Ilosone 200/Ilosone DS

Ilosone 200: Ilosone 200 is Erythromycin 2-(ethylsuccinate) (41342-53-4) C₄₃H₇₅NO₁₆ (862.1). Potency equivalent (C₃₇H₆₇NO₁₃)/mg calculated on the anhydrous basis. This cherry flavored product has a characteristic sweet fruit taste and appears as a pink powder that turns to a pink colored suspension upon reconstitution.
Each 5 mL (1 teaspoonful) of reconstituted suspension contains: Erythromycin (as ethylsuccinate) 200 mg.
Ilosone DS 250 mg/5 mL Suspension: A red or pinkish-red coloured, homogenous aqueous suspension having a pleasant cherry guarana odour and taste.
Each 5 mL of cherry flavoured suspension contains: Erythromycin (as estolate), EP 250 mg.

Antibacterial (Macrolide).
Pharmacology: Ilosone DS: Orally administered erythromycin estolate is readily and reliably absorbed. Because of acid stability, serum levels are comparable whether the estolate is taken in the fasting state or after food. After a single 250 mg dose, blood concentrations average 0.29, 1.2 and 1.2 mg/L respectively at 2, 4 and 6 hours. Following a 500 mg dose, blood concentrations average 3, 1.9 and 0.7 mg/L respectively at 2, 6 and 12 hours.
After oral administration, serum antibiotic levels consist of erythromycin base and propionyl erythromycin ester. The propionyl ester continuously hydrolyzes to the base form of erythromycin to maintain an equilibrium ratio of approximately 20% base and 80% ester in serum.
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 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. The effect of hepatic dysfunction of excretion of erythromycin by the liver into the bile is not known. After oral administration, less than 5% of the administered dose can be recovered as the active form in the urine.
Erythromycin crosses the placental barrier but fetal plasma levels are low. The drug is excreted in human milk.
Pharmacokinetics: Ilosone 200: Orally administered erythromycin ethylsuccinate suspensions and film-coated tablets are readily and reliably absorbed. Comparable serum levels of erythromycin are achieved in the fasting and nonfasting states. Erythromycin 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; the effect of hepatic dysfunction on excretion of erythromycin by the liver into the bile is not known. 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.
Microbiology: Ilosone DS: Erythromycin inhibits protein synthesis without affecting nucleic acid synthesis. Some strains of Haemophilus influenzae and staphylococci have demonstrated resistance to erythromycin. Some strains of H. influenzae that are resistant in vitro to erythromycin alone are susceptible to erythromycin and sulfonamides used concomitantly. If the Bauer-Kirby method of disk susceptibility testing is used, a 15-μg erythromycin disk should give a zone diameter of at least 18 mm when tested against an erythromycin-susceptible organism.
Antagonism has been demonstrated between clindamycin and erythromycin.
Ilosone 200: Erythromycin acts by inhibition of protein synthesis by binding 50S ribosomal subunits of susceptible organisms. It does not affect nucleic acid synthesis. Antagonism has been demonstrated in vitro between erythromycin and clindamycin, lincomycin, and chloramphenicol. Many strains of Haemophilus influenzae are resistant to erythromycin alone but are susceptible to erythromycin and sulfonamides used concomitantly. Staphylococci resistant to erythromycin may emerge during a course of therapy. Erythromycin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in Indications/Uses section.

Ilosone DS: Erythromycin (Ilosone) is indicated in children and adults for the treatment of the following conditions. Culture and susceptible testing should be done.
Upper respiratory tract infections of mild to moderate severity caused by Streptococcus pyogenes, viridans group streptococci, Streptococcus pneumoniae, or Haemophilus influenzae (when Erythromycin is used concomitantly with adequate doses of sulfonamides, since not all strains of H. influenzae are susceptible at the erythromycin concentrations ordinarily achieved).
Lower respiratory tract infections of mild to moderate severity caused by S. pyogenes, S. pneumoniae, Mycoplasma pneumoniae or Legionella pneumophila.
Primary syphilis caused by Treponema pallidum: Erythromycin is an alternate choice of treatment for primary syphilis in penicillin allergic patients. In primary syphilis, spinal fluid examination should be done before treatment and as part of follow up after therapy.
Diphtheriae: As an adjunct to antitoxin, to prevent establishment of carriers and to eradicate the organism in the carriers.
Erythrasma: In the treatment of infections due to Corynebacterium minutissimum.
Intestinal amebiasis caused by Entamoeba histolytica: Extraenteric amebiasis requires treatment with other agents.
Infections due to Listeria monocytogenes: Skin and soft tissue infections of mild to moderate severity caused by S. pyogenes or Staphylococcus aureus (resistant staphylococci may develop during treatment).
Pertussis caused by Bordetella pertussis: Erythromycin is effective in eliminating the organism from the nasopharynx of infected individuals, rendering them noninfectious. Some clinical studies suggest that erythromycin may be helpful in the prophylaxis of pertussis in exposed susceptible individuals.
Conjunctivitis of the newborn, pneumonia of infancy, the urogenital infections during pregnancy caused by Chlamydia trachomatis (see Precautions): When tetracyclines are contraindicated or not tolerated, erythromycin is indicated for the treatment of adults with uncomplicated urethral endocervical or rectal infections due to C. trachomatis.
Ilosone 200: For the treatment of upper and lower respiratory tract, skin and soft tissue infections of mild to moderate severity.

