Herb-Drug Interactions: Focus on Adverse Drug Reactions and Pharmacovigilance of Herbal Medicines

  • Kuppusamy Asokkumar
  • Subramaniam Ramachandran


Herbal products or herbal drugs are most commonly used by the patient and physician as an adjuvant therapy in many disease conditions along with allopathic or conventional drugs. Many studies and reports have been published on herbal drug-drug interactions or herb-drug interactions (HDIs) from countries like United States of America, European Union, Canada, China, Africa, Nigeria, Israel and Iran. A number of reports are available for interaction of herbal drugs with conventional drugs of various therapeutic category such as warfarin (anticoagulant), midazolam (benzodiazepine), digoxin (used in congestive heart failure), amitriptyline and trazodone (antidepressant), indinavir, lopinavir, ritonavir, saquinavir (anti-HIV), cyclosporine and irinotecan (anticancer), tacrolimus (immunosuppressant), ibuprofen (analgesic and anti-inflammatory), risperidone (antipsychotic) and theophylline (antiasthmatic).

Herbal drugs may interact with conventional drugs at different sites of the body, i.e., intestine, liver, kidney and other targets of action. The most common basic mechanisms for the reported HDIs are pharmacokinetic and/or pharmacodynamic interactions. In particular, cytochrome P450 (CYP450) enzyme induction and/or inhibition and effects on transport protein (P-glycoprotein) by HDIs considerably affect the circulating levels of drug and modify the clinical outcome. The CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 are most commonly induced and/or inhibited by HDIs.

Although significant HDIs reports are published from some countries, the contribution, documentation and creating awareness about the occurrence of potential HDIs from people of other countries on the use of herbal preparations are still lacking. Herbal drugs play a vital role in healthcare system for treating diseases; hence, use of pharmacovigilance programme will provide more information to the clinicians to prescribe the rational combination of conventional drugs with herbal medicine. It will be also helpful to other healthcare professionals and consumers to take a rational decision on safe combination of herbal products with conventional medicines.


Herbal-drug interaction Cytochrome P450 Pharmacovigilance HDI Anticoagulant Benzodiazepine Anti-HIV Anticancer Antipsychotic Antidepressant 


  1. Alemdaroglu NC, Dietz U, Wolffram S, Spahn-Langguth H, Langguth P. Influence of green and black tea on folic acid pharmacokinetics in healthy volunteers: potential risk of diminished folic acid bioavailability. Biopharm Drug Dispos. 2008;29:335–48.PubMedCrossRefPubMedCentralGoogle Scholar
  2. Almeida JC, Grimsley EW. Coma from the health food store: interaction between kava and alprazolam. Ann Intern Med. 1996;125:940–1.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 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;63:913–6.PubMedCrossRefPubMedCentralGoogle Scholar
  4. Aslam M, Stockley IH. Interaction between curry ingredient (karela) and drug (chlorpropamide). Lancet. 1979;1:607.PubMedCrossRefPubMedCentralGoogle Scholar
  5. Barbenel DM, Yusufi B, O’Shea D, Bench CJ. Mania in a patient receiving testosterone replacement post orchidectomy taking St John’s Wort and sertraline. J Psychopharmacol. 2000;14:84–6.PubMedCrossRefPubMedCentralGoogle Scholar
