To reduce the development of drug-resistant bacteria
and maintain the effectiveness of erythromycin and other antibacterial
drugs, erythromycin should be used only to treat or prevent infections
that are proven or strongly suspected to be caused by bacteria.
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.
Erythrocin Lactobionate (Sterile
Erythromycin Lactobionate, USP), is a soluble salt of erythromycin
suitable for intravenous administration. It is available as a sterile,
lyophilized powder in vials containing the equivalent of 500 mg or
1 g of erythromycin activity. It is prepared as a solution and lyophilized
in its final container.
is chemically known as erythromycin mono (4-0-β-D-galactopyranosyl-D-gluconate)
(salt). The structural formula is:
Erythromycin diffuses readily into most body fluids.
In the absence of meningeal inflammation, low concentrations are normally
achieved in the spinal fluid but the passage of the drug across the
blood-brain barrier increases in meningitis. Erythromycin crosses
the placental barrier and is excreted in breast milk. Erythromycin
is not removed by peritoneal dialysis or hemodialysis.
In the presence of normal hepatic function, erythromycin
is concentrated in the liver and is excreted in the bile; the effect
of hepatic dysfunction on biliary excretion of erythromycin is not
known. From 12 to 15 percent of intravenously administered erythromycin
is excreted in active form in the urine.
infusion of 500 mg of erythromycin lactobionate at a constant rate
over 1 hour in fasting adults produced a mean serum erythromycin level
of approximately 7 mcg/mL at 20 minutes, 10 mcg/mL at 1 hour, 2.6
mcg/mL at 2.5 hours, and 1 mcg/mL at 6 hours.
Erythromycin acts by inhibition of protein synthesis by binding 50
S ribosomal subunits of susceptible organisms. It does not affect
nucleic acid synthesis. Antagonism has been demonstrated in vitro between erythromycin and clindamycin,
lincomycin and chloramphenicol.
of Haemophilus influenzae are
resistant to erythromycin alone, but are susceptible to erythromycin
and sulfonamides together.
to erythromycin may emerge during a course of therapy. Culture and
susceptibility testing should be performed.
Erythromycin is usually active against the following organisms in vitro (prior to use, refer to INDICATIONS AND USAGE):
Gram-positive Bacteria: Staphylococcus aureus (resistant organisms may emerge during treatment),
Streptococcus pyogenes (Group A beta-hemolytic streptococcus), Alpha-hemolytic
streptococcus (viridans group), Streptococcus (diplococcus) pneumoniae,
Corynebacterium diphtheriae, Corynebacterium minutissimum.
Other Microorganisms: Chlamydia trachomatis,
Entamoeba histolytica, Treponema pallidum, Listeria monocytogenes.
Quantitative methods that require measurement
of zone diameters give the most precise estimates of antibiotic susceptibility.
One such standardized single-disc procedure has been recommended for
use with discs to test susceptibility to erythromycin.1 Interpretation involves correlation of the zone diameters obtained
in the disc test with minimal inhibitory concentration (MIC) values
Reports from the laboratory
giving results of the standardized single-disc susceptibility test
using a 15 mcg erythromycin disc should be interpreted according to
the following criteria:
produce zones of 18 mm or greater, indicating that the tested organism
is likely to respond to therapy.
produce zones of 13 mm or less, indicating that other therapy should
Organisms of intermediate susceptibility
produce zones of 14 to 17 mm. The “intermediate” category
provides a “buffer zone” which should prevent small,
uncontrolled technical factors from causing major discrepancies in
interpretations; thus, when a zone diameter falls within the “intermediate”
range, the results may be considered equivocal. If alternative drugs
are not available, confirmation by dilution tests may be indicated.
Standardized procedures require the use of control organisms.
The 15 mcg erythromycin disc should give zone diameters between 22
and 30 mm for the S. aureus ATCC 25923 control strain.
A bacterial isolate
may be considered susceptible if the MIC value2 for erythromycin
is not more than 2 mcg/mL. Organisms are considered resistant if the
MIC is 8 mcg/mL or higher. The MIC of erythromycin for S. aureus ATCC 29213 control strain
should be between 0.12 and 0.5 mcg/mL.
