SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Erythromycin Tablets BP 250 mg Rommix® 250 mg Tablets

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Erythromycin BP 250 mg For excipients, see 6.1

3.    PHARMACEUTICAL FORM

Gastro-resistant tablet.

Reddish-orange opaque film coated round tablet

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Erythromycin is an antibiotic effective in the treatment of bacterial disease caused by susceptible organisms. Examples of its use are in the treatment of:

Upper respiratory tract infections: Laryngitis, pharyngitis, sinusitis, secondary infections in colds and influenza, tonsillitis, peritonsillar abscess

Lower respiratory tract infections: Acute and chronic bronchitis, tracheitis, pneumonia, bronchiectasis, legionnaires disease

Eye infections: Blepharitis

Ear infections: Otitis media and otitis externa, mastoiditis Oral infection: Gingivitis, Vincent’s angina

Skin and soft tissue infections: Boils and carbuncles, abscesses, pustular acne, paronychia, impetigo, cellulitis, erysipelas

Gastro-intestinal infections: Staphylococcal enterocolitis, cholecysitis

Other infections: Gonorrhoea, syphilis, urethritis, osteomyelitis, lymphogranuloma venereum, diptheria, prostatitis, scarlet fever

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

Consideration should be given to national and/or local guidance on the appropriate use of antibacterial agents

4.2 Posology and method of administration

Oral use

Adults and elderly

The usual dose is 250mg every six hours, taken one hour before meals. 500 mg every twelve hours may be given if desired. Twice daily dosing schedules should not be used if the total daily dose exceeds one gram. For severe infections up to 4g daily may be given in divided doses.

Children

Age, weight and severity of the infection are important factors in determining the correct dose.

The usual dose is 30 - 50 mg/kg/day in divided doses given twice daily, or every six hours, one hour before meals. In severe infections, this dosage may be doubled; higher doses should be given every six hours.

4.3 Contraindications

Use in patients hypersensitive to erythromycin or to any of the excipients, and in patients    taking astemizole, terfenadine, cisapride, pimozide, ergotamine,

dihydroergotamine, simvastatin, tolterodine, mizolastine, amisulpride or sertindole.

4.4 Special warnings and precautions for use

Caution should be exercised in administering erythromycin to patients with impaired renal function.

Extended administration requires regular evaluation particularly of liver function. Therapy should be discontinued if significant hepatic dysfunction occurs. 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.

Prolonged use of erythromycin has caused overgrowth of nonsusceptible bacteria or fungi; this is a rare occurrence.

It has been reported that erythromycin may aggravate muscle weakness in patients with myasthenia gravis.

Patients receiving erythromycin concurrently with drugs which can cause prolongation of the QT interval should be carefully monitored; the concomitant use of erythromycin with some of these drugs is contraindicated (see sections 4.3 and 4.5).

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 weighed against the potential risk of developing IHPS. Parents should be informed to contact their physician if vomiting or irritability with feeding occurs.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including macrolides, and may range in severity from mild to life-threatening (see section.4.8). Clostridium difficile-associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents including erythromycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, which may lead to overgrowth of C. difficile. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

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.

Erythromycin interferes with the fluorometric determination of urinary catecholamines.

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

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant use of erythromycin with certain drugs metabolised by the cytochrome P450 system is likely to result in an increased frequency or seriousness of adverse effects associated with these drugs. The concomitant use of erythromycin with mizolastine, amisulpride, astemizole, cisapride, pimozide, sertindole and terfenadine is contraindicated due to the risk of QT prolongation and cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and Torsades de pointes. The concomitant use of erythromycin with ergotamine and dihydroergotamine is contraindicated due to the risk of ergot toxicity.

Concomitant use with simvastatin is contraindicated due to the risk of myopathy and rhabdomyolysis whilst concomitant use with tolterodine is contraindicated due to increased risk of overdose.

Other drugs metabolised by the cytochrome P450 system, such as acenocoumarol, atorvastatin, bromocriptine, buspirone, cabergoline, carbamazepine, ciclosporin, cilostazol, clozapine, digoxin, disopyramide, eletriptan, felodipine, hexobarbital, midazolam, phenytoin, quetiapine, quinidine, rifabutin, sildenafil, tacrolimus, tadalafil, theophylline, triazolam, valproate, warfarin and zopiclone, may be associated with elevated serum levels if administered concomitantly with erythromycin. Because of the risk of toxicity, appropriate monitoring should be undertaken, and dosage should be adjusted as necessary.

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

Erythromycin should be used with caution if administered concomitantly with lincomycin, clindamycin or chloramphenicol, as competitive inhibition may occur.

The concomitant use of erythromycin with alfentanil can significantly inhibit the clearance of alfentanil and may increase the risk of prolonged or delayed respiratory depression.

Patients receiving concomitant lovastatin and erythromycin should be carefully monitored as cases of rhabdomyolysis have been reported in seriously ill patients. Rhabdomyolysis has also been reported with concomitant simvastatin and erythromycin, and caution is therefore recommended when erythromycin is used concurrently with other HMG-CoA reductase inhibitors. It is recommended that therapy with simvastatin is suspended during the course of treatment.

