Last Updated on eMC 04-02-2014 View medicine  | Leo Laboratories Limited Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Correction of spelling/typing errors

Date of revision of text on the SPC:01-10-2013

Legal Category:POM

Black Triangle (CHM): NO

Reasons for adding or updating:

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:01-10-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 7 Marketing Authorisation Holder

LEO Laboratories Limited

Princes Risborough

Bucks

HP27 9RR

Horizon

Honey Lane

Hurley

Maidenhead

Berkshire

SL6 6RJ

UK

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:24-10-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



4.8       Undesirable effects


Hepatobiliary disorders

Not known:

Cholestasis


10      DATE OF REVISION OF THE TEXT

23 December 2011

24 October 2012


Reasons for adding or updating:

  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable Effects
  • Change to section 4.9 - Overdose
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:23-12-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



4.3       Contraindications

Contraindicated in patients with known hypersensitivity to fusidic acid and its salts.

Hypersensitivity to fusidic acid and its salts, or to any of the excipients.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsoprtion should not take this medicine.

4.4       Special warnings and precautions for use

Fucidin® must not be co-administered with statins. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination (see section 4.5). In patients where the use of systemic Fucidin® is considered essential, statin treatment should be discontinued throughout the duration of Fucidin® treatment. The patient should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, pain or tenderness. Statin therapy may be re-introduced seven days after the last dose of Fucidin®. In exceptional circumstances, where prolonged systemic Fucidin® is needed e.g for the treatment of severe infections, the need for co-administration of statin and Fucidin® should only be considered on a case by case basis and under close medical supervision.

Fusidic acid is metabolised in the liver and excreted in the bile.  Caution should be exercised with other antibiotics which have similar biliary excretion pathways e.g. lincomycin and rifampicin.  Elevated liver enzymes and jaundice have occurred during systemic therapy but are usually reversible on discontinuation of the drug (see section 4.8).

Periodic liver function tests should be carried out when high oral doses are used, when the drug is given for prolonged periods and in patients with liver dysfunction. the product is given:

·      in high oral doses

·      for prolonged periods

·      to patients with liver dysfunction

·      to patients taking potentially hepatotoxic medication

·      to patients with biliary tract obstruction

·      to patients taking concurrent medication with a similar excretion pathway.

Fucidin®Fusidic acid displaces bilirubin from its albumin binding site in vitro.  Caution is necessary if this product is administered to patients with impaired transport and metabolism of bilirubin.The clinical significance of this finding is uncertain and kernicterus has not been observed in neonates receiving Fucidin®. However, this observation should be borne in mind when the drug is given to pre-term, jaundiced, acidotic or seriously ill neonates.

The use of Fucidin® in combination with drugs that are CYP-3A4 biotransformed should be avoided. See Section 4.5.

Patients given Fucidin® systemically in combination with HMG-CoA reductase inhibitors should be closely clinically monitored. See Section 4.5.

Bacterial resistance has been reported to occur with the use of fusidic acid.  As with all antibiotics, extended or recurrent use may increase the risk of developing antibiotic resistance.

This medicinal product contains 0.45 mmol (11 mg) sodium per tablet.   This should be taken into consideration by patients on a controlled sodium diet.  


4.5       Interaction with other medicinal products and other forms of interaction

The risk of myopathy including rhabdomyolysis may be increased by the concomitant administration of systemic Fucidin® with statins. Co-administration of this combination may cause increased plasma concentrations of both agents. The mechanism of this interaction (whether it is pharmacodynamics or pharmacokinetic, or both) is yet unknown. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination. If treatment with Fucidin® is necessary, statin treatment should be discontinued throughout the duration of the Fucidin® treatment. Also see section 4.4.

Specific pathways of Fucidin® metabolism in the liver are not known, however, an interaction between Fucidin® and drugs being CYP-3A4 biotransformed can be suspected. The mechanism of this interaction is presumed to be a mutual inhibition of metabolism. There is insufficient data to characterise the effect of fusidic acid on CYPs in-vitro. The use of Fucidin® systemically should be avoided in patients treated with CYP-3A4 biotransformed drugs.

