ERYTHROMYCIN
DESCRIPTION:
Erythromycin is produced by a strain of Streptomyces Erythraeus and belongs to
the macrolide group of antibiotics. It is basic and readily forms salts with
acids. The base is white to off-white crystals or powder slightly soluble in
water, soluble in alcohol, in chloroform, and in ether. ERY-TAB (erythromycin
delayed-release tablets) is specially enteric-coated to protect the contents
from the inactivating effects of gastric acidity and to permit efficient
absorption of the antibiotic in the small intestine.
ERY-TAB is available in three dosage strengths, each tablet containing either
250 mg, 333 mg, or 500 mg of erythromycin as the free base.
INACTIVE INGREDIENTS: 250 mg tablet: cellulosic polymers, corn starch,
diacetylated monoglycerides, D&C red No. 30, iron oxide, magnesium hydroxide,
magnesium stearate, sodium starch glycolate, titanium dioxide and vanillin.
333 mg tablet: cellulosic polymers, diacetylated monoglycerides, FD&C blue No.
1, magnesium stearate, microcrystalline cellulose, povidone, sodium citrate,
soybean derivatives, talc, titanium dioxide and vanillin.
500 mg tablet: cellulosic polymers, diacetylated monoglycerides, FD&C red No.
40, iron oxide, magnesium stearate, microcrystalline cellulose, povidone, sodium
citrate, soybean derivatives, talc, titanium dioxide and vanillin.
ACTIONS/CLINICAL PHARMACOLOGY:
The mode of action of erythromycin is inhibition of protein synthesis without
affecting nucleic acid synthesis. Resistance to erythromycin of some strains of
Hemophilus Influenzae and staphylococci has been demonstrated. Culture and
susceptibility testing should be done. If the Kirby-Bauer method of disc
susceptibility is used, a 15 mcg erythromycin disc should give a zone diameter
of at least 18 mm when tested against an erythromycin susceptible organism.
Bioavailability data are available from Abbott Laboratories, Dept. 355.
ERY-TAB is well absorbed and may be given without regard to meals.
After absorption, erythromycin diffuses readily into most body fluids. In the
absence of meningeal inflammation, low concentrations are normally achieved in
the spinal fluid but passage of the drug across the blood-brain barrier
increases in meningitis. In the presence of normal hepatic function,
erythromycin is concentrated in the liver and excreted in the bile; the effect
of hepatic dysfunction on excretion of erythromycin by the liver into the bile
is not known. After oral administration, less than 5 percent of the activity of
the administered dose can be recovered in the urine.
Erythromycin crosses the placental barrier but fetal plasma levels are low.
INDICATIONS AND USAGE:
Streptococcus Pyogenes (Group A beta-hemolytic streptococcus): For upper and
lower respiratory tract, skin, and soft tissue infections of mild to moderate
severity.
Injectable benzathine penicillin G is considered by the American Heart
Association to be the drug of choice in the treatment and prevention of
streptococcal pharyngitis and in long-term prophylaxis of rheumatic fever.
When oral medication is preferred for treatment of the above conditions,
penicillin G, V, or erythromycin are alternate drugs of choice.
When oral medication is given, the importance of strict adherence by the patient
to the prescribed dosage regimen must be stressed. A therapeutic dose should be
administered for at least 10 days.
Alpha-Hemolytic Streptococci (Viridans Group): Although no controlled clinical
efficacy trials have been conducted, oral erythromycin has been suggested by the
American Heart Association and American Dental Association for use in a regimen
for prophylaxis against bacterial endocarditis in patients hypersensitive to
penicillin who have congenital heart disease, or rheumatic or other acquired
valvular heart disease when they undergo dental procedures and surgical
procedures of the upper respiratory tract. (REF.1) Erythromycin is not suitable
prior to genitourinary or gastrointestinal tract surgery. NOTE: When selecting
antibiotics for the prevention of bacterial endocarditis the physician or
dentist should read the full joint statement of the American Heart Association
and the American Dental Association. (REF.1)
Staphylococcus Aureus: For acute infections of skin and soft tissue of mild to
moderate severity. Resistant organisms may emerge during treatment.
