Possible Interaction: Amitriptyline and St John's Wort

“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.”

“ St John's wort also enhances the metabolism of other CYP3A4 substrates including the protease inhibitors indinavir and nevirapine, oral contraceptives, and tricyclic antidepressants such as amitriptyline.”

“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, … concentrations (and/or increases the clearance) of alprazolam, amitriptyline , atorvastatin, chlorzoxazone, ciclosporin, debrisoquine, digoxin, erythromycin, fexofenadine, gliclazide, imatinib, indinavir, irinotecan, ivabradine, …, nifedipine, omeprazole, oral contraceptives, quazepam, simvastatin, tacrolimus, talinolol, verapamil, voriconazole and warfarin.”

“Recently, a variety of case reports … interactions due to drug combinations with St. John's wort have been published (e.g. cellular rejection of pancreas-, kidney- as well as heart transplants with … of INR with oral anticoagulants, bleeding with oral contraceptives, reduction of plasma concentration of digoxin, indinavir, amitriptyline, …).”

“The results … that St John's wort (Hypericum perforatum) lowers blood concentrations of cyclosporin, amitriptyline , digoxin, indinavir, warfarin, phenprocoumon and theophylline; furthermore it causes intermenstrual bleeding, delirium or mild serotonin syndrome, respectively, when used concomitantly with oral contraceptives (ethinylestradiol/desogestrel), loperamide or selective serotonin-reuptake inhibitors (sertaline, paroxetine, nefazodone).”

“Perhaps the … is St. John's Wort (Hypericum perforatum), which reduces the … of many drugs such as amitriptyline , digoxin, theophylline, non-steroidal anti-inflammatories (NSAIDs), and oral contraceptive pills.13 St. John's Wort … increases the activity and expression of multidrug transporter P-glycoprotein efflux pumps in the duodenum.”