Possible Interaction: Midazolam and St John's Wort

“ St. John's wort (SJW) significantly decreased the AUC (p < 0.0001) and clearance (p = 0.007) of midazolam.”

“Lastly, multiple herb-drug interactions have been identified with St. John's wort that involve significantly reduced AUC and blood concentrations of warfarin, digoxin, indinavir, theophylline, cyclosporine, tacrolimus, amitriptyline, midazolam , and phenprocoumon.”

“Results from clinical studies and case reports indicate that self-administered SJW reduce steady state plasma concentrations of amitriptyline, cyclosporine, digoxin, fexofenadine, amprenavir, indonavir, lopinavir, ritonavir, saquinavir, benzodiazepines, theophyline, irinotecan, midazolan and warfarin.”

“ Hypericum perforatum (hypericum; St John's wort) decreased the blood concentrations of ciclosporin (cyclosporin), midazolam , tacrolimus, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline, but did not alter the pharmacokinetics of carbamazepine, pravastatin, mycophenolate mofetil and dextromethorphan.”

“Concurrently, midazolam clearance (CYP3A activity) increased by 224% (n = 13, p < 0.05) and further increased after SJW by 374% compared to baseline (n = 13, p < 0.05).”

“ SJW increased midazolam clearance by 47% (n = 13, p < 0.05) but failed to alter bosentan exposure and clearance consistently.”

“In clinical studies using midazolam or anticancer drugs (irinotecan and imatinib) as known CYP3A4 substrates in combination with SJW , decreased plasma levels of these drugs were observed, which was expected as a consequence of CYP3A4 induction.”

“For example, St John's wort significantly reduced the area under the plasma concentration-time curve (AUC) and blood concentrations of cyclosporine, midazolam , tacrolimus, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline.”

“Clinical trials indicate …’s wort Hypericum perforatum ), via cytochrome P450 (CYP) and/or P-glycoprotein induction, reduces the plasma concentrations (and/or increases … alprazolam, amitriptyline, atorvastatin, chlorzoxazone, ciclosporin, debrisoquine, digoxin, erythromycin, fexofenadine, gliclazide, imatinib, indinavir, irinotecan, ivabradine, mephenytoin, methadone, midazolam , nifedipine, omeprazole, oral contraceptives, quazepam, …, verapamil, voriconazole and warfarin.”

“RESULTS Apparent oral clearance of mi azolam wa s significantly increased after St John's wort ad ministration from 65.3 +/- 8.4 l h(-1) (day -14) to 86.8 +/- 17.3 l h(-1) (day 0).”

“ResultsAll SJW preparations tested resulted in a decrease in midazolam AUC, although the extent of the effect differed.”