RiteMED Erythromycin

RiteMED Erythromycin stearate 500 mg film-coated tablet: pink, oval, film-coated tablet with a break line on one surface.
Each film-coated tablet contains: Erythromycin (as stearate), BP 500 mg.

Pharmacologic Category: Antibacterial.
Pharmacology: Pharmacodynamics: Erythromycin inhibits protein synthesis by binding to the 50S ribosomal subunits of susceptible organisms, thereby inhibiting translocation of aminoacyl transfer-RNA and inhibiting polypeptide synthesis. As with other macrolide antibiotics, erythromycin readily penetrates into leukocytes and tissue macrophages.
Erythromycin is usually bacteriostatic, but may be bactericidal in high concentrations especially against highly susceptible organisms.
Pharmacokinetics: Erythromycin is readily absorbed after oral administration. Optimal serum levels of the drug are reached when taken in the fasting state or immediately before meals. Single oral doses of erythromycin generally produce peak serum concentrations within 1-4 hours. Higher peak serum concentrations are achieved when the drug is given four times a day than following single doses. Oral administration of erythromycin 250 mg, four times a day maintains antibacterial serum concentrations of 0.1 to 2 mcg/mL.
Erythromycin is widely distributed into most body tissues and fluids. Following oral administration of the drug, most tissues except the brain, have erythromycin concentrations that are higher and persist longer than serum concentrations. Only low concentrations of the drug (2-13% of serum concentrations) are distributed into the cerebrospinal fluid.
Erythromycin crosses the placenta, achieving fetal serum concentrations 5-20% of maternal serum concentrations. It is distributed into milk in concentrations about 50% plasma concentrations.
The serum half-life (t_1/2) of erythromycin in patients with normal renal function is usually 1.5-2 hours, but may range from 0.8-3 hours. In anuric patients, the serum t_1/2 may be prolonged to 6 hours, but this is not considered to be clinically important.
Erythromycin is partially metabolized by the cytochrome P-450 isoenzyme CYP3A4 in the liver by N-demethylation to inactive, unidentified metabolites. It is excreted mainly in the bile and undergoes intestinal absorption. About 2-5% of an oral dose is excreted in the urine. Only small amounts of erythromycin are removed by hemodialysis.
Microbiology: Antimicrobial Spectrum of Activity: Erythromycin is usually active against most strains of the following microorganisms both in vitro and in clinical infections: See Table 1.

Click on icon to see table/diagram/image

Erythromycin has demonstrated in vitro activity against the following microorganisms; however, clinical significance is unknown: Gram-positive organisms: Viridans group streptococci.
Gram-negative organisms: Moraxella catarrhalis.
It is suggested to carry out susceptibility tests.

For the treatment of the following infections caused by susceptible microorganisms: Upper respiratory tract infections: Laryngitis, pharyngitis, sinusitis, tonsilitis, peritonsillar abscess, otitis media, otitis externa, mastoiditis, secondary infections in influenza and common colds.
Lower respiratory tract infections: Acute and chronic bronchitis, bronchiectasis, pneumonia, tracheitis, Legionnaire's disease.
Gastrointestinal infections: Cholecystitis, staphylococcal enterocolitis, intestinal amebiasis (extraenteric amebiasis requires treatment with other agents).
Genitounitary infections: Urethritis, gonorrhea, primary syphilis, lymphogranuloma venereum, prostatitis.
Skin and skin structure infections: Boils, carbuncles, paronychia, abscesses, pustular acne, impetigo, cellulitis, erysipelas, erythrasma.
Other infections: Blepharitis, gingivitis, Vincent's angina, listeriosis, osteomyelitis, scarlet fever, diphtheria (as an adjunct to antitoxin, to prevent establishment of carriers, and to eradicate the organism in carriers).
As prophylaxis for the following infections caused by susceptible microorganisms: Pre- and post-operative trauma, burns, rheumatic fever, pertussis.

To be taken orally on an empty stomach or immediately before meals.
Usual Adult Dose: 250 mg given every 6 hours or 500 mg every 12 hours.
For severe infections: Dosage may be increased up to 4 g per day. However, a twice a day dosing schedule is not recommended when dosage greater than 1 g per day are administered.
For streptococcal infections: A therapeutic dosage of erythromycin should be administered for at least 10 days.
Recommended Dose in Adults for Specific Infections: See Table 2.

Click on icon to see table/diagram/image

Dose in Children (who can swallow tablets whole): 30 to 50 mg/kg body weight/day orally in 3 or 4 divided doses.
For more severe infections, this dosage may be doubled but should not exceed 4 g per day.
For prophylaxis against bacterial endocarditis in children allergic to penicillin with congenital heart disease, or rheumatic or other acquired valvular heart disease when undergoing dental procedures or surgical procedures of the upper respiratory tract: 20 mg/kg body weight orally 1.5 to 2 hours before the procedure, then 10 mg/kg body weight every 6 hours for 8 doses.
Or, as prescribed by a physician.

Clinical manifestations of erythromycin overdose include hearing loss, severe nausea, vomiting and diarrhea.
Treatment may include gastric lavage and general supportive measures.
Erythromycin serum levels are not appreciably altered by hemodialysis or peritoneal dialysis.

Hypersensitivity to erythromycin or any component of the product.
Severe hepatic impairment.
In patients taking astemizole, terfenadine, cisapride, pimozide, and ergotamine or dihydroergotamine.

Concomitant use of CYP3A inhibitors like nitroimidazole-antifungals can cause increased serum levels of erythromycin and probably increase the risk of cardiac arrhythmia. Concurrent use of diltiazem or verapamil with erythromycin should be avoided by persons at risk for heart irregularities or those with long QT manifestations.

