, or Rectal Infections

Oral

Erythromycin (base or stearate): 500 mg 4 times daily for 7 days. Alternatively, 666 mg every 8 hours for 7 days. If these regimens are not tolerated in pregnant women, a dosage of 500 mg every 12 hours, 333 mg every 8 hours, or 250 mg 4 times daily for at least 14 days.

Erythromycin (estolate): 500 mg 4 times daily for 7 days

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days. If this regimen is not tolerated in pregnant women, a dosage of 400 mg 4 times daily for 14 days may be used.

Presumptive Treatment of Chlamydial Infections in Adults with Gonorrhea

Oral

Erythromycin (base): 500 mg 4 times daily for 7 days.

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.

Lymphogranuloma venereum†

Oral

Erythromycin (base): 500 mg 4 times daily for 21 days.

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 21 days.

Diphtheria

Treatment of Diphtheria

Oral

Prevention of Diphtheria

Oral

Erythromycin: 1 g daily for 7–10 days.

Elimination of Diphtheria Carrier State

Oral

Erythromycin: 1 g daily for 7–10 days. Obtain follow-up cultures ≥2 weeks after completion of therapy; if cultures are positive, an additional 10-day course should be given and additional follow-up cultures obtained.

Granuloma Inguinale (Donovanosis)†

Oral

Erythromycin (base): 500 mg 4 times daily for ≥3 weeks or until all lesions have healed completely; consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients.

Relapse can occur 6–18 months after apparently effective treatment.

Legionnaires’ Disease

Oral

Erthromycin (base, ethylsuccinate, or stearate): 1–4 g daily in divided doses has been used alone or in conjunction with rifampin. Usual duration is 10–21 days.

IV

Erythromycin (lactobionate): 1–4 g daily in divided doses has been used alone or in conjunction with rifampin. After a response is obtained, rifampin can be discontinued and therapy changed to oral erythromycin. Usual duration is 10–21 days.

Early Localized or Early Disseminated Lyme Disease†

Oral

Erythromycin: 500 mg 4 times daily for 14–21 days. Alternatively, 250 mg 4 time daily for 14–21 days.

Nongonococcal Urethritis

Oral

Erythromycin (base or stearate): 500 mg 4 times daily for 7 days. Alternatively, 666 mg every 8 hours for ≥7 days. For recurrent and persistent urethritis, CDC recommends 500 mg 4 times daily for 7 days in conjunction with a single dose of oral metronidazole (2 g).

Pelvic Inflammatory Disease (PID)

IV, then Oral

Erythromycin (lactobionate): 500 mg every 6 hours for 3 days. Then switch to oral erythromycin (base or stearate) in a dosage of 250 mg every 6 hours for 7 days. Alternatively, use follow-up oral dosage of 333 mg of erythromycin (base or stearate) every 8 hours for 7 days or 500 mg (base or stearate) every 12 hours for 7 days.

Not included in CDC recommendations for treatment of PID.

Pertussis

Treatment or Prevention of Pertussis

Oral

1 g daily in divided doses for 14 days.

Syphilis

Oral

Erythromycin (base or stearate): 30–40 g given in divided doses over 10–15 days.

Erythromycin (estolate): 20 g given over 10 days.

Erythromycin (ethylsuccinate): 48–64 g given over 10–15 days.

CDC does not recommended erythromycin for treatment of syphilis.

Preoperative Intestinal Antisepsis

Adjunct to Mechanical Cleansing in Patients Undergoing Colorectal Surgery

Oral

Erythromycin (base): if surgery is scheduled for 8 a.m., given 1 g of erythromycin and 1 g of oral neomycin sulfate at 1 p.m., 2 p.m., and 11 p.m. on the day preceding surgery.

Prevention of Bacterial Endocarditis†

Patients Undergoing Certain Dental, Oral, Respiratory Tract, or Esophageal Procedures†

Oral

Erythromycin (ethylsuccinate): 800 mg 2 hours before the procedure and 400 mg 6 hours later.

Erythromycin (stearate): 1 g 2 hours before the procedure and 500 mg 6 hours later.

Prevention of Rheumatic Fever Recurrence

Oral

Erythromycin (base or stearate): 250 mg twice daily.

Erythromycin (ethylsuccinate): 400 mg twice daily.

Long-term continuous prophylaxis required.

Prevention of Perinatal Group B Streptococcal Disease†

Women at Risk Who Should Not Receive β-lactam Anti-infectives†

Erythromycin (lactobionate): 500 mg every 6 hours; initiate at time of labor or rupture of membranes and continue until delivery.

