Stéphanie Belaiche, Sophie Logerot, Paolo Malvezzi, Wen Qin, Rachel Tetaz, Thierry Romanet and Philippe Zaoui
We report the case of a 49-year-old renal and pancreatic female transplant recipient, who presented a drug interaction between tacrolimus, warfarin and pristinamycin. Three days after oral pristinamycin 1000 mg bid administrations, the patient presented nausea, vomiting, abdominal pain and violent headaches that required hospitalization. Tacrolimus trough level was 5 times higher (34.9 μg/l) than the target required (5-8 μg/l) and the INR was at 5.8 (therapeutic index between 2 and 3) despite a stable kidney function (serum creatinine 130 μmol/L) and no other organic disorders. Five days following discontinuation, drug monitoring revealed adequate tacrolimus plasma trough concentrations (8.9 μg/l) and the INR subsequently decreased.
Pristinamycin is an antibiotic effective against the majority of Gram positive bacteria. This drug is an inhibitor of the multidrug transporter P-glycoprotein (P-gp) that could lead to the accumulation of tacrolimus. Moreover, pristinamycin IIA is the active metabolite of quinupristin/dalfopristin which, is known to be an inhibitor of cytochrome P450 3A4 (CYP 3A4). Our case supposes that pristinamycin is also an inhibitor of CYP 3A4 that can lead to an increase of tacrolimus levels.
This case report brings to light potential drug interactions of pristinamycin with narrow therapeutic index drugs such as tacrolimus and warfarin.
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