INDICATIONS AND USAGE
Erythrocin Lactobionate-I.V. (Sterile Erythromycin
Lactobionate, USP) is indicated in the treatment of infections caused
by susceptible strains of the designated organisms in the diseases
listed below when oral administration is not possible or when the
severity of the infection requires immediate high serum levels of
erythromycin. Intravenous therapy should be replaced by oral administration
at the appropriate time.
Upper respiratory tract
infections of mild to moderate degree caused by Streptococcus pyogenes (Group A beta-hemolytic
streptococci); Streptococcus pneumoniae (Diplococcus pneumoniae); Haemophilus influenzae (when used concomitantly
with adequate doses of sulfonamides, since many strains of H. influenzae are not susceptible to
the erythromycin concentrations ordinarily achieved). (See appropriate
sulfonamide labeling for prescribing information.)
Lower respiratory tract infections of mild to moderate severity caused
by Streptococcus pyogenes (Group
A beta-hemolytic streptococci); Streptococcus
Respiratory tract infections due to Mycoplasma pneumoniae.
Skin and skin
structure infections of mild to moderate severity caused by Streptococcus pyogenes and Staphylococcus aureus (resistant staphylococci
may emerge during treatment).
an adjunct to antitoxin infections due to Corynebacterium diphtheriae to prevent establishment of
carriers and to eradicate the organism in carriers.
Erythrasma: In the treatment of infections due to Corynebacterium minutissimum .
Acute pelvic inflammatory disease caused by Neisseria gonorrhoeae: Erythrocin
Lactobionate-I.V. (Sterile Erythromycin Lactobionate,
USP) followed by erythromycin stearate of 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 thereafter.
Disease caused by Legionella pneumophila. Although no controlled clinical efficacy studies have been conducted, in vitro and limited preliminary clinical
data suggest that erythromycin may be effective in treating Legionnaires’
Prevention of Initial Attacks of Rheumatic
Fever: Penicillin is considered by the American Heart Association
to be the drug of choice in the prevention of initial attacks of rheumatic
fever (treatment of Group A beta-hemolytic streptococcal infections
of the upper respiratory tract e.g., tonsillitis, or pharyngitis).3 Erythromycin is indicated for the treatment of penicillin-allergic
patients. The therapeutic dose should be administered for ten days.
Prevention of Recurrent Attacks of Rheumatic Fever: Penicillin
or sulfonamides are considered by the American Heart Association to
be the drugs of choice in the prevention of recurrent attacks of rheumatic
fever. In patients who are allergic to penicillin and sulfonamides,
oral erythromycin is recommended by the American Heart Association
in the long-term prophylaxis of streptococcal pharyngitis (for the
prevention of recurrent attacks of rheumatic fever).3
Prevention of Bacterial Endocarditis: Although no controlled
clinical efficacy trials have been conducted, oral erythromycin has
been recommended by the American Heart Association for prevention
of bacterial endocarditis in penicillin-allergic patients with prosthetic
cardiac valves, most congenital cardiac malformations, surgically
constructed systemic pulmonary shunts, rheumatic or other acquired
valvular dysfunction, idiopathic hypertrophic subaortic stenosis (IHSS),
previous history of bacterial endocarditis and mitral valve prolapse
with insufficiency when they undergo dental procedures and surgical
procedures of the upper respiratory tract.4
To reduce the development of drug-resistant bacteria and
maintain the effectiveness of erythromycin and other antibacterial
drugs, erythromycin should be used only to treat or prevent infections
that are proven or strongly suspected to be caused by susceptible
bacteria. When culture and susceptibility information are available,
they should be considered in selecting or modifying antibacterial
therapy. In the absence of such data, local epidemiology and susceptibility
patterns may contribute to the empiric selection of therapy.
Erythromycin is contraindicated in patients with
known hypersensitivity to this antibiotic.
Erythromycin is contraindicated in patients taking terfenadine or
astemizole. (See PRECAUTIONS— Drug Interactions.)
