Erythromycin Ethyl Succinate Granules For Oral Suspension 250 Mg/5 Ml
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Erythromycin Ethyl Succinate Granules for Oral Suspension 250 mg/5 ml
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Erythromycin Ethyl Succinate Ph Eur 250 mg/5 ml when reconstituted.
For excipients see 6.1
3 PHARMACEUTICAL FORM
Granules for oral suspension
Yellow granules with a characteristic banana odour, giving a viscous smooth suspension upon reconstitution
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Antibiotic for the prophylaxis and treatment of infections caused by erythromycin sensitive organisms especially gram positive pyogenic cocci and some gram-positive bacteria. It may be used in a wide variety of clinical infections:
Prophylaxis: Pre or post-operative, endocarditis, rheumatic fever, severe trauma and burns.
Upper respiratory tract infection: Secondary infections in influenza and colds, sinusitis, laryngitis, pharyngitis, tonsillitis.
Lower respiratory tract infections: Acute and chronic bronchitis, legionnaires disease, tracheitis, bronchiectasis, pneumonia.
Skin and soft tissue infections: Acute infections of skin and soft tissue which are mild to moderately severe, including acne vulgaris.
Eye/Ear infections: Otitis media and Otitis externa, Mastoiditis, Chlamydial conjunctivitis, Blepharitis.
Oral infection: Gingivitis, Vincent's angina.
Gastro - intestinal infections: Staphylococcal enterocolitis, cholecystitis, campylobacter infections.
Other infections: Gonorrhoea, syphilis, urethritis, diphtheria, pertussis.
4.2 Posology and method of administration
Adults (including the elderly) and children over 8 years: For mild to moderate infections 2g daily in divided doses up to 4g daily in divided doses in severe infections.
Children:
2-8 years: 30mg/kg/day in divided doses. For severe infections up to 50mg/kg/day in divided doses.
Normal dose: 250mg four times a day or 500mg twice daily.
Children up to 2 years: 30mg/kg/day in divided doses. For severe infections up to 50mg/kg/day in divided doses.
Normal dose: 125mg four times a day or 250mg twice a day.
Duration of the dosage regimen is dependent on the nature of the infection and is at the discretion of the physician.
Administration: For oral use.
4.3 Contraindications
Hypersensitivity to erythromycin or to any ingredients of the preparation.
Concomitant use of drugs known to prolong the QT interval due to the increased risk of cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and torsade de pointes (e.g. astemizole, terfenadine, cisapride, amisulpride, pimozide; see also section 4.5).
Concomitant use of drugs metabolised via cytochrome P450 3A4 in whom increased drug levels may lead to an increase in the frequency or severity of adverse events (e.g. simvastatin, ergot derivatives, tolterodine; see also section 4.5).
Porphyria.
4.4 Special warnings and precautions for use
Erythromycin is excreted principally by the liver. Use with caution in patients with impaired renal or hepatic function or those receiving concomitantly potentially hepatotoxic agents. Hepatic dysfunction including increased liver enzymes and/or cholestatic hepatitis, with or without jaundice, has been infrequently reported with erythromycin.
It has been reported that erythromycin may aggravate muscle weakness in patients with myasthenia gravis.
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.
Pseudomembranous colitis has been reported with nearly all bacterial 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.
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 (see section 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-billious 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.
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Effect of other medications on erythromycin
Theophylline: There have been published reports suggesting serum concentrations of erythromycin may be significantly decreased during theophylline treatment, possibly resulting in subtherapeutic concentrations of erythromycin.
Cimetidine: An increased plasma concentration of erythromycin has been reported with concomitant administration with cimetidine, this will increase the risk of toxicity, including reversible deafness.
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.
Protease inhibitors: in concomitant administration of erythromycin and protease inhibitors, an inhibition of the decomposition of erythromycin has been observed.
