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Erythromycin Delayed-release Capsules contain enteric-coated pellets of erythromycin base for oral administration. 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, but it is the base which is microbiologically active. Each Erythromycin Delayed-release Capsule contains 250 milligrams of erythromycin base.
Inactive Ingredients: Cellulosic polymers, citrate ester, D&C Red No. 30, D&C Yellow No. 10, magnesium stearate and povidone. The capsule shell contains FD&C Blue No. 1, FD&C Red No. 3, gelatin, and titanium dioxide.
Erythromycin base is (3R*, 4S*, 5S*, 6R*, 7R*, 9R*, 11R*, 12R*, 13S*, 14R*)-4-[ (2,6-Dideoxy-3-C-methyl-3-0- methyl-(alpha)-L- ribo -hexopyranosyl)oxy]-14-ethyl-7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-6-[[3,4,6- trideoxy-3-(dimethylamino)-(beta)-D- xylo -hexopyranosyl]oxy] oxacyclotetradecane-2,10-dione. The structural formula is:
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C 37 H 67 NO 13 MW 734
Orally administered erythromycin base and its salts are readily absorbed in the microbiologically active form. Interindividual variations in the absorption of erythromycin are, however, observed, and some patients do not achieve acceptable serum levels. Erythromycin is largely bound to plasma proteins, and the freely dissociating bound fraction after administration of erythromycin base represents 90% of the total erythromycin absorbed. 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 the passage of the drug across the blood-brain barrier increases in meningitis.
Erythromycin is excreted in breast milk. The drug crosses the placental barrier but plasma levels are low.
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. After oral administration, less than 5% of the administered dose can be recovered in the active form in the urine.
The enteric coating of pellets in Erythromycin Delayed- release Capsules protects the erythromycin base from inactivation by gastric acidity. Because of their small size and enteric coating, the pellets readily pass intact from the stomach to the small intestine and dissolve efficiently to allow absorption of erythromycin in a uniform manner. After administration of a single dose of a 250 mg Erythromycin Delayed-release Capsule, peak serum levels in the range of 1.13 to 1.68 mcg/mL are attained in approximately 3 hours and decline to 0.30-0.42 mcg/mL in 6 hours. Optimal conditions for stability in the presence of gastric secretion and for complete absorption are attained when Erythromycin Delayed-release Capsules are taken on an empty stomach.
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 between clindamycin and erythromycin. Resistance to erythromycin of many strains of Haemophilus influenzae and some strains of staphylococci has been demonstrated. Specimens should be obtained for culture and susceptibility testing.
Erythromycin is usually active against the following organisms in vitro and in clinical infections:
Streptococcus pyogenes
Alpha-hemolytic streptococci (viridans group)
Staphylococcus aureus (Resistant organisms may emerge during treatment.)
Streptococcus pneumoniae
Mycoplasma pneumoniae (Eaton's Agent)
Haemophilus influenzae (Many strains are resistant to erythromycin alone, but are susceptible to erythromycin and sulfonamides together.)
Treponema pallidum
Corynebacterium diphtheriae
Corynebacterium minutissimum
Entamoeba histolytica
Listeria monocytogenes
Neisseria gonorrhoeae
Bordetella pertussis
Legionella pneumophila (agent of Legionnaires' disease)
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 for erythromycin.
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:
Susceptible organisms produce zones of 18 mm or greater, indicating that the tested organism is likely to respond to therapy.
Resistant organisms produce zones of 13 mm or less, indicating that other therapy should be selected.
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.
A bacterial isolate may be considered susceptible if the MIC value 2 (minimal inhibitory concentration) for erythromycin is not more than 2 mcg/mL. Organisms are considered resistant if the MIC is 8 mcg/mL or higher.
Erythromycin Delayed-release Capsules are indicated in adults and children for treatment of the following conditions:
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 pneumoniae (Diplococcus pneumoniae).
Respiratory tract infections due to Mycoplasma pneumoniae (Eaton's agent).
Pertussis (whooping cough) caused by Bordetella pertussis. Erythromycin is effective in eliminating the organism from the nasopharynx of infected individuals, rendering them noninfectious. Some clinical studies suggest that erythromycin may be helpful in the prophylaxis of pertussis in exposed susceptible individuals.
Diphtheria--As an adjunct to antitoxin in 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.
Intestinal amebiasis caused by Entamoeba histolytica (oral erythromycins only). Extraenteric amebiasis requires treatment with other agents.
Infections due to Listeria monocytogenes.
