Fusidic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation, other

Remarks:

epidemiological evidence

Type of information:

other: epidemiological evidence

Adequacy of study:

weight of evidence

Study period:

1969-2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Principles of method if other than guideline:

To identify cases reporting sensitisation and hypersensitivity in humans, a cumulative search in the LEO Pharma A/S safety database was done covering the period from 1969 to 2018.

Type of study:

other: epidemiological evidence

Test material

Test material information

Constituent 1

Reference substance name:

Fusidic acid

EC Number:

230-256-0

EC Name:

Fusidic acid

Cas Number:

6990-06-3

Molecular formula:

C31H48O6

IUPAC Name:

2-[(1Z,2S,3aS,3bS,5aS,6S,7R,9aS,9bS,10R,11aR)-2-(acetyloxy)-7,10-dihydroxy-3a,3b,6,9a-tetramethyl-hexadecahydro-1H-cyclopenta[a]phenanthren-1-ylidene]-6-methylhept-5-enoic acid

Test material form:

solid: crystalline

Details on test material:

Details are given for each individual study

Specific details on test material used for the study:

The search was done for the Fucidin (R) for topical use.
Fusidic acid is the active ingredient in Fucidin (R) topical.

Results and discussion

Positive control results:

Not relevant

In vitro / in chemico

Other effects / acceptance of results:

No cases reported events of sensitisation. A total of 80 hypersensitivity reactions were reported cumulatively. In the last 5 years, the number of reported hypersensitivity reactions has fluctuated between 2 and 11 events per year. The estimated patients exposure in the corresponding period has fluctuated between 17 and 20 million patients per year. The estimated number of patients exposed to Fucidin(R) topical is based on the total sales volume realised from LEO to LEO affiliates, distributors, etc.

When adverse events are reported, they are reported on product level. It is therefore not possible to determine whether the reported adverse event is caused by the active substance or excipient(s) in the product, unless it is specifically reported. As most of these reports are non-serious and reported by consumers, very limited information is available and it is therefore not known whether it is the active substance or excipient(s), which have caused the reaction.

According to the company core safety information (CCSI) for Fucidin (R) topical, use is contraindicated in patients with known hypersensitivity to the active substance or any of the excipients in the product. It is known that several of the excipients (e.g. butyl hydroxyanisole and sorbic acid and its salts) in the products can cause local skin reactions, and according to Martindale hydrous lanolin (wool fat) can cause sensitivity reactions and hypersensitivity reactions have occasionally been attributed to the presence of cetyl alcohol in topical preparations.

In vivo (non-LLNA)

Results

Key result

Remarks on result:

other: results are based on epidemiological evidence

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

It is concluded that compared to the high patient exposure, very few case reports concerning hypersensitivity reactions have been noted. No cases of sensitisation have been received. From the epidemiological evidence showing relatively low but no substantial incidence of allergic contact dermatitis in relation to relatively high exposure it is concluded that the substance does not meet the criteria for classification as skin sensitising.

Executive summary:

To identify cases reporting sensitisation and hypersensitivity, a cumulative search in the LEO Pharma A/S safety database was done covering the period from 1969 to 2018. In the last 5 years, the number of reported hypersensitivity reactions has fluctuated between 2 and 11 events per year. The estimated patients exposure in the corresponding period has fluctuated between 17 and 20 million patients per year. When adverse events are reported, they are reported on product level. It is therefore not possible to determine whether the reported adverse event is caused by the active substance or excipient(s) in the product.

From the epidemiological evidence showing relatively low but no substantial incidence of allergic contact dermatitis in relation to relatively high exposure it is concluded that the substance does not meet the criteria for classification as skin sensitising.