ERYTHROMYCIN, ERYTHROMYCIN ESTOLATE, ERYTHROMYCIN ETHYLSUCCINATE, ERYTHROMYCIN LACTOBIONATE, ERYTHROMYCIN GLUCEPTATE
Chemistry - A macrolide antibiotic produced from Streptomyces erythreus, erythromycin is aweak base that is available commercially in several salts and esters. It has a pKa of 8.9.
Erythromycin base occurs as a bitter-tasting, odorless or practically odorless, white to slightyellow, crystalline powder. Approximately 1 mg is soluble in 1 ml of water; it is soluble in alcohol.
Erythromycin estolate occurs as a practically tasteless and odorless, white, crystalline powder. It ispractically insoluble in water and approximately 50 mg are soluble in 1 ml of alcohol. Erythromycinestolate may also be known as erythromycin propionate lauryl sulfate.
Erythromycin ethylsuccinate occurs as a practically tasteless and odorless, white to slight yellow, crystalline powder. It is very slightly soluble in water and freely soluble in alcohol.
Erythromycin lactobionate occurs as white to slightly yellow crystals or powder. It may have afaint odor and is freely soluble in water and alcohol.
Erythromycin gluceptate occurs as a practically odorless, white, slightly hygroscopic powder thatis freely soluble in water and alcohol. It may also be known as erythromycin glucoheptonate.
Erythromycin ethylsuccinate tablets and powder for oral suspension should be stored in tightcontainers at room temperature. The commercially available oral suspension should be stored in therefrigerator to preserve palatability. After dispensing, the oral suspensions are stable for at least 14days at room temperature, but individual products may have longer labeled stabilities.
Erythromycin lactobionate powder for injection should be stored at room temperature. For initialreconstitution (vials), only sterile water for injection should be used. After reconstitution, the drug isstable for 24 hours at room temperature and 2 weeks if refrigerated. To prepare for administrationvia continuous or intermittent infusion, the drug is further diluted in 0.9% sodium chloride, Lactated
Ringer's, or Normosol-R. Other infusion solutions may be used, but first must be buffered with4% sodium bicarbonate injection (1 ml per 100 ml of solution). At pH's of <5.5, the drug isunstable and loses potency rapidly. Many drugs are physically incompatible with erythromycinlactobionate; refer to an appropriate reference (e.g., Trissell¯see bibliography) for moreinformation.
Erythromycin gluceptate powder for injection should be stored at room temperature. For initialreconstitution (vials), only sterile water for injection (without preservatives) should be used. Afterreconstitution, the drug is stable for 7 days if refrigerated. Many drugs are physically incompatiblewith erythromycin gluceptate; refer to an appropriate reference (e.g., Trissell¯see bibliography) formore information.
Erythromycin has in vitro activity against gram positive cocci (staphylococci, streptococci), gram positive bacilli (Bacillus anthracis, Corynebacterium, Clostridium sp., (not C. difficile), Listeria,
Erysipelothrix), some strains of gram negative bacilli, including Haemophilus, Pasturella, and Brucella. Some strains of Actinomyces, Mycoplasma, Chlamydia, Ureaplasma, and Rickettsia are also inhibited by erythromycin. Most strains of the family Enterobacteriaceae (Pseudomonas, E. coli, Klebsiella, etc.) are resistant to erythromycin.
Erythromycin is less active at low pH's and many clinicians suggest alkalinizing the urine if using the drug to treat UTI's.
Uses, Indications - Erythromycin is approved for use to treat infections caused by susceptible organisms in dogs, cats, swine, sheep, and cattle. It is often employed when an animal is hypersensitive to penicillins or if other antibiotics are ineffective against a certain organism.
Erythromycin is at the present time considered to be the treatment of choice (with rifampin) for the treatment of C. (Rhodococcus) equi infections in foals.
After IM or SQ injection of the polyethylene-based veterinary product (Erythro®-200;
Gallimycin®-200) in cattle, absorption is very slow. Bioavailabilities are only about 40% after SQ injection, and 65% after IM injection.
