ADVERSE REACTIONS SECTION.


ADVERSE REACTIONS. Themost frequent side effects of oral erythromycin preparations are gastrointestinaland are dose-related. They include nausea, vomiting, abdominal pain,diarrhea and anorexia. Symptoms of hepatitis, hepatic dysfunctionand/or abnormal liver function test results may occur. (See WARNINGS.)Onset of pseudomembranouscolitis symptoms may occur during or after antibacterial treatment. (See WARNINGS.)Erythromycin has been associated with QT prolongation and ventriculararrhythmias, including ventricular tachycardia and torsades de pointes.Allergic reactions ranging from urticariato anaphylaxis have occurred. Skin reactions ranging from mild eruptionsto erythema multiforme, Stevens-Johnson syndrome, and toxic epidermalnecrolysis have been reported rarely.There have been rare reports of pancreatitis and convulsions.There have been isolated reports of reversiblehearing loss occurring chiefly in patients with renal insufficiencyand in patients receiving high doses of erythromycin.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.


Carcinogenesis, Mutagenesis,Impairment of Fertility. Long-term (2-year) oral studies conducted in rats with erythromycinbase did not provide evidence of tumorigenicity. Mutagenicity studieshave not been conducted. There was no apparent effect on male orfemale fertility in rats fed erythromycin (base) at levels up to 0.25percent of diet.

CLINICAL PHARMACOLOGY SECTION.


CLINICAL PHARMACOLOGY. Orally administered erythromycin base and its salts are readily absorbedin the microbiologically active form. Interindividual variationsin the absorption of erythromycin are, however, observed, and somepatients do not achieve optimal serum levels. Erythromycin is largelybound to plasma proteins. After absorption, erythromycin diffusesreadily into most body fluids. In the absence of meningeal inflammation,low concentrations are normally achieved in the spinal fluid but thepassage of the drug across the blood-brain barrier increases in meningitis. Erythromycin crosses the placental barrier, but fetal plasma levelsare low. The drug is excreted in human milk. Erythromycin is notremoved by peritoneal dialysis or hemodialysis.In the presence of normal hepatic function, erythromycinis concentrated in the liver and is excreted in the bile; the effectof hepatic dysfunction on biliary excretion of erythromycin is notknown. After oral administration, less than 5% of the administereddose can be recovered in the active form in the urine.Orally administered ERYTHROCIN STEARATEtablets are readily and reliably absorbed. Optimal serum levels oferythromycin are reached when the drug is taken in the fasting stateor immediately before meals.. Microbiology. Erythromycin acts by inhibition of proteinsynthesis by binding 50 ribosomal subunits of susceptibleorganisms. It does not affect nucleic acid synthesis. Antagonismhas been demonstrated in vitro between erythromycinand clindamycin, lincomycin, and chloramphenicol.Many strains of Haemophilus influenzae are resistant to erythromycin alone, but are susceptible to erythromycinand sulfonamides used concomitantly.Staphylococci resistant to erythromycin may emerge during courseof erythromycin therapy. Erythromycin has been shown to be activeagainst most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.. Gram-positive organisms. Corynebacterium diphtheriaeCorynebacterium minutissimumListeria monocytogenesStaphylococcus aureus (resistant organisms may emerge during treatment)Streptococcus pneumoniaeStreptococcus pyogenes. Gram-negative organisms. Bordetella pertussisLegionella pneumophilaNeisseria gonorrhoeae Other microorganisms. Chlamydia trachomatisEntamoeba histolyticaMycoplasma pneumoniaeTreponema pallidumUreaplasma urealyticum The following in vitro data are available, but their clinical significanceis unknown.Erythromycin exhibits in vitro minimal inhibitoryconcentrations (MICs) of 0.5 ug/mL or less against most (>= 90%) strainsof the following microorganisms; however, the safety and effectivenessof erythromycin in treating clinical infections due to these microorganismshave not been established in adequate and well-controlled clinicaltrials.. Gram-positive organisms. Viridans group streptococci. Gram-negative organisms. Moraxella catarrhalis. Susceptibility Tests. Dilution TechniquesQuantitative methods are used to determineantimicrobial minimum inhibitory concentrations (MICs). These MICsprovide estimates of the susceptibility of bacteria to antimicrobialcompounds. The MICs should be determined using standardized procedure. Standardized procedures are based on dilution method1 (broth or agar) or equivalent with standardized inoculumconcentrations and standardized concentrations of erythromycin powder. The MIC values should be interpreted according to the following criteria:MIC (ug/mL)Interpretation <= 0.5Susceptible (S)1-4Intermediate (I)>= 8Resistant (R)A report of Susceptible indicatesthat the pathogen is likely to be inhibited if the antimicrobial compoundin the blood reaches the concentrations usually achievable. reportof Intermediate indicates that the result should be considered equivocal,and, if the microorganism is not fully susceptible to alternative,clinically feasible drugs, the test should be repeated. This categoryimplies possible clinical applicability in body sites where the drugis physiologically concentrated or in situations where high dosageof drug can be used. This category also provides buffer zone whichprevents small uncontrolled technical factors from causing major discrepanciesin interpretation. report of Resistant indicates that the pathogenis not likely to be inhibited if the antimicrobial compound in theblood reaches the concentrations usually achievable; other therapyshould be selected.Standardizedsusceptibility test procedures require the use of laboratory controlmicroorganisms to control the technical aspects of the laboratoryprocedures. Standard erythromycin powder should provide the followingMIC values:MicroorganismMIC (ug/mL) S. aureus ATCC 292130.12-0.5E. faecalis ATCC292121-4. Diffusion Techniques. Quantitative methods that require measurementof zone diameters also provide reproducible estimates of the susceptibilityof bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 15-ug erythromycinto test the susceptibility of microorganisms to erythromycin.Reports from the laboratory providing resultsof the standard single-disk susceptibility test with 15-ug erythromycindisk should be interpreted according to the following criteria:Zone Diameter (mm)Interpretation >= 23Susceptible (S)14-22Intermediate (I)<= 13Resistant (R)Interpretation should be as statedabove for results using dilution techniques. Interpretation involvescorrelation of the diameter obtained in the disk test with the MICfor erythromycin.As with standardizeddilution techniques, diffusion methods require the use of laboratorycontrol microorganisms that are used to control the technical aspectsof the laboratory procedures. For the diffusion technique, the 15-ugerythromycin disk should provide the following zone diameters in theselaboratory test quality control strains:MicroorganismZone Diameter (mm)S. aureus ATCC2592322-30.

