ERYTHROCIN ® STEARATE ERYTHROMYCIN STEARATE TABLETS, USP

250 mg tablet: Cellulosic polymers, corn starch, D&C Red No. 7, polacrilin potassium, polyethylene glycol, povidone, propylene glycol, sodium carboxymethylcellulose, sodium citrate, sorbic acid, sorbitan monooleate and titanium dioxide.

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: www.fda.gov/STIC.

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.

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.

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 (CDAD) has been reported with use of nearly all antibacterial agents, including ERYTHROCIN ^® STEARATE Film-coated tablets, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

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.)

Prescribing ERYTHROCIN ^® STEARATE Film-coated tablets in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Since 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).

Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome has been reported in patients receiving erythromycin therapy.

There have been reports of infantile hypertrophic pyloric stenosis (IHPS) occurring in infants following erythromycin therapy. In one cohort of 157 newborns who were given erythromycin for pertussis prophylaxis, seven neonates (5%) developed symptoms of non-bilious vomiting or irritability with feeding and were subsequently diagnosed as having IHPS requiring surgical pyloromyotomy. A possible dose-response effect was described with an absolute risk of IHPS of 5.1% for infants who took erythromycin for 8 to14 days and 10% for infants who took erythromycin for 15 to 21 days. ² Since erythromycin may be used in the treatment of conditions in infants which are associated with significant mortality or morbidity (such as pertussis or neonatal Chlamydia trachomatis infections), the benefit of erythromycin therapy needs to be weighed against the potential risk of developing IHPS. Parents should be informed to contact their physician if vomiting or irritability with feeding occurs.

Prolonged or repeated use of erythromycin may result in an overgrowth of nonsusceptible bacteria or fungi. If super-infection 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.

Observational studies in humans have reported cardiovascular malformations after exposure to drug products containing erythromycin during early pregnancy.

Patients should be counseled that antibacterial drugs including ERYTHROCIN ^® STEARATE Film-coated tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When ERYTHROCIN ^® STEARATE Film-coated tablets are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by ERYTHROCIN ^® STEARATE Film-coated tablets or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Erythromycin interferes with the fluorometric determination of urinary catecholamines.

Long-term oral dietary studies conducted with erythromycin stearate in rats up to 400 mg/kg/day and in mice up to about 500 mg/kg/day (approximately 1 to 2 fold of the maximum human dose on a body surface area basis) did not provide evidence of tumorigenicity. Erythromycin stearate did not show genotoxic potential in the Ames, and mouse lymphoma assays or induce chromosomal aberrations in CHO cells. There was no apparent effect on male or female fertility in rats treated with erythromycin base by oral gavage at 700 mg/kg/day (approximately 3 times the maximum human dose on a body surface area basis).

The effect of erythromycin on labor and delivery is unknown.

Erythromycin is excreted in human milk. Caution should be exercised when erythromycin is administered to a nursing woman.

See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION.

Elderly patients, particularly those with reduced renal or hepatic function, may be at increased risk for developing erythromycin-induced hearing loss (see ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION).

Elderly patients may be more susceptible to the development of torsades de pointes arrhythmias than younger patients (see WARNINGS).

Elderly patients may experience increased effects of oral anticoagulant therapy while undergoing treatment with erythromycin (see PRECAUTIONS - Drug Interactions).

Erythrocin Stearate Film-coated tablets (250 mg) contain 56.7 mg (2.5 mEq) of sodium and 5.0 mg (0.1 mEq) of potassium per tablet.

The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure.

The usual dosage is 250 mg every 6 hours; or 500 mg 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.

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 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

Oral erythromycin suspension 50 mg/kg/day in 4 divided doses for at least 2 weeks. ³

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.

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 or two erythromycin 333 mg tablets orally every 8 hours 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, one 333 mg tablet orally every 8 hours or 250 mg by mouth four times a day should be used for at least 14 days. ³

500 mg of erythromycin by mouth four times a day or two 333 mg tablets orally every 8 hours for at least 7 days. ³

500 mg of erythromycin by mouth four times a day or two 333 mg tablets orally every 8 hours for at least seven days. ³

30 to 40 g given in divided doses over a period of 10 to 15 days.

500 mg Erythrocin Lactobionate-I.V. (erythromycin lactobionate for injection, USP) every 6 hours for 3 days, followed by 500 mg of erythromycin base orally every 12 hours, or 333 mg of erythromycin base orally every 8 hours for 7 days.

Although optimal dosage and duration 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.

Although optimal dosage has not been established, doses utilized in reported clinical data were 1 to 4 g daily in divided doses.

Store below 86°F (30°C).