What Are Calcineurin Inhibitors?

Topical calcineurin inhibitors are medications that are applied to the skin that are used in the treatment of eczema, including atopic dermatitis. Topical calcineurin inhibitors are usually prescribed as second-line treatment, which means they are used after primary treatment with topical corticosteroids has already been tried and has not sufficiently improved symptoms of atopic dermatitis.

Protopic and Elidel

There are currently two topical calcineurin inhibitors that are available in the United States:

The Food and Drug Administration (FDA) has approved topical calcineurin inhibitors for short-term and non-continuous use to treat atopic dermatitis that has not responded to other topical treatments.1


One of the advantages of topical calcineurin inhibitors is that they do not cause thinning of the skin (atrophy) like long-term use of topical corticosteroids can. Topical calcineurin inhibitors can be used on any area of the skin, and they are particularly useful in sensitive skin areas, such as the face and skin folds, which may be more susceptible to side effects from topical corticosteroids. However, topical calcineurin inhibitors do have other potential side effects.1,2

How they work

Topical calcineurin inhibitors block calcineurin, a naturally produced chemical that activates T-cells. T-cells are a type of white blood cell involved in the immune system response. In atopic dermatitis, there is a dysfunction in the immune system causing excessive inflammation in the skin. Topical calcineurin inhibitors block cytokines (chemical messengers) that trigger the inflammatory response. Once absorbed into the skin, topical calcineurin inhibitors reduce symptoms of atopic dermatitis-like redness and itchiness.1


Topical calcineurin inhibitors are applied in a thin layer on affected areas of skin twice daily. Use of these medications should be discontinued when the signs and symptoms of atopic dermatitis resolve. If symptoms do not improve within 6 weeks, patients should be re-examined by their doctor.3,4

Protopic ointment is used to treat moderate to severe atopic dermatitis. Protopic comes in two strengths: 0.03% tacrolimus and 0.1% tacrolimus. The more potent strength Protopic, tacrolimus 0.1%, is only indicated in individuals 16 years and older. The tacrolimus 0.03% ointment can be used in individuals aged 2 years and older.3 Elidel cream only comes in one strength: 1% pimecrolimus. Elidel is used to treat mild to moderate atopic dermatitis in adults and children over the age of 2.4

Side effects

Common side effects experienced by patients using Protopic include skin burning or stinging when first applied. These side effects tend to lessen after several applications of the medication.3 The most common side effects experienced by people using Elidel include skin burning, headache, colds, cough, flu, and viral infections.4 Although no causal relationship has been established, the United States Food and Drug Administration (FDA) has issued a black box warning that rare cases of cancer (skin cancer and lymphoma) have been reported in patients using topical calcineurin inhibitors.1,5

These are not all the possible side effects of calcineurin inhibitors. Patients should talk to their doctor about what to expect with treatment with calcineurin inhibitors.

Additional things to know

Because topical calcineurin inhibitors have an immunosuppressant action, individuals with compromised immune systems should not use them. While using topical calcineurin inhibitors to treat atopic dermatitis, patients should avoid natural or artificial sunlight exposure, even when the medication is not on the skin.3,4

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Written by Emily Downward | Reviewed February 2022