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Interactions Between Herbal Medicines and Prescribed Drugs

An Updated Systematic Review

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Abstract

The concomitant use of herbal medicines and pharmacotherapy is wide spread. We have reviewed the literature to determine the possible interactions between seven popular herbal medicines (ginkgo, St John’s wort, ginseng, garlic, echinacea, saw palmetto and kava) and conventional drugs. Literature searches were performed using MEDLINE, Cochrane Library and EMBASE and we identified 128 case reports or case series, and 80 clinical trials.

Clinical trials indicate that St John’s wort (Hypericum perforatum), via cytochrome P450 (CYP) and/or P-glycoprotein induction, reduces the plasma concentrations (and/or increases the clearance) of alprazolam, amitriptyline, atorvastatin, chlorzoxazone, ciclosporin, debrisoquine, digoxin, erythromycin, fexofenadine, gliclazide, imatinib, indinavir, irinotecan, ivabradine, mephenytoin, methadone, midazolam, nifedipine, omeprazole, oral contraceptives, quazepam, simvastatin, tacrolimus, talinolol, verapamil, voriconazole and warfarin. 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. Ginkgo (Ginkgo biloba) decreases the plasma concentrations of omeprazole, ritonavir and tolbutamide. Clinical cases indicate interactions of ginkgo with antiepileptics, aspirin (acetylsalicylic acid), diuretics, ibuprofen, risperidone, rofecoxib, trazodone and warfarin. Ginseng (Panax ginseng) may interact with phenelzine and warfarin. Kava (Piper methysticum) increases the clearance of chlorzoxazone (a CYP2E1 substrate) and may interact with alprazolam, levodopa and paroxetine. Garlic (Allium sativum) interacts with chlorpropamide, fluindione, ritonavir and warfarin; it also reduces plasma concentrations of chlorzoxazone (a CYP2E1 probe). Echinacea might affect the clearance of caffeine (a CYP1A2 probe) and midazolam (a CYP3A4 probe). No interactions have been reported for saw palmetto (Serenoa repens.)

Numerous interactions between herbal medicines and conventional drugs have been documented. While the significance of many interactions is uncertain, several interactions, particularly those with St John’s wort, may have serious clinical consequences.

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Table I

References

  1. Ernst E, Pittler MH, Wider B. The desktop guide to complementary and alternative medicine: an evidence-based approach. Philadelphia (PA): Mosby Elsevier, 2006

    Google Scholar 

  2. Ernst E, Pittler MH, Wider B, et al. Oxford handbook of complementary medicine. Oxford: Oxford University Press, 2008

    Book  Google Scholar 

  3. Capasso F, Gaginella TS, Grandolini G, et al. Phytotherapy: a quick reference to herbal medicine. Berlin: Springer-Verlag, 2003

    Google Scholar 

  4. Bent S. Herbal medicine in the United States: review of efficacy, safety, and regulation — grand rounds at University of California, San Francisco Medical Center. J Gen Intern Med 2008; 23: 854–9

    Article  PubMed  Google Scholar 

  5. Zhou SF, Zhou ZW, Li CG, et al. Identification of drugs that interact with herbs in drug development. Drug Discov Today 2007; 12: 664–73

    Article  PubMed  CAS  Google Scholar 

  6. Tomlinson B, Hu M, Lee VW. In vivo assessment of herb-drug interactions: possible utility of a pharmacogenetic approach? Mol Nutr Food Res 2008; 52: 799–809

    Article  PubMed  CAS  Google Scholar 

  7. De Smet PA. Clinical risk management of herb-drug interactions. Br J Clin Pharmacol 2007; 63: 258–67

    Article  PubMed  Google Scholar 

  8. Izzo AA. Herb-drug interactions: an overview of the clinical evidence. Fundam Clin Pharmacol 2005; 19: 1–16

    Article  PubMed  CAS  Google Scholar 

  9. Butterweck V, Derendorf H. Potential of pharmacokinetic profiling for detecting herbal interactions with drugs. Clin Pharmacokinet 2008; 47(6): 383–97

    Article  PubMed  CAS  Google Scholar 

  10. Hu Z, Yang X, Ho PC, et al. Herb-drug interactions: a literature review. Drugs 2005; 65: 1239–82

    Article  PubMed  CAS  Google Scholar 

  11. Williamson EM. Drug interactions between herbal and prescription medicines. Drug Saf 2003; 26: 1075–92

    Article  PubMed  CAS  Google Scholar 

  12. Izzo AA, Borrelli F, Capasso R. Herbal medicine: the dangers of drug interaction. Trends Pharmacol Sci 2002; 23: 358–91

    Article  PubMed  CAS  Google Scholar 

  13. Yang GF, Huang X. Development of quantitative structure-activity relationships and its application in rational drug design. Curr Pharm Des 2006; 12: 4601–11

    Article  PubMed  CAS  Google Scholar 

  14. Zhou SF, Xue CC, Yu XQ, et al. Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring. Ther Drug Monit 2007; 29: 687–710

    Article  PubMed  CAS  Google Scholar 

  15. Gardiner P, Phillips R, Shaughnessy AF. Herbal and dietary supplement: drug interactions in patients with chronic illnesses. Am Fam Physician 2008; 77: 73–8

