Erythromycin 250mg Gastro-Resistant Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Erythromycin 250mg Gastro-resistant Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Erythromycin 250mg
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 is highly effective in the treatment of a great variety of clinical infections such as:
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 infections: Gingivitis, Vincent's angina
6. Skin and soft tissue infections: Boils and carbuncles, paronychia, abscesses, pustular 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
Adults and older children: Usual dosage is one tablet every four to six hours. This may be increased to 4g per day unusually severe infection.
Oral Use: Swallow whole with a glass of water. Do not crush or chew.
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.
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 and nearly with 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.
Rhabdomyolysis with or without renal impairment has been reported in seriously ill patients receiving erythromycin concomitantly with lovastatin.
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.
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, pimozide 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 (see sections 4.3 and 4.8). Death has been reported with the terfenadine/erythromycin combination.
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) 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.
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.
Pos-marketing reports indicate that 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 and ischaemia of the central nervous system, extremities and other tissues (see section 4.3)
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, theophylline, triazolam, valproate, and warfarin. Appropriate monitoring should be undertaken and dosage should be adjusted as necessary. Particular care should be taken with medications known to prolong the QTc 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 has been reported to increase concentrations of HMG-CoA reductase inhibitors (e.g. lovastatin and simvastatin). 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 has been reported to decrease the clearance of zopiclone and thus may increase the pharmacodynamic effects of this drug.
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 also a significant decrease in erythromycin serum concentrations. The decrease could result in sub therapeutic 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.
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.
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.
4.7 Effects on ability to drive and use machines
None stated
4.8 Undesirable effects
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. 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, and/or abnormal liver function test results may occur.
Blood and lymphatic system disorders:
Eosinophilia.
Cardiac disorders
QTc interval prolongation, torsades de pointes, palpitations, and cardiac rhythm disorders including ventricular tachyarrhythmias.
Ear and labyrinth disorders Deafness, tinnitus
There have been isolated reports of reversible hearing loss occurring chiefly in patients with renal insufficiency or high doses.
Gastrointestinal disorders
The most frequent side effects of oral erythromycin preparations are gastrointestinal and are dose-related. The following have been reported: upper abdominal discomfort, nausea, vomiting, diarrhoea, pancreatitis, anorexia, 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
Cholestatic hepatitis, jaundice, hepatic disfunction, hepatomegaly, hepatic failure, hepatocellular hepatitis (see section 4.4).
Immune system disorders
Allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis have occurred.
Investigations
Increased liver enzyme values.
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.
Psychiatric disorders
Hallucinations
Renal and urinary disorders
Interstitial nephritis
Skin and subcutaneous tissue disorders
Skin eruptions, prurituls, urticaria, exanthema, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.
Vascular disorders Hypotension.
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.
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.
6.1 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)
6.2 Incompatibilities
Not applicable
6.3 Shelf life
Tablet container:
Nature: Polypropylene tamper evident tablet container with polyethylene cap. Shelf Life: 2 years
Blister:
Nature: 250 um PVC/20 um aluminium blister packs
Shelf Life: 3 years
Bag:
Nature: Polyethylene sealed bag
Shelf Life: 2 Years
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: 250um PVC/20um 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
Nothing stated
7. Marketing Authorisation Holder
Medreich Plc Warwick House Plane Tree Crescent Feltham TW13 7HF
8 MARKETING AUTHORISATION NUMBER(S)
PL 21880/0069
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
28/07/2010
10 DATE OF REVISION OF THE TEXT
12/12/2013