CONTRAINDICATIONS SECTION.


CONTRAINDICATIONS. Erythromycinis contraindicated in patients with known hypersensitivity to thisantibiotic.Erythromycin is contraindicatedin patients taking terfenadine, astemizole, pimozide or cisapride. (See PRECAUTIONS Drug Interactions.).

DESCRIPTION SECTION.


DESCRIPTION. ERYTHROCIN STEARATE Filmtab tablets (erythromycinstearate tablets, USP) are an antibacterial product containing thestearate salt of erythromycin in unique film coating.Erythromycin is produced by strain of Saccharopolyspora erythraea (formerly Streptomyceserythraeus) and belongs to the macrolide group of antibiotics. It is basic and readily forms salts with acids. Erythromycin isa white to off-white powder, slightly soluble in water, and solublein alcohol, chloroform, and ether. Erythromycin stearate is knownchemically as erythromycin octadecanoate. The molecular formula oferythromycin stearate is C37H67NO13 oC18H36O2, and the molecularweight is 1018.43. The structural formula is:. Inactive Ingredients. 250 mg tablet. Cellulosic polymers, corn starch, D&CRed No. 7, polacrilin potassium, polyethylene glycol, povidone, propyleneglycol, sodium carboxymethylcellulose, sodium citrate, sorbic acid,sorbitan monooleate and titanium dioxide.. 500 mg tablet. Cellulosic polymers, cornstarch, FD&CRed No. 3, magnesium hydroxide, polacrilin potassium, povidone, propyleneglycol, sorbitan monooleate, titanium dioxide and vanillin.. Chemical structure of erythromycin stearate.

DOSAGE & ADMINISTRATION SECTION.