    PubMed  Google Scholar 

  16. Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs 2001; 61: 2163–75

    Article  PubMed  CAS  Google Scholar 

  17. Williamson EM. Interactions between herbal and conventional medicines. Expert Opin Drug Saf 2005; 4: 355–78

    Article  PubMed  CAS  Google Scholar 

  18. Ernst E. Herb-drug interactions: an update. Perfusion 2003; 16: 175–94

    Google Scholar 

  19. Ulbricht C, Chao W, Costa D, et al. Clinical evidence of herb-drug interactions: a systematic review by the natural standard research collaboration. Curr Drug Metab 2008; 9: 1062–119

    Article  Google Scholar 

  20. Cranwell-Bruce L. Herb-drug interactions. Medsurg Nurs 2008; 17: 52–4

    PubMed  Google Scholar 

  21. Calapai G, Caputi AP. Herbal medicines: can we do without pharmacologist? Evid Based Complement Alternat Med 2007; 4: 41–3

    Article  PubMed  Google Scholar 

  22. Bush TM, Rayburn KS, Holloway SW, et al. Adverse interactions between herbal and dietary substances and prescription medications: a clinical survey. Alternat Ther Health Med 2007; 13: 30–5

    Google Scholar 

  23. Kennedy J, Wang CC, Wu CH. Patient disclosure about herb and supplement use among adults in the US. Evid Based Complement Alternat Med 2008; 5: 451–6

    Article  PubMed  Google Scholar 

  24. Aslam M, Stockley IH. Interaction between curry ingredient (karela) and drug (chlorpropamide) [letter]. Lancet 1979; I: 607

    Article  Google Scholar 

  25. Pathak A, Léger P, Bagheri H, et al. Garlic interaction with fluindione: a case report. Therapie 2003; 58: 380–1

    Article  PubMed  Google Scholar 

  26. Laroche M, Choudhuri S, Gallicano K, et al. Severe gastrointestinal toxicity with concomitant ingestion of ritonavir and garlic. Can J Infect Dis 1998; 9: 471P

    Google Scholar 

  27. Sunter WH. Warfarin and garlic [letter]. PharmJ 1991;246: 772

    Google Scholar 

  28. Kupiec T, Raj V. Fatal seizures due to potential herb-drug interactions with Ginkgo biloba. J Anal Toxicol 2005; 29: 755–8

    PubMed  CAS  Google Scholar 

  29. Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract [letter]. N Engl J Med 1997; 336: 1108

    Article  PubMed  CAS  Google Scholar 

  30. Shaw D, Leon C, Kolev S, et al. Traditional remedies and food supplements: a 5-year toxicological study (1991–1995). Drug Saf 1997; 17: 342–56

    Article  PubMed  CAS  Google Scholar 

  31. Meisel C, Johne A, Roots I. Fatal intracerebral mass bleeding associated with Ginkgo biloba and ibuprofen [letter]. Atherosclerosis 2003; 167: 367

    Article  PubMed  CAS  Google Scholar 

  32. Lin YY, Chu SJ, Tsai SH. Association between priapism and concurrent use of risperidone and Ginkgo biloba. Mayo Clin Proc 2007; 82: 1289–90

    Article  PubMed  Google Scholar 

  33. Hoffman T. Ginkgo, vioxx and excessive bleeding: possible drug-herb interactions — case report [letter]. Hawaii Med J 2001; 60: 290

    PubMed  CAS  Google Scholar 

  34. Galluzzi S, Zanetti O, Binetti G, et al. Coma in a patient with Alzheimer’s disease taking low dose trazodone and gingko biloba. J Neurol Neurosurg Psychiatry 2000; 68: 679–80

    Article  PubMed  CAS  Google Scholar 

  35. Matthews Jr MK. Association of Ginkgo biloba with intracerebral hemorrhage. Neurology 1998; 50: 1933–4

    Article  PubMed  Google Scholar 

  36. Shader RI, Greenblatt DJ. Bees, ginseng and MAOIs revisited [letter]. J Clin Psychopharmacol 1988; 8: 235

    PubMed  CAS  Google Scholar 

  37. Jones BD, Runikis AM. Interaction of ginseng with phenelzine. J Clin Psychopharmacol 1987; 7: 201–2

    Article  PubMed  CAS  Google Scholar 

  38. Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng. Am J Health Syst Pharm 1997; 54: 692–3

    PubMed  CAS  Google Scholar 

  39. Almeida JC, Grimsley EW. Coma from the health food store: interaction between kava and alprazolam. Ann Intern Med 1996; 125: 940–1

    PubMed  CAS  Google Scholar 

  40. Schelosky L, Raffauf C, Jendroska K, et al. Kava and dopamine antagonism. J Neurol Neurosurg Psychiatry 1995; 58: 639–40

    Article  PubMed  CAS  Google Scholar 

  41. Rubin D, McGovern B, Kopelman RI. Back to basics. Am J Med 2006; 119: 482–3

    Article  PubMed  Google Scholar 

  42. Irefin S, Sprung J. A possible cause of cardiovascular collapse during anesthesia: long-term use of St John’s wort. J Clin Anesth 2000; 12: 498–9

    Article  PubMed  CAS  Google Scholar 

  43. Crowe S, McKeating K. Delayed emergence and St John’s wort. Anesthesiology 2002; 96: 1025–7

    Article  PubMed  Google Scholar 

  44. Milton JC, Abdulla A. Prolonged oro-facial dystonia in a 58 year old female following therapy with bupropion and St John’s wort. Br J Clin Pharmacol 2007; 64: 717–8

    Article  PubMed  Google Scholar 

  45. Spinella M, Eaton LA. Hypomania induced by herbal and pharmaceutical psychotropic medicines following mild traumatic brain injury. Brain Inj 2002; 16: 359–67

