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Drug Interactions between Prograf and st. john's wort

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

tacrolimus St. John's wort

Applies to: Prograf (tacrolimus) and st. john's wort

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.

References (14)
  1. (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
  2. (2001) "Product Information. Rapamune (sirolimus)." Wyeth-Ayerst Laboratories
  3. Ernst E (1999) "Second thoughts about safety of St John's wort." Lancet, 354, p. 2014-6
  4. Fugh-Berman A (2000) "Herb-drug interactions." Lancet, 355, p. 134-8
  5. Roby CA, Anderson GD, Kantor E, Dryer DA, Burstein AH (2000) "St John's Wort: Effect on CYP3A4 activity." Clin Pharmacol Ther, 67, p. 451-7
  6. Durr D, Stieger B, KullakUblick GA, Rentsch KM, Steinert HC, Meier PJ, Fattinger K (2000) "St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4." Clin Pharmacol Ther, 68, p. 598-604
  7. Izzo AA, Ernst E (2001) "Interactions between herbal medicines and prescribed drugs: a systematic review." Drugs, 61, p. 2163-75
  8. Dresser GK, Schwarz UI, Wilkinson GR, Kim RB (2003) "Coordinate induction of both cytochrome P4503A and MDR1 by St John's wort in healthy subjects." Clin Pharmacol Ther, 73, p. 41-50
  9. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  10. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  11. (2007) "Product Information. Torisel (temsirolimus)." Wyeth-Ayerst Laboratories
  12. Cerner Multum, Inc. "Australian Product Information."
  13. (2009) "Product Information. Afinitor (everolimus)." Novartis Pharmaceuticals
  14. Mai, Stoarmer E., Bauer S., Kruger H, Budde K, Roots I (2003) "Impact of St John's wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients." Nephrol Dial Transplant, 18, p. 819-22

Drug and food interactions

Moderate

tacrolimus food

Applies to: Prograf (tacrolimus)

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.

References (2)
  1. (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
  2. Hooks MA (1994) "Tacrolimus, a new immunosuppressant--a review of the literature." Ann Pharmacother, 28, p. 501-11
Moderate

St. John's wort food

Applies to: st. john's wort

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.

References (1)
  1. Patel S, Robinson R, Burk M (2002) "Hypertensive crisis associated with St. John's Wort." Am J Med, 112, p. 507-8

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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