Public Health Advisory Potential Risk Of Cancer With Eczema Treatments Pimecrolimus (ELIDEL) And Tacrolimus (PROTOPIC)

The Food and Drug Administration (FDA) issued a public health advisory on March 10, 2005 to inform patients and healthcare professionals about the potential risk of cancer with the use of two topical drugs, pimecrolimus (ELIDEL) and tacrolimus (PROTOPIC). These drugs are approved to treat eczema, an inflammatory condition of the skin characterized by redness, itching, and oozing vesicular lesions which become scaly, crusted, or hardened.

Specifically, pimecrolimus and tacrolimus were approved by the FDA for the short-term and intermittent long-term treatment of mild to moderate eczema in people with normal immune systems two years of age and older, in whom the use of alternative, conventional therapies is deemed inadvisable because of potential risks, or in the treatment of patients who are not adequately responsive to or intolerant of alternative, conventional therapies.

Pimecrolimus was approved by the FDA in December 2001 and tacrolimus in December 2000. The firms producing these drugs are Novartis Pharmaceuticals and Fujisawa Healthcare, Inc., respectively.

The FDA advisory indicates that a black box warning will be added to the professional product labeling, or package inserts, of both drugs. Each will be required to have a Medication Guide, written specifically for patients, distributed with each new and refill prescription. A black box warning is the strongest type of warning that the FDA can ask for in a drug’s professional product labeling. Medication Guides are FDA-approved written drug information for patients. They are reserved for those drugs that present significant public health problems.

Both pimecrolimus and tacrolimus are immunosuppressants. In addition to the topical product, tacrolimus is also available orally and as an injection. In these forms it is known as PROGRAF. PROGRAF is approved to prevent liver or kidney transplant rejection. It is also 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.

The FDA advisory recommends the following:

• Use pimecrolimus and tacrolimus only as second-line agents for short-term and intermittent treatment of eczema in patients unresponsive to or intolerant of other treatments.
• Avoid use of pimecrolimus and tacrolimus in children younger than two years of age. The effect of pimecrolimus and tacrolimus on the developing immune system infants and children is not known. In clinical studies, infants and children younger than two years old treated with pimecrolimus had a higher rate of upper respiratory infections than did those treated with placebo cream.
• Use pimecrolimus and tacrolimus only for short periods of time, not continuously. The long-term safety of pimecrolimus and tacrolimus are unknown.
• Children and adults with a weakened or compromised immune system should not use pimecrolimus and tacrolimus.
• Use the minimum amount of pimecrolimus and tacrolimus needed to control symptoms. In animals, increasing the dose resulted in higher rates of cancer.

As of December 2004, the FDA had received 10 postmarketing reports associating pimecrolimus with various cancer-related adverse events. Four cases occurred in children, three of these in children less than six years of age. The other six cases occurred in adults. The most serious outcome was one hospitalization in an adult. All other cases reported nonserious outcomes. The median time until diagnosis after initiation of treatment with pimecrolimus was 90 days, with a range between one week and 300 days.

Through December 2004, the FDA had received 19 postmarketing reports linking tacrolimus with cancer-related adverse events. Three cases occurred in children up to 16 years of age, and 16 cases occurred in adults. Two deaths in adults were reported related to complications of the cancers, and eight hospitalizations were reported, including two in pediatric patients.

The 19 reports included various types of cancer, seven of which occurred at the site of tacrolimus application. The median time until diagnosis after the starting of treatment with tacrolimus was 150 days, with a range between 21 days and 790 days.

What You Can Do

If pimecrolimus or tacrolimus is the only treatment option for you or a family member for eczema, follow the advice given by the FDA carefully.

See the box below for information on how to report an adverse effect from a drug to the FDA.