© 2003-17 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D. Published by
Elephant Care International
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Chemistry – A macrolide antibiotic produced from Streptomyces erythreus, erythromycin is a weak 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 slight yellow, 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 is practically insoluble in water and approximately 50 mg are soluble in 1 ml of alcohol. Erythromycin estolate 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 a faint odor and is freely soluble in water and alcohol. Erythromycin gluceptate occurs as a practically odorless, white, slightly hygroscopic powder that is 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 in tight containers at room temperature (15-30°C). Erythromycin estolate preparations should be protected from light. To retain palatability, the oral suspensions should be refrigerated.
Erythromycin ethylsuccinate tablets and powder for oral suspension should be stored in tight containers at room temperature. The commercially available oral suspension should be stored in the refrigerator to preserve palatability. After dispensing, the oral suspensions are stable for at least 14 days at room temperature, but individual products may have longer labeled stabilities.
Erythromycin lactobionate powder for injection should be stored at room temperature. For initial reconstitution (vials), only sterile water for injection should be used. After reconstitution, the drug is stable for 24 hours at room temperature and 2 weeks if refrigerated. To prepare for administration via 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 with 4% sodium bicarbonate injection (1 ml per 100 ml of solution). At pH’s of <5.5, the drug is unstable and loses potency rapidly. Many drugs are physically incompatible with erythromycin lactobionate; refer to an appropriate reference (e.g., Trissell—see bibliography) for more information.
Erythromycin gluceptate powder for injection should be stored at room temperature. For initial reconstitution (vials), only sterile water for injection (without preservatives) should be used. After reconstitution, the drug is stable for 7 days if refrigerated. Many drugs are physically incompatible with erythromycin gluceptate; refer to an appropriate reference (e.g., Trissell—see bibliography) for more information.
Pharmacology – Erythromycin is usually a bacteriostatic agent, but in high concentrations or against highly susceptible organisms it may be bactericidal. The macrolides (erythromycin and tylosin) are believed to act by binding to the 50S ribosomal subunit of susceptible bacteria, thereby inhibiting 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 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 the prostate, macrophages, and leukocytes. CSF levels are poor. Erythromycin may be 73-81% bound to serum proteins and the estolate salt, 96% bound. Erythromycin will cross the placenta and levels of 5-20% of those in the mother’s serum can be found in the fetal circulation. Erythromycin levels of about 50% of those found in the serum can be detected in milk. The volume of distribution for erythromycin 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/kg in cattle.
Erythromycin is primarily excreted unchanged in the bile, but is also partly metabolized by the liver via N-demethylation to inactive metabolites. Some of the drug is reabsorbed after biliary excretion. 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 dogs and 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 Effects below), 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 to posses serious teratogenic potential, it should only be used during pregnancy when the benefits outweigh the risks.
Adverse Effects/Warnings – Adverse effects are relatively infrequent with erythromycin when used in small animals, swine, sheep, or cattle. When injected IM, local reactions and pain at the injection site may occur. Oral erythromycin may cause GI disturbances with diarrhea, anorexia, and vomiting occasionally seen. Rectal edema and partial anal prolapse have been associated with erythromycin in swine. Intravenous injections must be given very slowly, as the intravenous forms can 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 pigs receiving erythromycin overdosages.
Drug Interactions – Because erythromycin, the lincosamides (clindamycin, lincomycin), and chloramphenicolall bind to the 50S ribosomal subunit, competition for binding can occur and some clinicians state these drugs should not be used concurrently. In vitro synergy with other antimicrobials (e.g., sulfonamides, rifampin) has been reported with erythromycin. The concomitant use of erythromycin with bactericidal antibiotics (e.g., penicillin) is controversial, but documentation of either clinical synergy, additive activity, or antagonism is apparently lacking.
Decreased clearance of theophylline may occur with resultant toxicity in patients receiving erythromycin (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.
For treatment of C. (Rhodococcus) equi infections in foals:
a) Erythromycin estolate or ethylsuccinate: 25 mg/kg PO tid with rifampin: 5 mg/kg PO tid. (Hillidge and Zertuche 1987)
b) Erythromycin estolate: 25 mg/kg PO q6h
Erythromycin gluceptate: 5 mg/kg IV q4-6h (Caprile and Short 1987)
c) Erythromycin estolate: 25 mg/kg PO qid
Erythromycin gluceptate: 5 mg/kg IV 4-6 times daily
Erythromycin base (veterinary) injectable: 10 mg/kg IM bid (Prescott, Hoover, and Dohoo 1983)
For susceptible infections:
a) Erythromycin estolate: 25 mg/kg PO q6h
Erythromycin ethylsuccinate: 25 mg/kg PO q8h
Erythromycin gluceptate: 5 mg/kg IV q4-6h
Erythromycin lactobionate: 3 – 5 mg/kg IV q6-8h (Brumbaugh 1987)
There are no published pharmacokinetic studies on erythromycin (or other macrolides and lincosamides) in elephants.
a) Severe gastrointestinal pain and upset may result after only 1-2 days (Schmidt, 1986).