  6. Baxter K, Stockley IH. Stockley’s drug interactions: a source book of interactions, their mechanisms, clinical importance, and management. Chicago: Pharmaceutical Press; 2008.Google Scholar
  7. Berka K, Hendrychova T, Anzenbacher P, Otyepka M. Membrane position of ibuprofen agrees with suggested access path entrance to cytochrome P450 2C9 active site. J Phys Chem A. 2011;115:11248–55.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Bilgi N, Bell K, Ananthakrishnan AN, Atallah E. Imatinib and Panax ginseng: a potential interaction resulting in liver toxicity. Ann Pharmacother. 2010;44:926–8.PubMedCrossRefPubMedCentralGoogle Scholar
  9. Bodeker G. Traditional health systems: policy, biodiversity, and global interdependence. J Altern Complement Med. 1995;1:231–43.PubMedCrossRefPubMedCentralGoogle Scholar
  10. Bonetto N, Santelli L, Battistin L, Cagnin A. Serotonin syndrome and rhabdomyolysis induced by concomitant use of triptans, fluoxetine and hypericum. Cephalalgia. 2007;27:1421–3.PubMedCrossRefPubMedCentralGoogle Scholar
  11. Borrelli F, Izzo AA. Herb-drug interactions with St John’s Wort (Hypericum perforatum): an update on clinical observations. AAPS J. 2009;11:710–27.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Breidenbach T, Hoffmann MW, Becker T, Schlitt H, Klempnauer J. Drug interaction of St John’s Wort with cyclosporin. Lancet. 2000;355:1912.PubMedCrossRefPubMedCentralGoogle Scholar
  13. Burckhardt G. Drug transport by Organic Anion Transporters (OATs). Pharmacol Ther. 2012;136:106–30.CrossRefGoogle Scholar
  14. Cambria-Kiely JA. Effect of soy milk on warfarin efficacy. Ann Pharmacother. 2002;36:1893–6.PubMedCrossRefPubMedCentralGoogle Scholar
  15. Carrasco MC, Vallejo JR, Pardo-de-Santayana M, Peral D, Martín MA, Altimiras J. Interactions of Valeriana officinalis L. and Passiflora incarnata L. in a patient treated with lorazepam. Phytother Res. 2009;23:1795–6.PubMedCrossRefPubMedCentralGoogle Scholar
  16. Chan TY. Interaction between warfarin and danshen (Salvia miltiorrhiza). Ann Pharmacother. 2001;35:501–4.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Chen Y, Liu WH, Chen BL, Fan L, Han Y, Wang G, Hu DL, Tan ZR, Zhou G, Cao S, Zhou HH. Plant polyphenol curcumin significantly affects CYP1A2 and CYP2A6 activity in healthy, male Chinese volunteers. Ann Pharmacother. 2010;44:1038–45.PubMedCrossRefPubMedCentralGoogle Scholar
  18. Choudhary N, Khajuria V, Gillani ZH, Tandon AR, Arora E. Effect of Carum carvi, a herbal bioenhancer on pharmacokinetics of antitubercular drugs: a study in healthy human volunteers. Perspect Clin Res. 2014;5:80–4.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Dalvi SS, Nayak VK, Pohujani SM, Desai NK, Kshirsagar NA, Gupta KC. Effect of gugulipid on bioavailability of diltiazem and propranolol. J Assoc Physicians India. 1994;42:454–5.PubMedPubMedCentralGoogle Scholar
  20. Dannawi M. Possible serotonin syndrome after combination of buspirone and St John’s Wort. J Psychopharmacol. 2002;16:401.PubMedCrossRefPubMedCentralGoogle Scholar
  21. Deahl M. Betel nut-induced extrapyramidal syndrome: an unusual drug interaction. Mov Disord. 1989;4:330–2.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Dresser GK, Wacher V, Wong S, Wong HT, Bailey DG. Evaluation of peppermint oil and ascorbyl palmitate as inhibitors of cytochrome P4503A4 activity in vitro and in vivo. Clin Pharmacol Ther. 2002;72:247–55.PubMedCrossRefPubMedCentralGoogle Scholar