Streptococcus Pneumoniae (Diplococcus Pneumoniae): For upper respiratory tract
infections (e.g., otitis media, pharyngitis) and lower respiratory tract
infection (e.g., pneumonia) of mild to moderate degree.
Mycoplasma Pneumoniae (Eaton Agent, PPLO): For respiratory infections due to
this organism.
Hemophilus Influenzae: For upper respiratory tract infections of mild to
moderate severity when used concomitantly with adequate doses of sulfonamides.
Not all strains of this organism are susceptible at the erythromycin
concentrations ordinarily achieved (see appropriate sulfonamide labeling for
prescribing information).
Chlamydia Trachomatis: Erythromycin is indicated for treatment of the following
infections caused by Chlamydia Trachomatis: conjunctivitis of the newborn,
pneumonia of infancy and urogenital infections during pregnancy. When
tetracyclines are contraindicated or not tolerated, erythromycin is indicated
for the treatment of uncomplicated urethral, endocervical, or rectal infections
in adults due to Chlamydia Trachomatis. (REF.2)
Treponema Pallidum: Erythromycin is an alternate choice of treatment for primary
syphilis in patients allergic to the penicillins. In treatment of primary
syphilis, spinal fluid examinations should be done before treatment and as part
of follow-up after therapy.
Corynebacterium Diphtheriae And C. Minutissimum: As an adjunct to antitoxin, to
prevent establishment of carriers, and to eradicate the organism in carriers.
In the treatment of erythrasma.
Entamoeba Histolytica: In the treatment of intestinal amebiasis only. Extra-
enteric amebiasis requires treatment with other agents.
Listeria Monocytogenes: Infections due to this organism.
Neisseria Gonorrhoeae: Erythrocin(R) Lactobionate-I.V. (erythromycin
lactobionate for injection, USP) in conjunction with erythromycin base orally,
as an alternative drug in treatment of acute pelvic inflammatory disease caused
by N. Gonorrhoeae in female patients with a history of sensitivity to
penicillin. Before treatment of gonorrhea, patients who are suspected of also
having syphilis should have a microscopic examination for T. Pallidum (by
immunofluorescence or darkfield) before receiving erythromycin, and monthly
serologic tests for a minimum of 4 months.
Bordetella Pertussis: Erythromycin is effective in eliminating the organism from
the nasopharynx of infected individuals, rendering them non- infectious. Some
clinical studies suggest that erythromycin may be helpful in the prophylaxis of
pertussis in exposed susceptible individuals.
Legionnaires' Disease: Although no controlled clinical efficacy studies have
been conducted, In Vitro and limited preliminary clinical data suggest that
erythromycin can be effective in treating Legionnaires' Disease.
CONTRAINDICATIONS:
Erythromycin is contraindicated in patients with known hypersensitivity to this
antibiotic.
WARNINGS:
There have been reports of hepatic dysfunction with or without jaundice,
occurring in patients receiving oral erythromycin products.
PRECAUTIONS:
General: Erythromycin is principally excreted by the liver. Caution should be
exercised when erythromycin is administered to patients with impaired hepatic
function. (See "Actions/Clinical Pharmacology" and "Warnings" sections).
Prolonged or repeated use of erythromycin may result in an overgrowth of
nonsusceptible bacteria or fungi. If superinfection occurs, erythromycin should
be discontinued and appropriate therapy instituted.
When indicated, incision and drainage or other surgical procedures should be
performed in conjunction with antibiotic therapy.
Laboratory Tests: Erythromycin interferes with the fluorometric determination of
urinary catecholamines.
Drug Interactions: Erythromycin use in patients who are receiving high doses of
theophylline may be associated with an increase in serum theophylline levels and
potential theophylline toxicity. In case of theophylline toxicity and/or
elevated serum theophylline levels, the dose of theophylline should be reduced
while the patient is receiving concomitant erythromycin therapy.
Concomitant administration of erythromycin and digoxin has been reported to
result in elevated digoxin serum levels.
