A National Bulk Type IAIN variation application under change code C.I.z to amend SmPC sections 4.3, 4.4, 4.5, 4.8 and corresponding sections of PIL, in line with PRAC recommendation

Hepatic impairment

Erythromycin should be used with caution in patients with impaired hepatic function (see sections 4.4 & 5.2).

Erythromycin is contraindicated in patients taking astemizole, terfenadine, domperidone, cisapride or pimozide.

4.4 Added:

Patients receiving erythromycin concurrently with drugs which can cause prolongation of the QT interval should be carefully monitored. The concomitant use of erythromycin with some of these drugs is contraindicated (See sections 4.3 & 4.5)

4.5 Added:

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

4.8 Removed Psychiatric disorders
4.9 Treatment changed to management
6.6 Added:

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements

Hepatic impairment

Erythromycin should be used with caution in patients with impaired hepatic function (see sections 4.4 & 5.2).

Erythromycin is contraindicated in patients taking astemizole, terfenadine, domperidone, cisapride or pimozide.

4.4 Added:

Patients receiving erythromycin concurrently with drugs which can cause prolongation of the QT interval should be carefully monitored. The concomitant use of erythromycin with some of these drugs is contraindicated (See sections 4.3 & 4.5)

4.5 Added:

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

4.8 Removed Psychiatric disorders
4.9 Treatment changed to management
6.6 Added:

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements

Section 4.1 (Therapeutic indications):

-        Grammatical update to title case.

Section 4.2 (Posology and method of administration):

-        Grammatical update to title case.

-        Updated dosing guidelines for adults and children.

-        Children’s dosing split into age bands to enable easier dose calculation.

Section 4.3 (Contraindications):

-        Updated hypersensitivity statement.

-        Removal of statement ‘Use in patients with serious impairment of liver function’ as this is documented in section 4.4.

Section 4.4 (Special warnings and precautions for use):

-        Grammatical update to title case.

-        Expansion of warnings for use in patients with pseudomembranous colitis.

-        Addition of warnings of reports of Clostridium difficile-associated diarrhoea (CDAD) with erythromycin use.

-        Deletion of paragraph discussing use of erythromycin in patients taking drugs metabolised by the cytochrome P450 system as this is documented in section 4.5.

Section 4.5 (Interactions with other medicinal products and other forms of interaction):

-        Grammatical update to title case.

-        Significant changes made to this section including

Section 4.6 (Fertility, pregnancy and lactation):

-        Title of section changed from ‘Pregnancy and lactation’

-        Amended section to read:

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.

Erythromycin is excreted in breast milk, therefore, caution should be exercised when erythromycin is administered to a nursing mother.

Section 4.8 (Undesirable effects):

-        Grammatical update to title case.

-        Sorted into system order class (SOC).

Section 5.1 (Pharmacodynamic properties):

-        Addition of information which specifies the strains of bacteria sensitive to erythromycin.

-        Deletion of paragraph below in this section as moved to section 5.2:

Erythromycin ethylsuccinate is less susceptible than erythromycin to the adverse effect of gastric acid.  It is absorbed from the small intestine. It is widely distributed throughout body tissues. Little metabolism occurs and only about 5% is excreted in the urine. It is excreted principally by the liver.

Section 5.2 (Pharmacokinetic properties):

-        Addition of deleted paragraph from section 5.1 above.

Section 5.3 (Preclinical safety data):

-        Grammatical update to title case.

Section 10 (Date of (partial) revision of the text):

-        Updated to read October 2012.

Section 4.1 (Therapeutic indications):

-        Grammatical update to title case.

Section 4.2 (Posology and method of administration):

-        Grammatical update to title case.

-        Updated dosing guidelines for adults and children.

-        Children’s dosing split into age bands to enable easier dose calculation.

Section 4.3 (Contraindications):

-        Updated hypersensitivity statement.

-        Removal of statement ‘Use in patients with serious impairment of liver function’ as this is documented in section 4.4.

Section 4.4 (Special warnings and precautions for use):

-        Grammatical update to title case.

-        Expansion of warnings for use in patients with pseudomembranous colitis.

-        Addition of warnings of reports of Clostridium difficile-associated diarrhoea (CDAD) with erythromycin use.

-        Deletion of paragraph discussing use of erythromycin in patients taking drugs metabolised by the cytochrome P450 system as this is documented in section 4.5.

Section 4.5 (Interactions with other medicinal products and other forms of interaction):

-        Grammatical update to title case.

-        Significant changes made to this section including

Section 4.6 (Fertility, pregnancy and lactation):

-        Title of section changed from ‘Pregnancy and lactation’

-        Amended section to read:

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.

Erythromycin is excreted in breast milk, therefore, caution should be exercised when erythromycin is administered to a nursing mother.

Section 4.8 (Undesirable effects):

-        Grammatical update to title case.

-        Sorted into system order class (SOC).

Section 5.1 (Pharmacodynamic properties):

-        Addition of information which specifies the strains of bacteria sensitive to erythromycin.

-        Deletion of paragraph below in this section as moved to section 5.2:

Erythromycin ethylsuccinate is less susceptible than erythromycin to the adverse effect of gastric acid.  It is absorbed from the small intestine. It is widely distributed throughout body tissues. Little metabolism occurs and only about 5% is excreted in the urine. It is excreted principally by the liver.

Section 5.2 (Pharmacokinetic properties):

-        Addition of deleted paragraph from section 5.1 above.

Section 5.3 (Preclinical safety data):

-        Grammatical update to title case.