a) Schmidt, M.J: Senior Research Veterinarian, Washington Park Zoo, Portland, Oregon, personal communication, 1986. In: Olsen,J.H., 1999. Antibiotic therapy in elephants. In: Fowler,M.E. and Miller R.E. (Editors), Zoo and Wild Animal Medicine: Current Therapy 4. W.B. Saunders, Philadelphia, PA,USA p. 538
Monitoring Parameters –
1) Clinical efficacy
2) Adverse effects (periodic liver function tests if patient receiving erythromycin estolate long-term; may not be necessary for foals receiving erythromycin and rifampin for Rhodococcus infections)
Client Information – The intramuscular 100 mg/ml (Erythro-100®) & 200 mg/ml products (Erythro-200®) have quite specific instructions on where and how to inject the drug. Refer to the label directions or package insert for more information before using.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times –
Erythromycin 100 mg/ml for IM Injection (with 2% butyl aminobenzoate as a local anesthetic) in 100 ml vials
Erythro-100® (Rhone Merieux); (OTC) Approved for use in dogs, cats, cattle, sheep, and swine. Milk withdrawal = 72 hours. Slaughter withdrawal for cattle, sheep, swine = 48 hours.
Erythromycin 200 mg/ml for IM Injection in 100 ml, 250 ml, and 500 ml vials
Erythro-200® (Rhone Merieux); (OTC) Approved for use in cattle, sheep, and swine. Milk withdrawal = 72 hours. Slaughter withdrawal for cattle =14 days (21 days to avoid excessive trimming). Slaughter withdrawal for sheep = 3 days (10 days to avoid excessive trimming). Slaughter withdrawal for swine = 7 days (10 days to avoid excessive trimming).
Erythromycin Mastitis Infusion Tube for Dry Cows; 600 mg erythromycin per 12 ml tube
Erythro®-Dry (Rhone Merieux); (OTC) Approved for use in dry dairy cattle. Milk withdrawal = 36 hours. Slaughter withdrawal = 14 days nor within 96 hours of calving. Calves born to treated cows may not be slaughtered for food at less than 10 days of age.
Erythromycin Mastitis Infusion Tube for Lactating Cows; 50 mg/ml of erythromycin per 6 ml tube
Erythro®-36 (Rhone Merieux); (OTC) Approved for use in dry dairy cattle. Milk withdrawal = 36 hours. Slaughter withdrawal = 14 days.
There are also several erythromycin premixes alone and in combination with other drugs for use in swine and/or poultry.
Erythromycin Base Oral Tablets enteric-coated 250 mg, 500 mg; Ery-Tab® (Abbott); E-Mycin® (Boots), Robimycin® Robitabs® (Robins);E-Base® (Barr); (Rx)
Erythromycin Base Oral Tablets film-coated 250 mg, 500 mg
Erythromycin Film-Tabs® (Abbott); (Rx)
Erythromycin Base Oral Capsules delayed release enteric-coated pellets 250 mg; Eryc® (Parke-Davis); (Rx)
Erythromycin Base Delayed Relased Tablets 333 mg, generic, (Rx)
Erythromycin Base Tablets with polymer coated particles 500 mg; PCE Dispertab ® (Abbott) (Rx)
Erythromycin Base Oral Capsules delayed release 250 mg; generic (Rx)
Erythromycin Estolate Tablets 500 mg (as estolate) Ilosone® (Dista) (Rx)
Erythromycin Estolate Capsules 250 mg (as estolate); Ilosone Pulvules® (Dista) (Rx); generic, (Rx)
Erythromycin Estolate Suspension: 125 mg (as estolate) per 5 ml in 480 mls and 250 mg (as estolate) per 5 ml in 100 & 480 mls; Ilosone® (Dista); generic, (Rx)
Erythromycin Stearate Film-coated tablets 250 mg, 500 mg; generic; (Rx)
Erythromycin Ethylsuccinate Chewable Tablets: 200 mg (as ethylsuccinate; equiv. to 125 mg of base); EryPed® (Abbott) (Rx)
Erythromycin Ethylsuccinate Tablets: 400 mg (as ethylsuccinate); E.E.S. 400; generic, (Rx)
Oral Suspension: 40 mg/ml (equiv. to 25 mg/ml base), 80 mg/ml (equiv. to 50 mg/ml base) in 100, 200, 480, and 500 ml bottles; 100 mg per 2.5 ml in 50 mls, 200 & 400 mg (as ethylsuccinate) per 5 ml in 60, 100, 200 and 480 ml and UD 5 ml (100’s); EryPed Drops® (Abbott); EryPed 400® (Abbott); E.E.S. 400; generic (Rx)
Powder for Oral Suspension: 200 mg (as ethylsuccinate) per 5 ml when reconstituted in 100 & 200 mls ; E.E.S. Granules® (Abbott) (Rx)
Granules for Oral Suspension: 400 mg (as ethylsuccinate) per 5 ml when reconstituted; EryPed Drops ® (Abbott)
Erythromycin Lactobionate Powder for Injection: 500 mg & 1 g (as lactobionate); generic (Rx)
Erythromycin Lactobionate Injection: 1 g erythromycin (as gluceptate) per vial in 30 mls; Ilotycin Gluceptate® (Dista) (Rx)