  23. Dresser GK, Schwarz UI, Wilkinson GR, Kim RB. Coordinate induction of both cytochrome P4503A and MDR1 by St John’s Wort in healthy subjects. Clin Pharmacol Ther. 2003;73:41–50.PubMedCrossRefPubMedCentralGoogle Scholar
  24. Eich-Höchli D, Oppliger R, Golay KP, Baumann P, Eap CB. Methadone maintenance treatment and St John’s Wort-a case report. Pharmacopsychiatry. 2003;36:35–7.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Etogo-Asse F, Boemer F, Sempoux C, Geubel A. 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.PubMedPubMedCentralGoogle Scholar
  26. Fan L, Mao XQ, Tao GY, Wang G, Jiang F, Chen Y, Li Q, Zhang W, Lei HP, Hu DL, Huang YF, Wang D, Zhou HH. Effect of Schisandra chinensis extract and Ginkgo biloba extract on the pharmacokinetics of talinolol in healthy volunteers. Xenobiotica. 2009a;39:249–54.PubMedCrossRefPubMedCentralGoogle Scholar
  27. Fan L, Tao GY, Wang G, Chen Y, Zhang W, He YJ, Li Q, Lei HP, Jiang F, Hu DL, Huang YF, Zhou HH. Effects of Ginkgo biloba extract ingestion on the pharmacokinetics of talinolol in healthy Chinese volunteers. Ann Pharmacother. 2009b;43:944–9.PubMedCrossRefPubMedCentralGoogle Scholar
  28. Fasinu PS, Bouic PJ, Rosenkranz B. An overview of the evidence and mechanisms of herb-drug interactions. Front Pharmacol. 2012;3:69. Scholar
  29. Frye RF, Fitzgerald SM, Lagattuta TF, Hruska MW, Egorin MJ. Effect of St John’s Wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther. 2004;76:323–9.PubMedCrossRefPubMedCentralGoogle Scholar
  30. Galluzzi S, Zanetti O, Binetti G, Trabucchi M, Frisoni GB. Coma in a patient with Alzheimer’s disease taking low dose trazodone and Gingko biloba. J Neurol Neurosurg Psychiatry. 2000;68:679–80.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Giveon SM, Liberman N, Klang S, Kahan E. Are people who use “natural drugs” aware of their potentially harmful side effects and reporting to family physician? Patient Educ Couns. 2004;53:5–11.PubMedCrossRefPubMedCentralGoogle Scholar
  32. Gordon JB. SSRIs and St John’s Wort: possible toxicity? Am Fam Physician. 1998;57:950.PubMedPubMedCentralGoogle Scholar
  33. Gordon RY, Becker DJ, Rader DJ. Reduced efficacy of rosuvastatin by St John’s Wort. Am J Med. 2009;122:e1–2.PubMedCrossRefPubMedCentralGoogle Scholar
  34. Griffiths AP, Beddall A, Pegler S. Fatal haemopericardium and gastrointestinal haemorrhage due to possible interaction of cranberry juice with warfarin. J R Soc Promot Heal. 2008;128:324–6.CrossRefGoogle Scholar
  35. Gujjarlamudi HB. Polytherapy and drug interactions in elderly. J Midlife Health. 2016;7(3):105–7.PubMedPubMedCentralGoogle Scholar
  36. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CY. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther. 2002;72:276–87.PubMedCrossRefPubMedCentralGoogle Scholar
  37. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CY. 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. 2005a;22:525–39.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Khan IA, Shah A. 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. 2005b;77:415–26.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Gutsch J. On the state of therapy of chronic myeloid leukemia in adults with the mistletoe preparation Helixor. Ärztezeitschrift für Naturheilverfahren. 1982;23:523–44.Google Scholar
