Erythromycin 125 mg / 5 ml Oral Suspension – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Erythromycin 125 mg / 5 ml Oral Suspension

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 5 ml of reconstituted product contains 125 mg of erythromycin as erythromycin ethyl succinate.

Excipients with known effect

Contains up to 3.125g sucrose per 125mg/5ml.

For full list of excipients see 6.1.

3 PHARMACEUTICAL FORM

Granules for Oral Suspension

Yellow granules with a banana odour.

4.1 Therapeutic indications

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

Erythromycin is highly effective in the treatment of a great variety of clinical infections such as:

1. 1. Upper respiratory tract infections: tonsillitis, peritonsillar abscess, pharyngitis, laryngitis, sinusitis, secondary infections in influenza and common colds.
2. 2. Lower respiratory tract infections: tracheitis, acute and chronic bronchitis, pneumonia (lobar pneumonia, bronchopneumonia, primary atypical pneumonia), bronchiectasis, Legionnaire's disease.
3. 3. Ear infections: otitis media and otitis externa, mastoiditis.
4. 4. Oral infections: gingivitis, Vincent's angina.
5. 5. Eye infections: blepharitis.
6. 6. Skin and soft tissue infections: boils and carbuncles, paronychia, abscesses, pustular acne, impetigo, cellulitis, erysipelas.
7. 7. Gastrointestinal infections: cholecystitis, staphylococcal enterocolitis.
8. 8. Prophylaxis: pre- and post- operative trauma, burns, rheumatic fever.
9. 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

Posology

Adults and children over 8 years:

For mild to moderate infections 2 g daily in divided doses.

For severe infections up to 4 g daily in divided doses.

Elderly:

No special dosage recommendations.

Paediatric population:

Children Aged 2 to 8 years: 30mg/kg/day in divided doses. For severe infections up to 50 mg/kg/day in divided doses.

Normal dose: 250mg four times a day or 500 mg twice daily.

Children up to 2 years : 30mg/kg/day in divided dosed. For severe infections up to 50 mg/kg/day in divided doses.

Normal dose: 125mg four times a day or 250 mg twice daily.

Duration of the dosage regimen is dependent on the nature of the infection and is at the discretion of the physician.

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 contra-indicated in patients taking simvastatin, tolterodine, mizolastine, amisulpiride, astemizole, terfenadine, domperidone, cisapride or pimozide. Erythromycin is contra-indicated with ergotamine and dihydroergotamine.

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

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 section 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 with ergotamine and dihydroergotamine.

4.4 Special warnings and precautions for use

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 & 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.

Erythromycin is excreted principally by the liver, so caution should be exercised in administering this 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.

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.

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.

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

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.

This product contains sucrose and therefore caution should be exercised when administering this antibiotic to patients with diabetes mellitus, hereditary fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase- isomaltase deficiency.

4.5 Interaction with other medicinal products and other forms of interaction

Increase in serum concentration of following drugs metabolised by the cytochrome P450 system an may occur: when they are administered concurrently with omeprazole, erythromycin, acenocoumarol, alfentanil, astemizole, bromocriptine, carbamazepine, cilostazol, cyclosporin, digoxin, dihydroergotamine, disopyramide, domperidone, ergotamine, hexobarbitone, methylprednisolone, midazolam, mizolastine, phenytoin, quinidine, rifabutin, sildenafil, tacrolimus, terfenadine, theophylline, triazolam, valproate , vinblastine, warfarin and antifungals e.g. fluconazole, ketoconazole and itraconazole. Appropriate monitoring should be undertaken and dosage should be adjusted accordingly.Particular care should be taken with medications known to prolong the OTc interval of the electrocardiogram.

Drugs that induce CYP3A4 (such as rifampicin, phenytoin, carbamazepine, phenobarbital, St John’s Wort) may induce the metabolism of erythromycin. This may lead to sub-therapeutic levels of erythromycin and a decreased effect. The induction decreases gradually during two weeks after discontinued treatment with CYP3A4 inducers. Erythromycin should not be used during and two weeks after treatment with CYP3A4 inducers.

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.

Contraceptives: some antibiotics may in rare cases decrease the effect of contraceptive pills by interfering with the bacterial hydrolysis of steroid conjugates in the intestine and thereby reabsorption of unconjugated steroid. As a result of this plasma levels of active steroid may decrease.

Antihistamine H1 antagonists: care should be taken in the coadministration of erythromycin with H1 antagonists such as terfenadine, astemizole and mizolastine due to the alteration of their metabolism by erythromycin.

