Clinical Controversy in Transplantation: Tacrolimus Versus Cyclosporine in Statin Drug Interactions.

To review the available literature that provides evidence for the absence of statin interactions with tacrolimus compared with cyclosporine. A literature search of PubMed was performed (1990 to June 2019) using the following search terms: , and . Clinical practice guidelines, article bibliographies, drug interaction database references, and product monographs were also reviewed. Relevant English-language studies describing the mechanism of interaction, the magnitude of pharmacokinetic alterations, and safety were evaluated. In vitro data and studies conducted in adult humans were considered. Studies demonstrate pharmacokinetic differences between cyclosporine and tacrolimus, particularly with regard to inhibition of 2 hepatic transporters: P-glycoprotein and organic anion transporting polypeptide (OATP). Compared with cyclosporine, tacrolimus does not affect these transporters, does not enhance statin exposure, and does not increase statin-associated safety events. Clinical practice guidelines allude to the need to reduce statin doses in the setting of tacrolimus. Some providers have adopted this practice, and doing so may prevent transplant recipients from attaining cardiovascular benefit, especially when increased or high-intensity doses are required. The pharmacokinetic differences between tacrolimus and cyclosporine highlight different interaction potential with statins. Clinicians need to be aware that tacrolimus and cyclosporine are not the same with regard to causing drug interactions with statins. Tacrolimus can be used with statins without the need for dose adjustments because of lack of an interaction.