Prescribing Limits

Pediatric Patients

Treatment of Infections

Oral

Maximum of 4 g daily.

Adults

Special Populations

Hepatic Impairment

It may be advisable to monitor serum erythromycin concentrations and modify dosage when indicated.

Renal Impairment

Dosage adjustments not necessary in patients with impaired renal function.

Cautions for Erythromycin (Systemic)

Contraindications

Hypersensitivity to erythromycins.
Concomitant use with certain drugs highly dependent on CYP3A for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., astemizole, cisapride, pimozide, terfenadine). (See Specific Drugs under Interactions.)
Erythromycin estolate in patients with hepatic dysfunction or preexisting liver disease.
Fixed combination of erythromycin ethylsuccinate and sulfisoxazole acetyl in patients hypersensitive to either component.

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible organisms. Institute appropriate therapy if superinfection occurs.

Treatment with anti-infectives may permit overgrowth of clostridia. Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.

Some mild cases of C. difficile-asssociated diarrhea and colitis may respond to discontinuance alone. Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.

Hepatic Effects

Hepatic effects, including increased hepatic enzymes and hepatocellular and/or cholestatic hepatitis (with or without jaundice) have been reported with the various oral erythromycins and with parenteral erythromycin.

Erythromycin estolate has been associated with hepatotoxicity more frequently than other erythromycins. Erythromycin estolate-induced hepatotoxicity is most likely to occur in patients who receive the drug for >10 days or in repeated courses.

Erythroomycin estolate is contraindicated and other erythromycins should be used with caution in patients with impaired hepatic function. In addition, monitoring of serum erythromycin concentrations and modification of dosage when indicated may be advisable in these patients.

Interactions

Concomitant use with lovastatin requires caution since rhabdomyolysis (with or without renal impairment) has been reported. (See Specific Drugs under Interactions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis has been reported. Urticaria, mild skin eruptions, Stevens-Johnson syndrome, and toxic epidermal necrolysis also reported rarely.

General Precautions

Cardiac Effects

Cardiac arrhythmias (ventricular tachycardia) have been reported.

Prolongation of the QT interval and development of ventricular arrhythmias, including atypical ventricular tachycardia (torsades de pointes), have been reported rarely with oral and IV erythromycin; limited data suggest that these adverse effects may depend on serum concentration and/or rate of infusion of the drug. Decreasing IV infusion rate may reduce the risk of cardiac toxicity, but may not eliminate the risk and discontinuance of the drug may be necessary.

There is some evidence that use of oral erythromycin is associated with an increased risk of sudden death from cardiac causes (usually ventricular tachyarrhythmia) by a factor of 2. Concomitant use of oral erythromycin (a drug metabolized by CYP3A) with drugs that inhibit CYP3A (i.e., fluconazole, ketoconazole, itraconazole, diltiazem, verapamil) has been associated with an increased risk of sudden death from cardiac causes.

Erythromycins should 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.

Myasthenia Gravis Patients

Possible aggravation of weakness reported in patients with myasthenia gravis.

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category B.

The fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole should not be used in pregnant women at term.

Lactation

Distributed into milk. Use with caution.

The fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole should not be used in mothers who are nursing infants <2 months of age.

Pediatric Use

The fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole should not be used in infants <2 months of age.

Hepatic Impairment

Principally eliminated by the liver. Use caution in patients with impaired hepatic function.

Common Adverse Effects

GI effects (abdominal pain and cramping, nausea, vomiting, diarrhea, anorexia). Venous irritation and thrombophlebitis with IV administration.

Interactions for Erythromycin (Systemic)

Metabolized by CYP3A isoenzymes. Inhibits CYP3A isoenzymes.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP isoenzymes with possible alteration in metabolism of erythromycin and/or the other drug.

