Drug Interaction Report

MONITOR: Coadministration of tigecycline with calcineurin inhibitors (e.g., tacrolimus, cyclosporine) may lead to an increase in serum trough concentrations of the calcineurin inhibitors. The mechanism for this interaction is unknown. In one case report, a transplant patient who had been receiving tacrolimus for 5 years post-transplant experienced a more than 3-fold increase in serum tacrolimus concentrations from baseline after 1 day of tigecycline therapy. The tacrolimus dose was reduced by 50% until treatment with tigecycline was discontinued at which time the dose was increased to maintain therapeutic serum levels. In another case report, a patient, 1 month post-transplant, experienced an increase in tacrolimus serum concentrations from a baseline of 11.5 ng/mL to 28.2 ng/mL and 43.6 ng/mL after 6 and 10 days, respectively, of treatment with tigecycline. Similarly, in another case report, a patient experienced an acute increase in serum cyclosporine concentrations after initiating therapy with tigecycline. The patient required a 50% reduction in the cyclosporine dose during treatment with tigecycline. When tigecycline was discontinued the cyclosporine dose was increased back to the original pre-tigecycline dose.

MANAGEMENT: Close monitoring is recommended whenever tigecycline is used concomitantly with a calcineurin inhibitor. Clinical and laboratory monitoring should be considered whenever tigecycline is added to or withdrawn from therapy with a calcineurin inhibitor, and the dosage of the calcineurin inhibitor adjusted as necessary. Patients should be monitored for development of adverse effects associated with the calcineurin inhibitor.

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.