Amdipharm Limited

Erythroped Adult Tablets

Active: Erythromycin

(as Erythromycin Ethylsuccinate) 500 mg tablet

Film - coated tablet

An oval yellow tablet with the Abbott logo impressed on side.

Erythromycin is indicated for the prophylaxis and treatment of infections caused by erythromycin sensitive organisms.

Adults only: For mild to moderate infections 2g/day in divided doses. For severe infections up to 4g/day.

Elderly: No special dosage recommendations.

Known hypersensitivity to macrolide antibiotics.

Use in patients with serious impairment of hepatic function.

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.

Cardiac arrhythmias have been reported rarely in patients receiving erythromycin therapy. There have been isolated reports of chest pain, dizziness and palpitations; however a cause and effect relationship has not been established.

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 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, hexabarbital, 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.

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 in pregnancy in human beings without adverse effect on 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 of cardiac effects such as chest pain, dizziness and palpitations; however, a cause and effect relationship has not been established in either case.

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

There have been reports of pancreatitis and convulsions.

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

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

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

Treatment: Gastric lavage, general supportive measures.

Erythromycin is not removed by peritoneal dialysis or haemodialysis.

Erythromycin ethylsuccinate is less susceptible than erythromycin to the adverse effect of gastric acid. 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.

Erythromycin ethylsuccinate tablets are readily and reliably absorbed when taken orally. The elimination half life is approximately 2 hours. Doses may be administered 2, 3 or 4 times a day.

Long - term (2 years) oral studies conducted in rats with erythromycin base did not provide evidence of tumorigenicity. Mutagenicity studies have not been conducted. There was no apparent effect on male or female fertility in rats fed erythromycin (base) at levels up to 0.25% of diet. There is no evidence of teratogenicity or any other adverse effect on reproduction in female rats fed erythromycin base (up to 0.25% of diet) prior to and during mating, during gestation and through weaning of 2 successive litters. There are, however, no adequate and well - controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used in pregnancy only if it is clearly needed. Erythromycin has been reported to cross the placental barrier in humans, but foetal plasma levels are generally low.

Core

Calcium hydrogen phosphate

Sodium starch glycollate

Starch maize

Povidone

Magnesium stearate

Film coating

Hypromellose

Macrogol 400

Macrogol 8000

Titanium dioxide

Quinoline yellow (E104) lake

Sorbic acid.

None Stated.

24 months.

Do not store above 25°C.

PVC / Aluminium blister packs of 4 or 28 tablets; or securitainers of 50, 100 or 500 tablets.

Not applicable

Amdipharm Limited

Temple Chambers

3 Burlington Road

Dublin 4

Ireland

PA 1142/6/4

27 January 1986/27 January 2001

November 2006