SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Erythromycin 250mg Tablets

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Each tablet contains 250mg Erythromycin.

For a full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Gastro-resistant tablets;

Reddish orange coloured round biconvex tablets, plain on both sides. They are made Gastro-resistant by enteric coating.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the prophylaxis and treatment of infections caused by Erythromycin-sensitive organisms.

Erythromycin has been shown to have in-vitro activity against the following microorganisms:

Gram positive cocci: Staphylococci and Streptococci.

Haemophilus influenzae, L-forms, Neisseria, Mycoplasma pneumoniae Legionella pneumophila, Branhamella catarrhalis, Bordetella pertussis Corynebacterium diphtheriae (as an adjunct to antitoxin)

Treponema pallidum, Chlamydia trachomatis, Ureaplasma urealytica Clostridia, Campylobacter.

Clinical inflations:

1. Upper respiratory tract infections: Tonsillitis, peritonsillar abscess, pharyngitis, laryngitis, sinusitis, secondary infections in influenza and common colds.

2. Lower respiratory tract infections: Tracheitis, acute and chronic bronchitis, pneumonia (lobar pneumonia, bronchopneumonia, primary atypical pneumonia), bronchiectasis, Legionnaire's disease

3.    Ear infections: Otitis media and otitis externa, mastoiditis.

4.    Eye infections: Blepharitis

5.    Oral/dental infections: Gingivitis, Vincent's angina

6.    Skin and soft tissue infections: Boils and carbuncles, paronychia, abscesses, ustular acne, impetigo, cellulitis, erysipelas

7.    Gastro-intestinal infections: cholecystitis, staphylococcal enterocolitis

8.    Prophylaxis: pre- and post- operative trauma, burns, rheumatic fever

9.    Other infections: osteomyelitis, urethritis, gonorrhoea, syphilis, lymphogranuloma venereum, diphtheria, prostatitis, scarlet fever

Note: Erythromycin has also proved to be of value in endocarditis and septicaemia, but in these conditions initial administration of erythromycin lactobionate by the intravenous route is advisable.

4.2 Posology and method of administration

For Oral Use

Adults: Usual dosage is 250mg every four to six hours. This may be increased to 4g or more per day according to the severity of the infection.

Children: Age, weight and severity of the infection are important factors in determining the correct dosage.

The usual regimen is 30mg/kg/day in divided doses. For more severe infections, this dosage should be 50mg/kg/day.

If administration on a twice daily schedule is desirable in adults or children, one half of the total daily dose may be given every 12 hours, one hour before meals.

Elderly:No special dosage recommendations.

4.3 Contraindications

Known hypersensitivity to erythromycin. Erythromycin is contraindicated in patients taking simvastatin, tolterodine, mizolastine, amisulpride, astemizole, terfenadine, and cisapride or pimozide.

Erythromycin is contraindicated with ergotamine and dihydroergotamine.

4.4 Special warnings and precautions for use

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/or cholestatic hepatitis, with or without jaundice, has been infrequently reported with erythromycin.

Caution should be exercised in administering this antibiotic to patients with renal impairment and patients with a predisposition to QT interval prolongation. This product should not be used in patients with porphyria.

Care should be taken when administering this product to patients who are pregnant or breastfeeding.

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.

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

Erythromycin interferes with the fluorometric determination of urinary catecholamines.

As with other broad-spectrum antibiotics, pseudomembranous colitis has been reported rarely with erythromycin.

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

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant use of erythromycin with simvastatin, tolterodine, mizolastine, amisulpride, terfenadine or astemizole is likely to result in an enhanced risk of cardio toxicity with these drugs. The concomitant use of erythromycin with either simvastatin, tolterodine, mizolastine, amisulpride, astemizole or terfenadine is therefore contra-indicated.

The metabolism of terfenadine and astemizole is significantly altered when either are taken concomitantly with erythromycin. Rare cases of serious cardio-vascular events have been observed, including torsades de pointes, other ventricular arrhythmias and cardiac arrest. Death has been reported with the terfenadine/erythromycin combination.

Elevated cisapride levels have been reported in patients receiving erythromycin and cisapride concomitantly. This may result in QT prolongation and cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and torsades de pointes.

Similar effects have been observed with concomitant administration of pimozide and clarithromycin, another macrolide antibiotic.

Concurrent use of erythromycin and ergotamine or dihydroergotamine has been associated in some patients with acute ergot toxicity, characterised by the rapid development of severe peripheral vasospasm and dysaesthesia.