  40. Gwilt PR, Lear CL, Tempero MA, Birt DD, Grandjean AC, Ruddon RW, Nagel DL. The effect of garlic extract on human metabolism of acetaminophen. Cancer Epidemiol Biomark Prev. 1994;3:155–60.Google Scholar
  41. Hanselin MR, Vande Griend JP, Linnebur SA. INR elevation with maitake extract in combination with warfarin. Ann Pharmacother. 2010;44:223–4.PubMedCrossRefPubMedCentralGoogle Scholar
  42. Hojo Y, Echizenya M, Ohkubo T, Shimizu T. Drug interaction between St John’s Wort and zolpidem in healthy subjects. J Clin Pharm Ther. 2011;36:711–5.PubMedCrossRefPubMedCentralGoogle Scholar
  43. Holman CP, Bell AFJ. A trial of evening primrose oil in the treatment of chronic schizophrenia. J Orthomol Psychiatry. 1983;12:302–4.Google Scholar
  44. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  45. Izzo AA. Herb-drug interactions: an overview of the clinical evidence. Fundam Clin Pharmacol. 2005;19:1–16.PubMedCrossRefPubMedCentralGoogle Scholar
  46. Jiang X, Williams KM, Liauw WS, Ammit AJ, Roufogalis BD, Duke CC, Day RO, McLachlan AJ. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Jiang W, Wang X, Xu X, Kong L. Effect of Schisandra sphenanthera extract on the concentration of tacrolimus in the blood of liver transplant patients. Int J Clin Pharmacol Ther. 2010;48:224–9.PubMedCrossRefPubMedCentralGoogle Scholar
  48. Johne A, Schmider J, Brockmöller J, Stadelmann AM, Störmer E, Bauer S, Scholler G, Langheinrich M, Roots I. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  49. Jones BD, Runikis AM. Interaction of ginseng with phenelzine. J Clin Psychopharmacol. 1987;7:201–2.PubMedCrossRefPubMedCentralGoogle Scholar
  50. Kalliokoski A, Niemi M. Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009;158:693–705.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Khawaja IS, Marotta RF, Lippmann S. Herbal medicines as a factor in delirium. Psychiatr Serv. 1999;50:969–70.PubMedCrossRefPubMedCentralGoogle Scholar
  52. Kolawole JA, Maduenyi A. Effect of zobo drink (Hibiscus sabdariffa water extract) on the pharmacokinetics of acetaminophen in human volunteers. Eur J Drug Metab Pharmacokinet. 2004;29:25–9.PubMedCrossRefPubMedCentralGoogle Scholar
  53. Kupiec T, Raj V. Fatal seizures due to potential herb-drug interactions with Ginkgo biloba. J Anal Toxicol. 2005;29:755–8.PubMedCrossRefPubMedCentralGoogle Scholar
  54. Lam AY, Elmer GW, Mohutsky MA. Possible interaction between warfarin and Lycium barbarum L. Ann Pharmacother. 2001;35:1199–201.PubMedCrossRefPubMedCentralGoogle Scholar
  55. Lambert JP, Cormier J. Potential interaction between warfarin and boldo-fenugreek. Pharmacotherapy. 2001;21:509–12.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  57. Laroche M, Choudhuri S, Gallicano K, Foster B. Severe gastrointestinal toxicity with concomitant ingestion of ritonavir and garlic. Can J Infect Dis. 1998;9:471P.Google Scholar
  58. Lee KJ, You HJ, Park SJ, Kim YS, Chung YC, Jeong TC, Jeong HG. Hepatoprotective effects of Platycodon grandiflorum on acetaminophen-induced liver damage in mice. Cancer Lett. 2001;174:73–81.PubMedCrossRefPubMedCentralGoogle Scholar
  59. Lee A, Chui PT, Aun CS, Gin T, Lau AS. Possible interaction between sevoflurane and Aloe vera. Ann Pharmacother. 2004;38:1651–4.PubMedCrossRefPubMedCentralGoogle Scholar