Erythromycin is distributed throughout the body into most fluids and tissues including theprostate, macrophages, and leukocytes. CSF levels are poor. Erythromycin may be 73-81% boundto serum proteins and the estolate salt, 96% bound. Erythromycin will cross the placenta and levelsof 5-20% of those in the mother's serum can be found in the fetal circulation. Erythromycin levelsof about 50% of those found in the serum can be detected in milk. The volume of distribution forerythromycin in dogs is reportedly 2 L/kg, 3.7 - 7.2 L/kg in foals, 2.3 L/kg in mares, and 0.8 L/kgin cattle.
Erythromycin is primarily excreted unchanged in the bile, but is also partly metabolized by theliver via N-demethylation to inactive metabolites. Some of the drug is reabsorbed after biliaryexcretion. Only about 2-5% of a dose is excreted unchanged in the urine.
The reported elimination half-life of erythromycin in various species are: 60-90 minutes in dogsand cats, 60-70 minutes in foals and mares, and 190 minutes in cattle.
Many clinicians believe that erythromycin is contraindicated in adult horses (see Adverse Effectsbelow), and oral erythromycin should not be used in ruminants as severe diarrheas may result.
While erythromycin has not demonstrated teratogenic effects in rats and the drug is not thought toposses serious teratogenic potential, it should only be used during pregnancy when the benefitsoutweigh the risks.
Oral erythromycin should not be used in ruminants as severe diarrheas may result.
In foals treated with erythromycin, a mild, self-limiting diarrhea may occasionally occur. Adult horses may develop severe, sometimes fatal diarrheas from erythromycin and the use of the drug in adults is very controversial.
Erythromycin may alter temperature homeostasis in foals. Foals between the ages of 2 and 4 months old have been reported to develop hyperthermia with associated respiratory distress and tachypnea. Physically cooling off these animals is reported to be successful in controlling this effect.
Decreased clearance of theophylline may occur with resultant toxicity in patients receivingerythromycin (particularly high dosages). Patients should be monitored for symptoms of theophylline toxicity and serum theophylline levels monitored if necessary.
Patients stabilized on warfarin anticoagulant therapy may develop prolonged prothrombin times and bleeding when erythromycin is added. Enhanced monitoring is recommended.
The metabolism of methylprednisolone may be inhibited by concurrent administration of erythromycin. The clinical significance of this interaction is unknown.
Erythromycin may increase the bioavailability of digoxin in a small percentage of human patients and can lead to digoxin toxicity. Veterinary significance of this interaction is questionable.
Interactions have also been reported with erythromycin and the following human drugs (rarely used in veterinary species¯refer to other references if necessary): carbamazepine, cyclosporine (systemic), and triazolam.
Drug/Laboratory Interactions - Erythromycin may cause falsely elevated values of AST (SGOT), and ALT (SGPT) when using colorimetric assays.
Fluorometric determinations of urinary catecholamines can be altered by concomitant erythromycin administration.
Erythromycin base occurs as a bitter-tasting, odorless or practically odorless, white to slightyellow, crystalline powder. Approximately 1 mg is soluble in 1 ml of water; it is soluble in alcohol.
Erythromycin estolate occurs as a practically tasteless and odorless, white, crystalline powder. It ispractically insoluble in water and approximately 50 mg are soluble in 1 ml of alcohol. Erythromycinestolate may also be known as erythromycin propionate lauryl sulfate.
Erythromycin ethylsuccinate occurs as a practically tasteless and odorless, white to slight yellow, crystalline powder. It is very slightly soluble in water and freely soluble in alcohol.
Erythromycin lactobionate occurs as white to slightly yellow crystals or powder. It may have afaint odor and is freely soluble in water and alcohol.
Erythromycin gluceptate occurs as a practically odorless, white, slightly hygroscopic powder thatis freely soluble in water and alcohol. It may also be known as erythromycin glucoheptonate.
Storage, Stability, Compatibility
Erythromycin (base) capsules and tablets should be stored intight containers at room temperature (15-30°C). Erythromycin estolate preparations should beprotected from light. To retain palatability, the oral suspensions should be refrigerated.Erythromycin ethylsuccinate tablets and powder for oral suspension should be stored in tightcontainers at room temperature. The commercially available oral suspension should be stored in therefrigerator to preserve palatability. After dispensing, the oral suspensions are stable for at least 14days at room temperature, but individual products may have longer labeled stabilities.