An increased plasma concentration of erythromycin has been reported with concomitant cimetidine treatment, leading to increased risk of toxicity, including reversible deafness.

Erythromycin may interfere with the determination of urinary catecholamines and 17-hydroxycorticosteroids.

4.6 Pregnancy and lactation

Pregnancy

Like all drugs erythromycin should be used in pregnancy only when clearly indicated._Erythromycin crosses the placental barrier.

Lactation

Erythromycin is excreted in human milk and should be used in lactating women only if clearly needed.

4.7. Effects on Ability to Drive and Use Machines

Not applicable

4.8 Undesirable effects

Modern clinical data required to determine the frequency of undesirable effects are lacking for erythromycin. Side effects associated with erythromycin therapy are usually mild. The most frequent side effects are gastrointestinal and are dose-related. There have been reports of serious allergic reactions, including anaphylaxis.

Blood and lymphatic system disorders: Eosinophilia

Infections and infestations: Superinfection including pseudomembranous colitis.

The possibility of superinfection should be considered during prolonged or repeated courses, especially when other antibacterial agents are used concurrently.

Immune system disorders: Hypersensitivity. Allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis have occurred.

Investigations: Increased liver enzyme values.

Psychiatric disorders: Hallucinations

Nervous system disorders: Dizziness, convulsions, there have been isolated reports of transient central nervous system side effects including confusion, seizures and vertigo; however, a cause and effect relationship has not been established.

Ear and labyrinth disorders:, Transient hearing disturbances, tinnitus and deafness (usually occurring at doses greater than 4 g daily). There have been isolated reports of reversible hearing loss occurring chiefly with renal insufficiency or high doses.

Cardiac disorders: Cardiac rhythm disorders including ventricular tachyarrhythmias, QTc interval prolongation and torsades de pointes, palpitations

Gastrointestinal disorders: Nausea, upper abdominal discomfort, diarrhoea, vomiting, pancreatitis, anorexia and infantile hypertrophic pyloric stenosis. Pseudomembranous colitis has been rarely reported in association with erythromycin therapy (see section 4.4).

General disorders and administration site conditions: Chest pain, fever, malaise.

Hepatobiliary disorders: Jaundice (cholestatic/hepatocellular), cholestatic hepatitis, hepatitis, hepatic disfunction, hepatomegaly, hepatic failure, abnormal liver function test values and hepatocellular hepatitis (see section 4.4).

Skin and subcutaneous tissue disorders: Skin eruptions, rash, urticaria, pruritus, exanthema, angioedema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis

Renal and urinary disorders: Interstitial nephritis Vascular disorders: Hypotension.

4.9 Overdose

Symptoms

Nausea, vomiting and diarrhoea have been reported.

Treatment

Gastric lavage and general supportive therapy. Erythromycin is not removed by peritoneal dialysis or haemodialysis.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Erythromycin is a macrolide antibiotic it is active against a wide variety of pathogenic organisms, gram-positive cocci-Pneumococci, staphylococci and Streptococci (including enterococci) - Meningococci, Mycoplasma, 1-forms, Haemophilus influenzae (majority of strains are susceptible to the concentrations reached after normal doses). Agents causing trachoma and Lymphogranuloma venereum, Clostridia, Chlamydia, Corynebacterium diptheriae (as adjunct to antitoxin), Bordetella, Neisseria, Treponema pallidium.

5.2. Pharmacokinetic Properties

Tmax:    4 hours

Cmax:    0.3-0.5 pg/ml

Vd:    0.78 ± 0.44 1/kg

T'A:    l.6 ± 0.7hours

Clearance:    9.1 - 4.1 ml/min/kg

5.3 Pre-clinical safety data

Oral hamster: LD₅₀3 0 1 8 mg/kg. Behavioural; lungs, thorax or respiration. Oral mouse: LD₅₀3112 mg/kg. No toxic effects noted.

Oral rat:    LD₅₀9272 mg/kg. No toxic effects noted.

(Registry of toxic effects of chemical substances 1985-6)

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Maize Starch

Croscarmellose Sodium Type A

Povidone

Talc

Magnesium Stearate Sub coat:

Hydroxypropyl methylcellulose Polyethylene Glycol 6000 Dispersed Red 18152 (E110 & E124)

Enteric coat:

Methacrylic acid copolymer Polyethylene Glycol 6000 Talc

Polysorbate 80

Dispersed Red 18152 (E110 & E124) 6.2. Incompatibilities

None known.

6.3 Shelf life

3 Years

6.4. Special Precautions for Storage

Protect from light, store in a dry place below 25°C.

6.5. Nature and Contents of Container

Tablet container (securitainer) with polyethylene tamper evident seals. Pack sizes 21, 100, 200, 500 and 1000 tablets.

Blister strips composed of 250 pm PVC and 20 pm A1.

Pack sizes: 28, 56, 84, 100 tablets.

6.6. Instructions for Use,Handling and Disposal

Not Applicable.

7 MARKETING AUTHORISATION HOLDER

Co-pharma Limited Unit 4, Metro Centre Tolpits Lane Watford Hertfordshire WD1 9SS

8    MARKETING AUTHORISATION NUMBER(S)

PL 13606/0016

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

23/06/2008

10 DATE OF REVISION OF THE TEXT

06/07/2015