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Erythromycin

Pronunciation

Class: Erythromycins
VA Class: AM200
CAS Number: 114-07-8
Brands: E.E.S., ERYC, EryPed, Ery-Tab, Erythrocin, Eryzole, PCE, Pediazole

Introduction

Antibacterial; macrolide antibiotic produced by Saccharopolyspora erythraeus.263 268 f

Uses for Erythromycin

Acute Otitis Media (AOM)

Treatment of AOM in children caused by susceptible Haemophilus influenzae.264 The fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole acetyl must be used;264 erythromycin is not effective when used alone for treatment of H. influenzae infections.264 c

The fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole acetyl is an alternative (not a preferred agent) for treatment of AOM.311 483 The drug is recommended as an alternative in patients with type I penicillin hypersensitivity.311 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.483

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci).242 262 263 268 311 392 441 472 f Generally effective in eradicating S. pyogenes from the nasopharynx, but efficacy in prevention of subsequent rheumatic fever has not been established to date.a

CDC, AAP, IDSA, AHA, and others recommend oral penicillin V or IM penicillin G benzathine as treatments of choice;243 311 392 441 472 oral cephalosporins and oral macrolides considered alternatives.311 392 441 472 Amoxicillin sometimes used instead of penicillin V, especially for young children.441

Erythromycin usually the preferred alternative for treatment of streptococcal pharyngitis in patients hypersensitive to penicillin.243 311 392 441 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.311 392 441 446

Respiratory Tract Infections

Treatment of respiratory tract infections caused by susceptible S. pneumoniae.263 268 f 268 269 270 f

Treatment of respiratory tract infections caused by Mycoplasma pneumoniae or C. pneumoniae.263 268 f 268 a c f

Erythromycin usually not effective when used alone for treatment of respiratory tract infections caused by H. influenzae.242 262 269 c f

Skin and Skin StructureInfections

Treatment of mild to moderate skin and skin structure infections caused by S. pyogenes or Staphylococcus aureus.263 268 f 268 a b c f Consider that erythromycin-resistant Staphylococci may develop during treatment.263 268 f a b c f

Treatment of erythrasma caused by Corynbacterium minutissimum.263 268 f 268 b c f

Acne

Treatment of acne.459

Amebiasis

Has been used for treatment of intestinal amebiasis caused by Entamoeba histolytica.242 262 263 268 f 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.259 311

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Anthrax

Alternative for treatment of anthrax.218 227 472

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.216 347 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);216 347 if meningitis is established or suspected, use IV ciprofloxacin (rather than doxycycline) and chloramphenicol, rifampin, or penicillin.216

Bartonella Infections

Has been used in conjunction with IM or IV ceftriaxone for treatment of bacteremia caused by Bartonella quintana (formerly Rochalimaea quintana).460

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.460 462 463

USPHS/IDSA suggests that long-term suppression with erythromycin or doxycycline be considered to prevent recurrence of Bartonella infection in HIV-infected patients.420

Campylobacter Infections

Treatment of symptomatic enteric infections caused by Campylobacter jejuni. Recommended by CDC,272 IDSA,271 and AAP311 as a treatment of choice.

Chancroid

Treatment of chancroid (genital ulcers caused by H. ducreyi).228 248 472

CDC and others recommend azithromycin, ceftriaxone, ciprofloxacin or erythromycin as drugs of choice for treatment of chancroid.228 248 472 HIV-infected patients and uncircumcised patients may not respond to treatment as well as those who are HIV-negative or circumcised.228 248 472 Some experts prefer the 7-day erythromycin regimen instead of single-dose azithromycin or ceftriaxone regimens in HIV-infected individuals.228

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.228 248 f Erythromycin is less effective than either azithromycin or doxycycline and GI effects associated with the drug may discourage patient compliance with the regimen;228 CDC recommends that the first dose be taken under supervision.228

A drug of choice for treatment of urogenital chlamydial infections in pregnant women and in young children.228

Alternative for presumptive treatment of coexisting chlamydial infections in patients receiving treatment for gonorrhea.228 311 Preferred drugs are azithromycin or doxycycline;228 erythromycin may be preferred in young children.311