    Article  PubMed  Google Scholar 

  46. Dannawi M. Possible serotonin syndrome after combination of buspirone and St John’s wort [letter]. J Psychopharmacol 2002; 16: 401

    Article  PubMed  Google Scholar 

  47. Bon S, Hartmann K, Kubn M. Johanniskraut: ein enzyminduktor? Schweitzer Apothekerzeitung 1999; 16: 535–6

    Google Scholar 

  48. Breidenbach T, Kliem V, Burg M, et al. Profound drop of cyclosporin A whole blood trough levels caused by St John’s wort (Hypericum perforatum). Transplantation 2000; 69: 2229–30

    Article  PubMed  CAS  Google Scholar 

  49. Breidenbach T, Hoffmann MW, Becker T, et al. Drug interaction of St John’s wort with cyclosporin [letter]. Lancet 2000 May 27; 355(9218): 1912

    Article  PubMed  CAS  Google Scholar 

  50. Roots I, Johne A, Mauer A, et al. Arzneimittel interaktionen von hypericum-extract. Proceedings from the German Society of Pharmacology; 2000 Jun 16–17; Berlin

  51. Rey JM, Walter G. Hypericum perforatum (St John’s wort) in depression: pest or blessing? Med J Aust 1998; 169: 583–6

    PubMed  CAS  Google Scholar 

  52. Ruschitzka F, Meier PJ, Turina M, et al. Acute heart transplant rejection due to Saint John’s wort. Lancet 2000; 355: 548–9

    Article  PubMed  CAS  Google Scholar 

  53. Barone GW, Gurley BJ, Ketel BL, et al. Drug interaction between St John’s wort and cyclosporine. Ann Pharmacother 2000; 34: 1013–6

    Article  PubMed  CAS  Google Scholar 

  54. Mai I, Krüger H, Budde K, et al. Hazardous pharmacokinetic interaction of Saint John’s wort (Hypericum perforatum) with the immunosuppressant cyclosporin. Int J Clin Pharmacol Ther 2000; 38: 500–2

    PubMed  CAS  Google Scholar 

  55. Karliova M, Treichel U, Malagò M, et al. Interaction of Hypericum perforatum (St John’s wort) with cyclosporin A metabolism in a patient after liver transplantation. J Hepatol 2000; 33: 853–5

    Article  PubMed  CAS  Google Scholar 

  56. Mandelbaum A, Pertzborn F, Martin-Facklam M, et al. Unexplained decrease of cyclosporin trough levels in a compliant renal transplant patient. Nephrol Dial Transplant 2000; 15: 1473–4

    Article  PubMed  CAS  Google Scholar 

  57. Turton-Weeks SM, Barone GW, Gurley BJ, et al. St John’s wort: a hidden risk for transplant patients. Prog Transplant 2001; 11: 116–20

    PubMed  CAS  Google Scholar 

  58. Ahmed SM, Banner NR, Dubrey SW. Low cyclosporin-A level due to Saint-John’s-wort in heart transplant patients [letter]. J Heart Lung Transplant 2001; 20: 795

    Article  PubMed  CAS  Google Scholar 

  59. Beer AM, Ostermann T. St John’s wort: interaction with cyclosporine increases risk of rejection for the kidney transplant and raises daily cost of medication. Med Klin (Munich) 2001; 96: 480–3

    Article  CAS  Google Scholar 

  60. Moschella C, Jaber BL. Interaction between cyclosporine and Hypericum perforatum (St John’s wort) after organ transplantation. Am J Kidney Dis 2001; 38: 1105–7

    Article  PubMed  CAS  Google Scholar 

  61. Alscher DM, Klotz U. Drug interaction of herbal tea containing St John’s wort with cyclosporine. Transpl Int 2003; 16: 543–4

    Article  PubMed  Google Scholar 

  62. Bonetto N, Santelli L, Battistin L, et al. Serotonin syndrome and rhabdomyolysis induced by concomitant use of triptans, fluoxetine and hypericum. Cephalalgia 2007; 27: 1421–3

    Article  PubMed  CAS  Google Scholar 

  63. Khawaja IS, Marotta RF, Lippmann S. Herbal medicines as a factor in delirium. Psychiatr Serv 1999; 50: 969–70

    PubMed  CAS  Google Scholar 

  64. Lantz MS, Buchalter E, Giambanco V. St John’s wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatry Neurol 1999; 12: 7–10

    Article  PubMed  CAS  Google Scholar 

  65. de Maat MM, Hoetelmans RM, Matht RA, et al. Drug interaction between St John’s wort and nevirapine. AIDS 2001; 15: 420–1

    Article  PubMed  Google Scholar 

  66. Yue QY, Bergquist C, Gerdén B. Safety of St John’s wort (Hypericum perforatum). Lancet 2000; 355: 576–7

    Article  PubMed  CAS  Google Scholar 

  67. Schwarz UI, Büschel B, Kirch W. Unwanted pregnancy on self-medication with St John’s wort despite hormonal contraception. Br J Clin Pharmacol 2003; 55: 112–3

    Article  PubMed  Google Scholar 

  68. Gordon JB. SSRIs and St John’s wort: possible toxicity? [letter]. Am Fam Phys 1998; 57: 950

    CAS  Google Scholar 

  69. Saraga M, Zullino DF. St John’s wort, corticosteroids, cocaine, alcohol … and a first manic episode [in French]. Praxis (Bern 1994) 2005; 94: 987–9