Increases in serum concentrations of the following drugs metabolised by the cytochrome P450 system may occur when administered concurrently with erythromycin: alfentanil, astemizole, bromocriptine, carbamazepine, cyclosporin, digoxin, dihydroergotamine, disopyramide, ergotamine, hexobarbitone, midazolam, phenytoin, quinidine, tacrolimus, terfenadine, theophylline, triazolam, valproate, and warfarin. Appropriate monitoring should be undertaken and dosage should be adjusted as necessary. Erythromycin has also been reported to potentiate the effects of corticosteroids.

Erythromycin has been reported to decrease the clearance of zopiclone and thus may increase the pharmacodynamic effects of this drug.

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.

4.6 Fertility, pregnancy and lactation

Erythromycin has been in widespread use for a number of years without apparent ill consequence. Animal studies have shown no hazard.

Erythromycin has been reported to cross the placental barrier in humans, but foetal plasma levels are generally low.

Erythromycin is excreted in breast milk, therefore, caution should be exercised when erythromycin is administered to a nursing mother.

4.7. Effects on Ability to Drive and Use Machines

None stated.

4.8. Undesirable Effects

Occasional side effects such as nausea, abdominal discomfort, vomiting and diarrhoea may be experienced. Reversible hearing loss associated with doses of erythromycin usually greater than 4g per day has been reported. Allergic reactions are rare and mild, although anaphylaxis has occurred. Skin reactions ranging from mild eruptions to erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis have rarely been reported. There are no reports implicating erythromycin products with abnormal tooth development, and only rare reports of damage to the blood, kidneys or central nervous system.

Cardiac arrhythmias have been very rarely reported 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.

Symptoms of hepatitis, hepatic dysfunction and/or abnormal liver function test results may occur.

4.9. Overdose

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

Treatment: gastric lavage, general supportive measures.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic Group: Macrolides- ATC Code: J01FA01

Erythromycin exerts its antimicrobial action by binding to the 50S ribosomal sub-unit of susceptible microorganisms and suppresses protein synthesis. Erythromycin is usually active against most strains of the following organisms both in vitro and in clinical infections:

Gram-positive bacteria - Listeria monocytogenes, Corynebacterium diphtheriae (as an adjunct to antitoxin), Staphylococci spp, Streptococci spp (including Enterococci/

Gram-negative bacteria - Haemophilus influenzae, Neisseria meningitidis, Neisseria gonorrhoeae, Legionella pneumophila, Moraxella (Branhamella) catarrhalis, Bordetellapertussis, Campylobacter spp.

Mycoplasma - Mycoplasma pneumoniae, Ureaplasma urealyticum

Other organisms - Treponema pallidum, Chlamydia spp, Clostridia spp, L-forms, the agents causing trachoma and lymphogranuloma venereum

Note: The majority of strains of Haemophilus influenzae are susceptible to the concentrations reached after ordinary doses.

5.2 Pharmacokinetic properties

Absorption and Fate

Erythromycin is adversely affected by gastric acid. For this reason erythromycin tablets are enteric coated.

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

t max	= 4h
C ^ max	= 0.3 - 0.5 ug/ml
Vd	= 0.78 + 0.44 1/kg
T 1/2	= 1.6 +/- 0.7h
CLEARANCE	= 9.1 - 4.1 ml/min/kg

5.3. Preclinical Safety Data

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

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Maize Starch

Croscarmellose Sodium Type A

Povidone

Talc

Magnesium Stearate (E572)

Sub coat:

Hypromellose (E464)

Macrogol 6000 Erythrosine (E127)

Talc

Enteric coat:

Methacrylic Acid ethylacrylate Copolymer (1:1) dispersion 30%

Macrogol 6000

Talc

Polysorbate 80 (E433)

Erythrosine (E127)

Incompatibilities

6.3. Shelf Life

24 months

6.4. Special Precautions for Storage

Do not store above 25°C.

(a)    Tablet container: Keep the container tightly closed. Store in the original container.

(b)    Blister: Store in the original container.

(c)    Bag: Keep container in the outer carton.

6.5 Nature and contents of container

Tablet container

Nature: Polypropylene tamper evident tablet container with polyethylene cap. Contents: 21, 100, 250, 500 and 1000 tablets

Blister:

Nature: 250 um PVC/20 um aluminium blister packs Contents: 28, 56, 84 and 100 tablets.

Bag:

Nature: Polyethylene sealed bag Contents: 5,000 and 10,000 tablets.

Not all pack sizes may be marketed.

6.6. Special precautions for disposal