Treatment of urethritis caused by Ureaplasma urealyticum.f

Treatment of chlamydial pneumonia in infants.f 248

Treatment of initial episodes and recurrences of chlamydial conjunctivitis in neonates.228 248 311 f

Alternative to doxycycline for treatment of lymphogranuloma venereum caused by invasive serotypes of C. trachomatis (serovars L1, L2, L3).228 248 311 Erythromycin may be the preferred regimen for pregnant and lactating women.228

Alternative for treatment of psittacosis when tetracyclines are contraindicated (e.g., in pregnant women, children younger than 9 years of age).311 451

Diphtheria

Adjunct to diphtheria antitoxin for treatment of diphtheria caused by Corynebacterium diphtheria.261 263 268 311 454 455 474 c f Diphtheria antitoxin is the most important aspect of treatment of respiratory diphtheria.261 311 454 455 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.311 454 455

Because diphtheria infection often does not confer immunity, active immunization with a diphtheria toxoid preparation should be initiated or completed during convalescence.311 455

Prevention of diphtheria in close contacts of patients with diphtheria.261 263 311 455 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.311 454 455 An age-appropriate diphtheria toxoid preparation also may be necessary depending on immunization status.261 311

Elimination of diphtheria carrier state in individuals known to carry toxigenic strains of C. diphtheriae.261 311 454 455

Granuloma Inguinale (Donovanosis)

Alternative for treatment of granuloma inguinale (donovanosis) caused by Calymmatobacterium granulomatis.228 450

CDC recommends doxycycline or co-trimoxazole as drugs of choice; ciprofloxacin, erythromycin, and azithromycin are alternatives.228 Erythromycin may be preferred in pregnant and lactating women.228

Legionnaires’ Disease

Treatment of Legionnaires’ disease caused by Legionella pneumophila; used with or without rifampin.242 262 263 268 270 311 452 453 472 c f

Lyme Disease

Alternative for treatment of early Lyme disease.214 310 311 394 395 397 399 472 473 476 477 478 IDSA, AAP, and others recommend doxycycline, amoxicillin, or cefuroxime as first-line agents; macrolides may be less effective.214 265 267 274 331 472 475

Nongonococcal Urethritis

Treatment of nongonococcal urethritis (NGU).228 242 248 262 263

CDC and others recommend azithromycin or doxycycline as drugs of choice for treatment of NGU;228 248 erythromycin (erythromycin base or ethylsuccinate) or fluoroquinolones (levofloxacin, ofloxacin) are alternatives.228 248 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.228

Pelvic Inflammatory Disease (PID)

IV erythromycin lactobionate followed by oral erythromycin has been used for treatment of PID) caused by N. gonorrhoeae,242 262 263 c f but erythromycins are not included in current CDC recommendations for treatment of PID.228

Pertussis

Treatment of Bordetella pertussis infection (pertussis, whooping cough);268 253 261 311 455 457 472 f a drug of choice.253 261 311 455 457 472

Prevention of pertussis in contacts of patients with the disease;253 261 268 311 455 457 472 f drug of choice.253 261 311 455 457 472

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.261 311 455 456 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.261

Syphilis

Has been used as an alternative for treatment of primary syphilis in penicillin-allergic individuals.262 263 268 f

Penicillin G is drug of choice for treatment of all stages of syphilis.228 248 Erythromycin is less effective than other possible penicillin alternatives275 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).228

Preoperative Intestinal Antisepsis

Adjunct to mechanical cleansing of the large intestine for intestinal antisepsis prior to elective colorectal surgery; used in conjunction with neomycin.237 262

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.302 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.436

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.436

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.436

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.311 392 c f

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.311 392

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.246 311 415

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.246 415

Penicillin G is the regimen of choice and ampicillin is the preferred alternative.246 415 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.415

Consider that S. agalactiae (group B streptococci) with in vitro resistance to clindamycin and erythromycin has been reported with increasing frequency;415 perform in vitro susceptibility tests of clinical isolates obtained during GBS prenatal screening.415 GBS resistant to erythromycin often are resistant to clindamycin, although this may not be evident in results of in vitro testing.415 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.415

