Tacrolimus interaction with nafcillin resulting in significant decreases in tacrolimus concentrations: A case report

Abstract

Tacrolimus (TAC) is subject to many drug interactions as a result of its metabolism primarily via CYP450 isoenzyme 3A4. Numerous case reports of TAC and CYP3A4 inducers and inhibitors have been described including antimicrobials, calcium channel antagonists, and antiepileptic drugs. We present the case of a 13-year-old patient with cystic fibrosis and a history of liver transplantation, where subtherapeutic TAC concentrations were suspected to be a result of concomitant TAC and nafcillin (NAF) therapy. The observed drug interaction occurred on two separate hospital admissions, during both of which the patient exhibited therapeutic TAC concentrations prior to exposure to NAF, a CYP3A4 inducer. Upon discontinuation of NAF, TAC concentrations recovered in both instances. This case represents a drug-drug interaction between TAC and NAF that has not previously been reported to our knowledge. Despite the lack of existing reports of interaction between these two agents, this case highlights the importance of therapeutic drug monitoring and assessing for any potential drug-drug or drug-food interactions in patients receiving TAC therapy.

Faculty Opinions recommendation of Synergistic and antagonistic drug interactions in the treatment of systemic fungal infections.

“…To investigate the mechanism of antagonism, we looked to other known drug interactions involving nafcillin. In particular, nafcillin antagonizes warfarin and other drugs in vivo by inducing cytochrome P450 enzymes through an unknown mechanism, which increases warfarin metabolism (King et al, 2018;Wungwattana and Savic, 2017). FLZ inhibits a fungal cytochrome P450 enzyme, 14a-demethylase, which halts ergosterol biosynthesis and fungal growth (Figure 5N; Odds et al, 2003).…”

Investigation of pharmacologic interactions between omeprazole and tacrolimus in a membranous nephropathy patient with CYP3A5 nonexpresser: a case report

“…Several studies showed that CYP3A4, CYP3A5 and ABCB1 gene polymorphisms play a crucial role in tacrolimus metabolism and excretion [8,9]. In particular, the pharmacokinetics of tacrolimus is mainly influenced by drug interaction, which is subject to numerous inhibitors or inducers of the CYP3A4/5 enzyme.…”