A National 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.

Resubmission of National Type IB variation application under change code C.1.z to amend SmPC sections 4.4, 4.8 and consequentially sections of the PIL, in line with the recommendations of PRAC with Erythromycin containing products

Following information has been added to Section 4.4 "As with other macrolides, rare serious allergic reactions, including acute generalised exanthematous pustulosis (AGEP) have been reported. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued."

Following information has been updated in Section 4.8: Frequency of Adverse Events has been added. 

4.2 added :

Hepatic impairment

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

4.3 added “domperidone”:

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)

6.6 Added:

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

4.2 added :

Hepatic impairment

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

4.3 added “domperidone”:

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)

6.6 Added:

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

List of updates to previous SPC for Erythrocin Tablets 250mg – October 2012

Section 4.1 (Therapeutic indications):

-        Grammatical update to title case.

-        Updated indications to read: ‘For the treatment of infections caused by erythromycin-sensitive organisms’.

Section 4.2 (Posology and method of administration):

-        Updated dosing guidelines for adults and children over 8 years.

-        Note to say that for younger children the erythromycin ethylsuccinate suspensions are recommended.

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):

-        Expansion of statement regarding reports of patients with pseudomembranous colitis following antibiotic therapy.

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

-        Addition of statement detailing infantile hypertrophic pyloric stenosis (IPHS) occurring in infants following erythromycin therapy.

-        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.

-        Significant changes made to this section including:

o        details of drugs which may have an increased serum level following erythromycin therapy due to the metabolism by the cytochrome P450 system

o        details of drugs which may cause sub therapeutic levels of erythromycin

o        interactions with contraceptives, antihistamines, protease inhibitors and other antibacterials

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):

-        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):

-        Updated to read:

Peak blood levels normally occur within one hour of dosing of erythromycin ethylsuccinate granules. The elimination half life is approximately two hours.  Doses may be administered two, three or four times a day.

.

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 5.3 (Pre clinical safety data)

-        Updated with current data available.

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

-        Updated to read October 2012.

List of updates to previous SPC for Erythrocin Tablets 250mg – October 2012

Section 4.1 (Therapeutic indications):

-        Grammatical update to title case.

-        Updated indications to read: ‘For the treatment of infections caused by erythromycin-sensitive organisms’.

Section 4.2 (Posology and method of administration):

-        Updated dosing guidelines for adults and children over 8 years.

-        Note to say that for younger children the erythromycin ethylsuccinate suspensions are recommended.

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):

-        Expansion of statement regarding reports of patients with pseudomembranous colitis following antibiotic therapy.

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

-        Addition of statement detailing infantile hypertrophic pyloric stenosis (IPHS) occurring in infants following erythromycin therapy.

-        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.

-        Significant changes made to this section including:

o        details of drugs which may have an increased serum level following erythromycin therapy due to the metabolism by the cytochrome P450 system

o        details of drugs which may cause sub therapeutic levels of erythromycin

o        interactions with contraceptives, antihistamines, protease inhibitors and other antibacterials

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):

-        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):

-        Updated to read:

Peak blood levels normally occur within one hour of dosing of erythromycin ethylsuccinate granules. The elimination half life is approximately two hours.  Doses may be administered two, three or four times a day.

.

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 5.3 (Pre clinical safety data)

-        Updated with current data available.

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

-        Updated to read October 2012.