Specific Drugs

Drug	Interaction	Comments
Antiarrhythmic agents (digoxin, disopyramide, quinidine)	Increased concentrations of the antiarrhythmic agent and increased risk of serious adverse cardiovascular effects	Use with caution and monitor closely
Anticoagulants, oral (warfarin)	Possible prolonged PT	Monitor PT or other appropriate tests closely if used with warfarin; reduce anticoagulant dosage if necessary
Antifungals, azoles (fluconazole, itraconazole, ketoconazole)	Possible increased erythromycin concentrations and increased risk of sudden death from cardiac causes	Avoid concomitant use
Antihistamines (astemizole, terfenadine)	Pharmacokinetic interaction and potential for serious or life-threatening reactions (e.g., cardiac arrhythmias) with astemizole or terfenadine (drugs no longer commercially available in the US)	Concomitant use contraindicated
Benzodiazepines (alprazolam, midazolam, triazolam)	Increased plasma concentrations of benzodiazepines; possible prolonged sedative and hypnotic effects of the drugs	Monitor carefully and adjust dosage of benzodiazepine as needed
Calcium-channel blocking agents	Diltiazem and Verapamil: Possible increased erythromycin concentrations and possible increased risk of sudden death from cardiac causes Nefedipine: No evidence of increased risk of sudden death from cardiac causes	Diltiazem and Verapamil: Avoid concomitant use
Carbamazepine	Increased carbamazepine concentrations and risk of carbamazepine toxicity	Monitored for evidence of carbamazepine toxicity; carbamazepine dosage should be reduced when necessary. Consider use of an alternative anti-infective agent.
Chloramphenicol	In vitro evidence of antagonism
Cisapride	Possible increased cisapride concentrations and increased risk of adverse effects (e.g., cardiac effects)	Concomitant use contraindicated
Clindamycin or lincomycin	In vitro evidence of antagonism
Ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine)	Possibility of pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., acute ergot toxicity)
HMG-CoA reductase inhibitors (lovastatin, simvastatin)	Increased concentrations of some HMG-CoA reductase inhibitors with potential for increased risk of myopathy (including rhabdomyolysis)	If used concomitantly with lovastatin, closely monitor CK and serum transaminase concentrations
Immunosuppressive agents (cyclosporine)	Increased cyclosporine concentrations and increased risk of cyclosporine toxicity	Use concomitantly with caution and monitor for evidence of cyclosporine toxicity. Monitor cyclosporine concentrations if possible; adjust dosage as needed when erythromycin is initiated or discontinued.
Pimozide	Possible increased pimozide concentrations and increased risk of life-threatening cardiac dysrhythmias	Concomitant use contraindicated
Sildenafil	Increased sildenafil concentrations	Consider reducing sildenafil dosage
Theophylline	Increased theophylline concentrations; possible decreased erythromycin concentrations	Use with caution; monitor serum theophylline concentrations and adjust theophylline dosage if indicated

Erythromycin (Systemic) Pharmacokinetics

Absorption

Bioavailability

Erythromycin base, estolate, ethylsuccinate, and stearate are readily absorbed from GI tract; peak serum concentrations attained within 1–4 hours.

Erythromycin base is highly susceptible to gastric acid inactivation, and commercially available tablets are coated with acid-resistant (enteric) coatings or are buffered to protect the drug from gastric acidity. The stearate also is highly susceptible to gastric acid inactivation, but the estolate and ethylsuccinate are acid stable.

Food

Most commercial erythromycin preparations are well absorbed in fasting or nonfasting state.

Distribution

Extent

Widely distributed into most body tissues and fluids.

Only low concentrations (2–13% of serum concentrations) are distributed into CSF.

Crosses the placenta and is distributed into milk.

Plasma Protein Binding

Erythromycin base is 73–81% bound and erythromycin estolate is approximately 96% bound to serum proteins.

Elimination

Metabolism

Erythromycin is partially metabolized in the liver by CYP3A4 by N-demethylation to inactive, unidentified metabolites.

Erythromycin ethylsuccinate is partially dissociated in the intestine where both erythromycin and the undissociated ester are absorbed; in the blood, the ester is partially hydrolyzed to release free erythromycin.

Erythromycin estolate dissociates in the upper intestine, liberating the inactive propanoate ester which is absorbed and partially hydrolyzed in the blood to release free erythromycin.

Elimination Route

Concentrated in the liver and eliminated in bile. Less than 5% of an oral dose eliminated unchanged in urine; 12–15% of an IV dose is eliminated unchanged in urine.

Not removed by hemodialysis or peritoneal dialysis.

Half-life

Serum half-life of erythromycin in patients with normal renal function usually is 1.5–2 hours, but may range from 0.8–3 hours.

Special Populations

Half-life may be prolonged in patients with hepatic impairment. The terminal elimination half-life in adults with alcoholic liver disease is similar to that in healthy adults, but the initial distribution half-life is slightly prolonged and average and peak serum concentrations were higher.

In anuric patients, serum half-life may be prolonged to 6 hours, but this is not considered clinically important.

Stability

Storage

Oral

Capsules

Erythromycin base (delayed-release): <30°C.

Tablets

Erythromycin base (delayed-release and film-coated): <30°C.

