FUCIDIN Oral Suspension Ref.[6872] Active ingredients: Fusidic acid

Statins (HMG-CoA reductase inhibitors) and systemic Fucidin must not be co-administered. There have been reports of rhabdomyolysis (including 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 treatment with systemic Fucidin. 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 systemic Fucidin. In exceptional circumstances, where prolonged systemic Fucidin is needed, e.g. for the treatment of severe infections, the need for co-administration of HMG-CoA reductase inhibitors and systemic Fucidin should only be considered on a case by case basis and under close medical supervision.

In a few cases, serious cutaneous reactions putting life at risk such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, toxic epidermal necrolysis (Lyell’s syndrome) and Stevens-Johnson syndrome have been reported with systemic Fucidin. Patients should be advised to monitor cutaneous reactions as well as signs and symptoms suggestive of these reactions which usually appear in the first weeks of therapy. If such reactions are suspected to be due to systemic Fucidin, treatment with systemic Fucidin should be stopped and it is recommended not to reintroduce the therapy.

Fusidic acid is metabolised in the liver and excreted in the bile. Elevated liver enzymes and jaundice have occurred during systemic Fucidin therapy but are usually reversible on discontinuation of the drug.

Systemic Fucidin should be given with caution and liver function should be monitored if used in patients with hepatic dysfunction or in patients taking potentially hepatotoxic drugs. Caution is required in patients with biliary disease and biliary tract obstruction. Caution is required in patients treated with HIV-protease inhibitors (See section 4.5). Fusidic acid competitively inhibits binding of bilirubin to albumin. Caution is necessary if systemic Fucidin is administered to patients with impaired transport and metabolism of bilirubin. Particular care is advised in neonates due to the theoretical risk of kernicterus.

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.

Patients with rare hereditary problems of fructose intolerance should not take this medicine due to its content of sorbitol (E420).

Patients with rare glucose-galactose malabsorption should not take this medicine due to its content of glucose.

This medicinal product contains 1.05 mmol (24 mg) sodium per 15 ml dose (i.e. 1.6 mg sodium per ml). This should be taken into consideration by patients on a controlled sodium diet.

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.

Oral anticoagulants

Systemic Fucidin administered 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.

HIV protease inhibitors

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

Concomitant use is not recommended. (See section 4.4).

Pregnancy

There are no or limited data (less than 300 pregnancy outcomes) from the use of fusidic acid in pregnant women. Animal studies do not indicate direct or indirect harmful effect with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of systemic Fucidin during pregnancy.

Breast-feeding

Physico-chemical data suggest excretion of fusidic acid in human milk. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from systemic Fucidin therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

There are no clinical studies with systemic Fucidin regarding fertility. Pre-clinical studies did not show any effect of sodium fusidate on the fertility in rats.

Fucidin has no or negligible influence on the ability to drive or to use machines.

The estimation of the frequency of undesirable effects is based on a pooled analysis of data from clinical trials and from spontaneous reporting.

The most frequently reported undesirable effects of Fucidin administered orally are gastrointestinal disorders like abdominal discomfort and pain, diarrhoea, dyspepsia, nausea and vomiting. Anaphylactic shock has been reported.

Undesirable effects are listed by MedDRA SOC and the individual undesirable effects are listed starting with the most frequently reported. Within each frequency group, adverse reactions are presented in the order of decreasing seriousness.

Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000)
Not known (cannot be estimated from available data)

Blood and lymphatic system disorders

Uncommon: Pancytopenia, Leukopenia^a, Thrombocytopenia, Anaemia

Immune system disorders

Uncommon: Anaphylactic shock/anaphylactic reaction

Rare: Hypersensitivity

Nervous system disorders

Uncommon: Headache, Somnolence

Gastrointestinal disorders

Common: Vomiting, Diarrhoea, Abdominal pain, Dyspepsia, Nausea, Abdominal discomfort

Hepatobiliary disorders

Uncommon: Hepatic failure, Cholestasis, Hepatitis^b, Jaundice^c, Hyperbilirubinaemia, Liver function test abnormal^d

Rare: Hepatic function abnormal

Skin and subcutaneous tissue disorders

Uncommon: Acute generalized exanthematous pustulosis, Urticaria, Pruritus, Rash^e, Erythema

Rare: Angioedema

Not known:__ Toxic epidermal necrolysis (Lyell’s syndrome)^f, Stevens-Johnson syndrome^f, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome^f

Musculoskeletal and connective tissue disorders

Uncommon: Rhabdomyolysis^g

Renal and urinary disorders

Uncommon: Renal failure^h

General disorders and administration site conditions

Common: Lethargy/Fatigue/Asthenia

^a Haematological disorders affecting the white cell line (neutropenia, granulocytopenia and agranulocytosis) have been reported.
^b Hepatitis also includes Hepatitis cholestatic/Cytolytic hepatitis
^c Jaundice also includes Jaundice cholestatic.
^d Including alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood bilirubin increased and gamma-glutamyltransferase increased.
^e Rash includes various types of rash reactions such as drug eruption, erythematous and maculo-papular rash.
^f These adverse reactions were identified through post-marketing surveillance. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency (see section 4.4)
^g Rhabdomyolysis may be fatal.
^h Renal failure also includes renal failure acute.

Paediatric population

Frequency, type and severity of adverse reactions in children are expected to be the same as in adults, based on limited data.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Not applicable.