DOSAGE AND ADMINISTRATION. Optimal serum levels of erythromycin are reached when ERYTHROCINSTEARATE (erythromycin stearate) is taken in the fasting state orimmediately before meals.. Adults. The usual dosage is 250 mg every hours;or 500 mg every 12 hours. Dosage may be increased up to g per dayaccording to the severity of the infection. However, twice-a-daydosing is not recommended when doses larger than g daily are administered.. Children. Age, weight, and severity of the infectionare important factors in determining the proper dosage. The usualdosage is 30 to 50 mg/kg/day, in equally divided doses. For moresevere infections this dosage may be doubled but should not exceed4 per day.. In the treatment of streptococcal infectionsof the upper respiratory tract (e.g., tonsillitis or pharyngitis),the therapeutic dosage of erythromycin should be administered forat least ten days.The AmericanHeart Association suggests dosage of 250 mg of erythromycin orally,twice day in long-term prophylaxis of streptococcal upper respiratorytract infections for the prevention of recurring attacks of rheumaticfever in patients allergic to penicillin and sulfonamides.3 Conjunctivitis of theNewborn Caused by Chlamydia trachomatis Oral erythromycin suspension 50 mg/kg/dayin divided doses for at least weeks.3 Pneumonia of InfancyCaused by Chlamydia trachomatis Although the optimal duration of therapyhas not been established, the recommended therapy is oral erythromycinsuspension 50 mg/kg/day in divided doses for at least weeks.. Urogenital InfectionsDuring Pregnancy Due to Chlamydia trachomatis Although the optimal dose and durationof therapy have not been established, the suggested treatment is 500mg of erythromycin by mouth four times day or two erythromycin 333mg tablets orally every hours on an empty stomach for at least 7days. For women who cannot tolerate this regimen, decreased doseof one erythromycin 500 mg tablet orally every 12 hours, one 333 mgtablet orally every hours or 250 mg by mouth four times day shouldbe used for at least 14 days.5 For Adults With UncomplicatedUrethral, Endocervical, or Rectal Infections Caused by Chlamydiatrachomatis, When Tetracycline is Contraindicated or NotTolerated. 500 mg oferythromycin by mouth four times day or two 333 mg tablets orallyevery hours for at least days.5 For Patients With NongonococcalUrethritis Caused by Ureaplasma urealyticum WhenTetracycline is Contraindicated or Not Tolerated. 500 mg of erythromycin by mouth four timesa day or two 333 mg tablets orally every hours for at least sevendays.5 Primary Syphilis. 30 to 40 given in divided doses overa period of 10 to 15 days.. Acute Pelvic InflammatoryDisease Caused by N. gonorrhoeae 500 mg Erythrocin Lactobionate-I.V. (erythromycinlactobionate for injection, USP) every hours for days, followedby 500 mg of erythromycin base orally every 12 hours, or 333 mg oferythromycin base orally every hours for days.. Intestinal Amebiasis. Adults. 500 mg every 12 hours, 333 mg every hoursor 250 mg every hours for 10 to 14 days.. Children. 30 to 50 mg/kg/day in divided doses for10 to 14 days.. Pertussis. Although optimal dosage and duration havenot been established, doses of erythromycin utilized in reported clinicalstudies were 40 to 50 mg/kg/day, given in divided doses for to 14days.. Legionnaires Disease. Although optimal dosage has not been established,doses utilized in reported clinical data were to g daily in divideddoses.

DRUG INTERACTIONS SECTION.


Drug Interactions. Erythromycin use in patients who are receivinghigh doses of theophylline may be associated with an increase in serumtheophylline levels and potential theophylline toxicity. In caseof theophylline toxicity and/or elevated serum theophylline levels,the dose of theophylline should be reduced while the patient is receivingconcomitant erythromycin therapy.Hypotension, bradyarrhythmias, and lactic acidosis have been observedin patients receiving concurrent verapamil, belonging to the calciumchannel blockers drug class.Concomitant administration of erythromycin and digoxin has been reportedto result in elevated digoxin serum levels.There have been reports of increased anticoagulanteffects when erythromycin and oral anticoagulants were used concomitantly. Increased anticoagulation effects due to interactions of erythromycinwith oral anticoagulants may be more pronounced in the elderly.Erythromycin is substrate and inhibitorof the 3A isoform subfamily of the cytochrome p450 enzyme system (CYP3A). Coadministration of erythromycin and drug primarily metabolizedby CYP3A may be associated with elevations in drug concentrationsthat could increase or prolong both the therapeutic and adverse effectsof the concomitant drug. Dosage adjustments may be considered, andwhen possible, serum concentrations of drugs primarily metabolizedby CYP3A should be monitored closely in patients concurrently receivingerythromycin.The following areexamples of some clinically significant CYP3A based drug interactions. Interactions with other drugs metabolized by the CYP3A isoform arealso possible. The following CYP3A based drug interactions have beenobserved with erythromycin products in post-marketing experience:. Ergotamine/dihydroergotamine. Concurrent use of erythromycin and ergotamineor dihydroergotamine has been associated in some patients with acuteergot toxicity characterized by severe peripheral vasospasm and dysesthesia.. Triazolobenzodiazepines(Such as triazolam and alprazolam) and Related Benzodiazepines. Erythromycin has been reported to decreasethe clearance of triazolam and midazolam, and thus, may increase thepharmacologic effect of these benzodiazepines.. HMG-CoA Reductase Inhibitors. Erythromycin has been reported to increaseconcentrations of HMG-CoA reductase inhibitors (e.g., lovastatin andsimvastatin). Rare reports of rhabdomyolysis have been reported inpatients taking these drugs concomitantly.. Sildenafil (Viagra). Erythromycin has been reported to increasethe systemic exposure (AUC) of sildenafil. Reduction of sildenafildosage should be considered. (See Viagra package insert.). There have been spontaneous or publishedreports of CYP3A based interactions of erythromycin with cyclosporine,carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine,methylprednisolone, cilostazol, vinblastine, and bromocriptine.Concomitant administration of erythromycinwith cisapride, pimozide, astemizole, or terfenadine is contraindicated. (See CONTRAINDICATIONS.)In addition, there have been reports of interactionsof erythromycin with drugs not thought to be metabolized by CYP3A,including hexobarbital, phenytoin, and valproate.Erythromycin has been reported to significantly alterthe metabolism of the nonsedating antihistamines terfenadine and astemizolewhen taken concomitantly. Rare cases of serious cardiovascular adverseevents, including electrocardiographic QT/QTc interval prolongation, cardiac arrest, torsades de pointes, andother ventricular arrhythmias, have been observed. (See CONTRAINDICATIONS.) In addition, deaths have been reported rarely with concomitantadministration of terfenadine and erythromycin.There have been post-marketing reports of drug interactionswhen erythromycin was co-administered with cisapride, resulting inQT prolongation, cardiac arrhythmias, ventricular tachycardia, ventricularfibrillation, and torsades de pointes, most likely due to the inhibitionof hepatic metabolism of cisapride by erythromycin. Fatalities havebeen reported. (See CONTRAINDICATIONS).