Erythromycin ethylsuccinate (chewable and film-coated): <30°C.

Erythromycin stearate (film-coated): <30°C.

For Suspension

Erythromycin ethylsuccinate: <30°C. After reconstitution of E.E.S. granules, refrigerate and use within 10 days. After reconstitution of EryPed, store at <25°C and use within 35 days.

Fixed combination of erythromycin ethylsuccinate and sulfisoxazole acetyl: <30°C. After reconstitution, refrigerate and discard after 14 days.

Suspension

Erythromycin ethylsuccinate: 2–8°C until dispensed; once dispensed, stable for 14 days at room temperature.

Parenteral

Powder for IV Infusion

Erythromycin lactobionate: preferably 15–30°C. Following reconstitution, administer within 8 hours if diluted in 0.9% sodium chloride or within 2 hours if diluted in 5% dextrose injection.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility (Erythromycin Lactobionate)HID

Compatible
Sodium chloride 0.9%
Incompatible
Dextrose 2½% in half-strength Ringer’s injection, lactated
Dextrose 5% in Ringer’s injection, lactated
Dextrose 10% in water
Multielectrolyte solution
Normosol M in dextrose 5%
Normosol R
Ringer’s injection
Variable
Dextrose 5% in sodium chloride 0.9%
Dextrose 5% in water
Ringer’s injection, lactated

Drug Compatibility

Admixture Compatibility (Erythromycin Lactobionate)HID
Compatible
Aminophylline
Ampicillin sodium
Cimetidine HCl
Diphenhydramine HCl
Hydrocortisone sodium succinate
Lidocaine HCl
Penicillin G potassium
Penicillin G sodium
Pentobarbital sodium
Polymyxin B sulfate
Potassium chloride
Prochlorperazine edisylate
Ranitidine HCl
Sodium bicarbonate
Verapamil HCl
Incompatible
Colistimethate sodium
Furosemide
Heparin sodium
Linezolid
Metaraminol bitartrate
Metoclopramide HCl
Vitamin B complex with C
Variable
Ascorbic acid injection

Y-Site Compatibility (Erythromycin Lactobionate)HID
Compatible
Acyclovir sodium
Amiodarone HCl
Bivalirudin
Cyclophosphamide
Dexmedetomidine HCl
Diltiazem HCl
Doxapram HCl
Enalaprilat
Esmolol HCl
Famotidine
Fenoldopam mesylate
Foscarnet sodium
Heparin sodium
Hetastarch in lactated electrolyte injection (Hextend)
Hydromorphone HCl
Idarubicin HCl
Labetalol HCl
Lorazepam
Magnesium sulfate
Meperidine HCl
Midazolam HCl
Morphine sulfate
Multivitamins
Nicardipine HCl
Perphenazine
Tacrolimus
Theophylline
Vitamin B complex with C (Berocca-C or Berocca-C 500)
Zidovudine
Incompatible
Ceftazidime
Fluconazole

Actions and Spectrum

Usually bacteriostatic; may be bactericidal in high concentrations or against highly susceptible organisms.
Inhibits protein synthesis in susceptible organisms by binding to 50S ribosomal subunits.
Spectrum of activity includes many gram-positive and -negative bacteria and some other organisms (e.g., Chlamydia, Mycoplasma, spirochetes). Inactive against fungi and viruses.
Gram-positive bacteria: active in vitro and in clinical infections against S. aureus (resistant strains may emerge during therapy), S. pyogenes (group A β-hemolytic streptococci), viridans streptococci, S. pneumoniae, Bacillus anthracis, Corynebacterium diphtheriae, C. minutissimum, and Listeria monocytogenes.
Gram-negative bacteria: active in vitro and in clinical infections against Bordetella pertussis, Legionella pneumophila, Moraxella catarrhalis, and Neisseria gonorrhoeae. Enterobacteriaceae (e.g., Escherichia coli, Enterobacter, Klebsiella, Proteus, Salmonella, Shigella) and Pseudomonas usually are resistant. Haemophilus influenzae usually are resistant to erythromycin alone, but are susceptible to erythromycin used in conjunction with sulfisoxazole.
Other organisms: active against Chlamydia psittaci, C. trachomatis, Mycoplasma pneumoniae, Ureoplasma urealyticum, Entamoeba histolytica, Borrelia burgdorferi, and Treponema pallidum.
Cross-resistance generally occurs among the macrolides, including erythromycin, azithromycin, and clarithromycin.

Advice to Patients

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.