    Article  CAS  Google Scholar 

  70. Barbenel DM, Yusufi B, O’Shea D, et al. Mania in a patient receiving testosterone replacement postorchidectomy taking St John’s wort and sertraline. J Psychopharmacol 2000; 14: 84–6

    Article  PubMed  CAS  Google Scholar 

  71. Bolley R, Zülke C, Kammerl M, et al. Tacrolimus-induced nephrotoxicity unmasked by induction of the CYP3A4 system with St John’s wort [letter]. Transplantation 2002; 73: 1009

    Article  PubMed  Google Scholar 

  72. Nebel A, Schneider BJ, Baker RK, et al. Potential metabolic interaction between St John’s wort and theophylline [letter]. Ann Pharmacother 1999; 33: 502

    Article  PubMed  CAS  Google Scholar 

  73. Etogo-Asse F, Boemer F, Sempoux C, et al. Acute hepatitis with prolonged cholestasis and disappearance of interlobular bile ducts following tibolone and Hypericum perforatum (St John’s wort): case of drug interaction? Acta Gastroenterol Belg 2008; 71: 36–8

    PubMed  CAS  Google Scholar 

  74. Bryant SM, Kolodchak J. Serotonin syndrome resulting from an herbal detox cocktail. Am J Emerg Med 2004; 22: 625–6

    Article  PubMed  Google Scholar 

  75. Prost N, Tichadou L, Rodor F, et al. St Johns wortvenlafaxine interaction. Presse Med 2000; 29: 1285–6

    PubMed  CAS  Google Scholar 

  76. Gorski JC, Huang SM, Pinto A, et al. The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo. Clin Pharmacol Ther 2004; 75: 89–100

    Article  PubMed  Google Scholar 

  77. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther 2004; 76: 428–40

    Article  PubMed  Google Scholar 

  78. Gurley BJ, Swain A, Hubbard MA, et al. Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St John’s wort, and echinacea. Mol Nutr Food Res 2008; 52: 755–63

    Article  PubMed  CAS  Google Scholar 

  79. Gurley BJ, Swain A, Williams DK, et al. Gauging the clinical significance of P-glycoprotein-mediated herbdrug interactions: comparative effects of St John’s wort, echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics. Mol Nutr Food Res 2008; 52: 772–9

    Article  PubMed  CAS  Google Scholar 

  80. Markowitz JS, Devane CL, Chavin KD, et al. Effects of garlic (Allium sativum L.) supplementation on cytochrome P450 2D6 and 3A4 activity in healthy volunteers. Clin Pharmacol Ther 2003; 74: 170–7

    Article  PubMed  CAS  Google Scholar 

  81. Gurley BJ, Gardner SF, Hubbard MA, et al. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John’s wort, garlic oil, Panax ginseng and Ginkgo biloba. Drugs Aging 2005; 22: 525–39

    Article  PubMed  CAS  Google Scholar 

  82. Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002; 72: 276–87

    Article  PubMed  CAS  Google Scholar 

  83. Jabbari A, Argani H, Ghorbanihaghjo A, et al. Comparison between swallowing and chewing of garlic on levels of serum lipids, cyclosporine, creatinine and lipid peroxidation in renal transplant recipients. Lipids Health Dis 2005; 4: 11

    Article  PubMed  CAS  Google Scholar 

  84. Cox MC, Low J, Lee J, et al. Influence of garlic (Allium sativum) on the pharmacokinetics of docetaxel. Clin Cancer Res 2006; 12: 4636–40

    Article  PubMed  CAS  Google Scholar 

  85. Gwilt PR, Lear CL, Tempero MA, et al. The effect of garlic extract on human metabolism of acetaminophen. Cancer Epidemiol Biomarkers Prev 1994; 3: 155–60

    PubMed  CAS  Google Scholar 

  86. Gallicano K, Foster B, Choudhri S. Effect of short-term administration of garlic supplements on single-dose ritonavir pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2003; 55: 199–202

    Article  PubMed  CAS  Google Scholar 

  87. Piscitelli SC, Burstein AH, Welden N, et al. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 2002; 34: 234–8

    Article  PubMed  Google Scholar 

  88. Macan H, Uykimpang R, Alconcel M, et al. Aged garlic extract may be safe for patients on warfarin therapy. J Nutr 2006; 136: 793S–5S

    PubMed  CAS  Google Scholar 

  89. Mohammed Abdul MI, Jiang X, Williams KM, et al. Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects. Br J Pharmacol 2008; 154: 1691–700

    Article  PubMed  CAS  Google Scholar 

  90. Gardner CD, Zehnder JL, Rigby AJ, et al. Effect of Ginkgo biloba (EGb 761) and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease: a randomized clinical trial. Blood Coagul Fibrinolysis 2007; 18: 787–93

    Article  PubMed  Google Scholar 

  91. Markowitz JS, Donovan JL, Lindsay DeVane C, et al. Multiple-dose administration of Ginkgo biloba did not affect cytochrome P-450 2D6 or 3A4 activity in normal volunteers. J Clin Psychopharmacol 2003; 23: 576–81

    Article  PubMed  CAS  Google Scholar 

  92. Aruna D, Naidu MU. Pharmacodynamic interaction studies of Ginkgo biloba with cilostazol and clopidogrel in healthy human subjects. Br J Clin Pharmacol 2007; 63: 333–8

    Article  PubMed  CAS  Google Scholar 

  93. Mohutsky MA, Anderson GD, Miller JW, et al. Ginkgo biloba: evaluation of CYP2C9 drug interactions in vitro and in vivo. Am J Ther 2006; 13: 24–31