Erythromycin Dosage and Administration

Administration

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

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

Oral Administration

Erthromycin delayed-release tablets (PCE Dispertab, Ery-Tab) may be given without regard to meals,262 b 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).b Erythromycin film-coated tablets should be administered in the fasting state (at least 30 minutes and, preferably, 2 hours before or after meals).d e

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.h The enteric-coated pellets contained in the capsules should not be chewed or crushed.h 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.h If the pellets are accidentally spilled, the dose preparation should be started over with a new capsule.h

Erythromycin ethylsuccinate oral suspensions,268 f chewable tablets,f and film-coated tablets268 f (E.E.S., EryPed) are given without regard to meals. Chewable tablets should not be swallowed whole.f

Erythromycin stearate preferably should be administered in the fasting state or immediately before a meal.263

Fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole acetyl is given without regard to meals.264

Reconstitution

Reconstitute erythromycin ethylsuccinate powders for oral suspension with water according to manufacturers’ directions.268 f

IV Infusion

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

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

Reconstitution

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

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.c

Dosage

Available as erythromycin base, estolate, ethylsuccinate, stearate, or lactobionate; dosage expressed in terms of erythromycin.a Dosage of the fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole acetyl is expressed in terms of the erythromycin or sulfisoxazole content.264

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.268 f 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.268 f

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.242 262 263 268 311 b d e f i

Dosage may be doubled for severe infections.242 262 268 311 b d e f

IV

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

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).264 Alternatively, the following approximate dosages expressed in terms of volumes of the fixed-combination suspension can be used.264 (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.242 262 268 d e f

Anthrax
IV

Erythromycin (lactobionate): 20–40 mg/kg daily given in divided doses every 6 hours.218

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.216 347

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.216 347

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.228

Uncomplicated Urethral, Endocervical, or Rectal Infections in Adolescents
Oral

Erythromycin (base or stearate): 500 mg 4 times daily for 7 days.228 242 248 262 311 d e Alternatively, 666 mg every 8 hours for 7 days.242 262

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.228

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.228 311

Presumptive Treatment of Chlamydial Infections in Adolescents with Gonorrhea
Oral

Erythromycin (base): 500 mg 4 times daily for 7 days.228

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.228

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.228 248 262 263 311 Follow-up is recommended and a second course of therapy may be necessary.228 311

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.228 248 263 311 Follow-up is recommended and a second course of therapy may be necessary.228 311

Diphtheria
Treatment of Diphtheria
Oral

Erythromycin: 40–50 mg/kg daily (maximum 2 g daily) for 14 days.261 311 Patients usually are no longer contagious 48 hours after initiation of anti-infective therapy.261 Eradication of the organism should be confirmed by 2 consecutive negative cultures following completion of therapy.261 311

Prevention of Diphtheria
Oral

Erythromycin: 40–50 mg/kg daily (maximum 2 g daily) for 7–10 days.261 311 455

Elimination of Diphtheria Carrier State
Oral

Erythromycin: 40–50 mg/kg daily (maximum 2 g daily) for 7–10 days.311 455 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.311 455

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.214 Alternatively, 30 mg/kg daily in 3 divided doses (or 250 mg 3 times daily) for 14–21 days.274

Nongonococcal Urethritis in Adolescents
Oral

Erythromycin (base): 500 mg 4 times daily for 7 days.228 Alternatively, 666 mg every 8 hours for ≥7 days.242 262 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).228

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.228 268 f 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).228

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.263 311 455

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.302

Erythromycin (stearate): 20 mg/kg 2 hours before the procedure and 10 mg/kg 6 hours later.302

Adults

General Adult Dosage
Treatment of Infections
Oral

Erythromycin (base): 250 mg every 6 hours,262 d e 333 mg every 8 hours,242 262 d or 500 mg every 12 hours.242 262 d e 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.242 262 e

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

Erythromycin (ethylsuccinate): 400 mg every 6 hours.268 f Dosage up to 4 g daily may be used for severe infections.268 f

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.263

Pharyngitis and Tonsillitis
Oral

Erythromycin (base): 250 mg every 6 hours,262 d e 333 mg every 8 hours,242 262 d or 500 mg every 12 hours242 262 d e for 10 days.