Ilosone DS: Adults: The usual dosage is 250 mg every 6 hours. This may be increased up to 4 g/day or more according to the severity of the infection.
Children: Age, weight, and severity of the infection are important factors in determining the proper dosage. The usual regimen is 30 to 50 mg/kg/day in divided doses. For more severe infections, this dosage may be doubled.
If the administration is desired on twice-a-day schedule in either adults or children, one-half of the total daily dose may be given every 12 hours. Twice-a-day dosing is not recommended when doses larger than 1 g daily are administered.
Streptococcal Infections: For the treatment of Streptococcal pharyngitis and tonsillitis, the usual dosage range is 20 to 50 mg/kg/day in divided doses. (See table.)

Click on icon to see table/diagram/image

In the treatment of group A β-hemolytic streptococcal infections, a therapeutic dosage of erythromycin should be administered for at least 10 days.
In continuous prophylaxis of streptococcal infections in persons with a history of rheumatic heart disease, the dosage is 250 mg twice a day. For prophylaxis against bacterial endocarditis in penicillin allergic patients with congenital heart disease or rheumatic or other acquired valvular heart disease when undergoing dental procedures or surgical procedures of the upper respiratory tract. The dosage schedule for adults is 1 g (20 mg/kg for children) orally one hour before the procedure and then 500 mg (10 mg/kg for children) orally 6 hours later.
Primary Syphilis: A regimen of 20 g of erythromycin estolate in divided doses over a period of 10 days has been shown to be effective in the treatment of primary syphilis.
Dysenteric Amebiasis: Dosage for adults is 250 mg 4 times daily for 10 to 14 days; for children, 30 to 50 mg/kg/day in divided doses for 10 to 14 days.
Pertussis: Although optimum dosage and duration have not been established, dosage of erythromycin utilized in reported clinical studies was 40 to 50 mg/kg/day, given in divided doses for 5 to 14 days.
Legionnaires' Disease: Although optimum doses have not been established, doses utilized in reported clinical data were those recommended above (1 to 4 g erythromycin estolate daily in divided doses).
Conjunctivitis of the Newborn Caused by C. trachomatis: Oral erythromycin suspension, 50 mg/kg/day in 4 divided doses for at least 2 weeks.
Pneumonia of Infancy Caused by C. trachomatis: Although the optimum 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 C. trachomatis: Although the optimum dose and duration of therapy have not been established, the suggested treatment is erythromycin, 500 mg orally 4 times a day for at least 7 days. For women who cannot tolerate this regimen, a decreased dose of 250 mg orally 4 times a day should be used for at least 14 days.
For adults with uncomplicated urethral, endocervical, or rectal infections caused by C. trachomatis in whom tetracyclines are contraindicated or not tolerated, 500 mg orally 4 times a day for at least 7 days.
Ilosone 200: Children: 1-2 yrs, 1.25 to 2.5 mL.
2-6 yrs, 2.5 to 5.0 mL.
6-12 yrs, 5.0 to 7.5 mL.
Two to three times a day or as prescribed by the physician.

Ilosone DS: Signs and Symptoms: Symptoms of oral overdose of erythromycin estolate may include nausea, vomiting, epigastric distress and diarrhea. The severity of the epigastric distress and the diarrhea are dose related. Reversible mild acute pancreatitis has been reported. Hearing loss, with or without tinnitus and vertigo, may occur, especially in patients with renal or hepatic insufficiency.
Treatment: In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in the patient.
Unless 5 times the normal single dose of erythromycin estolate has been ingested, gastrointestinal decontamination should not be necessary. An accidental ingestion of erythromycin should not be predicted to have minimal toxicity unless there is a good approximation of how much was ingested and unless only a single medication was involved.
Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which in many cases is more effective than emesis or lavage, consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal.
Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of erythromycin estolate.
Ilosone 200: Overdose and Treatment: 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.