    Article  PubMed  Google Scholar 

  94. Mauro VF, Mauro LS, Kleshinski JF, et al. Impact of Ginkgo biloba on the pharmacokinetics of digoxin. Am J Ther 2003; 10: 247–51

    Article  PubMed  Google Scholar 

  95. Robertson SM, Davey RT, Voell J, et al. Effect of Ginkgo biloba extract on lopinavir, midazolam and fexofenadine pharmacokinetics in healthy subjects. Curr Med Res Opin 2008; 24: 591–9

    Article  PubMed  CAS  Google Scholar 

  96. Greenblatt DJ, von Moltke LL, Luo Y, et al. Ginkgo biloba does not alter clearance of flurbiprofen, a cytochrome P450-2C9 substrate. J Clin Pharmacol 2006; 46: 214–21

    Article  PubMed  CAS  Google Scholar 

  97. Uchida S, Yamada H, Li XD, et al. Effects of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide and midazolam in healthy volunteers. J Clin Pharmacol 2006; 46: 1290–8

    Article  PubMed  CAS  Google Scholar 

  98. Yoshioka M, Ohnishi N, Koishi T, et al. Studies on interactions between functional foods or dietary supplements and medicines. IV: effects of Ginkgo biloba leaf extract on the pharmacokinetics and pharmacodynamics of nifedipine in healthy volunteers. Biol Pharm Bull 2004; 27: 2006–9

    CAS  Google Scholar 

  99. Yin OQ, Tomlinson B, Waye MM, et al. Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Pharmacogenetics 2004; 14: 841–50

    Article  PubMed  Google Scholar 

  100. Duche JC, Barre J, Guinot P, et al. Effect of Ginkgo biloba extract on microsomal enzyme induction. Int J Clin Pharmacol Res 1989; 9: 165–8

    PubMed  CAS  Google Scholar 

  101. Jiang X, Williams KM, Liauw WS, et al. Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2005; 59: 425–32

    Article  PubMed  CAS  Google Scholar 

  102. Engelsen J, Nielsen JD, Winther K. Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients: a randomised, double blind, placebo-crossover trial. Thromb Haemost 2002; 87: 1075–6

    PubMed  CAS  Google Scholar 

  103. Jiang X, Williams KM, Liauw WS, et al. Effect of St John’s wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2004; 57: 592–9

    Article  PubMed  CAS  Google Scholar 

  104. Lee SH, Ahn YM, Ahn SY, et al. Interaction between warfarin and Panax ginseng in ischemic stroke patients. J Altern Complement Med 2008; 14: 715–21

    Article  PubMed  Google Scholar 

  105. Gurley BJ, Swain A, Barone GW, et al. Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos 2007; 35: 240–5

    Article  PubMed  CAS  Google Scholar 

  106. Gurley BJ, Swain A, Hubbard MA, et al. Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo. Clin Pharmacol Ther 2008; 83: 61–9

    Article  PubMed  CAS  Google Scholar 

  107. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005; 77: 415–26

    Article  PubMed  CAS  Google Scholar 

  108. Markowitz JS, Donovan JL, Devane CL, et al. Multiple doses of saw palmetto (Serenoa repens) did not alter cytochrome P450 2D6 and 3A4 activity in normal volunteers. Clin Pharmacol Ther 2003; 74: 536–42

    Article  PubMed  CAS  Google Scholar 

  109. Markowitz JS, DeVane CL, Boulton DW, et al. Effect of St John’s wort (Hypericum perforatum) on cytochrome P-450 2D6 and 3A4 activity in healthy volunteers. Life Sci 2000; 66: PL133–9

    Article  PubMed  CAS  Google Scholar 

  110. Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St John’s wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 2003; 290: 1500–4

    Article  PubMed  CAS  Google Scholar 

  111. Arold G, Donath F, Maurer A, et al. No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St John’s wort extract. Planta Med 2005; 71: 331–7

    Article  PubMed  CAS  Google Scholar 

  112. Johne A, Schmider J, Brockmöller J, et al. Decreased plasma levels of amitriptyline and its metabolites on comedication with an extract from St John’s wort (Hypericum perforatum). J Clin Psychopharmacol 2002; 22: 46–54

    Article  PubMed  CAS  Google Scholar 

  113. Andrén L, Andreasson A, Eggertsen R. Interaction between a commercially available St John’s wort product (Movina) and atorvastatin in patients with hypercholesterolemia. Eur J Clin Pharmacol 2007; 63(10): 913–6

    Article  PubMed  Google Scholar 

  114. Burstein AH, Horton RL, Dunn T, et al. Lack of effect of St John’s wort on carbamazepine pharmacokinetics in healthy volunteers. Clin Pharmacol Ther 2000; 68: 605–12

    Article  PubMed  CAS  Google Scholar 

  115. Wang Z, Gorski JC, Hamman MA, et al. The effects of St John’s wort (Hypericum perforatum) on human cytochrome P450 activity. Clin Pharmacol Ther 2001; 70: 317–26

    PubMed  CAS  Google Scholar 

  116. Wang LS, Zhu B, Abd El-Aty AM, et al. The influence of St John’s wort on CYP2C19 activity with respect to genotype. J Clin Pharmacol 2004 Jun; 44(6): 577–81

    Article  PubMed  CAS  Google Scholar 

  117. Wenk M, Todesco L, Krähenbühl S. Effect of St John’s wort on the activities of CYP1A2, CYP3A4, CYP2D6, Nacetyltransferase 2, and xanthine oxidase in healthy males and females. Br J Clin Pharmacol 2004; 57: 495–9