Fucidin® administered systemically and concomitantly with oral anticoagulants such as coumarin derivatives or anticoagulants with similar actions may increase the plasma concentration of these agents enhancing the anticoagulant effect.  Anticoagulation should be closely monitored and a decrease of the oral anticoagulant dose may be necessary in order to maintain the desired level of anticoagulation.  Similarly, discontinuation of Fucidin® may require the maintenance dose of anticoagulant to be re-assessed. The mechanism of this suspected interaction remains unknown.

Co-administration of Fucidin® systemically and HMG-CoA reductase inhibitors such as statins may cause increased plasma concentrations of both agents and rare cases of rhabdomyolysis have been reported for this combination. Patients on this combination should be closely clinically monitored.

Co-administration of Fucidin® Tablets and HIV protease inhibitors such as ritonavir and saquinavir causes increased plasma concentrations of both agents which may result in hepatotoxicity.

Co-administration of Fucidin® systemically and ciclosporin has been reported to cause increased plasma concentration of ciclosporin.



4.8       Undesirable effects

In some patients, given Fucidin®, particularly in the young and elderly, a reversible jaundice has been reported.  Jaundice has been seen most frequently in patients receiving intravenous Fucidin® in high dosage, or where the drug has been infused too rapidly or at too high a concentration in the infusion fluid.  In some instances instituting oral therapy may be beneficial.  If the jaundice persists Fucidin® should be withdrawn, following which the serum bilirubin will invariably return to normal.  Reported reactions are gastro-intestinal upsets and, rarely, skin rashes and other allergic reactions including anaphylaxis.  Isolated cases of haematological abnormalities which can affect the 3 blood cell lines but mainly white blood cells e.g. bone marrow depression, neutropenia, granulocytopenia, agranulocytosis and pancytopenia have been reported. Reported less often is a depressive effect on the platelets and red blood cells with reports of thrombocytopenia and various anaemias.  These abnormalities have been observed especially with treatment of more than 15 days.  Acute renal failure has been described in patients with jaundice, particularly in the presence of other factors predisposing to renal failure.Based on clinical trial data, undesirable effects occurred in approximately 15% of patients receiving Fucidin® orally.  The most frequently reported undesirable effects to Fucidin® administered orally are dose dependent gastrointestinal disorders.   Various skin reactions, reversible jaundice, haematological disorders and generalised hypersensitivity reactions have been reported.

Undesirable effects are listed below, by MedDRA System Organ Class, in decreasing order of frequency within each class.  Where frequencies are given, these are based on the clinical trial data, using the stated frequency classification. Where the term ‘Not known’ is given, these effects are derived from spontaneous reports.

Frequency classification:

Very common >1/10

Common         >1/100 and <1/10

Uncommon     >1/1,000 and <1/100

Rare                 >1/10,000 and <1/1,000

Very rare         <1/10,000

·      Blood and lymphatic system disorders

Not known:     Pancytopenia

                        Leukopenia*

                        Thrombocytopenia

                        Anaemia

                        *Haematological disorders affecting the white cell line (neutropenia, granulocytopenia, agranulocytosis) and, more rarely, disorders affecting the other two cell lines have been reported, either as isolated events or associated.   These abnormalities have been observed especially with treatment of more than 15 days and are reversible upon drug withdrawal.

·      Immune system disorders

Rare:                Allergic reaction

Not known:     Anaphylactic reaction

·      Metabolism and nutrition disorders

Uncommon:    Anorexia

·      Nervous system disorders

Common:        Drowsiness

Dizziness

Uncommon:    Headache

·      Gastrointestinal system disorders

Common:        Diarrhoea

Vomiting

                        Abdominal Pain

                        Dyspepsia

                        Nausea

·      Hepatobiliary disorders

Not known:     Hyperbilirubinaemia

                        Jaundice (see section 4.4)

                        Hepatic enzymes increased (see section 4.4)

Hepatorenal syndrome

                        Liver function abnormalities like hyperbilirubinaemia with or without jaundice and increase in hepatic enzymes such as alkaline phosphatase and transaminases should lead to withdrawal of treatment.  Return of laboratory parameters to normal is usual and generally rapid.

