Risks of Using Elidel and Protopic for Eczema

Elidel (pimecrolimus) and Protopic (tacrolimus) are topical medications used for the treatment of atopic dermatitis (eczema). The drugs, classified topical calcineurin inhibitors (TCIs), were the first non-steroid topical medications developed to treat eczema.

Unlike topical steroids, TCIs do not cause skin thinning, pigment changes, stretch marks, spider veins, or the loss of response with prolonged use. They are also not absorbed into the body to any significant degree and can be used on any area of skin, including the face and eyelids.

Despite these benefits, Elidel and Protopic have their limitations and risks. Chief among them is their possible link to skin cancer and lymphoma, a concern which led the U.S. Food and Drug Administration (FDA) to issue a black box warning advising doctors and consumers about the risks.

Still, there remains considerable debate on how risky the drugs really are and whether the potential risks outweigh the benefits.

Topical calcineurin inhibitors work by blocking calcineurin, a naturally occurring compound that helps activate the immune system and stimulate the production of inflammatory cytokines. As a disease characterized by inflammation, eczema can be significantly relieved by this immune-modulating effect.

Elidel and Protopic are the topical versions of calcineurin inhibitor-class drugs. There are oral and intravenous versions, such as cyclosporine and tacrolimus, that are used to prevent organ rejection and treat autoimmune disorders ranging from rheumatoid arthritis and psoriasis to lupus and ulcerative colitis.

Elidel and Protopic are often prescribed to treat other inflammatory skin conditions, such as psoriasis, seborrheic dermatitis, cutaneous lupus erythematosus, oral lichen planus, and vitiligo.

Elidel and Protopic are recommended for the second-line treatment of moderate to severe eczema when topical steroids and other conservative therapies fail to provide relief. They are reserved for use in adults and children over two and applied twice daily to affected skin.

As with all drugs, Elidel and Protopic may cause side effects. Most are relatively mild and tend to resolve once the body adapts to treatment.

The most common side effects of Elidel (occurring in at least 2% of adults) include:

• Burning sensations (25.9%)
• Allergic reaction (14.6%)
• Flu-like symptoms (9.8%)
• Common cold (7.6%)
• Headache (7%)
• Skin infections (6.4%)
• Folliculitis (6.1%)
• Itching (5%)
• Cold sores (4%)
• Conjunctivitis (3%)
• Asthma (2.4%)
• Bronchitis (2.4%)
• Impetigo (2.4%)
• Skin redness (2.1%)
• Stuffy nose (2.1%)
• Cough (2%)

The most common side effects of Protopic (occurring in at least 2% of adults) include:

• Burning sensations (28%)
• Itching (25%)
• Flu-like symptoms (22%)
• Headache (13%)
• Skin redness (12%)
• Allergic reaction (9%)
• Skin infections (9%)
• Stuffy nose (6%)
• Folliculitis (4%)
• Cold sores (4%)
• Asthma (4%)
• Bronchitis (4%)
• Sore throat (4%)
• Conjunctivitis (3%)
• Cough (2%)
• Fever (2%)
• Inner ear infection (2%)
• Joint pain (2%)

With respect to both drugs, respiratory side effects are far more common in children, often occurring at rates three times that seen in adults.

A black box warning is the strictest warning put on the labeling of prescription drugs when there is reasonable evidence of a serious hazard. In January 2006, the FDA issued such a warning based on evidence that the drugs increased the risk of skin cancer and lymphoma (most especially T-cell lymphoma).

While acceding that the incidence of cancer was "rare" and a "causal link has not been established," the FDA decided that the advisement was warranted. It was a highly controversial decision and one that continues to be criticized by both the American Academy of Dermatology (AAD)and the American Academy of Allergy, Asthma, and Immunology (AAAAI).

According to the AAD and AAAAI, there has yet to be any reliable evidence that topical immunomodulators like Elidel or Protopic "cause" lymphoma or skin cancer. They argued that many of the studies used by the FDA were either inconclusive or statistically irrelevant and, in some cases, showed a decreased risk.

For their part, the FDA expressed concerns that the off-label use of Elidel and Protopic, particularly among infants and toddlers, justified the warning. According to the regulators, many doctors were over-prescribing the drugs to treat just about any itchy rash in children and adults, often in place of more appropriate over-the-counter hydrocortisone creams.

That is not to suggest that the FDA warning is without merit. Based on epidemiological research submitted to the FDA in 2011, Protopic did appear to increase the risk of T-cell lymphoma in 625,915 patients whose use was tracked for up to 10 years. While higher cumulative doses conferred to higher risk, the results were interpreted with caution due to the low number of actual cancer cases.

The same study concluded that there was no risk of lymphoma associated with Elidel.

With respect to skin cancer, the FDA based its conclusions on its experience with intravenous tacrolimus and cyclosporine in organ transplant recipients. Among this group of patients, the use of calcineurin inhibitor is associated with an increased risk of both skin cancer and non-Hodgkin lymphoma.

The same has not been seen—or has ever been seen—with topical TCIs.

Despite the controversy surrounding the FDA warning, many of the aims of the federal regulator have been achieved. As expected, the sales and off-label use among infants decreased dramatically within a year of the black box warning.

It is important to remember that Elidel and Protopic are indicated for the second-line treatment of eczema in adults and children two years and older. They should only be used if topical steroids fail to provide relief and should not be used as a moisturizer even in severe cases.

Because TCIs are more expensive, many doctors reserve their use for thinner areas of the skin, such as the face or hands, while using cheaper topical steroids on thicker skin, such as the arms, legs, hands, feet, neck, and trunk.

When used appropriately, Elidel and Protopic are safe and highly effective treatments for eczema and other inflammatory skin conditions. Speak with your dermatologist to decide if its the right choice for you or if there are other treatments worth exploring.