GENERAL PRECAUTIONS SECTION.


General. PrescribingERYTHROCIN STEARATE Filmtab tablets in the absence of proven orstrongly suspected bacterial infection or prophylactic indicationis unlikely to provide benefit to the patient and increases the riskof the development of drug-resistant bacteria.Since erythromycin is principally excreted by the liver,caution should be exercised when erythromycin is administered to patientswith impaired hepatic function. (See CLINICAL PHARMACOLOGY and WARNINGS.)Exacerbation of symptoms of myasthenia gravis and new onset of symptomsof myasthenic syndrome have been reported in patients receiving erythromycintherapy.There have been reportsof infantile hypertrophic pyloric stenosis (IHPS) occurring in infantsfollowing erythromycin therapy. In one cohort of 157 newborns whowere given erythromycin for pertussis prophylaxis, seven neonates(5%) developed symptoms of non-bilious vomiting or irritability withfeeding and were subsequently diagnosed as having IHPS requiring surgicalpyloromyotomy. possible dose-response effect was described withan absolute risk of IHPS of 5.1% for infants who took erythromycinfor 8-14 days and 10% for infants who took erythromycin for 15-21days.4 Since erythromycin may be usedin the treatment of conditions in infants which are associated withsignificant mortality or morbidity (such as pertussis or neonatal Chlamydia trachomatis infections), the benefit of erythromycintherapy needs to be weighed against the potential risk of developingIHPS. Parents should be informed to contact their physician if vomitingor irritability with feeding occurs.Prolonged or repeated use of erythromycin may result in an overgrowthof nonsusceptible bacteria or fungi. If superinfection occurs, erythromycinshould be discontinued and appropriate therapy instituted.When indicated, incision and drainage orother surgical procedures should be performed in conjunction withantibiotic therapy.

GERIATRIC USE SECTION.


Geriatric Use. Elderly patients, particularly those withreduced renal or hepatic function, may be at increased risk for developingerythromycin-induced hearing loss. (See ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION).Elderly patients may be more susceptible to the developmentof torsades de pointes arrhythmias than younger patients. (See ADVERSE REACTIONS).Elderlypatients may experience increased effects of oral anticoagulant therapywhile undergoing treatment with erythromycin. (See PRECAUTIONS- Drug Interactions).Erythrocin Stearate Filmtab (R) Tablets (250 mg) contain 56.7 mg (2.5mEq) of sodium and 5.0 mg (0.1 mEq) of potassium per tablet.Erythrocin Stearate Filmtab (R) Tablets (500mg) contain no sodium and 7.0 mg (0.2 mEq) of potassium per tablet.The geriatric population may respond witha blunted natriuresis to salt loading. This may be clinically importantwith regard to such diseases as congestive heart failure.

HOW SUPPLIED SECTION.


HOW SUPPLIED. ERYTHROCIN STEARATE Filmtab Tablets (erythromycinstearate tablets, USP) are supplied in the following strengths andpackages.ERYTHROCIN STEARATEFilmtab, 250 mg pink tablets imprinted with the corporate AbbottA logo and the Abbo-Code designation ES:Bottles of 100.................................................................(NDC 0074-6346-20)Bottles of 500.................................................................(NDC 0074-6346-53)ERYTHROCINSTEARATE Filmtab, 500 mg pink tablets imprinted with the corporate Abbott A logo and the Abbo-Code designation ET:Bottles of 100................................................................(NDC 0074-6316-13). Recommended Storage. Store below 86F (30C).

INDICATIONS & USAGE SECTION.