Amebiasis
Entamoeba histolytica Infections
Oral

Erythromycin (base or stearate): 250 mg every 6 hours,242 d e 333 mg every 8 hours,242 263 or 500 mg every 12 hours242 263 d for 10–14 days.

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

Erythromycin (ethylsuccinate): 400 mg 4 times daily for 10–14 days.268 f

Anthrax
IV

Erythromycin (lactobionate): 15–20 mg/kg (up to 4 g) daily given in divided doses every 6 hours.218

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.216 347

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.216 347

Chancroid
Oral

Erythromycin (base): 500 mg 3–4 times daily for 7 days.228 248

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.248

Chlamydial Infections
Uncomplicated Urethral, Endocervical, or Rectal Infections
Oral

Erythromycin (base or stearate): 500 mg 4 times daily for 7 days.228 248 242 262 263 d e Alternatively, 666 mg every 8 hours for 7 days.242 262 263 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.228 242 262 263

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

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.228 248 If this regimen is not tolerated in pregnant women, a dosage of 400 mg 4 times daily for 14 days may be used.228

Presumptive Treatment of Chlamydial Infections in Adults with Gonorrhea
Oral

Erythromycin (base): 500 mg 4 times daily for 7 days.228

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.228

Lymphogranuloma venereum
Oral

Erythromycin (base): 500 mg 4 times daily for 21 days.228 248

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 21 days.248

Diphtheria
Treatment of Diphtheria
Oral

Erythromycin: 40–50 mg/kg daily (maximum 2 g daily) for 14 days.261 311 Patients usually are no longer contagious 48 hours after initiation of anti-infective therapy.261 Eradication of the organism should be confirmed by 2 consecutive negative cultures following completion of therapy.261 311

Prevention of Diphtheria
Oral

Erythromycin: 1 g daily for 7–10 days.261 455

Elimination of Diphtheria Carrier State
Oral

Erythromycin: 1 g daily for 7–10 days.311 455 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.311 455

Granuloma Inguinale (Donovanosis)
Oral

Erythromycin (base): 500 mg 4 times daily for ≥3 weeks or until all lesions have healed completely;228 consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients.228

Relapse can occur 6–18 months after apparently effective treatment.228

Legionnaires’ Disease
Oral

Erthromycin (base, ethylsuccinate, or stearate): 1–4 g daily in divided doses has been used alone or in conjunction with rifampin.242 311 262 263 268 311 452 453 d e f Usual duration is 10–21 days.311 452 453

IV

Erythromycin (lactobionate): 1–4 g daily in divided doses has been used alone or in conjunction with rifampin.311 452 453 c After a response is obtained, rifampin can be discontinued and therapy changed to oral erythromycin.311 452 453 Usual duration is 10–21 days.311 452 453

Early Localized or Early Disseminated Lyme Disease
Oral

Erythromycin: 500 mg 4 times daily for 14–21 days.214 Alternatively, 250 mg 4 time daily for 14–21 days.274

Nongonococcal Urethritis
Oral

Erythromycin (base or stearate): 500 mg 4 times daily for 7 days.228 248 263 Alternatively, 666 mg every 8 hours for ≥7 days.242 262 263 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).228

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.228 248 268 f 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).228

Pelvic Inflammatory Disease (PID)
IV, then Oral

Erythromycin (lactobionate): 500 mg every 6 hours for 3 days.c Then switch to oral erythromycin (base or stearate) in a dosage of 250 mg every 6 hours for 7 days.c 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.242 262 263 d

Not included in CDC recommendations for treatment of PID.228

Pertussis
Treatment or Prevention of Pertussis
Oral

1 g daily in divided doses for 14 days.311 455

Syphilis
Oral

Erythromycin (base or stearate): 30–40 g given in divided doses over 10–15 days.242 262 263 d e

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

Erythromycin (ethylsuccinate): 48–64 g given over 10–15 days.268

CDC does not recommended erythromycin for treatment of syphilis.228

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.237 262

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.302

Erythromycin (stearate): 1 g 2 hours before the procedure and 500 mg 6 hours later.302

