Altered Bioavailability of Tacrolimus Following Intravenous Administration of Tigecycline

Tacrolimus interacts with many classes of medication.1Venkataramanan R. Swaminathan A. Prasad T. et al.Clinical pharmacokinetics of tacrolimus.Clin Pharmacokinet. 1995; 29: 404-430Crossref PubMed Scopus (644) Google Scholar We report a case of a possible drug interaction between tacrolimus and the glycyl cycline antibiotic tigecycline. A 51-year-old woman who had received a kidney transplant 5 years previously presented to our institution in septic shock. At the time of presentation, her creatinine level had increased to 3.5 mg/dL (309.4 μmol/L) from a baseline of 0.7 mg/dL (61.88 μmol/L; corresponding to an estimated glomerular filtration rate of 101.2 mL/min/1.73 m2 based on the 4-variable MDRD [Modification of Diet in Renal Disease] Study equation). Her immunosuppressant regimen consisted of mycophenolate mofetil, prednisolone, and tacrolimus. Blood culture was positive for Escherichia coli, which was sensitive to only tigecycline. During the course of tigecycline therapy, tacrolimus levels markedly increased, necessitating a decrease in tacrolimus dose (Fig 1). No other medications that potentially may have interacted with tacrolimus were administered. Upon discontinuing tigecycline therapy, the patient's tacrolimus levels became subtherapeutic. This was corrected with an increase in tacrolimus dose. The observation that treatment with tigecycline led to toxic tacrolimus levels that resolved with tigecycline therapy discontinuation suggests a possible interaction between these 2 medications. Tacrolimus is metabolized by the cytochrome P450 (CYP450) system.2Plosker G.L. Foster R.H. Tacrolimus: a further update of its pharmacology and therapeutic use in organ transplantation.Drugs. 2000; 59: 323-389Crossref PubMed Scopus (250) Google Scholar Drugs that interact with tacrolimus have been inducers or inhibitors of the CYP450 3A4 isoenzyme. Tigecycline acts by inhibiting bacterial protein synthesis and previously has not been described to interact with the CYP450 enzyme system.3Projan S.J. Preclinical pharmacology of GAR-936, a novel glycylcycline antibacterial agent.Pharmacotherapy. 2000; 20: S219-S223Crossref PubMed Google Scholar It has been reported that administration of Coumadin, which is metabolized by the CYP450 3A4 isoenzyme, with tigecycline results in increased biological activity of Coumadin. We hypothesize that tigecycline may exert a similar effect on tacrolimus, possibly through inhibition of CYP450 3A4.4Stein G.E. Craig W.A. Tigecycline: a critical analysis.Clin Infect Dis. 2006; 4: 518-524Crossref Scopus (232) Google Scholar Our case shows the need for monitoring tacrolimus levels while treating patients with intravenous tigecycline. Support: None. Financial Disclosure: The authors declare that they have no relevant financial interests.