There have been reports of hepatic dysfunction, with
or without jaundice occurring in patients receiving oral erythromycin
Clostridium difficile associated diarrhea
(CDAD) has been reported with the use of nearly all antibacterial
agents, including erythromycin, and may range in severity from mild
diarrhea to fatal colitis. Treatment with antibacterial agents alters
the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins
A and B which contribute to the development of CDAD. Hypertoxin producing
strains of C. difficile cause
increased morbidity and mortality, as these infections can be refractory
to antimicrobial therapy and may require colectomy. CDAD must be
considered in all patients who present with diarrhea following antibiotic
use. Careful medical history is necessary since CDAD has been reported
to occur over two months after the administration of antibacterial
If CDAD is suspected or confirmed, ongoing
antibiotic use not directed against C.
difficile may need to be discontinued. Appropriate fluid
and electrolyte management, protein supplementation, antibiotic treatment
of C. difficile, and surgical
evaluation should be instituted as clinically indicated.
Since erythromycin is principally excreted by the
liver, caution should be exercised when erythromycin is administered
to patients with impaired hepatic function. (See CLINICALPHARMACOLOGY and WARNINGS.)
There have been reports that erythromycin may aggravate
the weakness of patients with myasthenia gravis.
Prolonged or repeated use of erythromycin may result in an overgrowth
of non-susceptible 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.
Prescribing erythromycin in the absence of a proven or
strongly suspected bacterial infection or a prophylactic indication
is unlikely to provide benefit to the patient and increases the risk
of the development of drug-resistant bacteria.
Erythromycin interferes with the fluorometric determination
of urinary catecholamines.
Erythromycin use in patients who are receiving high
doses of theophylline may be associated with an increase of 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.
been published reports suggesting that when oral erythromycin is given
concurrently with theophylline there is a significant decrease in
erythromycin serum concentrations. This decrease could result in subtherapeutic
concentrations of erythromycin.
administration in patients receiving carbamazepine has been reported
to cause increased serum levels of carbamazepine with subsequent development
of signs of carbamazepine toxicity.
administration of erythromycin and digoxin has been reported to result
in elevated serum digoxin levels.
been reports of increased anticoagulant effects when erythromycin
and oral anticoagulants were used concomitantly.
Erythromycin has been reported to significantly alter the metabolism
of the nonsedating antihistamines, terfenadine and astemizole, when
taken concomitantly. Rare cases of serious cardiovascular adverse
events, including electrocardiographic QT/QTc interval prolongation,
cardiac arrest, torsades de pointes, and other ventricular arrhythmias,
have been observed. (See CONTRAINDICATIONS.) In addition, deaths have been reported rarely with concomitant
administration of terfenadine and erythromycin.
The use of erythromycin in patients concurrently taking drugs metabolized
by the cytochrome P450 system may be associated with elevations in
serum levels of these other drugs. There have been reports of interactions
of erythromycin with carbamazepine, cyclosporine, hexobarbital, phenytoin,
alfentanil, disopyramide, lovastatin, bromocriptine, valproate, terfenadine,
and astemizole. Serum concentrations of drugs metabolized by the cytochrome
P450 system should be monitored closely in patients concurrently receiving
Impairment of Fertility:
Long-term animal data with erythromycin lactobionate
for use in determination of possible carcinogenic effects are not
available. However, long-term oral studies in rats with erythromycin
ethylsuccinate and 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% of diet.
Pregnancy Category B: There was no evidence of teratogenicity or any other adverse effect
on reproduction in female rats fed erythromycin base (up to 0.25%
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
Erythromycin is excreted in breast milk. Caution
should be exercised when erythromycin is administered to a nursing
AND USAGE and DOSAGE AND
Elderly patients, particularly those with reduced
renal or hepatic function, may be at increased risk for developing
erythromycin-induced hearing loss, when Erythrocin® doses of 4 grams/day or higher are given. (See ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION.)
Elderly patients may be more susceptible to the development
of torsades de pointes arrhythmias than younger patients. (See ADVERSE REACTIONS.)
Elderly patients may experience increased effects of oral
anticoagulant therapy while undergoing treatment with Erythrocin®. (See PRECAUTIONS , Drug Interactions.)
Erythromycin Lactobionate does not contain sodium.
Information for Patients:
Patients should be counseled that antibacterial drugs
including erythromycin should only be used to treat bacterial infections.
They do not treat viral infections (e.g., the common cold). When erythromycin
is prescribed to treat a bacterial infection, patients should be told
that although it is common to feel better early in the course of therapy,
the medication should be taken exactly as directed. Skipping doses
or not completing the full course of therapy may (1) decrease the
effectiveness of the immediate treatment and (2) increase the likelihood
that bacteria will develop resistance and will not be treatable by
erythromycin or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibiotics which
usually ends when the antibiotic is discontinued. Sometimes after
starting treatment with antibiotics, patients can develop watery and
bloody stools (with or without stomach cramps and fever) even as late
as two or more months after having taken the last dose of the antibiotic.