Ilosone DS: Erythromycin is contraindicated in patients with known hypersensitivity to the antibiotic.
Erythromycin is contraindicated in patients taking terfenadine, astemizole, cisapride, pimozide, verapamil or diltiazem (see Drug Interactions under Interactions).
Ilosone 200: Erythromycin is contraindicated to patients with known hypersensitivity to this antibiotic. Erythromycin is contraindicated in patients taking terfenadine, astemizole, pimozide, or cisapride.

Ilosone DS: Hepatic dysfunction with or without jaundice has occurred chiefly in adults, in association with erythromycin estolate administration. It may be accompanied by malaise, nausea, vomiting, abdominal colic and fever. In some instances, severe abdominal pain may simulate an abdominal surgical emergency. If the previously mentioned findings occur, discontinue erythromycin estolate promptly.
Erythromycin estolate is contraindicated for patients with known history of sensitivity to this drug and for those with pre-existing liver disease.
The administration of erythromycin estolate has been associated with the infrequent occurrence of cholestatic hepatitis. Laboratory findings have been characterized by abnormal hepatic function test values, peripheral eosinophilia, and leukocytosis. Symptoms may include malaise, nausea, vomiting, abdominal cramps, and fever. Jaundice may or may not be present. In some instances severe abdominal pain may simulate the pain of biliary colic, pancreatitis, perforated ulcer, or an acute abdominal surgical problem. In other instances clinical symptoms and results of liver function tests have resembled findings in extrahepatic obstructive jaundice.
Initial symptoms have developed in some cases after a few days of treatment but generally have followed 1 or 2 weeks of continuous therapy. Symptoms reappear promptly, usually within 48 hours after the drug is readministered to sensitive patients. The symptoms seem to result from a form of sensitization, occurs chiefly in adults, and has been reversible when medication is discontinued.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including erythromycin estolate, and may range in severity from mild to life-threatening. Therefore, it is important to consider the diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, appropriate measures should be taken.
Rhabdomyolysis with or without renal impairment has been reported in patients receiving erythromycin concomitantly with HMG-CoA reductase inhibitors such as lovastatin and simvastatin. Therefore, patients receiving concomitant HMG-CoA reductase inhibitors and erythromycin should be very carefully monitored for creatine kinase (CK) and serum transaminase levels.
Ilosone 200: Concomitant use of CYP3A inhibitors like nitroimidazole antifungals can cause increased serum levels of erythromycin and probably increase the risk of cardiac arrhythmia. However, concurrent use of diltiazem or verapamil with erythromycin should be avoided by persons at risk for heart irregularities or those with long QT manifestations.

Ilosone DS: General: Since erythromycin is excreted principally by the liver, caution should be exercised in administering the antibiotic to patients with impaired hepatic function.
When indicated, incision and drainage or other surgical procedures should be performed in conjunction with antibiotic therapy.
Carcinogenesis/Mutagenesis: Two year oral studies conducted in rats with erythromycin did not provide evidence of tumorigenicity or mutagenicity.
Use in Pregnancy & Lactation: See USE IN PREGNANCY & LACTATION section for further information.
Use in children: Several reports of infantile hypertrophic pyloric stenosis have been reported in newborn infants receiving various erythromycin products, including erythromycin estolate. Erythromycin should be used cautiously in the first three months of life. (See Use in Pregnancy & Lactation, Indications/Uses and Dosage and Administration.)
Ilosone 200: Erythromycin should not be given to patients with impaired liver function or to patients who have developed jaundice or other symptoms of liver toxicity during previous treatment with erythromycin.

Ilosone DS: Use in Pregnancy: Reproduction studies have been performed in rats, mice and rabbits, using erythromycin and its various salts and esters of doses several times the usual human dose. No evidence of impaired fertility or harm to the fetus that appeared to be related to erythromycin was reported in these studies. There are however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response this drug should be used during pregnancy only if clearly needed.
Ilosone 200: Pregnancy: Pregnancy Category B. There is no evidence of teratogenicity or any other adverse effect on reproduction in female rats fed erythromycin base by oral gavage at 350 mg/kg/day (approximately twice the maximum recommended human dose on a body surface area) prior to and during mating, during gestation, and through weaning. No evidence of teratogenicity or embryotoxicity was observed when erythromycin base was given by oral gavage to pregnant rats and mice at 700 mg/kg/day and to pregnant rabbits at 125 mg/kg/day (approximately 1-3 times the maximum recommended human dose).
Labor and Delivery: The effect of erythromycin estolate on labor and delivery is unknown.
Nursing Mothers: Erythromycin is excreted in human milk. Caution should be exercised when erythromycin is administered to nursing women.