Prevention of Rheumatic Fever Recurrence
Oral

Erythromycin (base or stearate): 250 mg twice daily.242 263 311 392

Erythromycin (ethylsuccinate): 400 mg twice daily.268 f

Long-term continuous prophylaxis required.242 311 392

Prevention of Perinatal Group B Streptococcal Disease
Women at Risk Who Should Not Receive β-lactam Anti-infectives
IV

Erythromycin (lactobionate): 500 mg every 6 hours; initiate at time of labor or rupture of membranes and continue until delivery.415

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.a

Renal Impairment

Dosage adjustments not necessary in patients with impaired renal function.a

Cautions for Erythromycin

Contraindications

  • Hypersensitivity to erythromycins.263 268 f

  • 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).263 268 f (See Specific Drugs under Interactions.)

  • Erythromycin estolate in patients with hepatic dysfunction or preexisting liver disease.a

  • Fixed combination of erythromycin ethylsuccinate and sulfisoxazole acetyl in patients hypersensitive to either component.264

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible organisms.263 268 c f Institute appropriate therapy if superinfection occurs.263 268 c f

Treatment with anti-infectives may permit overgrowth of clostridia.263 268 467 468 469 470 471 b f Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.268 b f

Some mild cases of C. difficile-asssociated diarrhea and colitis may respond to discontinuance alone.263 268 467 468 469 470 471 b f 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.263 268 467 468 469 470 471 b f

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.217 222 223 224 263 268 c f

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

Erythroomycin estolate is contraindicated and other erythromycins should be used with caution in patients with impaired hepatic function.262 263 a In addition, monitoring of serum erythromycin concentrations and modification of dosage when indicated may be advisable in these patients.a

Interactions

Concomitant use with lovastatin requires caution since rhabdomyolysis (with or without renal impairment) has been reported.263 268 f (See Specific Drugs under Interactions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis has been reported.c f Urticaria, mild skin eruptions, Stevens-Johnson syndrome, and toxic epidermal necrolysis also reported rarely.244 c f

General Precautions

Cardiac Effects

Cardiac arrhythmias (ventricular tachycardia) have been reported.c

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.260 305 306 307 308 360 362 376 481 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.360 362

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 2.481 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.481

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.305 306 307 308 360 361 362 376

Myasthenia Gravis Patients

Possible aggravation of weakness reported in patients with myasthenia gravis.263 268 f

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.263 268 b c f

The fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole should not be used in pregnant women at term.264

Lactation

Distributed into milk.263 268 b c f Use with caution.263 268 b c f

The fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole should not be used in mothers who are nursing infants <2 months of age.264

Pediatric Use

The fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole should not be used in infants <2 months of age.264

Hepatic Impairment

Principally eliminated by the liver.268 c f Use caution in patients with impaired hepatic function.262 268 c f

Common Adverse Effects

GI effects (abdominal pain and cramping, nausea, vomiting, diarrhea, anorexia).263 268 a f Venous irritation and thrombophlebitis with IV administration.c

Interactions for Erythromycin

Metabolized by CYP3A isoenzymes.b Inhibits CYP3A isoenzymes.352 b

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.349 350 351 352 357 358 481 a b

Specific Drugs

Drug

Interaction

Comments

Antiarrhythmic agents (digoxin, disopyramide, quinidine)

Increased concentrations of the antiarrhythmic agent and increased risk of serious adverse cardiovascular effects298 299 309 393

Use with caution and monitor closely393

Anticoagulants, oral (warfarin)

Possible prolonged PT210 211 220 221

Monitor PT or other appropriate tests closely if used with warfarin; reduce anticoagulant dosage if necessary211 220 221

Antifungals, azoles (fluconazole, itraconazole, ketoconazole)

Possible increased erythromycin concentrations and increased risk of sudden death from cardiac causes481

Avoid concomitant use481

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)298 315 318 324 325 329

Concomitant use contraindicated315 320 324 439

Benzodiazepines (alprazolam, midazolam, triazolam)

Increased plasma concentrations of benzodiazepines; possible prolonged sedative and hypnotic effects of the drugs332 333

Monitor carefully and adjust dosage of benzodiazepine as needed239 333

Calcium-channel blocking agents

Diltiazem and Verapamil: Possible increased erythromycin concentrations and possible increased risk of sudden death from cardiac causes481