    Article  PubMed  CAS  Google Scholar 

  118. Dresser GK, Schwarz UI, Wilkinson GR, et al. Coordinate induction of both cytochrome P4503A and MDR1 by St John’s wort in healthy subjects. Clin Pharmacol Ther 2003; 73: 41–50

    Article  PubMed  CAS  Google Scholar 

  119. Mai I, Bauer S, Perloff ES, et al. Hyperforin content determines the magnitude of the St John’s wort-cyclosporine drug interaction. Clin Pharmacol Ther 2004; 76: 330–40

    Article  PubMed  CAS  Google Scholar 

  120. Roby CA, Dryer DA, Burstein AH. St John’s wort: effect on CYP2D6 activity using dextromethorphan-dextrorphan ratios. J Clin Psychopharmacol 2001; 21: 530–2

    Article  PubMed  CAS  Google Scholar 

  121. Johne A, Brockmöller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John’s wort (Hypericum perforatum). Clin Pharmacol Ther 1999; 66: 338–45

    Article  PubMed  CAS  Google Scholar 

  122. Mueller SC, Uehleke B, Woehling H, et al. Effect of St John’s wort dose and preparations on the pharmacokinetics of digoxin. Clin Pharmacol Ther 2004; 75: 546–57

    Article  PubMed  CAS  Google Scholar 

  123. Dürr D, Stieger B, Kullak-Ublick GA, et al. St John’s wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 2000; 68: 598–604

    Article  PubMed  Google Scholar 

  124. Wang Z, Hamman MA, Huang SM, et al. Effect of St John’s wort on the pharmacokinetics of fexofenadine. Clin Pharmacol Ther 2002; 71: 414–20

    Article  PubMed  CAS  Google Scholar 

  125. Xie R, Tan LH, Polasek EC, et al. CYP3A and P-glycoprotein activity induction with St John’s wort in healthy volunteers from 6 ethnic populations. J Clin Pharmacol 2005; 45: 352–6

    Article  PubMed  CAS  Google Scholar 

  126. Xu H, Williams KM, Liauw WS, et al. Effects of St John’s wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide. Br J Pharmacol 2008; 153: 1579–86

    Article  PubMed  CAS  Google Scholar 

  127. Frye RF, Fitzgerald SM, Lagattuta TF, et al. Effect of St John’s wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther 2004; 76: 323–9

    Article  PubMed  CAS  Google Scholar 

  128. Smith P, Bullock JM, Booker BM, et al. The influence of St John’s wort on the pharmacokinetics and protein binding of imatinib mesylate. Pharmacotherapy 2004; 24: 1508–14

    Article  PubMed  CAS  Google Scholar 

  129. Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir concentrations and St John’s wort. Lancet 2000; 355: 547–8

    Article  PubMed  CAS  Google Scholar 

  130. Mathijssen RH, Verweij J, de Bruijn P, et al. Effects of St John’s wort on irinotecan metabolism. J Natl Cancer Inst 2002; 94: 1247–9

    Article  PubMed  CAS  Google Scholar 

  131. Portolés A, Terleira A, Calvo A, et al. Effects of Hypericum perforatum on ivabradine pharmacokinetics in healthy volunteers: an open-label, pharmacokinetic interaction clinical trial. J Clin Pharmacol 2006; 46: 1188–94

    Article  PubMed  CAS  Google Scholar 

  132. Eich-Höchli D, Oppliger R, Golay KP, et al. Methadone maintenance treatment and St John’s wort: a case report. Pharmacopsychiatry 2003; 36: 35–7

    Article  PubMed  Google Scholar 

  133. Mai I, Störmer E, Bauer S, et al. Impact of St John’s wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients. Nephrol Dial Transplant 2003; 18: 819–22

    Article  PubMed  CAS  Google Scholar 

  134. Hall SD, Wang Z, Huang SM, et al. The interaction between St John’s wort and an oral contraceptive. Clin Pharmacol Ther 2003; 74: 525–35

    Article  PubMed  CAS  Google Scholar 

  135. Mueller SC, Majcher-Peszynska J, Uehleke B, et al. The extent of induction of CYP3A by St John’s wort varies among products and is linked to hyperforin dose. Eur J Clin Pharmacol 2006; 62: 29–36

    Article  PubMed  CAS  Google Scholar 

  136. Mueller SC, Majcher-Peszynska J, Mundkowski RG, et al. No clinically relevant CYP3A induction after St John’s wort with low hyperforin content in healthy volunteers. Eur J Clin Pharmacol 2009; 65: 81–7

    Article  PubMed  CAS  Google Scholar 

  137. Imai H, Kotegawa T, Tsutsumi K, et al. The recovery time-course of CYP3A after induction by St John’s wort administration. Br J Clin Pharmacol 2008; 65: 701–7

    Article  PubMed  Google Scholar 

  138. L’homme RF, Dijkema T, van der Ven AJ, et al. Brief report: enzyme inducers reduce elimination half-life after a single dose of nevirapine in healthy women. J Acquir Immune Defic Syndr 2006; 43: 193–6

    Article  PubMed  CAS  Google Scholar 

  139. Wang XD, Li JL, Su QB, et al. Impact of the haplotypes of the human pregnane X receptor gene on the basal and St John’s wort-induced activity of cytochrome P450 3A4 enzyme. Br J Clin Pharmacol 2009; 67: 255–61