Section 10 (Date of (partial) revision of the text):

-        Updated to read October 2012.

Update sections 2, 4.1, 4.4, 4.5, 5.1, 6.4 and 10 as noted below in bold following renewal of licence.

2.         Qualitative and Quantitative Composition

Erythromycin (as erythromycin ethylsuccinate) 125 mg per 5 ml

Excipients - Contains sorbitol (E420) 1182mg/5ml, Sodium methylhydroxybenzoate (E219) 5mg/5ml and sodium propylhydroxybenzoate (E217) 1mg/5ml. This medicinal product contains 4.21 mg of sodium per ml of suspension (equates to 21.05mg/5ml dose).

For a full list of excipients, see section 6.1

4.1       Therapeutic Indications

Erythromycin is indicated for the treatment of infections caused by erythromycin sensitive organisms. Consideration should be given to official guidance on the appropriate use of antibacterial agents.

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 hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been infrequently reported with erythromycin.

The use of erythromycin in patients concurrently taking drugs metabolised by the cytochrome P450 system may be associated with elevations in serum levels of these drugs (see sections 4.5).  Serum concentrations should be closely monitored in patients receiving erythromycin.

Prolonged or repeated use of erythromycin may result in overgrowth of non-susceptible bacteria.   If super-infection occurs, erythromycin should be discontinued and appropriate therapy instituted.

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 carefully considered against the potential risk of developing IHPS.  Parents should be informed to contact their physician if vomiting or irritability occur.

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.

As with other broad spectrum antibiotics, pseudomembranous colitis has been reported rarely with erythromycin (see section 4.8).

Rhabdomyolysis with or without renal impairment has been reported in seriously ill patients receiving erythromycin concomitantly with lovastatin (see section 4.5).

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

Colchicine toxicity has been reported in patients receiving erythromycin concomitantly with colchicines (see section 4.5).

Laboratory Tests:

Erythromycin interferes with the fluorometric determination of urinary catecholamines.

Contains sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take this medicine. Contains parahydroxybenzoates which may cause allergic reactions (possibly delayed).

This medicinal product contains 4.21 mg of sodium per ml of suspension (equates to 21.05 mg/5ml dose). This needs to be taken into consideration when prescribing for patients on a sodium-restricted diet.

4.5   Interactions with other medicinal products and other forms of interaction

5.1       Pharmacodynamic properties

ATC Code: J01FA

Pharmacotherapeutic group: Macrolides

Erythromycin ethylsuccinate is less susceptible than erythromycin to the adverse effect of gastric acid. It is absorbed from the small intestine. It is widely distributed throughout body tissues. Little metabolism occurs and only about 5% is excreted in the urine. It is excreted principally by the liver.

6.4       Special Precautions for Storage

Do not store above 25°C. Keep the bottle tightly closed.

10.       Date of (Partial) Revision of the Text

September 2010

Update sections 2, 4.1, 4.4, 4.5, 5.1, 6.4 and 10 as noted below in bold following renewal of licence.

2.         Qualitative and Quantitative Composition

Erythromycin (as erythromycin ethylsuccinate) 125 mg per 5 ml

Excipients - Contains sorbitol (E420) 1182mg/5ml, Sodium methylhydroxybenzoate (E219) 5mg/5ml and sodium propylhydroxybenzoate (E217) 1mg/5ml. This medicinal product contains 4.21 mg of sodium per ml of suspension (equates to 21.05mg/5ml dose).

For a full list of excipients, see section 6.1

4.1       Therapeutic Indications

Erythromycin is indicated for the treatment of infections caused by erythromycin sensitive organisms. Consideration should be given to official guidance on the appropriate use of antibacterial agents.

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 hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been infrequently reported with erythromycin.

The use of erythromycin in patients concurrently taking drugs metabolised by the cytochrome P450 system may be associated with elevations in serum levels of these drugs (see sections 4.5).  Serum concentrations should be closely monitored in patients receiving erythromycin.

Prolonged or repeated use of erythromycin may result in overgrowth of non-susceptible bacteria.   If super-infection occurs, erythromycin should be discontinued and appropriate therapy instituted.

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 carefully considered against the potential risk of developing IHPS.  Parents should be informed to contact their physician if vomiting or irritability occur.

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.

As with other broad spectrum antibiotics, pseudomembranous colitis has been reported rarely with erythromycin (see section 4.8).

Rhabdomyolysis with or without renal impairment has been reported in seriously ill patients receiving erythromycin concomitantly with lovastatin (see section 4.5).

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

Colchicine toxicity has been reported in patients receiving erythromycin concomitantly with colchicines (see section 4.5).

Laboratory Tests:

Erythromycin interferes with the fluorometric determination of urinary catecholamines.

Contains sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take this medicine. Contains parahydroxybenzoates which may cause allergic reactions (possibly delayed).

This medicinal product contains 4.21 mg of sodium per ml of suspension (equates to 21.05 mg/5ml dose). This needs to be taken into consideration when prescribing for patients on a sodium-restricted diet.

4.5   Interactions with other medicinal products and other forms of interaction

5.1       Pharmacodynamic properties

ATC Code: J01FA

Pharmacotherapeutic group: Macrolides

Erythromycin ethylsuccinate is less susceptible than erythromycin to the adverse effect of gastric acid. It is absorbed from the small intestine. It is widely distributed throughout body tissues. Little metabolism occurs and only about 5% is excreted in the urine. It is excreted principally by the liver.

6.4       Special Precautions for Storage

Do not store above 25°C. Keep the bottle tightly closed.

10.       Date of (Partial) Revision of the Text

September 2010