Cardiac Arrhythmias: Erythromycin should be used with caution in patients with a history of arrhythmias or a predisposition to QT interval prolongation. Certain medications may also increase the risk of arrhythmias (see Interactions).
Hepatic Impairment: Hepatic dysfunction including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been reported with erythromycin.
Since erythromycin is primarily excreted by the liver, the drug should be used with caution in patients with hepatic impairment or impaired biliary excretion or in those concomitantly receiving potentially hepatotoxic agents.
Clostridium difficile-associated diarrhea: This has been observed with the used of nearly all antibacterial agents, including erythromycin, and may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea following administration of antibacterial agents.
Rhabdomyolysis: Rhabdomyolysis with or without renal impairment has been reported in seriously ill patients receiving erythromycin concomitantly with lovastatin. Therefore, patients receiving concomitant erythromycin and lovastatin should be monitored carefully for creatinine kinase and serum transaminase levels.
Myasthenia gravis: Erythromycin may aggravate muscle weakness in patients with myasthenia gravis.
Syphilis: There have been reports suggesting that erythromycin does not reach the fetus in adequate concentrations to prevent congenital syphillis. Infants born to women treated during pregnancy with oral erythromycin for early syphillis should be treated with an appropriate penicillin regimen.
Patients should have a serologic test for syphillis before receiving erythromycin as treatment for gonorrhea and a follow-up serologic test for syphillis after 3 months.
Other Precautions: Erythromycin has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.
There have been reports of infantile hyperthropic pyloric stenosis (IHPS) occurring in infants after erythromycin treatment (see Use in Children as follows).
Prescribing erythromycin 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.
When indicated, incision and drainage or other surgical procedures should be performed in conjunction with antibiotic treatment.
As with other antibacterial drugs, long term or repeated use may result in overgrowth of non-susceptible organisms, including fungi.
Renal Impairment: Since renal excretion is not a major route of elimination of erythromycin and prolongation of serum t_1/2 of the drug is not clinically important, dosage modification is not necessary in patients with renal impairment.
Hepatic Impairment: As erythromycin is primarily excreted by the liver, caution should be exercised when administering erythromycin to patients with hepatic impairment.
Effects on Ability to Drive and Use Machines: None reported.
Use in Children: 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. Since erythromycin may be used in the treatment of conditions in infants which are associated with significant mortality or morbidity (such as pertussis or Chlamydia), the benefit of erythromycin treatment 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.

Pregnancy: (Pregnancy Category B) Erythromycin has been reported to cross the placental barrier in humans, but fetal plasma levels are generally low.
There are no adequate and well-controlled studies in pregnant women, and the drug should be used during pregnancy only when clearly needed. However, oral erythromycin is used for the treatment of urogenital chlamydial infections in pregnant women.
Lactation: Since erythromycin is excreted in breast milk, the drug should be used with caution in breastfeeding women.

The most frequent side effects of oral erythromycin are gastrointestinal effects and are usually dose-related.
Gastrointestinal: Upper abdominal pain/discomfort, abdominal cramping, heartburn, nausea, vomiting, diarrhea, pancreatitis, stomatitis, anorexia, infantile hypertrophic pyloric stenosis, melena, pruritus ani, pseudomembranous colitis, hairy tongue (associated with long-term treatment).
Body as a Whole: Chest pain, fever, malaise, hypothermia (in children).
Dermatologic/Hypersensitivity Reactions: Allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis; rash/maculopapular rashes, pruritus, exanthema, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.
Cardiovascular: Prolongation of the QT interval and development of ventricular arrhythmias, including atypical ventricular tachycardia (torsades de pointes), palpitations, hypotension.
Nervous System: There have been isolated reports of transient CNS side effects including confusion, hallucinations, seizures/convulsions, vertigo, and tinnitus; however, a causal relationship has not been established; psychoses (rarely).
Hepatobiliary: Cholestatic hepatitis, hepatocellular hepatitis, jaundice, hepatic dysfunction/hepatic failure, hepatomegaly, increased liver enzyme values/abnormal liver function test results; raised serum bilirubin.
Genitounitary: Interstitial nephritis.
Hematologic: Agranulocytosis, eosinophilia.
Special Senses: There have been isolated reports of reversible hearing loss particularly in patients with renal impairment or in those receiving high doses of erythromycin.
Other Adverse Effects: Aggravation of muscular weakness in myasthenia gravis patients; superinfection with resistant organisms.

See Table 3.

Click on icon to see table/diagram/image

Interference with Laboratory Tests: Erythromycin may falsely elevate concentrations of urinary catecholamines, 17-hydroxycorticosteroids, and 17-ketosteroids.
The drug may interfere with colorimetric assays resulting in falsely elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations. Falsely elevated AST concentrations without liver injury may result due to erroneous measurement of unidentified metabolites of erythromycin in colorimetric determinations.
Erythromycin may decrease serum folate assay results if a microbiologic method is used since the drug can inhibit the growth of Lactobacillus casei; results are unaffected if the chromatographic procedure of Landon is used.
The presence of erythromycin in the blood may interfere with the etiologic diagnosis of mycoplasma pneumonia by masking a rise in the titer of tetrazolium reduction inhibition neutralizing antibody to Mycoplasma pneumoniae.

Store at temperatures not exceeding 30°C.

Macrolides

J01FA01 - erythromycin ; Belongs to the class of macrolides. Used in the systemic treatment of infections.

Rx