Erythromycin significantly alters the metabolism of terfenadine, astemizole and pimozide when taken concomitantly. Rare cases of serious, potentially fatal, cardiovascular events including cardiac arrest, torsade de pointes and other ventricular arrhythmias have been observed (see section 4.3 and 4.8)

Anti-bacterial agents: an in vitro antagonism exists between erythromycin and the bactericidal beta-lactam antibiotics (e.g. penicillin, cephalosporin). Erythromycin antagonises the action of clindamycin, lincomycin and chloramphenicol. The same applies for streptomycin, tetracyclines and colistin.

Protease inhibitors: in concomitant administration of erythromycin and protease inhibitors, an inhibition of the decomposition of erythromycin has been observed.

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

Triazolobenzodiazepines (such as triazolam and alprazolam) and related benzodiazepines: erythromycin has been reported to decrease the clearance of triazolam, midazolam, and related benzodiazepines, and thus may increase the pharmacological effect of these benzodiazepines.

Post-marketing reports indicate that co-administration of erythromycin and ergotamine or di-hydroergotamine has been associated in some patients with acute ergot toxicity characterised by vasospasm and ischaemia of the central nervous system, extremities and other tissues (see section 4.3)

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.

Erythromycin use in patients who are receiving 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 concomitant erythromycin therapy. There have been published reports suggesting when oral erythromycin is given concurrently with theophylline there is a significant decrease in erythromycin serum concentrations. This decrease could result in subtherapeutic concentrations of erythromycin.

There have been post-marketing reports of colchicine toxicity with concomitant use of erythromycin and colchicine.

Hypotension, bradyarrhythmias and lactic acidosis have been observed in patients receiving concurrent verapamil, a calcium channel blocker.

Cimetidine may inhibit the metabolism of erythromycin which may lead to an increased plasma concentration.

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

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.

Lomitapide

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

Chloroquine/Hydroxychloroquine

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.

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

4.6 Pregnancy, lactation and fertility,

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 7 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. Breast-feeding

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

Fertility

No data available

4.7 Effects on ability to drive and use machines

None stated

4.8 Undesirable effects

The most frequent side effects of oral erythromycin preparations are gastrointestinal and are dose-related.

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

Very common (≥1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1,000 to <1/100)

Rare (≥1 / 10,000 to <1 / 1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data).:

*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.

**There have been isolated reports of reversible hearing loss occurring chiefly in patients with renal insufficiency or high doses.

***Pseudomembranous colitis has been rarely reported in association with erythromycin therapy (see section 4.4).

Reporting of suspected adverse reactions

Reporting 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 the Yellow Card Scheme at: 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.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group Antibacterials for systemic use. ATC code J01F A,

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

Clinical efficacy and safety

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

Gram negative bacteria - Heamophilus influenzae, Neisseria meningitidis, Neisseria gonorrhoeae, Legionella pneumophila, Moraxella (Branhamella) catarrhalis. Bordetella pertussis, Campylobacter spp.

Mycoplasma - Mycoplasma pneumoniae, Ureaplasma urealyticum.

Other organisms - Treponema pallidum, Chlamydia trachomatis, Clostridia spp, Lforms, the agents causing trachoma and lymphogranuloma venereum.

5.2 Pharmacokinetic properties

Absorption

Erythromycin ethylsuccinate is less susceptible than erythromycin to the adverse effect of gastric acid. Peak blood levels normally occur within 1 hour of dosing of erythromycin ethylsuccinate granules. It is absorbed from the small intestine.

Distribution

It is widely distributed throughout body tissues.

Biotransformation and elimination

Little metabolism occurs and only about 5% is excreted in the urine. The elimination half life is approximately 2 hours. Doses may be administered 2, 3 or 4 times a day. It is excreted principally by the liver.

5.3 Preclinical safety data

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

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Carboxymethylcellulose sodium

Sodium citrate

Banana flavour

Quinoline yellow E104

Saccharin sodium

Silica, colloidal anhydrous

Sucrose

6.2 Incompatibilities

Not Applicable

6.3 Shelf life

36 months unopened.

14 days after reconstitution.

6.4 Special precautions for storage

Store in the original container. Do not store above 25°C prior to reconstitution. After reconstitution, store suspension at 2°C - 8°C. Do not freeze.

6.5 Nature and contents of container

Nature: Amber type III glass bottle with polyethylene screw on cap. Contents: 62.5 g

Reconstitution of the granules provides 100 ml of suspension.

6.6 Special precautions for disposal

Add 60 ml of water, invert the bottle and shake vigorously for 1 minute.

7 MARKETING AUTHORISATION HOLDER

Chelonia Healthcare Limited

11 Boumpoulinas Street,

3^rd floor, 1060 Nicosia

Cyprus

8 MARKETING AUTHORISATION NUMBER(S)

PL 33414/0043

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

09/02/2009

10 DATE OF REVISION OF THE TEXT

05/06/2023