INDICATIONS AND USAGE. To reduce the development of drug-resistantbacteria and maintain the effectiveness of ERYTHROCIN STEARATE Filmtabtablets and other antibacterial drugs, ERYTHROCIN STEARATE Filmtabtablets should be used only to treat or prevent infections that areproven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they shouldbe considered in selecting or modifying antibacterial therapy. Inthe absence of such data, local epidemiology and susceptibility patternsmay contribute to the empiric selection of therapy.ERYTHROCIN STEARATE tablets are indicated in the treatmentof infections caused by susceptible strains of the designated microorganismsin the diseases listed below:Upper respiratory tract infections of mild to moderate degree causedby Streptococcus pyogenes; Streptococcuspneumoniae Haemophilus influenzae (whenused concomitantly with adequate doses of sulfonamides, since manystrains of H. influenzae are not susceptible to theerythromycin concentrations ordinarily achieved). (See appropriatesulfonamide labeling for prescribing information.)Lower respiratory tract infections of mild to moderateseverity caused by Streptococcus pyogenes or Streptococcus pneumoniae.Listeriosis caused by Listeria monocytogenes.Respiratory tract infections due to Mycoplasma pneumoniae.Skin and skin structure infections of mild to moderate severity causedby Streptococcus pyogenes or Staphylococcusaureus (resistant staphylococci may emerge during treatment).Pertussis (whooping cough) caused by Bordetella pertussis. Erythromycin is effective in eliminatingthe organism from the nasopharynx of infected individuals, renderingthem noninfectious. Some clinical studies suggest that erythromycinmay be helpful in the prophylaxis of pertussis in exposed susceptibleindividuals.Diphtheria: Infectionsdue to Corynebacterium diphtheriae, as an adjunctto antitoxin, to prevent establishment of carriers and to eradicatethe organism in carriers.Erythrasma:In the treatment of infections due to Corynebacterium minutissimum.Intestinal amebiasis causedby Entamoeba histolytica (oral erythromycins only). Extraenteric amebiasis requires treatment with other agents.Acute Pelvic Inflammatory Disease Causedby Neisseria gonorrhoeae: Erythrocin(R) Lactobionate-I.V.(erythromycin lactobionate for injection, USP) followed by erythromycinbase orally, as an alternative drug in treatment of acute pelvic inflammatorydisease caused by N. gonorrhoeae in female patientswith history of sensitivity to penicillin. Patients should havea serologic test for syphilis before receiving erythromycin as treatmentof gonorrhea and follow-up serologic test for syphilis after months.Erythromycins are Indicated for Treatmentof the Following Infections Caused by Chlamydia trachomatis: Conjunctivitis of the newborn, pneumonia of infancy, and urogenitalinfections during pregnancy. When tetracyclines are contraindicatedor not tolerated, erythromycin is indicated for the treatment of uncomplicatedurethral, endocervical, or rectal infections in adults due to Chlamydia trachomatis.When tetracyclines are contraindicated or not tolerated, erythromycinis indicated for the treatment of nongonococcal urethritis causedby Ureaplasma urealyticum.Primary syphilis caused by Treponema pallidum. Erythromycin (oral forms only) is an alternative choice of treatmentfor primary syphilis in patients allergic to the penicillins. Intreatment of primary syphilis, spinal fluid should be examined beforetreatment and as part of the follow-up after therapy.Legionnaires Disease caused by Legionellapneumophila. Although no controlled clinical efficacy studieshave been conducted, in vitro and limited preliminaryclinical data suggest that erythromycin may be effective in treatingLegionnaires Disease.. Prophylaxis. Prevention of InitialAttacks of Rheumatic Fever. Penicillin is considered by the American Heart Association to bethe drug of choice in the prevention of initial attacks of rheumaticfever (treatment of Streptococcus pyogenes infectionsof the upper respiratory tract e.g., tonsillitis, or pharyngitis).3 Erythromycin is indicated for the treatment of penicillin-allergicpatients. The therapeutic dose should be administered for ten days.. Prevention of RecurrentAttacks of Rheumatic Fever. Penicillin or sulfonamides are considered by the American Heart Associationto be the drugs of choice in the prevention of recurrent attacks ofrheumatic fever. In patients who are allergic to penicillin and sulfonamides,oral erythromycin is recommended by the American Heart Associationin the long-term prophylaxis of streptococcal pharyngitis (for theprevention of recurrent attacks of rheumatic fever).3.

INFORMATION FOR PATIENTS SECTION.


