Erythromycin Ethylsuccinate 500 mg film-coated Tablets – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Erythromycin Ethylsuccinate 500 mg film-coated Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains the active substance erythromycin as Erythromycin Ethylsuccinate Ph. Eur. 500 mg/tablet.

For the full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Yellow coloured, oval shaped, film-coated tablets (nominal dimensions - 18.7 mm x 8.7 mm x 7.4 mm) debossed “K” on one side and plain on other side.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the prophylaxis and treatment of infections caused by erythromycin-sensitive organisms (see section 5.1).

• Upper Respiratory Tract infections: tonsillitis, peritonsillar abscess, pharyngitis, laryngitis, sinusitis, secondary infections in influenza and common colds
• Lower Respiratory Tract infections: tracheitis, acute and chronic bronchitis, pneumonia (lobar pneumonia, bronchopneumonia, primary atypical pneumonia), bronchiectasis, Legionnaire's disease
• Ear infection: otitis media and otitis externa, mastoiditis
• Oral infections: gingivitis, Vincent's angina
• Eye infections: blepharitis
• Skin and soft tissue infections: boils and carbuncles, paronychia, abscesses, pustular acne, impetigo, cellulitis, erysipelas
• Gastrointestinal infections: cholecystitis, staphylococcal enterocolitis
• Prophylaxis: peri- and post- operative trauma, burns, rheumatic fever
• Other infections: osteomyelitis, urethritis, gonorrhoea, syphilis, lymphogranuloma venereum, diphtheria, prostatitis, scarlet fever.

Consideration should be given to official guidance on the appropriate use of antibacterial agents

4.2 Posology and method of administration

Posology

Adults and children over 8 years: For mild to moderate infections 2 g daily in divided doses. Up to 4 g daily in severe infections.

Elderly: No special dosage recommendations.

Paediatric population

Note: For younger children, infants and babies, erythromycin suspension is normally recommended. The recommended dose for children age 2 – 8, for mild to moderate infections, is 1 g daily in divided doses. The recommended dose for infants and babies, for mild to moderate infections, is 500 mg daily in divided doses. For severe infections doses may be doubled.

Method of administration

For oral administration.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Erythromycin is contraindicated in patients taking simvastatin, tolterodine, mizolastine, amisulpride, astemizole, terfenadine, domperidone, cisapride or pimozide.

Erythromycin should not be given to patients with a history of QT prolongation (congenital or documented acquired QT prolongation) or ventricular cardiac arrhythmia, including Torsades de Pointes (see sections 4.4 and 4.5).

Erythromycin should not be given to patients with electrolyte disturbances (hypokalaemia, hypomagnesaemia due to the risk of prolongation of QT interval).

Erythromycin is contraindicated in patients taking ergotamine and dihydroergotamine.

Concomitant administration of erythromycin and lomitapide is contraindicated (see section 4.5).

Concomitant administration of erythromycin and ivabradine is contraindicated due to increased exposure of ivabradine and may result in a higher risk of Torsade de Pointes and serious cardiac effects.

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.

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.

As with other macrolides, rare serious allergic reactions, including acute generalised exanthematous pustulosis (AGEP) have been reported. If an allergic reaction occurs, the drug should be discontinued, and appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.

Cardiovascular events

Prolongation of the QT interval, reflecting effects on cardiac repolarisation imparting a risk of developing cardiac arrhythmia and Torsades de Pointes, have been seen in patients treated with macrolides including erythromycin (see sections 4.3, 4.5 and 4.8). Fatalities have been reported.

Erythromycin should be used with caution in the following

• Patients with coronary artery disease, severe cardiac insufficiency, conduction disturbances or clinically relevant bradycardia.
• Patients concomitantly taking other medicinal products associated with QT prolongation (see sections 4.3 and 4.5).
• Elderly patients may be more susceptible to drug-associated effects on the QT interval (see section 4.8).

