What are topical calcineurin inhibitors?

Topical calcineurin inhibitors are treatments that alter the immune system and have been
developed for controlling eczema. There are two types available: Tacrolimus ointment
(Protopic) for moderate to severe eczema and Pimecrolimus cream (Elidel) for mild to
moderate eczema. They are sometimes referred to as ‘TCIs’. ‘Topical’ means ‘applied to the
skin’. ‘Calcineurin inhibitor’ means that they work with the immune system by blocking one
of the chemicals that can contribute to the flaring of atopic eczema.

When should topical calcineurin inhibitors be used?

TCIs can be used for adults and children over the age of 2 who have not responded adequately to
topical steroid treatments – i.e. they are an option if, in your prescribing doctor’s opinion, topical
steroids of the appropriate potency and properly applied have failed to work on your atopic eczema.

TCIs are particularly suitable for delicate areas of skin (e.g. face, neck, eyelids, skin folds and genitals) where prolonged treatment with topical steroids may be inappropriate. Both Tacrolimus and Pimecrolimus can be used short-term to treat flares and also longer-term to prevent them. TCIs are only available on prescription and can be prescribed by a GP.

How often should they be used?

TCIs need to be applied thinly to the affected skin, twice a day. They should only be applied to areas of active eczema (where there is redness) and used until the skin is clear (when the redness has gone). They should not be applied to mucous membranes (the nose, mouth and internal genital areas). A mild burning sensation may be experienced after the first few applications but this tends to settle down after a week.

Tacrolimus (Protopic) comes in two strengths (0.1% is stronger and 0.03% is weaker). Adults
normally start with the stronger 0.1% and apply it twice a day. Once the flare of eczema is better,
the weaker 0.03% can be prescribed for application just twice a week (e.g. Monday and Thursday
nights) to try to prevent (or lessen the number of) flares of eczema. Studies showed this to be effective over a 1-year period. Children normally use the weaker 0.03% ointment twice a day from the start of treatment for 3 weeks and then reduce to once a day until the atopic eczema is clear.
However, if there is no improvement after 6 weeks, Tacrolimus should be stopped.

Pimecrolimus (Elidel) should be applied twice daily at the first appearance of redness or itching or to treat established eczema. It should be used for as short a period as possible (i.e. until the eczema is under control). When prescribed for maintenance (i.e. in the long-term for the prevention of progression to flares), it should be applied just twice a week (e.g. Monday and Thursday nights). As with Tacrolimus, if there is no improvement after 6 weeks, Pimecrolimus cream should be stopped.

Can TCIs be used alongside other treatments?

TCIs can be used alongside other treatments (on the advice and instruction of your healthcare
professional) and always in addition to emollients (wash products and moisturisers). However, there are some important rules to follow when using TCIs with emollients. Emollients are a very important part of atopic eczema treatment and need to be used every day. Apply liberally as often as possible to keep the skin smooth, supple and well moisturised.

The recommendations from the manufacturer are that emollients should not be used within 2 hours of applying Tacrolimus. In practice, this means you should use emollient bath/wash products and moisturisers and then leave a 2-hour gap before Tacrolimus is applied.
In the case of Pimecrolimus, apply to dry skin and leave a short gap before putting on your

TCIs and topical steroids should not be used at the same time on the same areas of the body.
However, it is likely that your doctor will tell you to use TCIs alongside topical steroids on different parts of the body – for example, TCIs may be prescribed for unresponsive facial atopic eczema while you continue to use a topical steroid on your body.

As TCIs work by damping down the immune system, they could worsen skin infections by reducing the skin’s natural resistance. For this reason, TCIs should not be applied to skin that is infected either with bacteria (e.g. impetigo) or viruses (e.g. chickenpox, cold sores or warts). In addition, TCIs are not suitable for use under wet wraps.

Oral antibiotics may be used alongside TCIs for infected atopic eczema.

Are TCIs safe?

The main short-term side effects identified are an irritating, burning and itching feeling on the skin where TCIs are applied – this is estimated to occur in half of all people using them. As a patient you should be prepared to put up with this for a day or two as these symptoms seem to disappear within a week of use.

Other side effects include some increased skin redness, a sensation of warmth on the area of
application and ‘pins and needles’. A few people also experienced blocked skin pores (folliculitis), an increase in spots (acne) and viral skin infections such as cold sores and warts.
Although drinking alcohol is allowed, some people experience increased skin irritation and facial flushing during Tacrolimus treatment.

Tests have also been performed to see whether TCIs can pass into the bloodstream, and the risk of this happening to a significant degree appears to be very small. Tests conducted to see whether TCIs can cause the skin to become thinner show that this does not happen.

Do I need to take any precautions with TCIs?

The main precaution for TCIs is avoidance of excessive/strong sun exposure and ultraviolet light. This is because when similar treatments are taken by mouth over very many years there is an increased risk of skin cancer occurring, although there is no evidence of this happening in any patients using TCIs. It is very important that you do not use sun beds or have any other exposure or treatment such as phototherapy with ultraviolet light. A sunscreen (at least factor 15) should be used to protect your skin. Direct sunlight, particularly in the hottest part of the day (11.00am to 3.00pm) should be avoided.

For more information on topical calcineurin inhibitors, please see our Topical calcineurin inhibitors factsheet