INDICATIONS:

Gram-positive Organisms: Corynebacterium diphtheriae, Corynebacterium minutissimum, Listeria monocytogenes, Staphylococcus aureus (resistant organisms may emerge during treatment), Streptococcus pneumoniae, Streptococcus pyogenes.

Gram-negative Organisms: Bordetella pertussis, Legionella pneumophila, Neisseria gonorrhoeae.

Other Microorganisms: Chlamydia trachomatis, Entamoeba histolytica, Mycoplasma pneumoniae, Treponema pallidum, Ureaplasma urealyticum.

Upper respiratory tract infections of mild to moderate degree are caused by Streptococcus pyogenes, Streptococcus pneumoniae, or Haemophilus influenzae.

Lower-respiratory tract infections of mild to moderate severity caused by Streptococcus pneumoniae or Streptococcus pyogenes.

Listeriosis caused by Listeria monocytogenes.

Pertussis (whooping cough) caused by Bordetella pertussis.

Respiratory tract infections due to Mycoplasma pneumoniae.

Skin and skin structure infections of mild to moderate severity caused by Streptococcus pyogenes or Staphylococcus aureus.

Diphtheria: Infections due to Corynebacterium diphtheriae , as an adjunct to antitoxin, 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).

Acute pelvic inflammatory disease caused by Neisseria gonorrhoeae

Syphilis caused by Treponema pallidum : ERYTHROMYCIN is an alternate choice of treatment for primary syphilis in patients allergic to the penicillins.

ERYTHROMYCINs are indicated for the 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 nongonococcal urethritis caused by Ureaplasma urealyticum.

Legionnaires' Disease caused by Legionella pneumophila.

Prophylaxis

Prevention of Initial and Recurrent 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. ERYTHROMYCIN is indicated for the treatment of penicillin-allergic patients. The therapeutic dose should be administered for 10 days.

CONTRAINDICATIONS:

ERYTHROMYCIN is contraindicated in patients with known hypersensitivity to this antibiotic and also in patients taking terfenadine, astemizole, pimozide, or cisapride.

CLINICAL PHARMACOLOGY:

 Orally administered ERYTHROMYCIN ethylsuccinate (e.) is readily and reliably absorbed.

ERYTHROMYCIN (e.) diffuses readily into most body fluids. Only low concentrations are normally achieved in the spinal fluid, but passage of the drug across the blood-brain barrier increases in meningitis. In the presence of normal hepatic function, ERYTHROMYCIN is concentrated in the liver and excreted in the bile, Less than 5 percent of the orally administered dose of ERYTHROMYCIN is excreted in active form in the urine.

ERYTHROMYCIN crosses the placental barrier, but fetal plasma levels are low. The drug is excreted in human milk.

MECHANISM OF ACTION: ERYTHROMYCIN acts by inhibition of protein synthesis by binding 50 S ribosomal subunits of susceptible organisms.

WARNINGS: 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.

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.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including ERYTHROMYCIN, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of "antibiotic-associated colitis". After diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.

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 carefull monitored for creatine kinase (CK) and serum transaminase levels.

PRECAUTIONS:

General

Since ERYTHROMYCIN is principally excreted by the liver, caution should be exercised when ERYTHROMYCIN is administered to patients with impaired hepatic function.

There have been reports that ERYTHROMYCIN may aggravate the weakness of patients with myasthenia gravis.

There have been reports of infantile hypertrophic pyloric stenosis (IHPS) occurring in infants following ERYTHROMYCIN therapy.

Prolonged or repeated use of ERYTHROMYCIN may result in an superinfection occurs, ERYTHROMYCIN should be discontinued and appropriate therapy instituted.

Pregnancy: Pregnancy Category B

Nursing Mothers: ERYTHROMYCIN is excreted in human milk. Caution should be exercised when ERYTHROMYCIN is administered to a nursing woman.  

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. Increased anticoagulation effects due to interactions of ERYTHROMYCIN with various oral anticoagulants may be more pronounced in the elderly.

ERYTHROMYCIN is a substrate and inhibitor of the 3A isoform subfamily of the cytochrome p450 enzyme system (CYP3A). Coadministration of ERYTHROMYCIN and a drug primarily metabolized by CYP3A may be associated with elevations in drug concentrations that could increase or prolong both the therapeutic and adverse effects of the concomitant drug. Dosage adjustments may be considered, and when possible, serum concentrations of drugs primarily metabolized by CYP3A should be monitored closely in patients concurrently receiving ERYTHROMYCIN.