    Article  PubMed  CAS  Google Scholar 

  140. Wang LS, Zhou G, Zhu B, et al. St John’s wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. Clin Pharmacol Ther 2004; 75: 191–7

    Article  PubMed  CAS  Google Scholar 

  141. Pfrunder A, Schiesser M, Gerber S, et al. Interaction of St John’s wort with low-dose oral contraceptive therapy: a randomized controlled trial. Br J Clin Pharmacol 2003; 56: 683–90

    Article  PubMed  CAS  Google Scholar 

  142. Murphy PA, Kern SE, Stanczyk FZ, et al. Interaction of St John’s wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception 2005; 71: 402–8

    Article  PubMed  CAS  Google Scholar 

  143. Will-Shahab L, Bauer S, Kunter U, et al. St John’s wort extract (Ze 117) does not alter the pharmacokinetics of a low-dose oral contraceptive. Eur J Clin Pharmacol 2009; 65: 287–94

    Article  PubMed  Google Scholar 

  144. Donath F, Roots I, Langheinrich M, et al. Interaction of St John’s wort extract with phenprocoumon [abstract]. Eur J Clin Pharmacol 1999; 55: A22

    Google Scholar 

  145. Sugimoto K, Ohmori M, Tsuruoka S, et al. Different effects of St John’s wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther 2001; 70: 518–24

    Article  PubMed  CAS  Google Scholar 

  146. Bell EC, Ravis WR, Chan HM, et al. Lack of pharmacokinetic interaction between St John’s wort and prednisone. Ann Pharmacother 2007; 41: 1819–24

    Article  PubMed  CAS  Google Scholar 

  147. Kawaguchi A, Ohmori M, Tsuruoka S, et al. Drug interaction between St John’s wort and quazepam. Br J Clin Pharmacol 2004; 58: 403–10

    Article  PubMed  CAS  Google Scholar 

  148. Hebert MF, Park JM, Chen YL, et al. Effects of St John’s wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers. J Clin Pharmacol 2004; 44: 89–94

    Article  PubMed  CAS  Google Scholar 

  149. Schwarz UI, Hanso H, Oertel R, et al. Induction of intestinal P-glycoprotein by St John’s wort reduces the oral bioavailability of talinolol. Clin Pharmacol Ther 2007; 81: 669–78

    Article  PubMed  CAS  Google Scholar 

  150. Morimoto T, Kotegawa T, Tsutsumi K, et al. Effect of St John’s wort on the pharmacokinetics of theophylline in healthy volunteers. J Clin Pharmacol 2004; 44: 95–101

    Article  PubMed  CAS  Google Scholar 

  151. Tannergren C, Engman H, Knutson L, et al. St John’s wort decreases the bioavailability of R- and S-verapamil through induction of the first-pass metabolism. Clin Pharmacol Ther 2004; 75: 298–309

    Article  PubMed  CAS  Google Scholar 

  152. Rengelshausen J, Banfield M, Riedel KD, et al. Opposite effects of short-term and long-term St John’s wort intake on voriconazole pharmacokinetics. Clin Pharmacol Ther 2005; 78: 25–33

    Article  PubMed  CAS  Google Scholar 

  153. Smith PF, Bullock JM, Booker BM, et al. Induction of imatinib metabolism by hypericum perforatum. Blood 2004; 104: 1229–30

    Article  PubMed  CAS  Google Scholar 

  154. Freeman C, Spelman K. A critical evaluation of drug interactions with Echinacea spp. Mol Nutr Food Res 2008; 52: 789–98

    Article  PubMed  CAS  Google Scholar 

  155. Borrelli F, Capasso R, Izzo AA. Garlic (Allium sativum L.): adverse effects and drug interactions in humans. Mol Nutr Food Res 2007; 51: 1386–97

    Article  PubMed  CAS  Google Scholar 

  156. Engdal S, Nilsen OG. Inhibition of P-glycoprotein in Caco-2 cells: effects of herbal remedies frequently used by cancer patients. Xenobiotica 2008; 38: 559–73

    Article  PubMed  CAS  Google Scholar 

  157. Saw JT, Bahari MB, Ang HH, et al. Potential drug-herb interaction with antiplatelet/anticoagulant drugs. Ther Clin Pract 2006; 12: 236–41

    Article  Google Scholar 

  158. Fugh-Berman A, Ernst E. Herb-drug interactions: review and assessment of report reliability. Br J Clin Pharmacol 2001; 52: 587–95

    Article  PubMed  CAS  Google Scholar 

  159. Bone KM. Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence? Mol Nutr Food Res 2008; 52: 764–71

    Article  PubMed  CAS  Google Scholar 

  160. Fessenden JM, Wittenborn W, Clarke L. Gingko biloba: a case report of herbal medicine and bleeding postoperatively from a laparoscopic cholecystectomy. Am Surg 2001; 67: 33–5

    PubMed  CAS  Google Scholar 

  161. Jayasekera N, Moghal A, Kashif F, et al. Herbal medicines and postoperative haemorrhage. Anaesthesia 2005; 60: 725–6

    Article  PubMed  CAS  Google Scholar 

  162. Ernst E, Canter PH, Coon JT. Does Ginkgo biloba increase the risk of bleeding? A systemic review of case reports. Perfusion 2005; 18: 52–6

    Google Scholar 

  163. Savović J, Wider B, Ernst E. Effects of Ginkgo biloba on blood coagulation parameters: a systematic review of randomised clinical trials. Evid Based Integrative Med 2005; 2: 167–76

