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ERYTHROMYCIN 500 MG/5ML SUGAR FREE GRANULES FOR ORAL SUSPENSION

Active substance(s): ERYTHROMYCIN ETHYL SUCCINATE ESTER

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Erythromycin 500 mg/5 ml Sugar Free Granules for Oral Suspension

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 5 ml of reconstituted suspension contains 500 mg of Erythromycin (as
ethyl succinate ester).
For excipients, see 6.1

3.

PHARMACEUTICAL FORM
Granules for oral suspension.
Sugar free, orange flavour oral suspension.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Erythromycin is indicated for the treatment / prophylaxis of infections caused
by erythromycin-sensitive organisms:•









upper and lower respiratory tract infections
Skin and soft tissue infections
bone infections
gastro –intestinal infections
oral/dental infections
eye infections
sexually transmitted diseases
prophylaxis of whooping cough and diphtheria
as an alternative to penicillin for staphylococcal infections in sensitive
patients

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

4.2

Posology and method of administration
Weights expressed as Erythromycin equivalents
For oral administration only
Adults, including elderly and children over 8 years:
250 – 500 mg every six hours, up to 4 g daily for more severe infections
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 2 to 8 years:
250 mg every six hours, doubled for severe infections
30 mg/kg/day in divided doses.
For severe infections up to 50 mg/kg/day in divided doses.
Children up to 2 years:
125 mg every six hours, doubled for severe infections
30mg/kg/day in divided doses.
For severe infections up to 50 mg/kg/day in divided doses.
Renal Impairment
If impairment is severe (GFR< 10ml/min), the daily dose should not exceed
1.5 g due to risk of ototoxicity

4.3

Contraindications
Known sensitivity to erythromycin
Contra-indicated with either astemizole or terfenadine, cisapride, 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
catecholamines.

with

the

fluorometric

determination

of

urinary

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 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.
Patients with rare hereditary problems of fructose intolerance 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 of erythromycin overdosage include severe nausea, vomiting and
diarrhoea and loss of hearing. Treatment consists of gastric lavage and
symptomatic and supportive therapy as needed. Erythromycin is not
dialysable.

5.

PHARMACOLOGICAL PROPERTIES

5.1.

Pharmacodynamic properties
Macrolides and Lincosamides, Macrolides

J01F A01

Following hydrolysis to the biologically active Erythromycin, the molecule
acts by inhibition of protein synthesis. This is done by binding to the 50s
ribosome sub unit of susceptible microorganisms. This association is
reversible and binding can only occur when the sub unit is free from tRNA
with nascent polypeptides. Production of small peptides goes on normally in
the presence of the antibiotic, but the production of highly polymerised
homopeptides is suppressed.
Gram positive organisms accumulate more Erythromycin than do Gram
negative organisms. The non-ionised form is more permeable to cells, this
probably explains the increased anti-microbial activity observed at alkaline
pH.

5.2.

Pharmacokinetic properties
Erythromycin Ethylsuccinate passes through the stomach, virtually unaffected
by the gastric fluid. Hydrolysis occurs in the duodenum giving Erythromycin
base, which is absorbed from the upper part of the small intestine. Absorption
is facilitated if the stomach is empty.
Peak plasma concentrations are reached 1 to 2 hours post administration,
plasma half-life is ca 1.6 hours.
It is excreted in active form in both urine and faeces. It is concentrated in the
liver, where some may be inactivated by demethylation and excreted in the
active form in the bile. The drug is not removed by either peritoneal dialysis
or haemodialysis. It diffuses readily into intracellular fluids and antibacterial

activity can be achieved at essentially all sites. There is some retention in liver
and spleen. Only low concentrations are achieved in cerebrospinal fluid,
unless the meninges are inflamed.
Diffusion into the aqueous humour, but not the vitreous humour of the eye is
good.
A significant proportion is bound to serum proteins.
It traverses the placenta barrier but gives low concentrations ca 5-10%
maternal levels, in the foetal plasma. It appears in breast milk.

5.3.

Preclinical safety data
There are no preclinical data of relevance to the prescriber, which are
additional to that already included in other sections of the SPC.

6.

PHARMACEUTICAL PARTICULARS

6.1.

List of excipients
Colloidal anhydrous silica
Sorbitol
Riboflavin-5-sodium phosphate
Orange flavour (contains propylene glycol)
Glyceryl mono and distearate (Atmer 122 (Atmos 150))
Anhydrous disodium hydrogen phosphate
Carmellose sodium

6.2.

Incompatibilities
None known.

6.3

Shelf life
Unopened 3 years
Once reconstituted 14 days

6.4.

Special precautions for storage
Granules: Do not store above 25°C.

Following reconstitution: Store at 2°C - 8°C (in a refrigerator). Do not freeze.
When storing keep the cap tightly closed. The reconstituted granules have a
shelf life of 14 days. Shake well before administration. Keep out of the reach
and sight of children.

6.5.

Nature and contents of container
Amber (Type III) glass bottle with tamper evident polypropylene cap (100 ml,
140 ml, and 150 ml).
White HDPE plastic bottles with wadded, tamper evident polypropylene cap
(100 ml, 125 ml, 140 ml, and 150 ml).
Pack sizes 60 ml, 100 ml
Not all pack sizes may be marketed.

6.6.

Instruction for use and handling (and disposal)
60 ml suspension: To reconstitute add 36 ml water and shake the bottle
vigorously. The resulting suspension is yellow in colour.
100 ml suspension: To reconstitute add 60 ml water and shake the bottle
vigorously. The resulting suspension is yellow in colour.

7.

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

8.

MARKETING AUTHORISATION NUMBER
PL 04917/0050

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
22/06/2009

10

DATE OF REVISION OF THE TEXT
03/11/2015

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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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