  60. Lei HP, Yu XY, Xie HT, Li HH, Fan L, Dai LL, Chen Y, Zhou HH. Effect of St John’s Wort supplementation on the pharmacokinetics of bupropion in healthy male Chinese volunteers. Xenobiotica. 2010;40:275–81.PubMedCrossRefPubMedCentralGoogle Scholar
  61. Leung H, Hung A, Hui AC, Chan TY. Warfarin overdose due to the possible effects of Lycium barbarum L. Food Chem Toxicol. 2008;46:1860–2.PubMedCrossRefPubMedCentralGoogle Scholar
  62. Lin YY, Chu SJ, Tsai SH. Association between priapism and concurrent use of risperidone and Ginkgo biloba. Mayo Clin Proc. 2007;82:1289–90.PubMedCrossRefPubMedCentralGoogle Scholar
  63. López Galera RM, Ribera Pascuet E, Esteban Mur JI, Montoro Ronsano JB, Juárez Giménez JC. Interaction between cat’s claw and protease inhibitors atazanavir, ritonavir and saquinavir. Eur J Clin Pharmacol. 2008;64:1235–6.PubMedCrossRefPubMedCentralGoogle Scholar
  64. Lu FR, Shen L, Qin Y, Gao L, Li H, Dai Y. Clinical observation on Trigonella foenum-graecum L. total saponins in combination with sulfonylureas in the treatment of type 2 diabetes mellitus. Chin J Integr Med. 2008;14:56–60.PubMedCrossRefPubMedCentralGoogle Scholar
  65. Lu H, Lu Z, Li X, Li G, Qiao Y, Borris RP, Zhang Y. Interactions of 172 plant extracts with human organic anion transporter 1 (SLC22A6) and 3 (SLC22A8): a study on herb-drug interactions. Peer J. 2017;5:e3333. Scholar
  66. Ma XH, Zheng CJ, Han LY, Xie B, Jia J, Cao ZW, Li YX, Chen YZ. Synergistic therapeutic actions of herbal ingredients and their mechanisms from molecular interaction and network perspectives. Drug Discov Today. 2009;14:579–88.PubMedCrossRefPubMedCentralGoogle Scholar
  67. Ma L, Zhao L, Hu H, Qin Y, Bian Y, Jiang H, Zhou H, Yu L, Zeng S. Interaction of five anthraquinones from rhubarb with human organic anion transporter 1(SLC22A6) and 3 (SLC22A8) and drug-drug interaction in rats. J Ethnopharmacol. 2014;153:864–71.PubMedCrossRefPubMedCentralGoogle Scholar
  68. de Maat MM, Hoetelmans RM, Math t RA, van Gorp EC, Meenhorst PL, Mulder JW, Beijnen JH. Drug interaction between St. John’s Wort and nevirapine. AIDS. 2001;15:420–1.PubMedCrossRefPubMedCentralGoogle Scholar
  69. Mahmoud BM, Ali HM, Homeida MM, Bennett JL. Significant reduction in chloroquine bioavailability following co-administration with the Sudanese beverages Aradaib, Karkadi and Lemon. J Antimicrob Chemother. 1994;33:1005–9.PubMedCrossRefPubMedCentralGoogle Scholar
  70. Mamindla S, Prasad KVSRG, Koganti B. Herb-drug interactions: an overview of mechanisms and clinical aspects. Int J Pharm Sci Res. 2016;7:3576–86.Google Scholar
  71. Marchetti S, Mazzanti R, Beijnen JH, Schellens JH. Concise review: clinical relevance of drug-drug and herb-drug interactions mediated by the ABC transporter ABCB1 (MDR1, P-glycoprotein). Oncologist. 2007;12:927–41.PubMedCrossRefPubMedCentralGoogle Scholar
  72. Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang JS, Chavin KD. Effect of St John’s Wort on drug metabolism by induction of cytochrome P4503A4 enzyme. JAMA. 2003;290:1500–4.PubMedCrossRefPubMedCentralGoogle Scholar
  73. Mathijssen RH, Verweij J, de Bruijn P, Loos WJ, Sparreboom A. Effects of St John’s Wort on irinotecan metabolism. J Natl Cancer Inst. 2002;94:1247–9.PubMedCrossRefPubMedCentralGoogle Scholar
  74. Mazzari AL, Prieto JM. Corrigendum: herbal medicines in Brazil: pharmacokinetic profile and potential herb-drug interactions. Front Pharmacol. 2015;6:23. Scholar
