Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Elidel (Novartis)

15 mg tubes containing 1% cream

Approved indication: atopic dermatitis

Australian Medicines Handbook section 8.1

Sirolimus and tacrolimus are immunosuppressants that can be used to prevent the rejection of kidney transplants. These drugs act by inhibiting the activation of T-lymphocytes. Pimecrolimus acts in a similar way and prevents the release of inflammatory mediators from mast cells. It has therefore been studied in conditions such as atopic eczema.

As atopic eczema is common in children, pimecrolimus cream has been compared with placebo in 186 infants. After a six-week double-blind trial the dermatitis had improved in 55% of the infants given pimecrolimus and in 24% of those given a placebo cream.1Pooled results of short-term studies in older children show the eczema cleared in 35% of those given pimecrolimus and 18% of those given placebo.

In other studies, pimecrolimus has been compared with corticosteroid creams. An early study suggested that the efficacy of pimecrolimus 1% cream was less than that of betamethasone 0.1% cream.2Another trial studied 713 patients for up to one year to see if pimecrolimus could stop their eczema flaring up. They applied pimecrolimus or its vehicle and added topical corticosteroids if the eczema flared up. The eczema was controlled in 28% of patients given the vehicle and in 51% of those applying pimecrolimus.3The drug has therefore been given approval for intermittent long-term treatment, as well as short-term use.

The cream is applied twice a day. Only a small amount is absorbed through the skin. Most of the absorbed drug is metabolised by the liver and excreted in the faeces.

Nearly half the infants dropped out of the placebo-controlled clinical trials. This was mainly because of a poor response to the placebo. In the long-term study 52% of the control group dropped out compared with 32% of the pimecrolimus group.3Suspected drug-related adverse effects occurred in 25% of the patients given pimecrolimus and 19% of the control group.3Burning at the site of application is a common complaint with pimecrolimus, but it is also associated with skin infections such as folliculitis. Although phototoxicity was not a major problem in clinical trials, pimecrolimus enhanced the carcinogenicity of ultraviolet light in animal studies. Patients should therefore minimise their exposure to sunlight.

Although pimecrolimus will reduce the need to expose children to the adverse effects of topical corticosteroids, it may expose them to other risks of immunosuppression. In long-term studies fever and viral infections such as influenza occurred more frequently in association with pimecrolimus. Lymphomas and thyroid adenomas have occurred in animal studies. Long-term therapy should therefore be restricted to intermittent use by patients who cannot be managed with topical corticosteroids, which cost less. If there is no response to six weeks of treatment pimecrolimus should be stopped.

References

  1. Ho VC, Gupta A, Kaufmann R, Todd G, Vanaclocha F, Takaoka R, et al. Safety and efficacy of nonsteroid pimecrolimus cream 1% in the treatment of atopic dermatitis in infants. J Paediatr 2003;142:155-62.
  2. Luger T, Van Leent EJ, Graeber M, Hedgecock S, Thurston M, Kandra A, et al. SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis. Br J Dermatol 2001;144:788-94.
  3. Wahn U, Bos JD, Goodfield M, Caputo R, Papp K, Manjra A, et al. Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children. Pediatrics 2002;110:e2. http://pediatrics.aappublications.org/cgi/content/full/110/1/e2