Ilosone DS: The most frequent side effects of erythromycin preparations are gastrointestinal (eg. abdominal cramping and discomfort) and are dose related. Nausea, vomiting, and diarrhea occur frequently with usual oral doses. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see Warnings).
During prolonged or repeated therapy, there is a possibility of overgrowth of nonsusceptible bacteria or fungi. If such infections arise, the drug should be discontinued and appropriate therapy instituted.
Mild allergic reactions such as urticaria and other skin rashes have occurred. Serious allergic reactions, including anaphylaxis, have been reported.
There have been isolated reports of hearing loss and/or tinnitus in patients receiving erythromycin. The ototoxic effect of the drug is usually reversible with drug discontinuance; however, in rare instances involving intravenous administration, the ototoxic effect has been irreversible. Ototoxic effects occur chiefly in patients with renal or hepatic insufficiency and in patients receiving high doses of erythromycin.
Very rarely erythromycin has been associated with QT prolongation and ventricular arrhythmias, including ventricular tachycardia and torsades de pointes.
Several reports of infantile hypertrophic pyloric stenosis have been reported in newborn infants receiving various erythromycin products, including erythromycin estolate. Erythromycin should be used cautiously in the first three months of life.

Ilosone DS: Drug/Laboratory Interactions: Erythromycin may interfere with AST (SGOT) determinations if a zone-fast violet B or diphenylhydrazine colorimetric determinations are used.
Erythromycin interferes with the fluorometric determination of urinary catecholamine.
Drug Interactions: Erythromycin significantly alters the metabolism of terfenadine when taken concomitantly. Rare cases of serious cardiovascular adverse events, including death, cardiac arrest, torsades de pointes, and other ventricular arrhythmias, have been observed (see Contraindications).
Since probenecid inhibits tubular reabsorption of erythromycin in animals, it prolongs maintenance of plasma levels.
Lincomycin or clindamycin therapy should be avoided in treatment of infections due to erythromycin resistant organisms.
Erythromycin use in patients who are receiving high doses of theophylline may be associated with 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 this drug interaction may be more pronounced in the elderly.
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.
Erythromycin has been reported to decrease the clearance of triazolam and midazolam and thus may increase the pharmacologic effect of these benzodiazepines.
The use of erythromycin in patients concurrently taking drugs metabolized by the cytochrome P450 system may be associated with elevations in serum concentrations of these other drugs. Elevated serum concentrations of the following drugs have been reported or may occur when administered concurrently with erythromycin, carbamazepine, cyclosporine, hexobarbital, phenytoin, alfentanil, disopyramide, quinidine, HMG-CoA reductase inhibitors such as simvastatin and lovastatin, bromocriptine, PDE5 inhibitors such as sildenafil, tadalafil, and vardenafil. Serum concentrations, when available and appropriate, of these and other drugs metabolized by the cytochrome P450 system should be monitored closely in patients concurrently receiving erythromycin, and dosage adjustments made as needed.
Elevated cisapride levels have been reported in patients receiving erythromycin and cisapride concomitantly. This may result in QT prolongation and lead to serious cardiac arrhythmias, including torsades de pointes, ventricular tachycardia, and ventricular fibrillation. Fatalities have been reported. (See Contraindications.)
Ilosone 200: 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 as follows). There have been postmarketing 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 as follows). 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.)
Theophylline: 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. There have been published reports suggesting that when oral erythromycin is given concurrently with theophylline there is a decrease in erythromycin serum concentrations of approximately 35%. The mechanism by which this interaction occurs is unknown. The decrease in erythromycin concentrations due to co-administration of theophylline could result in subtherapeutic concentrations of erythromycin.
Verapamil: Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving concurrent verapamil, belonging to the calcium channel blockers drug class.
Digoxin: Concomitant administration of erythromycin and digoxin has been reported to result in elevated digoxin serum levels.
Anticoagulants: 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: Post-marketing reports indicate that co-administration of erythromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system. Concomitant administration of erythromycin with ergotamine or dihydroergotamine is contraindicated.
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/QTc 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 co-administered 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.

Ilosone 200: Direction for Reconstitution: To make up to 60 mL, add 42 mL of water and shake until all the powder are evenly suspended. The reconstituted suspension is stable for 7 days at temperatures not exceeding 30°C and 14 days when refrigerated (2-8°C).

Store at temperatures not exceeding 30°C.
Ilosone 200: Protect from light.

Macrolides

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

Rx