Erythrocin IV Lactobionate 1.0g Powder for Solution for Infusion

Section 4.4 updated with the following wording:$0As 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. $0$0$0$0$0Section 4.8 updated with the following wording:$0$0acute generalised exanthematous pustulosis (AGEP)$0

Section 4.4 updated with the following wording:$0As 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. $0$0$0$0$0Section 4.8 updated with the following wording:$0$0acute generalised exanthematous pustulosis (AGEP)$0

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

Sections 2,4.1-4.6,4.8,5.1-5.2,6.1,6.6,7,9 & 10 are updated

Sections 2,4.1-4.6,4.8,5.1-5.2,6.1,6.6,7,9 & 10 are updated

Section 4.1 (Therapeutic indications):

-        Updated to read ‘Erythromycin is indicated for the prophylaxis and treatment of infections caused by erythromycin sensitive organisms.’

 

Section 4.2 (Posology and method of administration):

-        Updated dilution and administration guidelines to enable user to have a clearer understanding of recommended use of product.

 

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.

-        Added statement ‘Bolus injection (IV push) is an unacceptable route of administration.’

 

Section 4.4 (Special warnings and precautions for use):

-        Added warning regarding rare reports of prolongation of QTc interval and ventricular arrhythmias in patients receiving IV erythromycin.

-        Added warning alerting user to benzyl alcohol in product associated with fatal ‘Gasping Syndrome’ in premature patients.

-        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 case.

-        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

 

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:

 

Following intravenous infusion, erythromycin is widely distributed throughout body tissues, including lung tissues.

 

Section 5.2 (Pharmacokinetic properties):

-        Addition of deleted paragraph from section 5.1 above.

-        Deletion of following paragraphs:

o        Intravenous infusion of 500mg Erythromycin Lactobionate at a constant rate over 1 hour in fasting adults produced a mean serum erythromycin level of approximately 7 mcg/ml at 20 minutes, 10 mcg/ml at 1 hour, 2.6 mcg/ml at 2.5 hours and 1 mcg/ml at 6 hours. Erythromycin diffuses readily into most body fluids. Only low concentrations are normally achieved in the spinal fluid, but passage of the drug across the blood - brain barrier increases in meningitis.

 

In the presence of normal hepatic function, erythromycin is concentrated in the liver and excreted in the bile; the effect of hepatic dysfunction on excretion of erythromycin by the liver into the bile is not known.   From 12 - 15% of intravenously administered erythromycin is excreted in active form in the urine.

 

Section 6.1 (List of excipients):

-        Grammatical update to title case.

 

Section 6.2 (Incompatibilities)

-        Updated to read ‘This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6’

 

Section 6.3 (Shelf life)

-        Updated to read:

 

            3 years.

Once opened the product should be used immediately after reconstitution. When aseptically prepared the solution may be kept for not more than 24 hours if stored under refrigeration at a temperature between 2ºC and 8ºC.

 

Section 6.4 (Special precautions for storage)

-        Updated to advise user to check section 6.3.

 

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

-        Updated to read October 2012.

Section 4.1 (Therapeutic indications):

-        Updated to read ‘Erythromycin is indicated for the prophylaxis and treatment of infections caused by erythromycin sensitive organisms.’

 

Section 4.2 (Posology and method of administration):

-        Updated dilution and administration guidelines to enable user to have a clearer understanding of recommended use of product.

 

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.

-        Added statement ‘Bolus injection (IV push) is an unacceptable route of administration.’

 

Section 4.4 (Special warnings and precautions for use):

-        Added warning regarding rare reports of prolongation of QTc interval and ventricular arrhythmias in patients receiving IV erythromycin.

-        Added warning alerting user to benzyl alcohol in product associated with fatal ‘Gasping Syndrome’ in premature patients.

-        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 case.

-        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

 

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:

 

Following intravenous infusion, erythromycin is widely distributed throughout body tissues, including lung tissues.

 

Section 5.2 (Pharmacokinetic properties):

-        Addition of deleted paragraph from section 5.1 above.

-        Deletion of following paragraphs:

o        Intravenous infusion of 500mg Erythromycin Lactobionate at a constant rate over 1 hour in fasting adults produced a mean serum erythromycin level of approximately 7 mcg/ml at 20 minutes, 10 mcg/ml at 1 hour, 2.6 mcg/ml at 2.5 hours and 1 mcg/ml at 6 hours. Erythromycin diffuses readily into most body fluids. Only low concentrations are normally achieved in the spinal fluid, but passage of the drug across the blood - brain barrier increases in meningitis.

 

In the presence of normal hepatic function, erythromycin is concentrated in the liver and excreted in the bile; the effect of hepatic dysfunction on excretion of erythromycin by the liver into the bile is not known.   From 12 - 15% of intravenously administered erythromycin is excreted in active form in the urine.

 

Section 6.1 (List of excipients):

-        Grammatical update to title case.

 

Section 6.2 (Incompatibilities)

-        Updated to read ‘This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6’

 

Section 6.3 (Shelf life)

-        Updated to read:

 

            3 years.

Once opened the product should be used immediately after reconstitution. When aseptically prepared the solution may be kept for not more than 24 hours if stored under refrigeration at a temperature between 2ºC and 8ºC.

 

Section 6.4 (Special precautions for storage)

-        Updated to advise user to check section 6.3.

 

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

-        Updated to read October 2012.

Product: Erythromycin IV Lactobionate

PA Number: PA 1142/8/1

Type of Variation: Type II

Reason for variation: To update sections of the SPC, Labelling and PIL at the request of the IMB.

Date of Approval: 25/02/08

Product: Erythromycin IV Lactobionate

PA Number: PA 1142/8/1

Type of Variation: Type II

Reason for variation: To update sections of the SPC, Labelling and PIL at the request of the IMB.

Date of Approval: 25/02/08