Information for Patients. Patients should be counseled that antibacterial drugs including ERYTHROCINSTEARATE Filmtab tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). WhenERYTHROCIN STEARATE Filmtab tablets are prescribed to treat bacterialinfection, patients should be told that although it is common to feelbetter early in the course of therapy, the medication should be takenexactly as directed. Skipping doses or not completing the full courseof therapy may (1) decrease the effectiveness of the immediate treatmentand (2) increase the likelihood that bacteria will develop resistanceand will not be treatable by ERYTHROCIN STEARATE Filmtab tablets orother antibacterial drugs in the future.Diarrhea is common problem caused by antibioticswhich usually ends when the antibiotic is discontinued. Sometimesafter starting treatment with antibiotics, patients can develop wateryand bloody stools (with or without stomach cramps and fever) evenas late as two or more months after having taken the last dose ofthe antibiotic. If this occurs, patients should contact their physicianas soon as possible.

LABOR & DELIVERY SECTION.


Labor and Delivery. The effect of erythromycin on labor and delivery is unknown.

NURSING MOTHERS SECTION.


Nursing Mothers. Erythromycin is excreted in human milk. Caution should be exercised when erythromycin is administered toa nursing woman.

OVERDOSAGE SECTION.


OVERDOSAGE. In case of overdosage, erythromycin shouldbe discontinued. Overdosage should be handled with the prompt eliminationof unabsorbed drug and all other appropriate measures should be instituted.Erythromycin is not removed by peritonealdialysis or hemodialysis.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.


Principal Display Panel. Erythrocin(R) Stearate Filmtab(R) (Erythromycin Stearate Tablets, USP) 250mg 28 TabletsNDC 10544-594-28. 250mg 28ct.

PEDIATRIC USE SECTION.


Pediatric Use. See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION.

PRECAUTIONS SECTION.


