Tacrolimus and pimecrolimus are members of a new class of topical immunomodulators and belong to the class of immunosuppressant drugs known as calcineurin inhibitors. They work mainly by reducing inflammation through the suppression of T-lymphocyte responses, a different mechanism of action to topical corticosteroids. Although tacrolimus and pimecrolimus have similar mechanisms of action, they have different licensed indications (see Sections 3.1 and 3.2).
3.1.1 Tacrolimus ointment (Fujisawa) is available in two strengths (0.1% and 0.03%), both of which are licensed for the treatment of moderate to severe atopic eczema in adults (16 years and above) who have not adequately responded to, or are intolerant of, conventional therapies. The lower strength is also licensed for the treatment of moderate to severe atopic eczema in children aged 2 years and older whose condition has not responded adequately to conventional therapies.
3.1.2 The Summary of Product Characteristics states that tacrolimus should "be prescribed by physicians with experience in the treatment of atopic dermatitis".
3.1.3 Tacrolimus is applied as a thin layer to affected areas of the skin twice daily and may be used on any part of the body, including the face, neck and flexural areas. The Summary of Product Characteristics states that the treatment of each affected region of the skin should be continued until the area is clear, and then be discontinued. It also states that treatment for adults should be started with 0.1% tacrolimus twice a day, that twice-daily treatment with 0.1% tacrolimus should be restarted if symptoms recur, and that an attempt should be made to reduce the frequency of application or to use the lower strength 0.03% tacrolimus if the clinical condition allows. For children, only the 0.03% strength is licensed, and the Summary of Product Characteristics states that the frequency of application should be reduced to once a day after a maximum of 3 weeks.
3.1.4 Tacrolimus can be used for short-term and intermittent long-term treatment. The net price is £21.60 for 30 g and £41.04 for 60 g (0.1% tacrolimus) and £19.44 for 30 g and £36.94 for 60 g (0.03% tacrolimus) (British National Formulary, 46th edition). Costs may vary in different settings because of negotiated procurement discounts.
3.1.5 Side effects include a burning or tingling sensation, pruritus, erythema, folliculitis, herpes simplex infection, acne, increased sensitivity to hot and cold, and alcohol intolerance. Lymphadenopathy has also been reported. The Summary of Product Characteristics states that before commencing treatment with tacrolimus, clinical infections at treatment sites should be cleared. It also states that emollients should not be applied to the same area within 2 hours of applying tacrolimus. When taken orally for other indications, tacrolimus has a number of well-recognised adverse effects, including renal toxicity and hypertension. The Summary of Product Characteristics states that, beyond 4 years of treatment, the potential for local immunosuppression (possibly resulting in infections or cutaneous malignancies) is unknown. For full details of side effects and contraindications, see the Summary of Product Characteristics.
3.2.1 Pimecrolimus cream 1.0% (Novartis) is licensed in patients with mild to moderate atopic eczema aged 2 years and older, for short-term treatment of signs and symptoms and intermittent long-term treatment to prevent flare-ups.
3.2.2 Pimecrolimus is applied as a thin layer to affected skin twice daily and may be used on all skin areas, including the head, face, neck and intertriginous areas (where opposing skin surfaces touch and may rub, such as skin folds of the groin, axillae and breasts). The treatment of each affected region of the skin is continued until the area is clear and is then discontinued. Because of the low level of systemic absorption, there are no restrictions on the total daily dose applied, the body surface area that can be treated or the duration of treatment. The Summary of Product Characteristics states that emollients can be applied immediately after using pimecrolimus. The net price is £19.69 for 30 g, £37.41 for 60 g and £59.07 for 100 g (British National Formulary, 46th edition). Costs may vary in different settings because of negotiated procurement discounts.
3.2.3 Side effects include a burning sensation, pruritus, erythema, skin infections (including folliculitis and rarely impetigo, herpes simplex and zoster and molluscum contagiosum), papilloma (rarely) and local reactions such as pain, paraesthesia, peeling, dryness, oedema and worsening of eczema. The Summary of Product Characteristics states that pimecrolimus should not be applied to areas affected by acute cutaneous viral infections, and that before commencing treatment with pimecrolimus, clinical infections at treatment sites should be cleared. It also states that long-term effect on the local skin immune response and on the incidence of skin malignancies is unknown. For full details of side effects and contraindications, see the Summary of Product Characteristics.