There have been reports of increased anticoagulant effects when erythromycin and
oral anticoagulants were used concomitantly.
Concurrent use of erythromycin and ergotamine or dihydroergotamine has been
associated in some patients with acute ergot toxicity characterized by severe
peripheral vasospasm and dysesthesia.
Erythromycin has been reported to decrease the clearance of triazolam and thus
may increase the pharmacologic effect of triazolam.
The use of erythromycin in patients concurrently taking drugs metabolized by the
cytochrome P450 system may be associated with elevations in serum erythromycin
with carbamazepine, cyclosporine, hexobarbital and phenytoin. Serum
concentrations of drugs metabolized by the cytochrome P450 system should be
monitored closely in patients concurrently receiving erythromycin.
Troleandomycin significantly alters the metabolism of terfenadine when taken
concomitantly; therefore, observe caution when erythromycin and terfenadine are
used concurrently.
Patients receiving concomitant lovastatin and erythromycin should be carefully
monitored; cases of rhabdomyolysis have been reported in seriously ill patients.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term (2-year) oral
studies conducted in rats with erythromycin base did not provide evidence of
tumorigenicity. Mutagenicity studies have not been conducted. There was no
apparent effect on male or female fertility in rats fed erythromycin (base) at
levels up to 0.25 percent of diet.
Pregnancy: Pregnancy Category B: There is no evidence of teratogenicity or any
other adverse effect on reproduction in female rats fed erythromycin base (up to
0.25 percent of diet) prior to and during mating, during gestation, and through
weaning of two successive litters. There are, however, no adequate and well-
controlled studies in pregnant women. Because animal reproduction studies are
not always predictive of human response, this drug should be used during
pregnancy only if clearly needed. Erythromycin has been reported to cross the
placental barrier in humans, but fetal plasma levels are generally low.
Labor And Delivery: The effect of erythromycin on labor and delivery is unknown.
Nursing Mothers: Erythromycin is excreted in breast milk, therefore, caution
should be exercised when erythromycin is administered to a nursing woman.
Pediatric Use: See "Indications and Usage" and "Dosage and Administration"
sections.
DRUG INTERACTIONS:
Erythromycin use in patients who are receiving high doses of theophylline may be
associated with an increase in serum theophylline levels and potential
theophylline toxicity. In case of theophylline toxicity and/or elevated serum
theophylline levels, the dose of theophylline should be reduced while the
patient is receiving concomitant erythromycin therapy.
Concomitant administration of erythromycin and digoxin has been reported to
result in elevated digoxin serum levels.
There have been reports of increased anticoagulant effects when erythromycin and
oral anticoagulants were used concomitantly.
Concurrent use of erythromycin and ergotamine or dihydroergotamine has been
associated in some patients with acute ergot toxicity characterized by severe
peripheral vasospasm and dysesthesia.
Erythromycin has been reported to decrease the clearance of triazolam and thus
may increase the pharmacologic effect of triazolam.
The use of erythromycin in patients concurrently taking drugs metabolized by the
cytochrome P450 system may be associated with elevations in serum erythromycin
with carbamazepine, cyclosporine, hexobarbital and phenytoin. Serum
concentrations of drugs metabolized by the cytochrome P450 system should be
monitored closely in patients concurrently receiving erythromycin.
Troleandomycin significantly alters the metabolism of terfenadine when taken
concomitantly; therefore, observe caution when erythromycin and terfenadine are
used concurrently.
Patients receiving concomitant lovastatin and erythromycin should be carefully
monitored; cases of rhabdomyolysis have been reported in seriously ill patients.
(See Also PRECAUTIONS)
ADVERSE REACTIONS:
The most frequent side effects of oral erythromycin preparations are
gastrointestinal and are dose-related. They include nausea, vomiting, abdominal
pain, diarrhea and anorexia. Symptoms of hepatic dysfunction and/or abnormal
liver function test results may occur (see "Warnings" section). Pseudomembranous
colitis has been rarely reported in association with erythromycin therapy.
There have been isolated reports of transient central nervous system side
effects including confusion, hallucinations, seizures, and vertigo; however, a
cause and effect relationship has not been established.