  75. Meisel C, Johne A, Roots I. Fatal intracerebral mass bleeding associated with Ginkgo biloba and ibuprofen. Atherosclerosis. 2003;167:367.PubMedCrossRefPubMedCentralGoogle Scholar
  76. Michl J, Jennings HM, Kite GC, Ingrouille MJ, Simmonds MS, Heinrich M. Is aristolochic acid nephropathy a widespread problem in developing countries? A case study of Aristolochia indica L. in Bangladesh using an ethnobotanical-phytochemical approach. J Ethnopharmacol. 2013;149:235–44.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Mo SL, Zhou ZW, Yang LP, Wei MQ, Zhou SF. New insights into the structural features and functional relevance of human cytochrome P4502C9. Part I. Curr Drug Metab. 2009;10:1075–126.PubMedCrossRefPubMedCentralGoogle Scholar
  79. Mueller SC, Uehleke B, Woehling H, Petzsch M, Majcher-Peszynska J, Hehl EM, Sievers H, Frank B, Riethling AK, Drewelow B. Effect of St John’s Wort dose and preparations on the pharmacokinetics of digoxin. Clin Pharmacol Ther. 2004;75:546–57.PubMedCrossRefPubMedCentralGoogle Scholar
  80. Murphy PA, Kern SE, Stanczyk FZ, Westhoff CL. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  81. Ohkawa S, Yoneda Y, Ohsumi Y, Tabuchi M. Warfarin therapy and chlorella. (in Japanese. Rinsho Shinkeigaku. 1995;35:806–7.PubMedPubMedCentralGoogle Scholar
  82. Ondieki G, Nyagblordzro M, Kikete S, Liang R, Wang L, He X. Cytochrome P450 and P-Glycoprotein-mediated interactions involving African herbs indicated for common noncommunicable diseases. Evid Based Complement Alternat Med. 2017;2017:2582463. Scholar
  83. Page RL, Lawrence JD. Potentiation of warfarin by dong quai. Pharmacotherapy. 1999;319:870–6.CrossRefGoogle Scholar
  84. Pathak A, Léger P, Bagheri H, Senard JM, Boccalon H, Montastruc JL. Garlic interaction with fluindione: a case report. Therapie. 2003;58:380–1.PubMedCrossRefPubMedCentralGoogle Scholar
  85. Pfrunder A, Schiesser M, Gerber S, Haschke M, Bitzer J, Drewe J. Interaction of St John’s Wort with low-dose oral contraceptive therapy: a randomized controlled trial. Br J Clin Pharmacol. 2003;56:683–90.PubMedPubMedCentralCrossRefGoogle Scholar
  86. Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J. Indinavir concentrations and St John’s Wort. Lancet. 2000;355:547–8.PubMedCrossRefPubMedCentralGoogle Scholar
  87. Piscitelli SC, Burstein AH, Welden N, Gallicano KD, Falloon J. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis. 2002;34:234–8.PubMedCrossRefPubMedCentralGoogle Scholar
  88. Portolés A, Terleira A, Calvo A, Martínez I, Resplandy G. Effects of Hypericum perforatum on ivabradine pharmacokinetics in healthy volunteers: an open-label, pharmacokinetic interaction clinical trial. J Clin Pharmacol. 2006;46:1188–94.PubMedCrossRefPubMedCentralGoogle Scholar
  89. Prasad GV, Wong T, Meliton G, Bhaloo S. Rhabdomyolysis due to red yeast rice (Monascus purpureus) in a renal transplant recipient. Transplantation. 2002;74:1200–1.PubMedCrossRefPubMedCentralGoogle Scholar
  90. Qiu F, Wang G, Zhang R, Sun J, Jiang J, Ma Y. Effect of danshen extract on the activity of CYP3A4 in healthy volunteers. Br J Clin Pharmacol. 2010;69:656–62.PubMedPubMedCentralCrossRefGoogle Scholar
  91. Rajnarayana K, Reddy MS, Vidyasagar J, Krishna DR. Study on the influence of silymarin pre-treatment on metabolism and disposition of metronidazole. Arzneimittelforschung. 2004;54:109–13.PubMedPubMedCentralGoogle Scholar
