Drug Interaction Report

ADJUST DOSING INTERVAL: Sodium bicarbonate has been reported to cause widely variable trough plasma levels and reduced blood concentrations of tacrolimus when given close to the time of administration of tacrolimus. No other details were available in the report. Based on in vitro data, the mechanism appears to involve a pH-mediated degradation of tacrolimus. A 75% loss of tacrolimus was observed within 24 hours when tacrolimus was incubated in simulated gastric fluid with sodium bicarbonate. Other antacids tested (aluminum-magnesium hydroxide, magnesium oxide, calcium carbonate) also led to loss of tacrolimus.

MANAGEMENT: Until more data are available, it may be prudent to separate the times of administration of tacrolimus and sodium bicarbonate by at least two hours.

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.