Epidemiological studies investigating the risk of adverse cardiovascular outcomes with macrolides have shown variable results. Some observational studies have identified a rare short-term risk of arrhythmia, myocardial infarction and cardiovascular mortality associated with macrolides including erythromycin. Consideration of these findings should be balanced with treatment benefits when prescribing erythromycin.

Carefully consider the balance of benefits and risks before prescribing erythromycin for any patients taking hydroxychloroquine or chloroquine, because of the potential for an increased risk of cardiovascular events and cardiovascular mortality (see section 4.5). 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.

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

Paediatric population

There have been reports of infantile hypertrophic pyloric stenosis (IHPS) occurring in infants following erythromycin therapy. Epidemiological studies including data from meta-analyses suggest a 2-3-fold increase in the risk of IHPS following exposure to erythromycin in infancy. This risk is highest following exposure to erythromycin during the first 14 days of life. Available data suggests a risk of 2.6% (95% CI: 1.5 - 4.2%) following exposure to erythromycin during this time period. The risk of IHPS in the general population is 0.1-0.2%. 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

Erythromycin Ethylsuccinate 500 mg film-coated Tablets contain sodium starch glycolate

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant use of erythromycin with terfenadine or astemizole is likely to result in an enhanced risk of cardiotoxicity with these drugs. The concomitant use of erythromycin with either astemizole or terfenadine is therefore contraindicated.

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

Mizolastine has a weak potential to prolong QT interval and has not been associated with arrhythmias, however the metabolism of mizolastine is inhibited by erythromycin, therefore concomitant use should be avoided.

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: acenocoumarol, alfentanil, astemizole, bromocriptine, carbamazepine, cilostazol, cyclosporin, digoxin, dihydroergotamine, disopyramide, ergotamine, hexobarbitone, methylprednisolone, midazolam, omeprazole, phenytoin, quinidine, rifabutin, sildenafil, tacrolimus, terfenadine, domperidone, theophylline, triazolam, valproate, vinblastine, warfarin and antifungals e.g. fluconazole, ketoconazole and itraconazole. Appropriate monitoring should be undertaken and dosage should be adjusted as necessary. 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.

There have been reports of increased anticoagulant effects when erythromycin and oral anticoagulants (e.g. warfarin, rivaroxaban) are used concomitantly.

Observational data have shown that co-administration of azithromycin with hydroxychloroquine in patients with rheumatoid arthritis is associated with an increased risk of cardiovascular events and cardiovascular mortality. Because of the potential for a similar risk with other macrolides when used in combination with hydroxychloroquine or chloroquine, careful consideration should be given to the balance of benefits and risks before prescribing erythromycin for any patients taking hydroxychloroquine or chloroquine.

Concomitant administration of erythromycin with lomitapide is contraindicated due to the potential for markedly increased transaminases (see section 4.3).

Hydroxychloroquine and chloroquine: Erythromycin should be used with caution in patients receiving these medicines known to prolong the QT interval due to the potential to induce cardiac arrhythmia and serious adverse cardiovascular events.

Corticosteroids: Caution should be exercised in concomitant use of erythromycin with systemic and inhaled corticosteroids that are primarily metabolised by CYP3A due to the potential for increased systemic exposure to corticosteroids. If concomitant use occurs, patients should be closely monitored for systemic corticosteroid undesirable effects.

HMG-CoA Reductase Inhibitors: Erythromycin is contraindicated in patients receiving the HMG-CoA reductase inhibitors lovastatin and simvastatin (see section 4.3). Erythromycin has been reported to increase concentrations of HMG-CoA reductase inhibitors. Rare reports of rhabdomyolysis have been reported in patients taking these drugs concomitantly.

Concomitant administration of erythromycin with lomitapide is contraindicated due to the potential for markedly increased transaminases (see section 4.3).

Erythromycin is an inhibitor of CYP3A4 and is liable to interact with ivabradine and influence its metabolism and pharmacokinetics to a clinically significant extent. Interaction studies have established that CYP3A4 inhibitors increase ivabradine plasma concentrations. Increased plasma concentrations of ivabradine may be associated with the risk of excessive bradycardia, Torsades de Pointes and serious cardiac effects.