PRECAUTIONS. General. PrescribingERYTHROCIN STEARATE Filmtab tablets in the absence of proven orstrongly suspected bacterial infection or prophylactic indicationis unlikely to provide benefit to the patient and increases the riskof the development of drug-resistant bacteria.Since erythromycin is principally excreted by the liver,caution should be exercised when erythromycin is administered to patientswith impaired hepatic function. (See CLINICAL PHARMACOLOGY and WARNINGS.)Exacerbation of symptoms of myasthenia gravis and new onset of symptomsof myasthenic syndrome have been reported in patients receiving erythromycintherapy.There have been reportsof infantile hypertrophic pyloric stenosis (IHPS) occurring in infantsfollowing erythromycin therapy. In one cohort of 157 newborns whowere given erythromycin for pertussis prophylaxis, seven neonates(5%) developed symptoms of non-bilious vomiting or irritability withfeeding and were subsequently diagnosed as having IHPS requiring surgicalpyloromyotomy. possible dose-response effect was described withan absolute risk of IHPS of 5.1% for infants who took erythromycinfor 8-14 days and 10% for infants who took erythromycin for 15-21days.4 Since erythromycin may be usedin the treatment of conditions in infants which are associated withsignificant mortality or morbidity (such as pertussis or neonatal Chlamydia trachomatis infections), the benefit of erythromycintherapy needs to be weighed against the potential risk of developingIHPS. Parents should be informed to contact their physician if vomitingor irritability with feeding occurs.Prolonged or repeated use of erythromycin may result in an overgrowthof nonsusceptible bacteria or fungi. If superinfection occurs, erythromycinshould be discontinued and appropriate therapy instituted.When indicated, incision and drainage orother surgical procedures should be performed in conjunction withantibiotic therapy.. Information for Patients. Patients should be counseled that antibacterial drugs including ERYTHROCINSTEARATE Filmtab tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). WhenERYTHROCIN STEARATE Filmtab tablets are prescribed to treat bacterialinfection, patients should be told that although it is common to feelbetter early in the course of therapy, the medication should be takenexactly as directed. Skipping doses or not completing the full courseof therapy may (1) decrease the effectiveness of the immediate treatmentand (2) increase the likelihood that bacteria will develop resistanceand will not be treatable by ERYTHROCIN STEARATE Filmtab tablets orother antibacterial drugs in the future.Diarrhea is common problem caused by antibioticswhich usually ends when the antibiotic is discontinued. Sometimesafter starting treatment with antibiotics, patients can develop wateryand bloody stools (with or without stomach cramps and fever) evenas late as two or more months after having taken the last dose ofthe antibiotic. If this occurs, patients should contact their physicianas soon as possible.. Drug Interactions. Erythromycin use in patients who are receivinghigh doses of theophylline may be associated with an increase in serumtheophylline levels and potential theophylline toxicity. In caseof theophylline toxicity and/or elevated serum theophylline levels,the dose of theophylline should be reduced while the patient is receivingconcomitant erythromycin therapy.Hypotension, bradyarrhythmias, and lactic acidosis have been observedin patients receiving concurrent verapamil, belonging to the calciumchannel blockers drug class.Concomitant administration of erythromycin and digoxin has been reportedto result in elevated digoxin serum levels.There have been reports of increased anticoagulanteffects when erythromycin and oral anticoagulants were used concomitantly. Increased anticoagulation effects due to interactions of erythromycinwith oral anticoagulants may be more pronounced in the elderly.Erythromycin is substrate and inhibitorof the 3A isoform subfamily of the cytochrome p450 enzyme system (CYP3A). Coadministration of erythromycin and drug primarily metabolizedby CYP3A may be associated with elevations in drug concentrationsthat could increase or prolong both the therapeutic and adverse effectsof the concomitant drug. Dosage adjustments may be considered, andwhen possible, serum concentrations of drugs primarily metabolizedby CYP3A should be monitored closely in patients concurrently receivingerythromycin.The following areexamples of some clinically significant CYP3A based drug interactions. Interactions with other drugs metabolized by the CYP3A isoform arealso possible. The following CYP3A based drug interactions have beenobserved with erythromycin products in post-marketing experience:. Ergotamine/dihydroergotamine. Concurrent use of erythromycin and ergotamineor dihydroergotamine has been associated in some patients with acuteergot toxicity characterized by severe peripheral vasospasm and dysesthesia.. Triazolobenzodiazepines(Such as triazolam and alprazolam) and Related Benzodiazepines. Erythromycin has been reported to decreasethe clearance of triazolam and midazolam, and thus, may increase thepharmacologic effect of these benzodiazepines.. HMG-CoA Reductase Inhibitors. Erythromycin has been reported to increaseconcentrations of HMG-CoA reductase inhibitors (e.g., lovastatin andsimvastatin). Rare reports of rhabdomyolysis have been reported inpatients taking these drugs concomitantly.. Sildenafil (Viagra). Erythromycin has been reported to increasethe systemic exposure (AUC) of sildenafil. Reduction of sildenafildosage should be considered. (See Viagra package insert.). There have been spontaneous or publishedreports of CYP3A based interactions of erythromycin with cyclosporine,carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine,methylprednisolone, cilostazol, vinblastine, and bromocriptine.Concomitant administration of erythromycinwith cisapride, pimozide, astemizole, or terfenadine is contraindicated. (See CONTRAINDICATIONS.)In addition, there have been reports of interactionsof erythromycin with drugs not thought to be metabolized by CYP3A,including hexobarbital, phenytoin, and valproate.Erythromycin has been reported to significantly alterthe metabolism of the nonsedating antihistamines terfenadine and astemizolewhen taken concomitantly. Rare cases of serious cardiovascular adverseevents, including electrocardiographic QT/QTc interval prolongation, cardiac arrest, torsades de pointes, andother ventricular arrhythmias, have been observed. (See CONTRAINDICATIONS.) In addition, deaths have been reported rarely with concomitantadministration of terfenadine and erythromycin.There have been post-marketing reports of drug interactionswhen erythromycin was co-administered with cisapride, resulting inQT prolongation, cardiac arrhythmias, ventricular tachycardia, ventricularfibrillation, and torsades de pointes, most likely due to the inhibitionof hepatic metabolism of cisapride by erythromycin. Fatalities havebeen reported. (See CONTRAINDICATIONS).. Drug/Laboratory TestInteractions. Erythromycininterferes with the fluorometric determination of urinary catecholamines.. Carcinogenesis, Mutagenesis,Impairment of Fertility. Long-term (2-year) oral studies conducted in rats with erythromycinbase did not provide evidence of tumorigenicity. Mutagenicity studieshave not been conducted. There was no apparent effect on male orfemale fertility in rats fed erythromycin (base) at levels up to 0.25percent of diet.. Pregnancy. Teratogenic effects. Pregnancy Category B. There is no evidence of teratogenicityor any other adverse effect on reproduction in female rats fed erythromycinbase (up to 0.25 percent of diet) prior to and during mating, duringgestation, 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 ofhuman response, this drug should be used during pregnancy only ifclearly needed.. Labor and Delivery. The effect of erythromycin on labor and delivery is unknown.. Nursing Mothers. Erythromycin is excreted in human milk. Caution should be exercised when erythromycin is administered toa nursing woman.. Pediatric Use. See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION.. Geriatric Use. Elderly patients, particularly those withreduced renal or hepatic function, may be at increased risk for developingerythromycin-induced hearing loss. (See ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION).Elderly patients may be more susceptible to the developmentof torsades de pointes arrhythmias than younger patients. (See ADVERSE REACTIONS).Elderlypatients may experience increased effects of oral anticoagulant therapywhile undergoing treatment with erythromycin. (See PRECAUTIONS- Drug Interactions).Erythrocin Stearate Filmtab (R) Tablets (250 mg) contain 56.7 mg (2.5mEq) of sodium and 5.0 mg (0.1 mEq) of potassium per tablet.Erythrocin Stearate Filmtab (R) Tablets (500mg) contain no sodium and 7.0 mg (0.2 mEq) of potassium per tablet.The geriatric population may respond witha blunted natriuresis to salt loading. This may be clinically importantwith regard to such diseases as congestive heart failure.