Erythromycin lactobionate powder for injection should be stored at room temperature. For initialreconstitution (vials), only sterile water for injection should be used. After reconstitution, the drug isstable for 24 hours at room temperature and 2 weeks if refrigerated. To prepare for administrationvia continuous or intermittent infusion, the drug is further diluted in 0.9% sodium chloride, Lactated
Ringer's, or Normosol-R. Other infusion solutions may be used, but first must be buffered with4% sodium bicarbonate injection (1 ml per 100 ml of solution). At pH's of <5.5, the drug isunstable and loses potency rapidly. Many drugs are physically incompatible with erythromycinlactobionate; refer to an appropriate reference (e.g., Trissell¯see bibliography) for moreinformation.
Erythromycin gluceptate powder for injection should be stored at room temperature. For initialreconstitution (vials), only sterile water for injection (without preservatives) should be used. Afterreconstitution, the drug is stable for 7 days if refrigerated. Many drugs are physically incompatiblewith erythromycin gluceptate; refer to an appropriate reference (e.g., Trissell¯see bibliography) formore information.
Pharmacology - ERYTHROMYCIN, ERYTHROMYCIN ESTOLATE, ERYTHROMYCIN ETHYLSUCCINATE, ERYTHROMYCIN LACTOBIONATE, ERYTHROMYCIN GLUCEPTATE
Erythromycin is usually a bacteriostatic agent, but in high concentrations oragainst highly susceptible organisms it may be bactericidal. The macrolides (erythromycin andtylosin) are believed to act by binding to the 50S ribosomal subunit of susceptible bacteria, therebyinhibiting peptide bond formation.Erythromycin has in vitro activity against gram positive cocci (staphylococci, streptococci), gram positive bacilli (Bacillus anthracis, Corynebacterium, Clostridium sp., (not C. difficile), Listeria,
Erysipelothrix), some strains of gram negative bacilli, including Haemophilus, Pasturella, and Brucella. Some strains of Actinomyces, Mycoplasma, Chlamydia, Ureaplasma, and Rickettsia are also inhibited by erythromycin. Most strains of the family Enterobacteriaceae (Pseudomonas, E. coli, Klebsiella, etc.) are resistant to erythromycin.
Erythromycin is less active at low pH's and many clinicians suggest alkalinizing the urine if using the drug to treat UTI's.
Uses, Indications - Erythromycin is approved for use to treat infections caused by susceptible organisms in dogs, cats, swine, sheep, and cattle. It is often employed when an animal is hypersensitive to penicillins or if other antibiotics are ineffective against a certain organism.
Erythromycin is at the present time considered to be the treatment of choice (with rifampin) for the treatment of C. (Rhodococcus) equi infections in foals.
Pharmacokinetics - ERYTHROMYCIN, ERYTHROMYCIN ESTOLATE, ERYTHROMYCIN ETHYLSUCCINATE, ERYTHROMYCIN LACTOBIONATE, ERYTHROMYCIN GLUCEPTATE
Erythromycin is absorbed after oral administration in the upper small intestine. Several factors can influence the bioavailability of erythromycin, including salt form, dosage form, GI acidity, food in the stomach, and stomach emptying time. Both erythromycin base and stearate are susceptible to acid degradation, and enteric coatings are often used to alleviate this. Both the ethylsuccinate and estolate forms are dissociated in the upper small intestine and then absorbed.After IM or SQ injection of the polyethylene-based veterinary product (Erythro®-200;
Gallimycin®-200) in cattle, absorption is very slow. Bioavailabilities are only about 40% after SQ injection, and 65% after IM injection.
Erythromycin is distributed throughout the body into most fluids and tissues including theprostate, macrophages, and leukocytes. CSF levels are poor. Erythromycin may be 73-81% boundto serum proteins and the estolate salt, 96% bound. Erythromycin will cross the placenta and levelsof 5-20% of those in the mother's serum can be found in the fetal circulation. Erythromycin levelsof about 50% of those found in the serum can be detected in milk. The volume of distribution forerythromycin in dogs is reportedly 2 L/kg, 3.7 - 7.2 L/kg in foals, 2.3 L/kg in mares, and 0.8 L/kgin cattle.