·      Skin and subcutaneous tissue disorders

Uncommon:    Rash*

Urticaria

Pruritus

*Rash includes various types of reactions such as erythematous, maculo-papular and pustular.

·      Musculoskeletal and connective tissue disorders

Not known:     Rhabdomyolysis (see Section 4.4 and 4.5)

                        Rhabdomyolysis may be fatal.   Examples of signs and symptoms are: muscle weakness, muscle swelling and muscle pain, dark urine, myoglobinuria, elevated serum creatine kinase, acute renal failure, cardiac arrhythmia.

·      Renal and urinary disorders

Not known:     Renal failure

Acute renal failure has been described in patients with jaundice, in particular in the presence of other factors predisposing to renal failure.

·      General disorders and administration site conditions

Uncommon:    Asthenia

Fatigue

Malaise


4.9       Overdose

Acute symptoms of overdose include gastrointestinal disturbances and possible effects on liver function.There has been no experience of overdosage with Fucidin®.  Treatment should be restricted to symptomatic and supportive measures.  Dialysis is of no benefit, since the drug is not significantly dialysed.Dialysis will not increase the clearance of fusidic acid.



10      DATE OF REVISION OF THE TEXT

April 2006  February 2010

April 2011

23 December 2011

Reasons for adding or updating:

  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:28-09-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



4.3       Contraindications

Concomitant treatment with statins, see section 4.5. In patients where the use of Fucidin® is considered essential, statin treatment must be temporarily discontinued.

Hypersensitivity to fusidic acid and its salts, or to any of the excipients.

Contraindicated in patients with known hypersensitivity to fusidic acid and its salts.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsoprtion should not take this medicine.


4.4       Special warnings and precautions for use

Fucidin® must not be co-administered with statins. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination (see section 4.5). In patients where the use of systemic Fucidin® is considered essential, statin treatment should be discontinued throughout the duration of Fucidin® treatment. The patient should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, pain or tenderness. Statin therapy may be re-introduced seven days after the last dose of Fucidin®. In exceptional circumstances, where prolonged systemic Fucidin® is needed e.g for the treatment of severe infections, the need for co-administration of statin and Fucidin® should only be considered on a case by case basis and under close medical supervision including appropriate laboratory monitoring.

Caution should be exercised with other antibiotics which have similar biliary excretion pathways e.g. lincomycin and rifampicin.  Periodic liver function tests should be carried out when high oral doses are used, when the drug is given for prolonged periods and in patients with liver dysfunction

Fucidin® displaces bilirubin from its albumin binding site in vitro.  The clinical significance of this finding is uncertain and kernicterus has not been observed in neonates receiving Fucidin®. However, this observation should be borne in mind when the drug is given to pre-term, jaundiced, acidotic or seriously ill neonates.

The use of Fucidin® in combination with drugs that are CYP-3A4 biotransformed should be avoided. See Section 4.5

Patients given Fucidin® systemically in combination with HMG CoA reductase inhibitors should be closely clinically monitored. See section 4.5


4.5       Interaction with other medicinal products and other forms of interaction

Co-administration of Fucidin® systemically and HMG-CoA reductase inhibitors such as statins may causes significantly increased plasma concentrations of both agents.  This may result in an elevation of creatinine kinase level and risk of rhabdomyolysis, muscle weakness and pain.  Concomitant treatment with statins is therefore contraindicated (see section 4.3).

