Amdipharm Limited

Erythrocin 500 mg Tablets

Each tablet contains 500mg Erythromycin as Erythromycin Stearate.

For excipients see section 6.1.

Film-coated Tablets

White, elongated tablets with the Abbott monogram on one face.

For the treatment of infections due to micro-organisms sensitive to erythromycin.

For oral administration, when fasting or one hour before meals.

Adults

Mild to moderate infections: 1 to 2 grams daily in divided doses.

Severe infections: A dose of 4 grams daily in divided doses may be given.

Elderly

No special dosage recommendations.

Children

Mild to moderate infections: 30mg/kg/day in divided doses. For severe infections, up to 50mg/kg/day in divided doses may be given.

Known hypersensitivity to macrolide antibiotics.

Use in patients with serious impairment of hepatic function.

Use in conjunction with penicillins and cephalosporins except where specifically warranted

Concomitant administration of erythromycin and any of the following drugs is contraindicated: terfenadine, astemizole, cisapride, pimozide, ergotamine and dihydroergotamine (see section 4.5)

Erythromycin is excreted principally by the liver, so caution should be exercised in administering the antibiotic to patients with impaired hepatic function or concomitantly receiving potentially hepatotoxic agents. Hepatic dysfunction including increased liver enzymes and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been infrequently reported with erythromycin.

The use of erythromycin in patients concurrently taking drugs metabolised by the cytochrome P450 system may be associated with elevations in serum levels of these drugs (see section 4.5). Serum concentrations should be closely monitored in patients receiving erythromycin.

Prolonged or repeated use of erythromycin may result in overgrowth of non-susceptible bacteria. If super-infection occurs, erythromycin should be discontinued and appropriate therapy instituted.

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. 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 therapy needs to be carefully considered against the potential risk of developing IHPS. Parents should be informed to contact their physician if vomiting or irritability occur (see section 4.8).

There have been reports suggesting erythromycin does not reach the foetus in adequate concentrations 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.

As with other broad spectrum antibiotics, pseudomembranous colitis has been

reported rarely with erythromycin (see section 4.8).

Rhabdomyolysis with or without renal impairment has been reported in seriously ill patients receiving erythromycin concomitantly with lovastatin. (See section 4.5)

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

Colchicine toxicity has been reported in patients receiving erythromycin concomitantly with colchicine (see section 4.5).

Laboratory Tests:

Erythromycin interferes with the fluorometric determination of urinary catecholamines.

Erythromycin significantly alters the metabolism of terfenadine and astemizole when taken concomitantly. Rare cases of serious cardiovascular adverse events, including cardiac arrest, Torsade de Pointes, and other ventricular arrhythmias, and also, in the case of terfenadine, death, have been observed. Elevated cisapride levels have been reported in patients receiving erythromycin concomitantly. This may result in QT prolongation and cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and Torsade de Pointes. Similar effects have been observed with concomitant administration of pimozide and other macrolide antibiotics, e.g. clarithromycin.

Post-marketing reports indicate that co-administration of erythromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterised by vasospasm and ischemia of the extremities and other tissues including the central nervous system (see section 4.3).

The concomitant use of the above drugs with erythromycin is contraindicated (see 4.3 Contraindications).

Concurrent use of Erythromycin and 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 erythromycin therapy.

When oral erythromycin is given concurrently with theophylline, there is also a significant decrease in erythromycin serum concentrations. The decrease could result in subtherapeutic concentrations of erythromycin.

The use of erythromycin in patients who are receiving digoxin, may result in potentiation of the effects of digoxin due to reduction in the rate of excretion. Monitoring of serum digoxin levels should be considered.

Rhabdomyolysis with or without renal impairment has been reported in seriously ill patients receiving erythromycin concomitantly with lovastatin.

Erythromycin is an inhibitor of CYP 3A4.The use of erythromycin in patients concurrently taking drugs metabolised by the cytochrome P450 system may be associated with elevations in serum levels of these other drugs. There have been reports of interactions of erythromycin with astemizole, carbamazepine, cyclosporin, hexobarbital, phenytoin, alfentanil, disopyramide, bromocriptine, valproate, tacrolimus, quinidine, cilostazol, methylprednisolone, rifabutin, sildenafil, vinblastine, terfenedine. Serum concentrations of drugs metabolised by the cytochrome P450 system should be monitored closely in patients concurrently receiving erythromycin.

There have been reports of increased anticoagulant effects when erythromycin and oral anticoagulants were used concomitantly.

Triazolobenzodiazepines (such as triazolam and alprazolam) and related benzodiazepines: Erythromycin has been reported to decrease the clearance of triazolam, midazolam, and zopiclone and thus may increase 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 (see section 4.4).

There have been post-marketing reports of colchicine toxicity with concomitant use of erythromycin and colchicine (see section 4.4)

This drug should not be used in pregnancy unless considered essential by a physician. Erythromycin has been used during pregnancy in human beings without adverse effect in offspring. Erythromycin should not be used in women breast feeding infants.

None reported

The most frequently reported side effects of oral erythromycin preparations are gastrointestinal and are dose-related. They include nausea, vomiting, abdominal pain, diarrhoea and anorexia.

As with other macrolides, hepatic dysfunction including increased liver enzymes and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been infrequently reported with erythromycin.

Pseudomembranous colitis has been rarely reported in association with erythromycin therapy, and may range in severity from mild to life threatening (see section 4.4).

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

There have been isolated reports of transient central nervous system side effects including confusion, hallucinations, seizures, tinnitus and vertigo and also of cardiac effects such as chest pain, dizziness and palpitations, however, a cause and effect relationship has not been established in either case.

There have been rare reports of pancreatitis and convulsions.

As with other macrolides, QT prolongation, ventricular tachycardia, and Torsades de Pointes have rarely been reported with erythromycin.

Allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis, erythema multiforme, Stevens-Johnson Syndrome and toxic epidermal necrolysis have rarely been reported.

There have been isolated reports of reversible hearing loss occurring chiefly in patients with renal insufficiency and in patients receiving high doses of erythromycin.

There have been reports of interstitial nephritis coincident with erythromycin use.

Cases of infantile hypertrophic pyloric stenosis (IHPS) occurring in infants following erythromycin therapy have been reported (see section 4.4.). This has been associated with vomiting and irritability with feeding in infants.

Symptoms: Hearing loss, severe nausea, vomiting and diarrhoea.

Treatment: Gastric lavage, general supportive measures.

Erythromycin is not removed by peritoneal dialysis or haemodialysis.

It is absorbed from the small intestine. It is widely distributed throughout body tissues. Little metabolism occurs and only about 5% is excreted in the urine. It is excreted principally by the liver.

Orally administered erythromycin stearate is readily and reliably absorbed. Optimal serum levels of erythromycin are reached when the drug is taken in the fasting state, or immediately before meals.

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

Povidone

Starch, Maize

Magnesium hydroxide

Polacrilin potassium

Macrogol 8000

Macrogol 400

Hypromellose

Sorbic acid.

Not Applicable

5 years

Bottles

Do not store above 25°C. Store in the original container and keep container tightly closed.

Blisters

Do not store above 25°C. Store in the original package and keep container in the outer carton.

PVC/Aluminium foil blister packs containing 10, 15 or 56 tablets, glass bottles or high density polyethylene bottle with urea cap securitainers - of 100 or 500 tablets.

No special requirements

Amdipharm Limited

Temple Chambers

3 Burlington Road

Dublin 4

Ireland

PA 1142/8/3

01/04/77, 01/04/82, 01/04/87, 01/04/92, 01/04/97

November 2006