Frågedatum: 2005-10-28
RELIS database 2005; id.nr. 22243, DRUGLINE
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Does azithromycin interact with tacrolimus?/nThe question concerns a 54-year-old woman treated with



Fråga: Does azithromycin interact with tacrolimus? The question concerns a 54-year-old woman treated with tacrolimus who started treatment with azithromycin due to an upper respiratory tract infection. A couple of days after starting azithromycin she contacts her physician because she is not feeling well. The doctor now wonders whether her condition may be due to increased tacrolimus concentration as result of drug interaction with azithromycin.

Sammanfattning: Although azithromycin has been reported to have minimal effects on CYP, the increase of the tacrolimus concentration reported in the above mentioned case indicates that interaction between tacrolimus and azithromycin may occur. This prediction awaits further clinical confirmation.

Svar: Tacrolimus is a potent macrolide immunosuppressive agent and undergoes extensive metabolism in the liver by cytochrome P450 CYP3A4 isoenzymes. The metabolism of tacrolimus may therefore be affected by interaction with several drugs metabolized by CYP3A4 (1).

Macrolide antibiotics (eg erythromycin) are known inhibitors of CYP3A4. Combination of macrolide antibiotics and tacrolimus has been reported to increase the blood concentration of tacrolimus (2). Azithromycin though, is reported to have little or no effect on hepatic cytochromes (1,3) and it has been suggested that azithromycin is less likely to interact with tacrolimus (4).

We found however one case report concerning a 27-year-old woman who received tacrolimus treatment (0.02 mg/kg/day, given intravenously) after a bone marrow transplantation. Her tacrolimus blood levels raised on the third day after starting treatment with azithromycin (500 mg/daily, given orally) due to a folliculitis. The tacrolimus concentration ranged from 15.8-17.5 ng/ml before starting treatment with azithromycin and raised to over the measurable level without dilution (>30 ng/ml) after three days of this combination. No other drug known to affect CYP isoenzyme was administered during this period (1).

In our case we recommended the physician to monitor tacrolimus levels, but also to exclude other reasons for the patients condition.

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