The risk of myopathy including rhabdomyolysis may be increased by the concomitant administration of systemic Fucidin® with statins. Co-administration of this combination may cause increased plasma concentrations of both agents. The mechanism of this interaction (whether it is pharmacodynamics or pharmacokinetic, or both) is yet unknown. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination. If treatment with Fucidin® is necessary, statin treatment should be discontinued throughout the duration of the Fucidin® treatment. Also see section 4.4.

Specific pathways of Fucidin® metabolism in the liver are not known. However, an interaction between Fucidin® and drugs being CYP-3A4 biotransformed can be suspected. The mechanism of this interaction is presumed to be a mutual inhibition of metabolism. There is insufficient data to characterise the effect of fusidic acid on CYPs in-vitro. The use of Fucidin® systemically should be avoided in patients treated with CYP-3A4 biotransformed drugs.

Fucidin® administered systemically and concomitantly with oral anticoagulants such as coumarin derivatives or anticoagulants with similar actions may increase the plasma concentration of these agents enhancing the anticoagulant effect.  Anticoagulation should be closely monitored and a decrease of the oral anticoagulant dose may be necessary in order to maintain the desired level of anticoagulation.  Similarly, discontinuation of Fucidin® may require the maintenance dose of anticoagulant to be re-assessed. The mechanism of this suspected interaction remains unknown.

Co-administration of Fucidin® systemically and HMG CoA reductase inhibitors such as statins may cause increased plasma concentrations of both agents and rare cases of rhabdomyolysis, have been reported for this combination. Patients on this combination should be closely clinically monitored.

Co-administration of Fucidin® systemically and ciclosporin has been reported to cause increased plasma concentration of ciclosporin.


4.8       Undesirable effects

In some patients, given Fucidin®, particularly in the young and elderly, a reversible jaundice has been reported.  Jaundice has been seen most frequently in patients receiving intravenous Fucidin® in high dosage, or where the drug has been infused too rapidly or at too high a concentration in the infusion fluid.  In some instances instituting oral therapy may be beneficial.  If the jaundice persists Fucidin® should be withdrawn, following which the serum bilirubin will invariably return to normal.  Reported reactions are gastro-intestinal upsets and, rarely, skin rashes and other allergic reactions including anaphylaxis.  Isolated cases of haematological abnormalities which can affect the 3 blood cell lines but mainly white blood cells e.g. bone marrow depression, neutropenia, granulocytopenia, agranulocytosis and pancytopenia have been reported. Reported less often is a depressive effect on the platelets and red blood cells with reports of thrombocytopenia and various anaemias.  These abnormalities have been observed especially with treatment of more than 15 days.  Acute renal failure has been described in patients with jaundice, particularly in the presence of other factors predisposing to renal failure.  Rhabdomyolysis (examples of signs and symptoms are: muscle weakness, muscle swelling and muscle pain, dark urine, myoglobinuria, elevated serum creatine kinase, acute reneal failure, cardiac arrhythmia), see section 4.4 and 4.5. Rhabdomyolysis may be fatal.


10      DATE OF REVISION OF THE TEXT

April 2006

September 2009

 November 2010

June 2011

July 2011

Reasons for adding or updating:

  • Change to section 4.3 - Contraindications
  • Change to section 6.1 - List of Excipients
  • Change to section 6. 4 - Special Precautions for Storage
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:01-04-2006

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.3: Addition of 'Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.'
Section 6.1: Change in excipients - gelatin and polyvinylpyrolidone deleted, all-rac-a-tocopherol added.
Section 6.4: Amendment from 'Do not store above 25C' to 'This medicinal product does not require any special storage conditions.'

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 (date of (partial) revision of the text

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 (date of (partial) revision of the text

Reasons for adding or updating:

  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.5 - Interactions with other Medicaments and other forms of Interaction
  • Change to section 10 (date of (partial) revision of the text

Reasons for adding or updating:

  • Transferred from eMC version 1

Reasons for adding or updating:

  • No reasons supplied

Reasons for adding or updating:

  • No reasons supplied