Effect of erythromycin on other medications
CYP3A4 and CYP1A2 substrates: Erythromycin is an inhibitor of the cytochrome P450 isoenzyme system 3A4 (and to a lesser extent 1A2) and it can be expected to interact with drugs which are hepatically metabolised via this enzyme system. Such interactions may lead to an increase in the frequency or seriousness of adverse effects associated with the concomitantly administered drugs. For example the concomitant use of erythromycin with ergotamine, dihydroergotamine and methysergide is contraindicated due to the risk of ergot toxicity characterised by vasospasm and ischaemia of the central nervous system, extremities and other tissues (see section 4.3); concomitant use with tolterodine is contraindicated due to increased risk of tolterodine overdose (see section 4.3).
Other drugs metabolised via cytochrome P450 3A4, such as acenocoumarol, alfentanil, astemizole, bromocriptine, buspirone, cabergoline, carbamazepine, ciclosporin, cilostazol, clozapine, digoxin, dihydroergotamine, disopyramide, eletriptan, ergotamine, felodipine, hexobarbital, methylprednisolone, midazolam, omeprazole, phenytoin, quinidine, reboxetine, rifabutin, sildenafil, tacrolimus, tadalafil, terfenadine, theophylline, triazolam, valproate, vinblastine, zopiclone and antifungals e.g. fluconazole, ketoconazole and itraconazole may be associated with elevated serum levels if administered concomitantly with erythromycin. Appropriate monitoring should be undertaken, and dosage should be adjusted as necessary.
HMG-CoA Reductase Inhibitors: erythromycin has been reported to increase concentrations of HMG-CoA reductase inhibitors (e.g. lovastatin, simvastatin). Rare reports of rhabdomyolysis have been reported in patients taking these drugs concomitantly.
Drugs causing QT prolongation: There is a slight risk of QT prolongation associated with the use of oral erythromycin (the risk is higher with intravenous erythromycin) and so the use of erythromycin with other drugs known to cause QT prolongation is not recommended as the additive effect may result in cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and Torsades de pointes. The risk of cardiac toxicity is obviously greater if erythromycin also inhibits the metabolism of a drug which causes QT prolongation. The concomitant use of erythromycin with drugs whose metabolism it inhibits and for which there is also a risk of QT interval prolongation, such as cisapride, clarithromycin, disopyramide, mizolastine, astemizole, pimozide, quetiapine, quinidine, sertindole and terfenadine is therefore contraindicated (see section 4.3).
The concomitant administration of erythromycin with drugs known to have a high risk of QT prolongation such as amisulpride and certain antiarrhythmics should only be undertaken with extreme care (concomitant administration of these drugs with IV erythromycin is contraindicated). Care is needed when erythromycin is administered with drugs which may cause QT prolongation such as artemether and moxifloxacin.
Digoxin: Digoxin toxicity has been reported in digitalized patients given erythromycin, this is thought to occur because erythromycin inhibits digoxin metabolism by the gut flora.
Theophylline: 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. An increase in theophylline levels, possibly caused by an effect on hepatic metabolism, may occur during concomitant use of erythromycin.
Corticosteroids: Erythromycin has been reported to increase the therapeutic and adverse effects of methylprednisolone, probably by altering drug clearance.
Oral anticoagulants: The use of erythromycin in patients receiving oral anticoagulants (e.g. warfarin) may result in the potentiation of anticoagulant activity.
Erythromycin decreases the availability of vitamin K and likewise the dose of vitamin K antagonists (such as warfarin) required to maintain a given prolongation of prothrombin time. Prothrombin times should therefore be checked particularly carefully if erythromycin is given to any patient receiving an anticoagulant.
Laboratory tests: Erythromycin may interfere with the determination of urinary catecholamines and 17-hydroxycorticosteroids. It may also interfere with colorimetric assays resulting in falsely increased AST (SGOT) and ALT (SGPT) concentrations.
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.
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.
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.
Erythromycin has been reported to decrease the clearance of zopiclone and thus may increase the pharmacodynamic effects of this drug.
4.6 Fertility, Pregnancy and lactation
There are no adequate and well-controlled studies in pregnant women. However, 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.
As with all drugs, special care should be taken in the treatment of pregnant women.
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
Not applicable.
4.8 Undesirable effects
There are no modern clinical data available with which to determine the frequency of undesirable effects.
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.
Blood and lymphatic system disorders: Eosinophilia.
Immune system disorders: Hypersensitivity: anaphylaxis.
