St John’s wort, taken for two weeks, halved levels of a singledose of voriconazole, which may be clinically relevant.
Clinical evidence,mechanism, importance and management
A single 400mg dose of oral voriconazole was given alone and on first and last day of St John’s wort (Jarsin, Lichtwer Pharma) given at a dose of 300mg three times daily for 15 days to 17 healthy subjects. One day of St John’s wort had no effect on voriconazole AUC0-:6.2pt; font-weight:normal; color:#000000″>∞, but slightly increased maximum serum level and AUC0-10 by 22%. However, when voriconazole was given on day 15, AUC of voriconazole was decreased by 59 % and there was a 2.4-fold increase in oral clearance (See reference number 1).
These results suggest that short-term effect of St John’s wort is to slightly enhance absorption of voriconazole, whereas longer-term effect is to induce absorption-limiting transport proteins and intestinal metabolism via cytochrome P450 isoenzymes (See reference number 1).
The slight increase in voriconazole absorption with a single dose of St John’s wort is not clinically relevant. However, reduction in voriconazole levels after 15 days of St John’s wort could impact on clinical efficacy. This suggests that patients requiring voriconazole should be asked about current or recent use of St John’s wort, since this may indicate need to use an increased voriconazole dose, at least initially. Patients taking voriconazole should be advised not to take St John’s wort.
1. Rengelshausen J,Banfield M, Riedel KD, Burhenne J, Mikus G, et al. Opposite effects ofshort-term and long-term St John’s wort on voriconazole pharmacokinetics. Clin Pharmacol Ther (2005) 78, 25–33.