4.6 Fertility, pregnancy and lactation

Pregnancy

The available epidemiological studies on the risk of major congenital malformations with use of macrolides including erythromycin during pregnancy provide conflicting results. Some observational studies in humans have reported cardiovascular malformations after exposure to medicinal products containing erythromycin during early pregnancy.

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

There have been reports that maternal macrolide antibiotics exposure within 10 weeks of delivery may be associated with a higher risk of infantile hypertrophic pyloric stenosis (IHPS).

Erythromycin should be used by women during pregnancy only if clearly needed.

There is a large amount of data from observational studies performed in several countries on exposure to erythromycin during pregnancy, compared to no antibiotic use or use of another antibiotic during the same period (>24,000 first trimester exposures). While most studies do not suggest an association with adverse foetal effects such as major congenital malformations, cardiovascular malformations or miscarriage, there is limited epidemiological evidence of a small increased risk of major congenital malformations, specifically cardiovascular malformations following first trimester exposure to erythromycin.

Breast-feeding

Erythromycin can be excreted into breast milk. Caution should be exercised when administering erythromycin to lactating mothers due to reports of infantile hypertrophic pyloric stenosis in breast-fed infants.

There have been reports that maternal macrolide antibiotics exposure within 7 weeks of delivery may be associated with a higher risk of infantile hypertrophic pyloric stenosis (IHPS).

Fertility

No data available.

4.7 Effects on ability to drive and use machines

No data available.

4.8 Undesirable effects

The list of undesirable effects shown below is presented by system organ class, MedDRA preferred terminology, and frequency using the following frequency conventions:

Very common: (>1/10)

Common (≥ 1/100, <1/10)

Uncommon (≥ 1/1,000, <1/100)

Rare (≥1/10,000, <1/1000)

Very rare (<1/10,000)

Not known: frequency cannot be estimated from the available data.

* Associated with doses of erythromycin usually greater than 4 g per day has been reported.

** There have been isolated reports of chest pain, dizziness and palpitations, however, a cause and effect relationship has not been established.

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.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Schemewebsite: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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: Antibacterials for systemic use, ATC Code: J01FA01.

Mechanism of action

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, Bordetella pertussis, 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.

Susceptibility testing breakpoints

EUCAST clinical MIC breakpoints for erythromycin (Version 14.0, valid from 2024-01-01):

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is known and the utility of the agent in at least some types of infections is questionable.

5.2 Pharmacokinetic properties

Absorption

Erythromycin ethylsuccinate is less susceptible than erythromycin to the adverse effect of gastric acid. It is absorbed from the small intestine. Peak blood levels normally occur within 1 hour of dosing of erythromycin ethylsuccinate granules. Doses may be administered 2, 3 or 4 times a day.

Distribution

Biotransformation

Little metabolism occurs and only about 5% is excreted in the urine.

Elimination

The elimination half-life is approximately 2 hours. Erythromycin is excreted principally by the liver.

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 SmPC.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core

Pregelatinized starch, anhydrous calcium hydrogen phosphate, sodium starch glycolate, povidone and magnesium stearate.

Tablet coating

Hypromellose, titanium dioxide, macrogol, quinoline, Yellow Aluminium Lake and iron oxide yellow.

6.2 Incompatibilities

Not applicable

6.3 Shelf life

4 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Blister: PVC/Aluminium

Pack sizes: 10, 12, 14, 24, 28, 30, 56 & 84 film-coated tablets Not all pack sizes may be marketed

6.6 Special precautions for disposal

No special requirements

Any unused product or waste material should be disposed of in accordance with local requirements

7 MARKETING AUTHORISATION HOLDER

Dawa Limited

5 Sandridge Close,

Harrow, Middlesex,

HA1 1XD,

United Kingdom.

8 MARKETING AUTHORISATION NUMBER(S)

PL 30684/0229

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

24/12/2024

10 DATE OF REVISION OF THE TEXT

11/03/2026