Drug Interaction Report

GENERALLY AVOID: Coadministration with St. John's wort may alter the pharmacokinetics of antineoplastic agents that are substrates of the CYP450 3A4 isoenzyme (e.g., abiraterone, bexarotene, bortezomib, busulfan, cyclophosphamide, dasatinib, docetaxel, doxorubicin, etoposide, exemestane, ifosfamide, imatinib, irinotecan, letrozole, paclitaxel, sorafenib, sunitinib, tamoxifen, temsirolimus, teniposide, thiotepa, toremifene, tretinoin, vandetanib, vinca alkaloids). The mechanism is induction of CYP450 3A4 metabolism by constituents of St. John's wort, which is expected to reduce the systemic levels and pharmacologic effects of many of these agents. In contrast, some agents such as cyclophosphamide and ifosfamide are prodrugs that are converted to active metabolites by CYP450 3A4, thus pharmacologic effects may be enhanced by St. John's wort. However, clinical data are currently limited.

MANAGEMENT: Until more information is available, the use of St. John's wort should probably be avoided before and during the entire course of chemotherapy. It is not known how much time should elapse between the discontinuation of St. John's wort and initiation of chemotherapy. Patients should be advised to consult with their caregivers before using any herbal or alternative medicines.

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.