Calcineurin Inhibitors

There are two types of topical calcineurin inhibitors called tacrolimus ointment (Protopic 0.03% and 0.1%) and pimecrolimus cream (Elidel). They are classified as immunomodulating agents. They act on the immune system to reduce skin inflammation. Both tacrolimus and pimecrolimus block a chemical called calcineurin, which activates inflammation in the skin and causes redness and itching of the skin.

Tacrolimus ointment and pimecrolimus cream are licensed in the UK to treat atopic eczema (atopic dermatitis) in adults and children over two years. Tacrolimus comes in two strengths; 0.03% (weaker) and 0.1% (stronger); the weaker preparation is licensed for children between the ages of 2 and 16, and the stronger preparation in adults over the age of 16. Tacrolimus ointment is also licensed for the prevention of flares of atopic eczema in adults. These topical treatments can also be prescribed for some other inflammatory skin conditions such as psoriasis (particularly on the face), seborrhoeic eczema (seborrhoeic dermatitis), lichen planus, lichen sclerosus, vitiligo, cutaneous lupus erythematosus, and pityriasis alba, but the calcineurin inhibitors are not officially licensed for these skin conditions.

No, but they may control inflammation and help settle flares. You should expect to see some improvement within one week. If you have eczema that is tending to flare frequently, other treatments may be recommended. Your doctor or dermatologist will be able to discuss the options with you.

Topical application is usually twice daily, but you should use calcineurin inhibitors as instructed by your doctor as it may be decided that you need a different regime depending on your clinical circumstances. If preventative treatment is recommended, you should apply the treatment twice weekly to help keep the skin clear. However, if the condition flares during this maintenance phase, the treatment should be applied twice daily.

If you are prescribed tacrolimus ointment or pimecrolimus cream once a day, you should apply it in the evening or at night, if twice daily, then morning and evening/night. If you have eczema or psoriasis, you should ensure that you continue to use an emollient (moisturizers) while using the calcineurin inhibitor.

To determine the amount of treatment to be applied it is recommended that an adult fingertip unit length (the length of ointment squeezed out of a tube that reaches from the crease overlying the joint at the end of the index finger to the end of the finger) should be applied to twice the area of a handprint (adult palm plus fingers). This amount is about 0.5 grams; therefore, for an adult arm, up to 3 grams may be needed if the whole arm is affected. Your doctor should give an estimate of the amount of treatment required daily.

Calcineurin inhibitors should not be applied if the affected area of your skin is infected, e.g., if the skin has sore, weeping, or crusted spots because it can cause infection to spread. Clinical trials have demonstrated that neither tacrolimus nor pimecrolimus affects the development of responses to vaccinations. It is recommended that calcineurin inhibitors should not be used if you are pregnant, breastfeeding, or have a weakened immune system. Exposure of the skin to sunlight should be minimized, and the use of ultraviolet light treatments or sunbeds should be avoided. You should inform the prescribing doctor if you have had previous skin cancer. 

About 50% of patients develop some local skin irritation or a burning or itching sensation when these treatments are started, particularly with tacrolimus ointment. However, these side-effects are usually temporary and not a reason to discontinue the treatment because they usually settle within a week. 

It is important to persevere with treatment during this time. It is also possible to experience redness, tingling, or a feeling of warmth on the skin where the treatment is applied.

Occasionally folliculitis (inflamed or infected hair follicles) may occur. Irritation is much more likely to occur if tacrolimus is applied to an area of severe atopic eczema. As illustrated in the diagram, topical calcineurin inhibitors should not be used when the atopic dermatitis is most severe but can be gradually introduced as the severity reduces.

It is a good idea to use a calcineurin inhibitor on a test area of active atopic dermatitis to see if any irritation occurs before applying it to larger areas. There is a small increased risk of developing cold sores (herpes simplex infection) on the treated skin during the first few weeks of treatment.

When a drug such as a calcineurin inhibitor is taken by mouth, it can lead to adverse effects because it suppresses the immune system. One possible consequence of immune suppression is an increased risk of non-melanoma skin cancer and lymphoma.

When calcineurin inhibitors are topically applied, the amount absorbed into the body is very much less than occurs after taking the drug by mouth. The amount of topical calcineurin inhibitor absorbed is less than 0.1 % of the applied dose.

As a result, calcineurin inhibitors applied topically do not cause significant suppression of the immune system. There is no evidence from extensive epidemiological studies that topical calcineurin inhibitors are associated with an increased risk of lymphoma or non-melanoma skin cancer.

It is not known whether topical calcineurin inhibitors will harm an unborn baby. You should tell your dermatologist or GP if you are pregnant or plan to become pregnant while using tacrolimus or pimecrolimus. 

Yes, but you may find that your face may become red and flushed.