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ERYTHROMYCIN ETHYLSUCCINATE 250 MG/5 ML GRANULES FOR ORAL SUSPENSION

Active substance(s): ERYTHROMYCIN ETHYL SUCCINATE / ERYTHROMYCIN ETHYL SUCCINATE / ERYTHROMYCIN ETHYL SUCCINATE

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1

NAME OF THE MEDICINAL PRODUCT
Erythromycin ethyl succinate 250 mg/5 ml Granules for Oral Suspension

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION
Erythromycin ethylsuccinate ep 250 mg/5 ml
(where each mg of base is taken to be equivalent to 1000 units of activity)

3.

PHARMACEUTICAL FORM

Granules for Oral Suspension

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Antibiotic for treatment of infections caused by erythromycin sensitive organisms
especially gram positive pyogenic cocci and some gram-negative bacteria. It may be
used in a wide variety of clinical infections.
Erythromycin is an appropriate alternative to penicillin in hypersensitive patients
especially in pre or post operative patients.
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.
Eye/Ear infections:
Otitis media and otitis externa mastoiditis, chlamydial conjunctivitis, blepharitis.
Oral infections:
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
Route of Administration: Oral
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;
250-500 mg every 6 hours or 0.5-1 g every 12 hours

For acne vulgaris the usual dose is 250 mg three times daily before meals for one to
four weeks and then reduced to twice daily until improvement occurs
Children Aged 2 to 8 years
For mild to moderate infections 1 g daily in divided doses;
250 mg every 6 hours

30 mg/kg/day in divided doses. For severe infections up to 50 mg/kg/day in divided
doses.
Infants and Babies up to 2 Years
For mild to moderate infections 500 mg daily in divided doses;
125 mg every 6 hours

30mg/kg/day in divided doses. For severe infections up to 50 mg/kg/day in divided
doses.
Elderly
No special dosage recommendations
For severe infections dosage may be doubled.
Duration of dosage regimen is dependant on the nature of the infection and is at the discretion
of the physician

4.3

Contraindications
Known hypersensitivity to erythromycin.
Erythromycin is contraindicated in patients taking astemizole, terfenadine, cisapride
or pimozide, 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.
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.
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.

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 nonbilious 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

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, vinblastine, and antifungals e.g. fluconazole, ketoconazole
and itraconazole. 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 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 sections 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) 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 with ergotamine or
dihydroergotamine has been associated 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 QTc 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 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.
Erythromycin has been reported to decrease the clearance of zopiclone and thus may increase
the pharmacodynamic effects of this drug.

4.6

Pregnancy and lactation
Erythromycin crosses the placenta resulting in low foetal plasma concentrations. As
with all drugs, erythromycin should be used in pregnancy only when clearly
indicated. Erythromycin is excreted in breast milk in concentrations that may exceed
maternal serum concentrations. Although problems in breast –fed infants has not been
documented, there are three potential problems for the nursing infant:•



modification of bowel flora
direct effects on the infant such as allergy/sensitisation
interference with the interpretation of culture results when a pyrexia of
unknown origin occurs

Erythromycin should only be used in lactating women only if clearly needed.

4.7.

Effects on Ability to Drive and Use Machines
None known

4.8
Undesirable Effects
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 taking 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, pruritus, urticaria, exanthema, angioedema, Stevens-Johnson syndrome, toxic
epidermal necrolysis, erythema multiforme.
Vascular disorders
Hypotension.
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:
Treatment:

Mainly confined to nausea, vomiting and diarrhoea
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:
Gram-positive bacteria such as staph aureus, staph epidermis, strop pyogenes, strep
Pneumoniae, strep viridans, corynebacterium diptheriae and listeria monocytogenes;
Gram-negative bacteria such as h influenzae, n meningitidis, n gonorrhoea, b
pertussis, campylobacter strains and legionella pneumophila; treponema pallidum ;
mycoplasma pneumoniae ; chlamydia trachomatis.

5.2.

Pharmacokinetic Properties

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 ug/ml (from a 250 mg dose) ;
t1/2= 1.6 ± 0.7 hours
Erythromycin is excreted in high concentrations in the bile and up to 5 % of an oral dose may
appear in the urine; considerable amounts may also be inactivated in the body

5.3.

Preclinical Safety Data

None stated

6.

PHARMACEUTICAL PARTICULARS

6.1.

List of Excipients
Sodium Carboxymethylcellulose
Sodium Citrate
Banana Flavour E4210 SD
Quinoline Yellow 14031 E104
Sodium Saccharin
Colloidal Silicon Dioxide
Sucrose (Caster Sugar)

6.2.

Incompatibilities
Not appropriate

6.4.

Special precautions for storage
Granules:
Reconstituted syrup:

6.4.

Special Precautions for Storage
Granules:
Reconstituted Syrup:

6.5.

3 years (Glass)
3 years (Plastic)
14 days (Glass and Plastic)

Do not store above 250c
Do not store above 150c

Nature and Contents of Container

Amber glass bottles with pilfer evident cap
High density polyethylene bottles with pilfer proof screw caps
Pack sizes 100 ml and 140 ml.
High density polyethylene bottles with Child Resistant Closures (CRC caps).

6.6.

Instructions for Use, Handling and Disposal

Reconstitute with water to 100 ml before use.
Reconstitute with water to 140 ml before use.

7.

MARKETING AUTHORISATION HOLDER
Pinewood Laboratories Limited
Ballymacarbry,
Clonmel,
Co Tipperary,
Ireland

8.

MARKETING AUTHORISATION NUMBER(S)

PL 04917/0014

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
31/03/2006

10

DATE OF REVISION OF THE TEXT
03/11/2015

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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