    Article  Google Scholar 

  164. Kiefer D, Pantuso T. Panax ginseng. Am Fam Physician 2003; 68: 1539–42

    PubMed  Google Scholar 

  165. Beckert BW, Concannon MJ, Henry SL, et al. The effect of herbal medicines on platelet function: an in vivo experiment and review of the literature. Plast Reconstr Surg 2007; 120: 2044–50

    Article  PubMed  CAS  Google Scholar 

  166. Yuan CS, Wei G, Dey L, et al. Brief communication: American ginseng reduces warfarin’s effect in healthy patients — a randomized, controlled trial. Ann Intern Med 2004; 141: 23–7

    PubMed  CAS  Google Scholar 

  167. Shader RI, Greenblatt DJ. Phenelzine and the dream machine: ramblings and reflections [letter]. J Clin Psychopharmacol 1985; 5: 65

    Article  PubMed  CAS  Google Scholar 

  168. Avins AL, Bent S, Staccone S, et al. A detailed safety assessment of a saw palmetto extract. Complement Ther Med 2008; 16: 147–54

    Article  PubMed  Google Scholar 

  169. Agbabiaka TB, Pittler MH, Wider B, et al. Serenoa repens (saw palmetto): a systematic review of adverse events. Drug Saf 2009; 32(8): 637–47

    Article  PubMed  Google Scholar 

  170. Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database Syst Rev 2008; (4): CD000448

  171. Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 118–27

    Article  PubMed  CAS  Google Scholar 

  172. Knüppel L, Linde K. Adverse effects of St John’s wort: a systematic review. J Clin Psychiatry 2004; 65: 1470–9

    Article  PubMed  Google Scholar 

  173. Di Carlo G, Borrelli F, Ernst E, et al. St John’s wort: Prozac from the plant kingdom. Trends Pharmacol Sci 2001; 22: 292–7

    Article  PubMed  Google Scholar 

  174. Izzo AA. Drug interactions with St John’s wort (Hypericum perforatum): a review of the clinical evidence. Int J Clin Pharmacol Ther 2004; 42: 139–48

    PubMed  CAS  Google Scholar 

  175. Mannel M. Drug interactions with St John’s wort: mechanisms and clinical implications. Drug Saf 2004; 27: 773–97

    Article  PubMed  CAS  Google Scholar 

  176. Di YM, Li CG, Xue CC, et al. Clinical drugs that interact with St John’s wort and implication in drug development. Curr Pharm Des 2008; 14: 1723–42

    Article  PubMed  CAS  Google Scholar 

  177. Mills E, Montori VM, Wu P, et al. Interaction of St John’s wort with conventional drugs: systematic review of clinical trials. BMJ 2004; 329: 27–30

    Article  PubMed  Google Scholar 

  178. Madabushi R, Frank B, Drewelow B, et al. Hyperforin in St John’s wort drug interactions. Eur J Clin Pharmacol 2006; 62: 225–33

    Article  PubMed  CAS  Google Scholar 

  179. Bressler R. Herb-drug interactions: St John’s wort and prescription medications. Geriatrics 2005; 60: 21–3

    PubMed  Google Scholar 

  180. Ernst E. St John’s wort supplements endanger the success of organ transplantation. Arch Surg 2002; 137: 316–9

    Article  PubMed  CAS  Google Scholar 

  181. Murphy PA. St John’s wort and oral contraceptives: reasons for concern? J Midwifery Womens Health 2002; 47: 447–50

    Article  PubMed  Google Scholar 

  182. Izzo AA, Di Carlo G, Borrelli F, et al. Cardiovascular pharmacotherapy and herbal medicines: the risk of drug interaction. Int J Cardiol 2005; 98: 1–14

    Article  PubMed  Google Scholar 

  183. Van den Bout-van den Beukel CJ, Koopmans PP, van der Ven AJ, et al. Possible drug-metabolism interactions of medicinal herbs with antiretroviral agents. Drug Metab Rev 2006; 38: 477–514

    Article  PubMed  CAS  Google Scholar 

  184. Erickson DA, Mather G, Trager WF, et al. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450. Drug Metab Dispos 1999; 27: 1488–95

    PubMed  CAS  Google Scholar 

  185. Meijerman I, Beijnen JH, Schellens JH. Herb-drug interactions in oncology: focus on mechanisms of induction. Oncologist 2006; 11: 742–52

    Article  PubMed  CAS  Google Scholar 

  186. Werneke U, Turner T, Priebe S. Complementary medicines in psychiatry: review of effectiveness and safety. Br J Psychiatry 2006; 188: 109–21

    Article  PubMed  Google Scholar 

  187. Ernst E, Rand JI, Barnes J, et al. Adverse effects profile of the herbal antidepressant St John’s wort (Hypericum perforatum L.). Eur J Clin Pharmacol 1998; 54(8): 589–94

    Article  PubMed  CAS  Google Scholar 

  188. Johne A, Perloff ES, Bauer S, et al. Impact of cytochrome P-450 inhibition by cimetidine and induction by carbamazepine on the kinetics of hypericin and pseudohypericin in healthy volunteers. Eur J Clin Pharmacol 2004; 60: 617–22

    Article  PubMed  CAS  Google Scholar 

  189. Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA 2001; 286: 208–16

    Article  PubMed  CAS  Google Scholar 

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No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Izzo, A.A., Ernst, E. Interactions Between Herbal Medicines and Prescribed Drugs. Drugs 69, 1777–1798 (2009). https://doi.org/10.2165/11317010-000000000-00000

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