Possible Interaction: Tacrolimus and St John's Wort

“… St. John's wort … tacrolimus AUC (306.9 μg•h/L ±175.8 μg•h/L vs. 198.7 μg•h/L ± 139.6 μg•h/L; … steady state (11.5 L/kg ± 4.3 L/kg vs. 17.6 L/kg ± 9.6 L/kg; p = 0.04).”

“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.”

“ 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.”

“Since then, subsequent research has shown that SJW altered the pharmacokinetics of drugs such as digoxin, tacrolimus , indinavir, warfarin, alprazolam, simvastatin, or oral contraceptives.”

“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.”

“Case reports or case series suggest interactions of St John’s wort with adrenergic vasopressors, anaesthetics, bupropion, buspirone, ciclosporin, eletriptan, loperamide, nefazodone, nevirapine, oral contraceptives, paroxetine, phenprocoumon, prednisone, sertraline, tacrolimus , theophylline, tibolone, tryptophan, venlafaxine and warfarin.”

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

“Significantly reduced concentrations of various therapeutic drugs such as digoxin, theophylline, cyclosporine, tacrolimus , tricyclic antidepressants, warfarin, and protease inhibitors can be observed due to interaction of these drugs with St. John's wort , causing treatment failure.”

“CONCLUSIONS Administration of SJ ex tract to patients receiving TAC tr eatment can result in a serious drug interaction leading to markedly reduced TAC blood concentrations associated with the risk of organ rejection.”

“ TAC … St John's wort (SJW), cranberry, rooibos tea, and boldo in human models by induction of the CYP450 system and/or P-gp efflux pump, meanwhile, … juice, pomelo, and ginger in human and or animal models by inhibition effect on CYP450 system and/or P-gp efflux pump.”