Psychiatric disorders: Hallucinations.
Nervous system disorders: 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: Tinnitus. Transient hearing disturbances and deafness (usually occurring at doses greater than 4g daily).
Cardiac disorders: Cardiac arrhythmias including ventricular tachyarrhythmias; chest pain; QT interval prolongation, torsades de pointes, palpitations.
Vascular disorders: Hypotension.
Gastrointestinal disorders: Nausea, abdominal discomfort, diarrhoea, vomiting, pancreatitis, anorexia, infantile hypertrophic pyloric stenosis.
Pseudomembraneous colitis has been rarely reported in association with erythromycin therapy (see section 4.4).
Hepato-biliary disorders: Jaundice, cholestatic/hepatocellular hepatitis, hepatic dysfunction; abnormal liver function test results, hepatomegaly, hepatic failure (see section 4.4).
Skin and subcutaneous tissue disorders: Rash, skin eruptions, pruritis, exanthema, angioedema, urticaria, erythema multiforme, Stevens-Johnson Syndrome; toxic epidermal necrolysis.
Renal and urinary disorders: Interstitial nephritis.
General disorders and administration site conditions: Chest pain, fever, malaise.
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.
4.9 Overdose
Symptoms are mainly confined to hearing loss, nausea, vomiting and diarrhoea. Treatment is gastric lavage and general supportive measures.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Erythromycin is a macrolide antibiotic which acts by interfering with bacterial protein synthesis and is bacteriostatic or bactericidal depending on its concentration and the type of organism. Sensitive organisms include:
1. Gram-positive bacteria such as Staph. aureus, epidermis, Strep. pyogens, Strep. pneumoniae, Strep. viridans, Corynebacterium diphtheria and Listeria monocytogenes.
2. Gram-positive bacteria such as H. influenzae, N. meningitidis, N. gonorrhoeae, B. pertussis, Campylobacter strains and Legionella pneumophilia.
3. Treponema pallidum
4. Mycoplasma pneumoniae
5. Chlamydia trachomatis
5.2 Pharmacokinetic properties
An ester well absorbed from the gastrointestinal tract, absorption may be slightly delayed by food and the highest and earliest peak serum levels occur under fasting conditions.
Tmax: 2-4 hours
Cmax: Approx. 0.5 pg/ml (from a 250 mg dose)
TV: 1.6 ± 0.7 hours
Erythromycin is excreted in high concentrations in the bile and up to 5% of an oral dose may occur in the urine; considerable amounts may also be inactivated in the body.
5.3 Preclinical safety data
Oral hamster: LD50 3018 mg/kg. Behavioural; lungs, thorax or respiration. Oral mouse: LD50 3112 mg/kg. No toxic effects noted Oral rat: LD50 9272 mg/kg. No toxic effects noted
(Registry of toxic effects of chemical substances 1985-6)
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Carboxymethylcellulose Sodium Sodium Citrate Banana Flavour E4210 SD Quinoline Yellow 14031 E104 Sodium Saccharin Colloidal Anhydrous Silica Sucrose (Caster Sugar)
6.2 Incompatibilities
None known.
6.3 Shelf life
3 years
Shelf life (after reconstitution) : 14 days
6.4 Special precautions for storage
Granules: Store below 25°C.
Reconstituted suspension: Store in a refrigerator (2-8°C).
6.5 Nature and contents of container
Amber Type III glass bottle with polyethylene screw-on cap. Pack size: 100 ml when reconstituted.
6.6 Special precautions for disposal
To the Pharmacist: To prepare add 60 ml water to make up to 100 ml and shake until all of the granules are dissolved.
To the patient: For oral use, use as instructed by physician. Keep tightly closed and store in a refrigerator (2-8 °C). Shake well before each use. Use within 14 days of preparation. Dispose of any unused suspension.
7 MARKETING AUTHORISATION HOLDER
Medreich Plc Warwick House Plane Tree Crescent Feltham TW13 7HF
8 MARKETING AUTHORISATION NUMBER(S)
PL 21880/0165
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION 23/06/2008
10 DATE OF REVISION OF THE TEXT
30/09/2014