ERYTHROMYCIN- erythromycin_tablet, film coated

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 optimal serum levels. Erythromycin is largely bound to plasma proteins. 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 crosses the placental barrier, but fetal plasma levels are low. The drug is excreted in human 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. After oral administration, less than 5% of the administered dose can be recovered in the active form in the urine. Optimal blood levels are obtained when erythromycin tablets are given in the fasting state (at least 1/2 hour and preferably 2 hours before meals). Bioavailability data are available from Arbor Pharmaceuticals. Microbiology Mechanism of Action Erythromycin acts by inhibition of protein synthesis by binding 50S ribosomal subunits of susceptible organisms. It does not affect nucleic acid synthesis. Resistance The major route of resistance is modification of the 23S rRNA in the 50S ribosomal subunit to insensitivity while efflux can also be significant. Interactions with Other Antimicrobials Antagonism exists in vitro Antimicrobial Activity Erythromycin has been shown to be active against most isolates of the following bacteria both in vitro INDICATIONS AND USAGE Gram-positive Bacteria: Corynebacterium diphtheriae Corynebacterium minutissimum Listeria monocytogenes Staphylococcus aureus (resistant organisms may emerge during treatment) Streptococcus pneumoniae Streptococcus pyogenes Gram-negative Bacteria: Bordetella pertussis Haemophilus influenzae Legionella pneumophila Neisseria gonorrhoeae Other Microorganisms: Chlamydia trachomatis Entamoeba histolytica Mycoplasma pneumoniae Treponema pallidum Ureaplasma urealyticum The following in vitro but their clinical significance is unknown. in vitro Gram-positive Bacteria: Viridans group streptococci Gram-negative Bacteria: Moraxella catarrhalis Susceptibility Testing For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of erythromycin tablets, USP and other antibacterial drugs, erythromycin tablets, USP 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 tablets, USP are indicated in the treatment of infections caused by susceptible strains of the designated microorganisms in the diseases listed below: Upper respiratory tract infections of mild to moderate degree caused by Streptococcus pyogenes Streptococcus pneumoniae Haemophilus influenzae H. influenzae Lower respiratory tract infections of mild to moderate severity caused by Streptococcus pyogenes Streptococcus pneumoniae Listeriosis caused by Listeria monocytogenes Respiratory tract infections due to Mycoplasma pneumoniae Skin and skin structure infections of mild to moderate severity caused by Streptococcus pyogenes Staphylococcus aureus Pertussis (whooping cough) caused by Bordetella pertussis Diphtheria: Infections due to Corynebacterium diphtheriae Erythrasma: In the treatment of infections due to Corynebacterium minutissimum Intestinal amebiasis caused by Entamoeba histolytica Acute pelvic inflammatory disease caused by Neisseria gonorrhoeae TM N. gonorrhoeae Erythromycins are indicated for treatment of the following infections caused by Chlamydia trachomatis Chlamydia trachomatis 3 When tetracyclines are contraindicated or not tolerated, erythromycin is indicated for the treatment of nongonococcal urethritis caused by Ureaplasma urealyticum 3 Primary syphilis caused by Treponema pallidum Legionnaires' Disease caused by Legionella pneumophila in vitro Prophylaxis 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 Streptococcus pyogenes infections of the upper respiratory tract e.g., tonsillitis or pharyngitis). 1 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). 1

In most patients, Erythromycin Tablets are well absorbed and may be dosed orally without regard to meals. However, optimal blood levels are obtained when Erythromycin Tablets are given in the fasting state (at least 1/2 hour and preferably 2 hours before meals). Adults The usual dosage of Erythromycin Tablets is one 250 mg tablet four times daily in equally spaced doses or one 500 mg tablet every 12 hours. Dosage may be increased up to 4 g per day according to the severity of the infection. However, twice-a-day dosing is not recommended when doses larger than 1 g daily are administered. Children Age, weight and severity of the infection are important factors in determining the proper dosage. The usual dosage is 30 mg/kg/day to 50 mg/kg/day, in equally divided doses. For more severe infections this dosage may be doubled but should not exceed 4 g per day. In the treatment of streptococcal infections of the upper respiratory tract (e.g., tonsillitis or pharyngitis), the therapeutic dosage of erythromycin should be administered for at least 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. 1 Conjunctivitis of the Newborn Caused by Chlamydia trachomatis Oral erythromycin suspension 50 mg/kg/day in 4 divided doses for at least 2 weeks. 3 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. 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 of erythromycin 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 one erythromycin 500 mg tablet orally every 12 hours or 250 mg by mouth four times a day should be used for at least 14 days. 3 For adults with uncomplicated urethral, endocervical or rectal infections caused by Chlamydia trachomatis, when tetracycline is contraindicated or not tolerated 500 mg of erythromycin by mouth four times a day for at least 7 days. 3 For patients with nongonococcal urethritis caused by Ureaplasma urealyticum when tetracycline is contraindicated or not tolerated 500 mg of erythromycin by mouth four times a day for at least seven days. 3 Primary syphilis 30 to 40 g given in divided doses over a period of 10 days to 15 days. Acute Pelvic Inflammatory Disease Caused by N. gonorrhoeae 500 mg Erythrocin TM Intestinal Amebiasis Adults 500 mg every 12 hours or 250 mg every 6 hours for 10 days to 14 days. Children 30 mg/kg/day to 50 mg/kg/day in divided doses for 10 days to 14 days. Pertussis Although optimal dosage and duration have not been established, doses of erythromycin utilized in reported clinical studies were 40 mg/kg/day to 50 mg/kg/day, given in divided doses for 5 days to 14 days. Legionnaires' Disease Although optimal dosage has not been established, doses utilized in reported clinical data were 1g to 4g daily in divided doses.