If this occurs, patients should contact their physician as soon as
Side effects following the use of intravenous erythromycin
are rare. Occasional venous irritation has been encountered, but if
the infusion is given slowly, in dilute solution, preferably by continuous
intravenous infusion or intermittent infusion in no less than 20 to
60 minutes, pain and vessel trauma are minimized.
Life-threatening episodes of ventricular tachycardia associated with
prolonged QT interval (torsades de pointes) have been reported in
some patients after intravenous administration of erythromycin lactobionate.
Susceptibility to the development of torsades de pointes
arrhythmias, a rare but serious cardiac condition, is related to electrolyte
imbalance, hepatic dysfunction, myocardial ischemia, left ventricular
dysfunction, idiopathic Q-T prolongation, and concurrent antiarrhythmic
therapy.5 Elderly patients exhibit a greater frequency
of decreased hepatic function, cardiac function, and of concomitant
disease and other drug therapy, and therefore should be monitored
carefully during Erythrocin® therapy.
Allergic reactions ranging from urticaria to anaphylaxis have occurred.
Skin reactions ranging from mild eruptions to erythema multiforme,
Stevens-Johnson syndrome, and toxic epidermal necrolysis have been
There have been isolated reports
of reversible hearing loss occurring chiefly in patients with renal
insufficiency and in patients receiving high doses of erythromycin.
Elderly patients, particularly those with reduced renal
or hepatic function, may also be at increased risk for developing
this effect when Erythrocin® doses of 4 grams/day
or higher are given. (See DOSAGE
AND ADMINISTRATION .)
In the case of overdosage, erythromycin infusion
should be discontinued and all other appropriate measures should be
Erythromycin is not removed by peritoneal
dialysis or hemodialysis.
DOSAGE AND ADMINISTRATION
For the treatment of severe infections in adults
and pediatric patients, the recommended intravenous dose of erythromycin
lactobionate is 15 to 20 mg/kg/day. Higher doses, up to 4 g/day, may
be given for severe infections.
of doses of ≥ 4 g/day may increase the risk for the development
of erythromycin-induced hearing loss in elderly patients, particularly
those with reduced renal or hepatic function. Erythrocin Lactobionate-I.V.
(Sterile Erythromycin Lactobionate, USP) must be administered by continuous
or intermittent intravenous infusion only. Due to the irritative properties
of erythromycin, I.V. push is an unacceptable route of administration.
Continuous infusion of erythromycin lactobionate is preferable
due to the slower infusion rate and lower concentration of erythromycin;
however, intermittent infusion at six hour intervals is also effective.
Intravenous erythromycin should be replaced by oral erythromycin as
soon as possible.
For slow continuous infusion:
The final diluted solution of erythromycin lactobionate is prepared
to give a concentration of 1 g per liter (1 mg/mL).
For intermittent infusion: Administer one-fourth the total daily
dose of erythromycin lactobionate by intravenous infusion in 20 to
60 minutes at intervals not greater than every six hours. The final
diluted solution of erythromycin lactobionate is prepared to give
a concentration of 1 to 5 mg/mL. No less than 100 mL of I.V. diluent
should be used. Infusion should be sufficiently slow to minimize pain
along the vein.
For treatment of acute pelvic
inflammatory disease caused by N. Gonorrhoeae, in female patients hypersensitive to penicillins, administer 500
mg erythromycin lactobionate every six hours for three days, followed
by oral administration of 250 mg erythromycin stearate or base every
six hours for seven days.
For treatment of Legionnaires’
Disease: Although optimal doses have not been established, doses utilized
in reported clinical data were 1 to 4 grams daily in divided doses.
