Drug Interaction Report

GENERALLY AVOID: Coadministration with St. John's Wort may significantly decrease the blood concentrations and pharmacologic effects of the immunosuppressants everolimus, temsirolimus, sirolimus, and tacrolimus. The mechanism may involve accelerated clearance of these medicines due to induction of the hepatic/intestinal CYP450 3A4 isoenzyme and intestinal P-glycoprotein (P-gp) efflux transporter by constituents of St. John's Wort. Administration of St. John's Wort extract (600 mg once a day for 14 days) in ten stable renal transplant patients receiving tacrolimus and mycophenolic acid led to significant reductions in tacrolimus exposure, as well as peak and trough blood concentrations, which may increase the risk of organ rejection. Reductions in peak concentration and systemic exposure have also been reported with the coadministration of these medicines with the potent CYP450 3A4 and P-gp inducer rifampin.

MANAGEMENT: The use of everolimus, temsirolimus, sirolimus, or tacrolimus in combination with St. John's Wort should generally be avoided and an alternative agent with less potential for induction considered. If coadministration is required, the manufacturer's product labeling should be consulted for specific dosing information. Patients should be advised to consult their doctor before using any alternative medicines.

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.

GENERALLY AVOID: An isolated case report suggests that foods containing large amounts of tyramine may precipitate a hypertensive crisis in patients treated with St. John's wort. The mechanism of interaction is unknown, as St. John's wort is not thought to possess monoamine oxidase (MAO) inhibiting activity at concentrations achieved in vivo. The case patient was a 41-year-old man who had been taking St. John's wort for seven days prior to presentation at the emergency room with confusion and disorientation. The patient recalled last eating aged cheese and having a glass of red wine approximately 10 hours prior to admission. No other cause of delirium or hypertension could be identified. In addition, alcohol may potentiate some of the pharmacologic effects of St. John's wort. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Until further information is available, patients treated with St. John's wort should consider avoiding consumption of protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, yogurt, papaya products, meat tenderizers, fava beans, protein extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. Patients should also be advised to avoid or limit consumption of alcohol.