Nefedipine: No evidence of increased risk of sudden death from cardiac causes481

Diltiazem and Verapamil: Avoid concomitant use481

Carbamazepine

Increased carbamazepine concentrations and risk of carbamazepine toxicity210 220 221

Monitored for evidence of carbamazepine toxicity; carbamazepine dosage should be reduced when necessary.210 220 221

Consider use of an alternative anti-infective agent.221

Chloramphenicol

In vitro evidence of antagonisma

Cisapride

Possible increased cisapride concentrations and increased risk of adverse effects (e.g., cardiac effects)422 479 480

Concomitant use contraindicated263 268 f

Clindamycin or lincomycin

In vitro evidence of antagonisma

Ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine)

Possibility of pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., acute ergot toxicity)b

HMG-CoA reductase inhibitors (lovastatin, simvastatin)

Increased concentrations of some HMG-CoA reductase inhibitors with potential for increased risk of myopathy (including rhabdomyolysis)359 391 b

If used concomitantly with lovastatin, closely monitor CK and serum transaminase concentrationsb

Immunosuppressive agents (cyclosporine)

Increased cyclosporine concentrations and increased risk of cyclosporine toxicity231 232 233 234 235 236

Use concomitantly with caution and monitor for evidence of cyclosporine toxicity.231 232 233 234 236

Monitor cyclosporine concentrations if possible; adjust dosage as needed when erythromycin is initiated or discontinued.231 232 233 234 236

Pimozide

Possible increased pimozide concentrations and increased risk of life-threatening cardiac dysrhythmias 263 268 f

Concomitant use contraindicated263 268 f

Sildenafil

Increased sildenafil concentrationsb

Consider reducing sildenafil dosageb

Theophylline

Increased theophylline concentrations;210 220 221 possible decreased erythromycin concentrations210 220 221

Use with caution; monitor serum theophylline concentrations and adjust theophylline dosage if indicated210 220 221

Erythromycin Pharmacokinetics

Absorption

Bioavailability

Erythromycin base, estolate, ethylsuccinate, and stearate are readily absorbed from GI tract;263 268 f peak serum concentrations attained within 1–4 hours.a

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.a The stearate also is highly susceptible to gastric acid inactivation, but the estolate and ethylsuccinate are acid stable.a

Food

Most commercial erythromycin preparations are well absorbed in fasting or nonfasting state.263 268 f

Distribution

Extent

Widely distributed into most body tissues and fluids.263 268 c f

Only low concentrations (2–13% of serum concentrations) are distributed into CSF.263 268 c f

Crosses the placenta and is distributed into milk.263 268 c f

Plasma Protein Binding

Erythromycin base is 73–81% bound and erythromycin estolate is approximately 96% bound to serum proteins.219

Elimination

Metabolism

Erythromycin is partially metabolized in the liver by CYP3A4 by N-demethylation to inactive, unidentified metabolites.482 a

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.a

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.a

Elimination Route

Concentrated in the liver and eliminated in bile.263 268 c f Less than 5% of an oral dose eliminated unchanged in urine;263 268 12–15% of an IV dose is eliminated unchanged in urine.c

Not removed by hemodialysis or peritoneal dialysis.c

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.a

Special Populations

Half-life may be prolonged in patients with hepatic impairment.a 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.a

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

Stability

Storage

Oral

Capsules

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

Tablets

Erythromycin base (delayed-release and film-coated): <30°C.262 b d

Erythromycin ethylsuccinate (chewable and film-coated): <30°C.268 f

Erythromycin stearate (film-coated): <30°C.263

For Suspension

Erythromycin ethylsuccinate: <30°C.268 f After reconstitution of E.E.S. granules, refrigerate and use within 10 days.268 After reconstitution of EryPed, store at <25°C and use within 35 days.f

Fixed combination of erythromycin ethylsuccinate and sulfisoxazole acetyl: <30°C. After reconstitution, refrigerate and discard after 14 days.264

Suspension

Erythromycin ethylsuccinate: 2–8°C until dispensed; once dispensed, stable for 14 days at room temperature.268

