Drug interactions between st. john's wort and Xanax

MONITOR: Long-term (10 days or more) administration of St. John's wort may significantly decrease the oral bioavailability and/or plasma concentrations of benzodiazepines that are exclusively metabolized by CYP450 3A4 such as alprazolam, midazolam, and triazolam. The proposed mechanism is induction of CYP450 3A4-mediated intestinal (first-pass) and hepatic metabolism by constituents of St. John's wort. In 12 healthy volunteers, pretreatment with St. John's wort (300 mg, containing 0.9 mg hypericin, orally 3 times a day for 2 weeks) decreased the mean peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and bioavailability of oral midazolam (5 mg single dose) by 43%, 52% and 45%, respectively, compared to administration of midazolam alone. The oral clearance of midazolam approximately doubled with St. John's wort, while the elimination half-life was not significantly altered. In contrast, St. John's wort decreased the AUC of intravenous midazolam (0.05 mg/kg single dose) by only 21% and increased its clearance by 27% compared to control, and the difference was not statistically significant. Another study found that systemic clearance of IV midazolam increased by 44% while oral clearance increased by 168% after pretreatment with St. John's wort for 12 days. The interaction has also been reported with alprazolam. In 12 heathy volunteers, mean AUC and elimination half-life of alprazolam (2 mg single dose) reduced by approximately one-half and oral clearance more than doubled following treatment with St. John's wort for 2 weeks. However, effects of the interaction may be highly variable due to differences in composition of commercial St. John's wort products and deviation from labeled claims of many herbal products. A clinical study found no consistent effects on alprazolam with the use of recommended dosages of St. John's wort in seven healthy subjects.

MANAGEMENT: In general, patients should be advised to consult their healthcare provider before using any herbal or alternative medicines. If St. John's wort is prescribed with alprazolam, midazolam or triazolam, the possibility of a diminished therapeutic response to the benzodiazepine should be considered. Patients should be monitored more closely following the addition, withdrawal or change of dosage of St. John's wort, and the benzodiazepine dosage adjusted as necessary.