The following are examples of some clinically significant CYP3A based drug interactions. Interactions with other drugs metabolized by the CYP3A isoform are also possible. The following CYP3A based drug interactions have been observed with ERYTHROMYCIN products in post-marketing experience:

Ergotamine/dihydroergotamine: 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.

Triazolobenzodiazepines (such as triazolam and alprazolam) and related benzodiazepines: ERYTHROMYCIN has been reported to decrease the clearance of triazolam and midazolam, and thus, may increase the pharmacologic effect of these benzodiazepines.

HMG-CoA Reductase Inhibitors: ERYTHROMYCIN has been reported to increase concentrations of HMG-CoA reductase inhibitors (e.g., lovastatin and simvastatin). Rare reports of rhabdomyolysis have been reported in patients taking these drugs concomitantly.

Sildenafil (Viagra): ERYTHROMYCIN has been reported to increase the systemic exposure (AUC) of sildenafil. Reduction of sildenafil dosage should be considered.

There have been spontaneous or published reports of CYP3A based interactions of ERYTHROMYCIN with cyclosporine, carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine, methylprednisolone, cilostazol, vinblastine, and bromocriptine.

Concomitant administration of ERYTHROMYCIN with cisapride, pimozide, astemizole, or terfenadine is contraindicated. In addition, there have been reports of interactions of ERYTHROMYCIN with drugs not thought to be metabolized by CYP3A, including hexobarbital, phenytoin, and valproate.

ERYTHROMYCIN has been reported to significantly alter the metabolism of the nonsedating antihistamines terfenadine and astemizole when taken concomitantly. Rare cases of serious cardiovascular adverse events, including electrocardiographic QT/QT c interval prolongation, cardiac arrest, torsades de pointes, and other ventricular arrhythmias have been observed. In addition, deaths have been reported rarely with concomitant administration of terfenadine and ERYTHROMYCIN.

There have been post-marketing reports of drug interactions when ERYTHROMYCIN is coadministered with cisapride, resulting in QT prolongation, cardiac arrhythmias, ventricular tachycardia, ventricular fibrillation, and torsades de pointes, most likely due to inhibition of hepatic metabolism of cisapride by ERYTHROMYCIN. Fatalities have been reported.

SIDE EFFECTS:

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.

Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment.

ERYTHROMYCIN has been associated with QT prolongation and ventricular arrhythmias, including ventricular tachycardia and torsades de pointes.

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 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.

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.

DOSAGE AND ADMINISTRATION:

 ERYTHROMYCIN (e.) tablets may be administered without regard to meals.

Children: Age, weight, and severity of the infection are important factors in determining the proper dosage. In mild to moderate infections the usual dosage of ERYTHROMYCIN (e.) for children is 30 to 50 mg/kg/day in equally divided doses every 6 hours. For more severe infections this dosage may be doubled. Doses may also be given three times daily.

Adults: 400 mg ERYTHROMYCIN (e.) every 6 hours is the usual dose. Dosage may be increased up to 4 g per day according to the severity of the infection.  

In the treatment of streptococcal infections, therapeutic dosage of ERYTHROMYCIN (e.) should be administered for at least 10 days. In continuous prophylaxis against recurrences of streptococcal infections in persons with a history of rheumatic heart disease, the usual dosage is 400 mg twice a day.

For treatment of urethritis due to C. trachomatis or U. urealyticum: 800 mg three times a day for 7 days.

For treatment of primary syphilis: Adults: 48 to 64g given in divided doses over a period of 10 to 15 days.

For intestinal amebiasis: Adults: 400 mg four times daily for 10 to 14 days. Children: 30 to 50 mg/kg/day in divided doses for 10 to 14 days.

For use in pertussis: 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.

For treatment of Legionnaires ‘disease: Dose is recommended above (1.6 to 4 g daily in divided doses.)

How Supplied: Protect from light and wet, Store tablets below 30° C.

Reference: PDR 2000, page  440

                  USPDI for Professional Health Care, 2004, Page 1285

                  Martindale 2004, Page 208

Manufactured by Rouz Darou Pharmaceutical Company, TEHRAN, IRAN