Erythromycin is primarily excreted unchanged in the bile, but is also partly metabolized by theliver via N-demethylation to inactive metabolites. Some of the drug is reabsorbed after biliaryexcretion. Only about 2-5% of a dose is excreted unchanged in the urine.
The reported elimination half-life of erythromycin in various species are: 60-90 minutes in dogsand cats, 60-70 minutes in foals and mares, and 190 minutes in cattle.
Contraindications, Precautions, Reproductive Safety
Erythromycin is contraindicated in patients hypersensitive to it. In humans, the estolate form has been associated rarely with the development of cholestatic hepatitis. This effect has not apparently been reported in veterinary species, but the estolate should probably be avoided in patients with preexisting liver dysfunction.Many clinicians believe that erythromycin is contraindicated in adult horses (see Adverse Effectsbelow), and oral erythromycin should not be used in ruminants as severe diarrheas may result.
While erythromycin has not demonstrated teratogenic effects in rats and the drug is not thought toposses serious teratogenic potential, it should only be used during pregnancy when the benefitsoutweigh the risks.
Adverse Effects, Warnings
Adverse effects are relatively infrequent with erythromycin whenused in small animals, swine, sheep, or cattle. When injected IM, local reactions and pain at theinjection site may occur. Oral erythromycin may cause GI disturbances with diarrhea, anorexia, andvomiting occasionally seen. Rectal edema and partial anal prolapse have been associated witherythromycin in swine. Intravenous injections must be given very slowly, as the intravenous formscan readily cause thrombophlebitis. Allergic reactions can occur, but are thought to be very rare.Oral erythromycin should not be used in ruminants as severe diarrheas may result.
In foals treated with erythromycin, a mild, self-limiting diarrhea may occasionally occur. Adult horses may develop severe, sometimes fatal diarrheas from erythromycin and the use of the drug in adults is very controversial.
Erythromycin may alter temperature homeostasis in foals. Foals between the ages of 2 and 4 months old have been reported to develop hyperthermia with associated respiratory distress and tachypnea. Physically cooling off these animals is reported to be successful in controlling this effect.
Overdosage, Acute Toxicity
With the exception of the adverse effects outlined above, erythromycin is apparently quite non-toxic. However, shock reactions have been reported in baby pigsreceiving erythromycin overdosages.Drug Interactions
Because erythromycin, the lincosamides (clindamycin, lincomycin), andchloramphenicol all bind to the 50S ribosomal subunit, competition for binding can occur andsome clinicians state these drugs should not be used concurrently. In vitro synergy with otherantimicrobials (e.g., sulfonamides, rifampin) has been reported with erythromycin. The concomitantuse of erythromycin with bactericidal antibiotics (e.g., penicillin) is controversial, but documentationof either clinical synergy, additive activity, or antagonism is apparently lacking.Decreased clearance of theophylline may occur with resultant toxicity in patients receivingerythromycin (particularly high dosages). Patients should be monitored for symptoms of theophylline toxicity and serum theophylline levels monitored if necessary.
Patients stabilized on warfarin anticoagulant therapy may develop prolonged prothrombin times and bleeding when erythromycin is added. Enhanced monitoring is recommended.
The metabolism of methylprednisolone may be inhibited by concurrent administration of erythromycin. The clinical significance of this interaction is unknown.
Erythromycin may increase the bioavailability of digoxin in a small percentage of human patients and can lead to digoxin toxicity. Veterinary significance of this interaction is questionable.
Interactions have also been reported with erythromycin and the following human drugs (rarely used in veterinary species¯refer to other references if necessary): carbamazepine, cyclosporine (systemic), and triazolam.
Drug/Laboratory Interactions - Erythromycin may cause falsely elevated values of AST (SGOT), and ALT (SGPT) when using colorimetric assays.
Fluorometric determinations of urinary catecholamines can be altered by concomitant erythromycin administration.