Occasional case reports of cardiac arrhythmias such as ventricular tachycardia
have been documented in patients receiving erythromycin therapy. There have been
isolated reports of other cardiovascular symptoms such as chest pain, dizziness,
and palpitations; however, a cause and effect relationship has not been
established.
Allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis
have occurred.
There have been isolated reports of reversible hearing loss occurring chiefly in
patients with renal insufficiency and in patients receiving high doses of
erythromycin.
OVERDOSAGE:
In case of overdosage, erythromycin should be discontinued. Overdosage should be
handled with the prompt elimination of unabsorbed drug and all other appropriate
measures.
Erythromycin is not removed by peritoneal dialysis or hemodialysis.
DOSAGE AND ADMINISTRATION:
ERY-TAB (erythromycin delayed-release tablets) is well absorbed and may be given
without regard to meals.
Adults: The usual dose is 250 mg four times daily in equally spaced doses. The
333 mg tablet is recommended if dosage is desired every 8 hours. If twice-a-day
dosage is desired, the recommended dose is 500 mg every 12 hours.
Dosage may be increased up to 4 or more grams per day according to the severity
of the infection. Twice-a-day dosing is not recommended when doses larger than 1
gram daily are administered.
Children: Age, weight, and severity of the infection are important factors in
determining the proper dosage. 30 to 50 mg/kg/day, in divided doses, is the
usual dose. For more severe infections, this dose may be doubled.
In the treatment of streptococcal infections, a therapeutic dosage of
erythromycin should be administered for at least 10 days. In continuous
prophylaxis of streptococcal infections in persons with a history of rheumatic
heart disease, the dose is 250 mg twice a day.
For prophylaxis against bacterial endocarditis (REF.1) in patients with
congenital heart disease, or rheumatic or other acquired valvular heart disease
when undergoing dental procedures or surgical procedures of the upper
respiratory tract, give 1 g (20 mg/kg for children) orally 1 1/2 to 2 hours
before the procedure, and then, 500 mg (10 mg/kg in children) orally every 6
hours for 8 doses.
For conjunctivitis of the newborn caused by Chlamydia Trachomatis: Oral
erythromycin suspension 50 mg/kg/day in 4 divided doses for at least 2 weeks.
(REF.2)
For pneumonia of infancy caused by Chlamydia Trachomatis: Although the optimal
duration of therapy has not been established, the recommended therapy is oral
erythromycin suspension 50 mg/kg/day in 4 divided doses for at least 3 weeks.
(REF.2)
For urogenital infections during pregnancy due to Chlamydia trachomatis:
Although the optimal dose and duration of therapy have not been established, the
suggested treatment is erythromycin 500 mg, by mouth, 4 times a day for at least
7 days. For women who cannot tolerate this regimen, a decreased dose of 250 mg,
by mouth, 4 times a day should be used for at least 14 days. (REF.2)
For adults with uncomplicated urethral, endocervical, or rectal infections
caused by Chlamydia Trachomatis in whom tetracyclines are contraindicated or not
tolerated: 500 mg, by mouth, 4 times a day for at least 7 days. (REF.2)
For treatment of primary syphilis: 30 to 40 grams given in divided doses over a
period of 10 to 15 days.
For treatment of acute pelvic inflammatory disease caused by N. Gonorrhoeae:
After initial treatment with Erythrocin(R) Lactobionate-I.V. (erythromycin
lactobionate for injection, USP) 500 mg every 6 hours for 3 days, the oral
dosage recommendation is 250 mg every 6 hours for 7 days.
For dysenteric amebiasis: 250 mg four times daily for 10 to 14 days, for adults;
30 to 50 mg/kg/day in divided doses for 10 to 14 days, for children.
For use in pertussis: Although optimal dosage and duration have not been
established, doses of erythromycin utilized in reported clinical studies were 40
to 50 mg/kg/day, given in divided doses for 5 to 14 days.
For treatment of Legionnaires' Disease: Although optimal doses have not been
established, doses utilized in reported clinical data were 1 to 4 grams
erythromycin base daily in divided doses.