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 hepatitis, hepatic dysfunction and/or abnormal liver function test results may occur (See WARNINGS Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment (See WARNINGS Erythromycin has been associated with QT prolongation and ventricular arrhythmias, including ventricular tachycardia and torsades de pointes (See WARNINGS 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 reported rarely. There have been reports of interstitial nephritis coincident with erythromycin use. There have been rare reports of pancreatitis and convulsions. There have been isolated reports of reversible hearing loss occurring chiefly in patients with renal insufficiency and in patients receiving high doses of erythromycin. To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Erythromycin is contraindicated in patients with known hypersensitivity to this antibiotic. Erythromycin is contraindicated in patients taking terfenadine, astemizole, cisapride, pimozide, ergotamine or dihydroergotamine. (See PRECAUTIONS - Drug Interactions Do not use erythromycin concomitantly with HMG CoA reductase inhibitors (statins) that are extensively metabolized by CYP 3A4 (lovastatin or simvastatin), due to the increased risk of myopathy, including rhabdomyolysis.

WARNINGS
Hepatotoxicity There have been reports of hepatic dysfunction, including increased liver enzymes and hepatocellular and/or cholestatic hepatitis, with or without jaundice, occurring in patients receiving oral erythromycin products. QT Prolongation Erythromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving erythromycin. Fatalities have been reported. Erythromycin should be avoided in patients with known prolongation of the QT interval, patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval. Syphilis in Pregnancy There have been reports suggesting that erythromycin does not reach the fetus in adequate concentration to prevent congenital syphilis. Infants born to women treated during pregnancy with oral erythromycin for early syphilis should be treated with an appropriate penicillin regimen. Clostridium difficile Associated Diarrhea Clostridium difficile C.difficile C. difficile C. difficile If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile C. difficile Drug Interactions Serious adverse reactions have been reported in patients taking erythromycin concomitantly with CYP3A4 substrates. These include colchicine toxicity with colchicine; rhabdomyolysis with simvastatin, lovastatin and atorvastatin; and hypotension with calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem) (see PRECAUTIONS - Drug Interactions There have been post-marketing reports of colchicine toxicity with concomitant use of erythromycin and colchicine. This interaction is potentially life-threatening and may occur while using both drugs at their recommended doses (see PRECAUTIONS - Drug Interactions Rhabdomyolysis with or without renal impairment has been reported in seriously ill patients receiving erythromycin concomitantly with lovastatin. Therefore, patients receiving concomitant lovastatin and erythromycin should be carefully monitored for creatine kinase (CK) and serum transaminase levels. (See package insert for lovastatin).
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 should be instituted. Erythromycin is not removed by peritoneal dialysis or hemodialysis.
REFERENCES
1. Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the American Heart Association: Prevention of Rheumatic Fever. Circulation. 78(4):1082-1086, October 1988. 2. Honein, M.A., et. al.: Infantile hypertrophic pyloric stenosis after pertussis prophylaxis with erythromycin: a case review and cohort study. The Lancet 1999:354 (9196): 2101-5. 3. Data on file, Arbor Pharmaceuticals, LLC. Please address medical inquiries to, MedicalAffairs@zydususa.com or Tel.: 1-877-993-8779. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. The brands listed above are trademarks of their respective owners.

Zydus Pharmaceuticals USA Inc.

ERYTHROMYCIN- erythromycin_tablet, film coated Product manual source documgent