Flushing tacrolimus

Recurrent episodes of diffuse flushing of the arms, the face, and the trunk reportedly occurred about 2 hours after each dose of ciclosporin in a 24-year-old man who had received a renal transplant 6 years before (151). These episodes were noted from the beginning of treatment, but worsened after he changed to Neoral, the microemulsion form of ciclosporin, and completely resolved after ciclosporin was replaced by tacrolimus. 

Ramsay HM, Harden PN. Cyclosporin-induced flushing in a renal transplant recipient resolving after substitution with tacrolimus. Br J Dermatol 2000 142(4) 832-3. 

Alcohol may cause facial flushing or skin eiythema in patients being treated with tacrolimus ointment this reaction appears to be fairiy common. Aicohoi intoieranee has been reported rarely with pimecroiimus cream. 

Three patients experienced application site erythema following the consumption of alcohol after using topical tacrolimus or pimecrolimus for the treatment of facial dermatoses. Two of the patients then participated in a double-blind, controlled evaluation of the reaction. Both patients consumed alcohol (240 mL of red or white wine) without experiencing flushing, but following tacrolimus or pimecrolimus application, they experienced moderate or severe facial flushing (limited to the area of application) 5 to 10 minutes after alcohol consumption. The intensity of the erythema was sharply reduced after taking aspirin 325 mg twice daily for 3 days before alcohol consumption, but cetirizine 10 mg daily with cime-tidine 400 mg twice daily for 3 days appeared to have little effect. ... 

There are other reports of this interaction between tacrolimus and alcohol. The reaction is usually confined to the face and the intensity may be related to the amount of alcohol ingested. In an open study of 316 patients, alcohol intolerance (facial flushing) was observed in 19% of the patients using tacrolimus 0.1% ointment and in a controlled study, 6.9% of patients experienced the reaction with tacrolimus 0.1% ointment, and 3.4% of patients experienced the reaction with tacrolimus 0.03% ointment. ... 

The interaction between topical tacrolimus and alcohol is established and appears to occur in about 6 to 7% of patients treated with tacrolimus 0.1% ointment. Patients should be warned of the possibility of a flushing reaction with alcohol and that consumption of alcohol may need to be avoided if this occurs. Clinicians should be aware of the interaction and obtain a careful history, including alcohol use, in patients who present with new acute symptoms while using tacrolimus. It has been suggested that aspirin may possibly reduce the symptoms of this reaction, but this needs further study. Alcohol intolerance with pimecrolimus has been reported, but appears to be rare. ... 

Milingou M, Antille C, Sorg O, Saurat J-H, Liibbe J. Alcohol intolerance and facial flushing in patients treated with topical tacrolimus. Arch Dermatol (2004) 140, 1542-4. 

Liibbe J, Milingou M. Tacrolimus ointment, alcohol, and facial flushing. NEnglJ Med (2004) 351,2740. 

The association between flushing of the face and alcohol consumption occurs in 6-7% of patients who use topical tacrolimus. The pathophysiological mechanism is not known, but there are four hypotheses. 

Facial flushing should be recognized as an adverse effect of topical calcineurin inhibitors, both pimecrohmus and tacrolimus, independently from the skin disease. 

Stinco G, Piccirillo F, Sallustio M, Patrone P. Facial flush reaction after alcohol ingestion during topical pimecrolimus and tacrolimus treatment. Dermatology 2009 218(1) 71-2. 

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