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Fucidin Suspension

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SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

FUCIDIN SUSPENSION

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 5ml of Suspension contains 250mg Fusidic Acid Ph.Eur. (therapeutically equivalent to 175mg Sodium Fusidate Ph.Eur.).

3. PHARMACEUTICAL FORM

Suspension for oral administration.

4. CLINICAL PARTICULARS

4.1. Therapeutic Indications

Fucidin is indicated in the treatment of all staphylococcal infections due to susceptible organisms such as: osteomyelitis, pneumonia, septicaemia, wound infections, endocarditis, superinfected cystic fibrosis, cutaneous infections.

Fucidin should be administered intravenously whenever oral therapy is inappropriate, which includes cases where absorption from the gastrointestinal tract is unpredictable.

4.2 Posology and method of administration

Each 5ml of Fucidin® Suspension is therapeutically equivalent to 175mg of sodium fusidate owing to its lower oral bioavailability. Therefore the following dosages are recommended:

Adults:    15ml three times daily.

Children:    0-1 year :    1ml/kg bodyweight daily, divided into 3

equal doses

1-5 years    :    5ml three times daily

5-12 years    :    10ml three times daily

Elderly:    No dosage alterations are necessary in the elderly

Since Fucidin® is excreted in the bile, no dosage modifications are needed in renal impairment.

The dosage in patients undergoing haemodialysis needs no adjustment as Fucidin® is not significantly dialysed.

The Suspension should be shaken well before use and dilution is not recommended.

4.3. Contraindications

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

Patients with rare hereditary problems of fructose intolerance or glucose-galactose malabsorption 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 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.

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 use of Fucidin® in combination with drugs that are CYP-3A4 biotransformed should be avoided. 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 1.3 mmol (30 mg) sodium per 15 ml dose (i.e. 2 mg sodium per ml). 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® Suspension 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.

4.6. Pregnancy and Lactation

There is inadequate evidence of safety in human pregnancy. Animal studies and many years of clinical experience suggest that fusidic acid is devoid of teratogenic effects. There is evidence to suggest that when given systemically, fusidic acid can cross the placental barrier. If the administration of Fucidin to pregnant patients is considered essential, its use requires that the potential benefits be weighed against the possible hazards to the foetus.

Safety in nursing mothers has not been established. When fusidic acid (as the sodium salt) has been given systemically, levels have been detected in the breast milk. Caution is therefore required when Fucidin is used in mothers who wish to breast feed.

4.7. Effects on Ability to Drive and Use Machines

None known.

4.8 Undesirable effects

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.

Cholestasis

•    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. Treatment should be restricted to symptomatic and supportive measures. Dialysis will not increase the clearance of fusidic acid.

5.    PHARMACOLOGICAL PROPERTIES

5.1.    Pharmacodynamic Properties

Fusidic acid and its salts are potent anti-staphylococcal agents with unusual ability to penetrate tissue. Bactericidal levels have been assayed in bone and necrotic tissue. Concentrations of 0.03-0.12 mcg/ml inhibit nearly all strains of staphylococcus aureus. Fusidic acid is active against staphylococcus epidermidis and methicillin resistant staphylococci.

5.2. Pharmacokinetic Properties

Blood levels are cumulative, reaching concentrations of 50-100 mcg/ml after oral administration of 1.5g daily for three to four days.

Fucidin is excreted mainly in the bile, little or none being excreted in the urine.

In severe or deep-seated infections and when prolonged therapy may be required, systemic Fucidin should generally be given concurrently with other anti-staphylococcal antibiotic therapy.

5.3. Pre-clinical Safety Data

There are no pre-clinical 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

Acesulfame potassium, banana flavour, citric acid, disodium phosphate dihydrate, hydroxyethylcellulose, glucose liquid, methylcellulose, orange dry flavour, sodium benzoate, sorbitol, purified water.

6.2.    Incompatibilities

Not applicable.

6.3.    Shelf-Life

3 years.

6.4    Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5.    Nature and Content of Container

Bottles of 50ml.

6.6.    Instructions for Use, Handling and Disposal

None.

7 MARKETING AUTHORISATION HOLDER

LEO Laboratories Limited

Horizon

Honey Lane

Hurley

Maidenhead

Berkshire

SL6 6RJ

UK

8.    MARKETING AUTHORISATION NUMBER(S)

PL 0043/5014R

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

United Kingdom 11/11/1986 and 11/11/1991

10 DATE OF REVISION OF THE TEXT

02/12/2013