Cancer risk to be indicated on eczema drugs

The US FDA (Food and Drug Administration) has announced changes to the labelling of two topical eczema drugs following concerns about a possible risk of cancer.

Novartis' Elidel Cream and (pimecrolimus) and Astellas Pharma's (formerly Fujisawa Healthcare) Protopic Ointment (tacrolimus) will now feature a boxed warning about the possible cancer risk, and a Medication Guide (FDA-approved patient labelling) will be distributed to help ensure that patients using the prescription medicines are aware of the new warning.

The new labelling will also clarify the drugs' recommendations as second-line rather than first-line treatments.

Eczema, or atopic dermatitis, is one of the most common skin disorders in infants and children in the US, affecting 10-15% of the childhood population. Although its cause is not known, it is thought, according to the FDA, that there may be an allergic or immune mediated component. As Elidel or Protopic, both of which are applied to the affected area of skin, are thought, but unproven, to have various effects on the body's immune system, the FDA recommends that children and adults with 'a weakened or compromised immune system' should not use either drug.

On 15 February 2005 the FDA's Pediatric Advisory Committee recommended that the labelling should be updated with a boxed warning and a Medication Guide about the possible cancer risk for these drugs. The FDA then issued a Public Health Advisory in March 2005 advising physicians about the possible cancer risk and indicated it would recommend updating the labelling to address this possible risk.

An FDA Public Health Advisory statement made at the time read: 'This concern is based on information from animal studies, case reports in a small number of patients, and how these drugs work. It may take human studies of ten years or longer to determine if use of Elidel or Protopic is linked to cancer. In the meantime, this risk is uncertain.

'Animal studies have shown that three different species of animals developed cancer following exposure to these drugs applied topically or given by mouth, including mice, rats and a recent study of monkeys. These studies were conducted at doses higher than generally used by patients and the risk of cancer increased with increasing drug dose and duration.

'In addition to an ointment, tacrolimus, also comes as a pill or by injection, this form is known as (Prograf). Prograf is approved to prevent liver or kidney transplant rejection. It is known to cause both skin cancers and lymphoma in humans by suppressing the body's normal immune defenses against cancer. The cancer risk increases with higher doses and longer treatment courses of Prograf. Both Elidel and Protopic are sometimes absorbed through the skin, though usually at very low amounts. Occasionally, children who have been treated with Elidel or Protopic have had high blood levels of these drugs.

'Protopic was approved in December 2000 and Elidel in December 2001. Since their approval, FDA has received reports of lymphoma and skin cancer in children and adults treated with Elidel or Protopic; whether the reported cancers are associated with these products has not been clearly established.'