New drug comment - pimecrolimus

Editor, – The review of pimecrolimus (Elidel) in the 'New drugs' section (Aust Prescr 2003;26:146-51) states that children may be exposed to 'risks of immunosuppression'. Contrary to this view, clinical signs of systemic immunosuppression were not seen in the long-term paediatric studies.^1,2 Some systemic adverse events were more common in the pimecrolimus group, but these were not significant when the time on study drug was taken into account. Pharmacokinetic studies demonstrated that blood concentrations of pimecrolimus following dermal application were below the limits of detection in the majority of paediatric patients, thus minimising the likelihood of a systemic effect.

Contrary to the review pimecrolimus did not enhance the carcinogenicity of UV light in animal models (see TGA-approved product information). The lymphoma and thyroid adenomas mentioned by the reviewer were observed in animal studies only following oral administration of pimecrolimus, in which systemic exposure was much higher than that observed following clinical use of pimecrolimus cream. To date, clinical trial and postmarketing surveillance data do not indicate an increase in the risk of malignancy. Nevertheless Novartis recommends that patients avoid exposing skin areas treated with pimecrolimus to sunlight.

Incorporating pimecrolimus into the management of atopic dermatitis was shown to improve long-term disease control and reduce the number of flares when compared with reactive use of topical corticosteroids.^1,2 Pimecrolimus has not been associated with skin atrophy and is approved for use on all skin areas including the face, neck and intertriginous areas.

Natalie Jenkins
Senior Medical Information Associate
Victor Ferrari
Medical Adviser
Novartis Pharmaceuticals Australia
North Ryde, NSW

It is reassuring to learn that postmarketing surveillance data have not yet shown evidence of malignancy in patients treated with pimecrolimus. However, unlike the Australian product information, the US product information does report an increase in the incidence of tumours in animals following dermal application of pimecrolimus.

While pimecrolimus may not enhance the carcinogenicity of UV light, the topical cream base enhances the development of skin tumours induced by UV radiation. Although the company advises patients to avoid sunlight, this may pose practical problems for patients applying pimecrolimus to the face or neck.

Although blood concentrations are low after topical application, absorption does occur. References 1 and 2 above did adjust for the duration of follow-up, but still showed a higher frequency of systemic symptoms, such as cough and fever, in children treated with pimecrolimus.

Until more data are available, the Editorial Executive Committee still believes that pimecrolimus is not a first-line treatment and caution is needed, particularly when prescribing to infants. Neither the USA nor the UK have approved pimecrolimus for children under the age of two years.