Parenteral

Powder for IV Infusion

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

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.a

  • Inhibits protein synthesis in susceptible organisms by binding to 50S ribosomal subunits.268 a c f

  • Spectrum of activity includes many gram-positive and -negative bacteria and some other organisms (e.g., Chlamydia, Mycoplasma, spirochetes).a Inactive against fungi and viruses.a

  • 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.268 a c f

  • Gram-negative bacteria: active in vitro and in clinical infections against Bordetella pertussis, Legionella pneumophila, Moraxella catarrhalis, and Neisseria gonorrhoeae.268 c f Enterobacteriaceae (e.g., Escherichia coli, Enterobacter, Klebsiella, Proteus, Salmonella, Shigella) and Pseudomonas usually are resistant.a Haemophilus influenzae usually are resistant to erythromycin alone, but are susceptible to erythromycin used in conjunction with sulfisoxazole.268 f

  • Other organisms: active against Chlamydia psittaci, C. trachomatis, Mycoplasma pneumoniae, Ureoplasma urealyticum, Entamoeba histolytica, Borrelia burgdorferi, and Treponema pallidum.240 268 289 290 292 293 296 a c f

  • Cross-resistance generally occurs among the macrolides, including erythromycin, azithromycin, and clarithromycin.a

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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Erythromycin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, delayed-release (containing enteric-coated pellets)

250 mg*

ERYC (with povidone)

Warner Chilcott

Erythromycin Delayed-Release Capsules

Abbott, Barr, Major, Parmed, Purepac

Tablets, delayed-release (containing enteric-coated particles)

333 mg

PCE Dispertab (with povidone and propylene glycol)

Abbott

500 mg

PCE Dispertab (with povidone and propylene glycol)

Abbott

Tablets, delayed-release (enteric-coated)

250 mg

Ery-Tab

Abbott

333 mg

Ery-Tab (with povidone)

Abbott

500 mg

Ery-Tab (with povidone)

Abbott

Tablets, film-coated

250 mg

Erythromycin Base Filmtab (with propylene glycol)

Abbott

500 mg

Erythromycin Base Filmtab (with propylene glycol)

Abbott

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Erythromycin Estolate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

250 mg (of erythromycin)*

Erythromycin Estolate Capsules

Barr

Suspension

125 mg (of erythromycin) per 5 mL*

Erythromycin Estolate Suspension

Alpharma

250 mg (of erythromycin) per 5 mL*

Erythromycin Estolate Suspension

Alpharma

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Erythromycin Ethylsuccinate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

For suspension

100 mg (of erythromycin) per 2.5 mL

EryPed Drops

Abbott

200 mg (of erythromycin) per 5 mL

E.E.S. Granules

Abbott

EryPed

Abbott

400 mg (of erythromycin) per 5 mL

EryPed

Abbott

Suspension

200 mg (of erythromycin) per 5 mL*

E.E.S. Liquid (with parabens)

Abbott

400 mg (of erythromycin) per 5 mL*

E.E.S. Liquid (with parabens)

Abbott

Tablets, chewable

200 mg (of erythromycin)

EryPed (scored)

Abbott

Tablets, film-coated

400 mg (of erythromycin)*

E.E.S. Filmtab (with propylene glycol)

Abbott

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Erythromycin Ethylsuccinate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

For suspension

200 mg (of erythromycin) per 5 mL with Sulfisoxazole Acetyl 600 mg (of sulfisoxazole) per 5 mL*

Eryzole

Alra

Pediazole

Ross

Erythromycin Lactobionate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion only

500 mg (of erythromycin)

Erythrocin Lactobionate-I.V. ADD-Vantage

Abbott

1 g (of erythromycin)

Erythrocin Lactobionate-I.V. (with benzyl alcohol 180 mg)

Abbott

Erythrocin Lactobionate-I.V. ADD-Vantage

Abbott

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Erythromycin Stearate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

250 mg (of erythromycin)*

Erythrocin Stearate Filmtab (with povidone propylene glycol and sorbic acid)

Abbott

Erythromycin Stearate Tablets

Mylan

500 mg (of erythromycin)*

Erythrocin Stearate Filmtab (with povidone and propylene glycol)

Abbott

Erythromycin Stearate Tablets

Mylan

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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