PREGNULLNCY SECTION.


Pregnancy. Teratogenic effects. Pregnancy Category B. There is no evidence of teratogenicityor any other adverse effect on reproduction in female rats fed erythromycinbase (up to 0.25 percent of diet) prior to and during mating, duringgestation, 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 ofhuman response, this drug should be used during pregnancy only ifclearly needed.

REFERENCES SECTION.


REFERENCES. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteriathat Grow Aerobically Third Edition. Approved StandardNCCLS Document M7-A3, Vol. 13, No. 25 NCCLS, Villanova PA, December1993.National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disk Susceptibility Tests, Fifth Edition. Approved Standard NCCLS Document M2-A5, Vol. 13,No. 24 NCCLS, Villanova PA, December 1993.Committee on Rheumatic Fever, Endocarditis, and KawasakiDisease of the Council on Cardiovascular Disease in the Young, theAmerican Heart Association: Prevention of Rheumatic Fever. Circulation. 78(4):1082-1086, October 1988.Honein, M.A., et. al.: Infantile hypertrophic pyloric stenosisafter pertussis prophylaxis with erythromycin: case review andcohort study. The Lancet 1999;354 (9196):2101-5.Data on file, Abbott Laboratories.. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteriathat Grow Aerobically Third Edition. Approved StandardNCCLS Document M7-A3, Vol. 13, No. 25 NCCLS, Villanova PA, December1993.. National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disk Susceptibility Tests, Fifth Edition. Approved Standard NCCLS Document M2-A5, Vol. 13,No. 24 NCCLS, Villanova PA, December 1993.. Committee on Rheumatic Fever, Endocarditis, and KawasakiDisease of the Council on Cardiovascular Disease in the Young, theAmerican Heart Association: Prevention of Rheumatic Fever. Circulation. 78(4):1082-1086, October 1988.. Honein, M.A., et. al.: Infantile hypertrophic pyloric stenosisafter pertussis prophylaxis with erythromycin: case review andcohort study. The Lancet 1999;354 (9196):2101-5.. Data on file, Abbott Laboratories.

SPL UNCLASSIFIED SECTION.


To reduce the development of drug-resistantbacteria and maintain the effectiveness of ERYTHROCIN STEARATE Filmtabtablets and other antibacterial drugs, ERYTHROCIN STEARATE Filmtabtablets should be used only to treat or prevent infections that areproven or strongly suspected to be caused by bacteria.

TERATOGENIC EFFECTS SECTION.


Teratogenic effects. Pregnancy Category B. There is no evidence of teratogenicityor any other adverse effect on reproduction in female rats fed erythromycinbase (up to 0.25 percent of diet) prior to and during mating, duringgestation, 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 ofhuman response, this drug should be used during pregnancy only ifclearly needed.

WARNINGS SECTION.


WARNINGS. There have been reports of hepatic dysfunction,including increased liver enzymes, and hepatocellular and/or cholestatichepatitis, with or without jaundice, occurring in patients receivingoral erythromycin products.Therehave been reports suggesting that erythromycin does not reach thefetus in adequate concentration to prevent congenital syphilis. Infantsborn to women treated during pregnancy with oral erythromycin forearly syphilis should be treated with an appropriate penicillin regimen.Clostridium difficile associateddiarrhea (CDAD) has been reported with use of nearly all antibacterialagents, including ERYTHROCIN(R) STEARATE Filmtab(R) Tablets, and may rangein severity from mild diarrhea to fatal colitis. Treatment with antibacterialagents alters the normal flora of the colon leading to overgrowthof C. difficile.C. difficile produces toxins and which contributeto the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, asthese infections can be refractory to antimicrobial therapy and mayrequire colectomy. CDAD must be considered in all patients who presentwith diarrhea following antibiotic use. Careful medical history isnecessary since CDAD has been reported to occur over two months afterthe administration of antibacterial agents.If CDAD is suspected or confirmed, ongoing antibioticuse not directed against C. difficile may need tobe discontinued. Appropriate fluid and electrolyte management, proteinsupplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.Rhabdomyolysis with or without renal impairmenthas been reported in seriously ill patients receiving erythromycinconcomitantly with lovastatin. Therefore, patients receiving concomitantlovastatin and erythromycin should be carefully monitored for creatinekinase (CK) and serum transaminase levels. (See package insert forlovastatin.).