Skin and soft tissue infections of mild to moderate severity caused by Streptococcus pyogenes and Staphylococcus aureus (resistant staphylococci may emerge during treatment).
Primary syphilis caused by Treponema pallidum. Erythromycin (oral forms only) is an alternate choice of treatment for primary syphilis in patients allergic to the penicillins. In treatment of primary syphilis, spinal fluid should be examined before treatment and as part of the follow-up after therapy. The use of erythromycin for the treatment of in utero syphilis is not recommended. (See " CLINICAL PHARMACOLOGY " section.)
Erythromycins are 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. 3
Legionnaires' 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' Disease.
Therapy with erythromycin should be monitored by bacteriological studies and by clinical response. (See " CLINICAL PHARMACOLOGY -- Microbiology " section.)
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.
Although no controlled clinical efficacy trials have been conducted, erythromycin has been suggested by the American Heart Association and the American Dental Association for use in a regimen for prophylaxis against bacterial endocarditis in patients allergic to penicillin who have congenital and/or rheumatic or other acquired valvular heart disease when they undergo dental procedures and surgical procedures of the upper respiratory tract. 3 (Erythromycin is not suitable prior to genitourinary surgery where the organisms likely to lead to bacteremia are gram-negative bacilli or the enterococcal group of streptococci.)
NOTE: When selecting antibiotics for the prevention of bacterial endocarditis the physician or dentist should read the full joint 1984 statement of the American Heart Association and the American Dental Association. 3
Erythromycin is contraindicated in patients with known hypersensitivity to this antibiotic.
There have been a few reports of hepatic dysfunction, with or without jaundice, occurring in patients receiving oral erythromycin products.
General: Erythromycin is principally excreted by the liver. Caution should be exercised when erythromycin is administered to patients with impaired hepatic function. (See " 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.
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.
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.
Administration of a dose of Erythromycin Delayed-release Capsules in the presence of food lowers the blood levels of systemically available erythromycin. Although the blood levels obtained upon administration of enteric-coated erythromycin products in the presence of food are still above minimum inhibitory concentrations (MICs) of most organisms for which erythromycin is indicated, optimum blood levels are obtained on a fasting stomach (administration at least 1 / 2 hour and preferably two hours before or after a meal).
Adults: The usual dose is 250 mg every 6 hours taken one hour before meals. If twice-a-day dosage is desired, the recommended dose is 500 mg every 12 hours. Dosage may be increased up to 4 grams per day, according to the severity of 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. The usual dosage is 30 to 50 mg/kg/day, in divided doses. For the treatment of more severe infections this dosage may be doubled.
Streptococcal infections: A therapeutic dosage of oral erythromycin should be administered for at least ten days. For continuous prophylaxis against recurrences of streptococcal infections in persons with a history of rheumatic heart disease, the dose is 250 mg twice a day.
For the prevention of bacterial endocarditis in penicillin-allergic patients with valvular heart disease who are to undergo dental procedures or surgical procedures of the upper respiratory tract, the adult dose is 1 gram orally (20 mg/kg for children) one hour prior to the procedure and then 500 mg (10 mg/kg for children) orally 6 hours later. 3 (See " INDICATIONS AND USAGE " section.)
Primary syphilis: 30 to 40 g given in divided doses over a period of 10 to 15 days.
Intestinal amebiasis: 250 mg every 6 hours for 10 to 14 days for adults; 30 to 50 mg/kg/day in divided doses for 10 to 14 days for children.
Legionnaires' disease: Although optimal doses have not been established, doses utilized in reported clinical data were those recommended above (1 to 4 g daily in divided doses).
Urogenital infections during pregnancy due to Chlamydia trachomatis: Although the optimal dose and duration of therapy have not been established, the suggested treatment is 500 mg by mouth four times a day on an empty stomach for at least 7 days. For women who cannot tolerate this regimen, a decreased dose of 250 mg by mouth four times a day should be used for at least 14 days. 4
For adults with uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis, when tetracycline is contrainidicated or not tolerated, 500 mg of erythromycin by mouth four times a day for at least 7 days. 4
Pertussis: Although optimum dosage and duration of therapy 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.
Erythromycin Delayed-release Capsules, USP, are clear and opaque maroon capsules with pink and yellow particles containing 250 mg of erythromycin supplied in bottles of 100 ( NDC 0074-6301-13) and 500 ( NDC 0074-630l-53).
Storage Conditions: Protect from moisture and excessive heat. Store below 86°F (30°C).
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Revised: September, 1991
Ref. 01-2563-R4