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CALCINEURIN INHIBITIORS (TACROLIMUS / PIMECROLIMUS) FOR THE TREATMENT OF ATOPIC DERMATITS (ECZEMA)

In recent years, a new group of drugs called topical calcineurin inhibitors have been introduced for treating eczema (atopic dermatitis). These medications do not contain steroids but have an anti-inflammatory effect on eczema and relieve itching. They can be used as a monotherapy and also in combination with topical corticosteroids.

They are a type of immunosuppressant that reduces the effects of the body’s immune system. Calcineurin inhibitors are normally used in predominantly mild to moderate cases of eczema, when coticosteroids or other medications cannot be used or are not effective; they are used for short periods and intermittently in long-term treatments.

All calcineurin inhibitors are typically used twice a day. When used in combination with coricisteroids, the treatment of atopic dermatitis is sometimes started with corticosteroids and then switched over to calcineurin inhibitors once the inflammation subsides. At other times, practitioners layer the two medications, applying the corticosteroid first, followed 30 minutes later by application of topical calcineurin inhibitors, and reducing the steroid dosage or discontinuing it, once the condition of the atopic dermatitis improves.

Formulations

Two formulations of the calcineurin inhibitor drugs, tacrolimus and pimecrolimus, are being offered for treatment and both have been approved for children over the age of two. Both formulations are effective in reducing the extent, severity and symptoms of atopic dermatitis. Numerous studies have proved both formulations safe and effective in patients up to 1 year of age and tacrolimus safe and effective in patients up to 4 years. Both drugs provide progressive and sustained disease improvement with long-term therapy.

Tacrolimus is used for treating moderate to severe types of eczema. It is available as an ointment in concentrations of 0.03% and 0.1%. The higher concentration is given to patients older than 16 years. Studies have shown that tacrolimus 0.1% is as or more effective than the high potency class 5 corticosteroids and tacrolimus 0.03% is more effective than low potency corticosteroids, but not as effective as the middle order corticosteroids.

Pimecrolimus is effective in the treatment of mild to moderate types of AD and is available as a 1% cream.

Studies comparing tacrolimus and pimecrolimus showed that tacrolimus 0.1% is more effective than pimecrolimus; 0.03% tacrolimus was as effective as pimecrolimus 1% in mild eczema; and 0.03% tacrolimus is better than pimecrolimus 1% in reducing the itching in eczema. Tacrolimus works more rapidly than pimecrolimus with symptoms showing improvement in the first week of treatment.

Side effects

Calcineurin inhibitors do not have the more serious side effects of corticosteroids and can therefore be safely used in places where the skin is thin, such as the eyelids, face, mucous membranes and genitalia without the risk of skin atrophy.

However, calcineurin inhibitors make the skin sensitive to light. After applying this medication, sunlight, sunlamp and ultraviolet light exposure should be avoided. The most frequent side effect is burning at the application site, especially in tacrolimus, which however improves in due course. Other local side effects are itching and erythema. Less common side effects include acne, asthma, cough, headache, increased sensitivity of the skin to hot and cold temperatures, allergic reactions and flu-like symptoms. Noncomparative trials showed that cases of cutaneous viral infections were more in patients treated with calcineurin inhibitors.

Safety concerns

Calcineurin inhibitors are new drugs and although efficacy is evident, their safety profile and long-term effects are yet not known. The U.S. regulatory body FDA has advised caution in the use of these drugs based on animal studies and reported cases of cancer in children and adults, though links between the drugs and cancer is yet to be established. Because of this reservation, in the USA these drugs have what is called a “black box” warning label on them. This warning label essentially emphasizes that the long term effect of using these drugs is not known.

The FDA has therefore recommended that both tacrolimus and pimecrolimus should be used only as a second line of medication in short term and intermittent treatment of eczema in patients unresponsive to, or intolerant, of other treatments. They also recommended that calcineurin inhibitors should not be used in children less than 2 years old.

The effect of tacrolimus and pimecrolimus on the developing immune systems in infants and children is not known. Clinical studies have shown that, children less than two years, treated with these formulations had a higher rate of upper respiratory problems than those treated with placebo cream.

Since the long term safety of tacrolimus and pimecrolimus is unknown, they should be used only for short periods. Also, these drugs should not be used in children with a weakened immune system. It is recommended that as small an amount needed to control the patient’s symptoms should be used.