Products
Tacrolimus is commercially available for external use as an ointment in two concentrations (Protopic). It has been approved in many countries since 2001.
Structure and properties
Tacrolimus (C44H69NO12 – H2O, Mr = 822.0 g/mol) is a complex macrolide formed by the fungus-like bacterium. It is present in drugs as tacrolimus monohydrate, white crystals, or a crystalline powder that is practically insoluble in water.
Effects
Tacrolimus (ATC D11AH01) is immunosuppressive and anti-inflammatory. Its effects are due to binding to the cytoplasmic immunophilin FKBP-12, which inhibits the phosphatase calcineurin, blocks T-cell activation and differentiation, and reduces the synthesis of inflammatory mediators such as interleukins, interferons, and TNF-α.
Indications
As a 2nd-line agent for short-term treatment of acute exacerbation of moderate to severe atopic dermatitis. Tacrolimus is also used to treat other skin conditions, such as contact dermatitis and vitiligo, but has not yet been approved for this purpose in many countries (off-label).
Dosage
According to the drug label. The ointment is applied 1-2 times daily until the symptoms have regressed. Subsequently, the treatment can be maintained for one week. Do not use for long-term treatment. Protect treated areas from sun with appropriate measures. Do not apply under occlusion to avoid systemic absorption.
Contraindications
Tacrolimus is contraindicated in hypersensitivity and in children younger than 2 years of age. Refer to the drug label for complete precautions.
Interactions
Tacrolimus is a potent inhibitor of CYP3A4 systemically. Interactions via this mechanism are unlikely due to low uptake through the skin into the bloodstream, but cannot be completely excluded. Alcohol should not be consumed during treatment because intolerance reactions may occur. Because of the immunomodulatory properties, a time interval of at least 2 weeks must be observed from vaccinations.
Adverse effects
Possible adverse effects include local reactions such as a skin burning sensation, itching, sensory disturbance, warm sensation, skin redness, pain, irritation, and rash. Due to the immunosuppressive properties, increased herpesvirus infections and folliculitis have been observed. Rarely, cases of lymphoma and skin cancer have also been reported. The risk is increased with long duration and high concentration, which is why the ointment is not intended for long-term therapy. Alcohol intolerance with reddening of the skin may occur when alcoholic beverages are consumed.