Administration of doses of ≥ 4 g/day may increase
the risk for the development of erythromycin-induced hearing loss
in elderly patients, particularly those with reduced renal or hepatic
In the treatment of Group A beta-hemolytic
streptococcal infections of the upper respiratory tract (e.g., tonsillitis
or pharyngitis), the therapeutic dosage of erythromycin should be
administered for ten days. The American Heart Association suggests
a dosage of 250 mg of erythromycin orally, twice a day in long-term
prophylaxis of streptococcal upper respiratory tract infections for
the prevention of recurring attacks of rheumatic fever in patients
allergic to penicillin and sulfonamides.3
In prophylaxis against bacterial endocarditis (see INDICATIONS AND USAGE) the oral
regimen for penicillin allergic patients is erythromycin 1 gram, 1
hour before the procedure followed by 500 mg six hours later.4
PREPARE THE INITIAL SOLUTION OF ERYTHROCIN® LACTOBIONATE-I.V. BY ADDING 10 ML OF STERILE WATER FOR INJECTION,
USP, TO THE 500 MG VIAL OR 20 ML OF STERILE WATER FOR INJECTION, USP,
TO THE 1 G VIAL. Use only Sterile Water for Injection, USP, as other
diluents may cause precipitation during reconstitution. Do not use
diluents containing preservatives or inorganic salts.
After reconstitution, each mL contains 50 mg of erythromycin
activity. The initial solution is stable at refrigerator temperature
for two weeks, or for 24 hours at room temperature.
ADD THE INITIAL DILUTION TO ONE OF THE FOLLOWING
DILUENTS BEFORE ADMINISTRATION to give a concentration of 1 g of erythromycin
activity per liter (1 mg/mL) for continuous infusion or 1 to 5 mg/mL
for intermittent infusion:
THE FOLLOWING SOLUTIONS MAY ALSO BE USED PROVIDING
THEY ARE FIRST BUFFERED WITH NEUT ® (4% SODIUM
BICARBONATE, HOSPIRA) by adding 1 mL of Neut® per
100 mL of solution:
5% DEXTROSE INJECTION,
5% DEXTROSE AND LACTATED RINGER’S
5% DEXTROSE AND 0.9% SODIUM
CHLORIDE INJECTION, USP
Neut® (4% sodium bicarbonate, Hospira)
must be added to these solutions so that their pH is in the optimum
range for erythromycin lactobionate stability. Acidic solutions of
erythromycin lactobionate are unstable and lose their potency rapidly.
A pH of at least 5.5 is desirable for the final diluted solution of
No drug or chemical
agent should be added to an erythromycin lactobionate-I.V. fluid admixture
unless its effect on the chemical and physical stability of the solution
has first been determined.
diluted solution of erythromycin lactobionate should be completely
administered within 8 hours, since it is not suitable for storage.
Parenteral drug products should be inspected visually
for particulate matter and discoloration prior to administration,
whenever solution and container permit.
Erythrocin Lactobionate-I.V. (Sterile Erythromycin
Lactobionate, USP) is supplied as a sterile, lyophilized powder in
packages of ten vials (NDC 0409-6482-01), each vial containing the
equivalent of 500 mg of erythromycin.
at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]
National Committee for Clinical Laboratory Standards,
Approved Standard: Performance Standards
for Antimicrobial Disk Susceptibility Tests, 3rd Edition,
Vol. 4(16):M2-A3, Villanova, PA, December 1984.
Ericson, H.M., Sherris, J.C., Antibiotic Sensitivity
Testing Report of an International Collaborative Study, Acta Pathologica etMicrobiologica Scandinavica Section
B Suppl. 217:1-90, 1971.
Committee on Rheumatic Fever and Infective Endocarditis
of the Council on Cardiovascular Disease of the Young: Prevention
of Rheumatic Fever, Circulation 70(6):1118A-1122A, December 1984.
Committee on Rheumatic Fever and Infective Endocarditis
of the Council on Cardiovascular Disease of the Young: Prevention
of Bacterial Endocarditis, Circulation 70(6):1123A-1127A, December 1984.
Gilter, B., et al, Torsades
de Pointes Induced by Erythromycin, Chest, Volume 105: 368-72, February
Hospira, Inc., Lake Forest,
IL 60045 USA
erythromycin lactobionate injection, powder, lyophilized, for solution
HUMAN PRESCRIPTION DRUG
Item Code (Source)
Route of Administration
Name (Active Moiety)
Erythromycin Lactobionate (Erythromycin)
500 MILLIGRAM In 10 MILLILITER
contains a PACKAGE
This package is contained within the CASE (0409-6482-01) and
contains a VIAL
This package is contained within a PACKAGE and a CASE (0409-6482-01)