  92. Rengelshausen J, Banfield M, Riedel KD, Burhenne J, Weiss J, Thomsen T, Walter-Sack I, Haefeli WE, Mikus G. Opposite effects of short-term and long-term St John’s Wort intake on voriconazole pharmacokinetics. Clin Pharmacol Ther. 2005;78:25–33.PubMedCrossRefPubMedCentralGoogle Scholar
  93. Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med. 1997;336:1108.PubMedCrossRefPubMedCentralGoogle Scholar
  94. Rubin D, McGovern B, Kopelman RI. Back to basics. Am J Med. 2006;119:482–3.PubMedCrossRefPubMedCentralGoogle Scholar
  95. Sachin BS, Monica P, Sharma SC, Satti NK, Tikoo MK, Tikoo AK, Suri KA, Gupta BD, Johri RK. Pharmacokinetic interaction of some antitubercular drugs with caraway: implications in the enhancement of drug bioavailability. Hum Exp Toxicol. 2009;28:175–84.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 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.CrossRefGoogle Scholar
  97. Schelosky L, Raffauf C, Jendroska K, Poewe W. Kava and dopamine antagonism. J Neurol Neurosurg Psychiatry. 1995;58:639–40.PubMedPubMedCentralCrossRefGoogle Scholar
  98. Schwarz UI, Hanso H, Oertel R, Miehlke S, Kuhlisch E, Glaeser H, Hitzl M, Dresser GK, Kim RB, Kirch W. Induction of intestinal P-glycoprotein by St John’s Wort reduces the oral bioavailability of talinolol. Clin Pharmacol Ther. 2007;81:669–78.PubMedCrossRefPubMedCentralGoogle Scholar
  99. Segal R, Pilote L. Warfarin interaction with Matricaria chamomilla. CMAJ. 2006;174:1281–2.PubMedPubMedCentralCrossRefGoogle Scholar
  100. Shader RI, Greenblatt DJ. Bees, ginseng and MAOIs revisited. J Clin Psychopharmacol. 1988;8:235.PubMedPubMedCentralGoogle Scholar
  101. Shaw D, Graeme L, Pierre D, Elizabeth W, Kelvin C. Pharmacovigilance of herbal medicine. J Ethnopharmacol. 2012;140:513–8.PubMedCrossRefPubMedCentralGoogle Scholar
  102. Sheeja K, Shihab PK, Kuttan G. Antioxidant and anti-inflammatory activities of the plant Andrographis paniculata Nees. Immunopharmacol Immunotoxicol. 2006;28:129–40.PubMedCrossRefPubMedCentralGoogle Scholar
  103. Sobieraj DM, Freyer CW. Probable hypoglycemic adverse drug reaction associated with prickly pear cactus, glipizide, and metformin in a patient with type 2 diabetes mellitus. Ann Pharmacother. 2010;44:1334–7.PubMedCrossRefPubMedCentralGoogle Scholar
  104. Sugimoto K, Ohmori M, Tsuruoka S, Nishiki K, Kawaguchi A, Harada K, Arakawa M, Sakamoto K, Masada M, Miyamori I, Fujimura A. Different effects of St John’s Wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther. 2001;70:518–24.PubMedCrossRefPubMedCentralGoogle Scholar
  105. Tannergren C, Engman H, Knutson L, Hedeland M, Bondesson U, Lennernäs H. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  106. Taylor JR, Wilt VM. Probable antagonism of warfarin by green tea. Ann Pharmacother. 1999;33:426–8.PubMedCrossRefPubMedCentralGoogle Scholar
  107. Tongia A, Tongia SK, Dave M. Phytochemical determination and extraction of Momordica charantia fruit and its hypoglycemic potentiation of oral hypoglycemic drugs in diabetes mellitus (NIDDM). Indian J Physiol Pharmacol. 2004;48:241–4.PubMedPubMedCentralGoogle Scholar
  108. Tu JH, Hu DL, Dai LL, Sun Y, Fan L, Zhang M, Tan ZR, Chen Y, Li Z, Zhou HH. Effect of glycyrrhizin on CYP2C19 and CYP3A4 activity in healthy volunteers with different CYP2C19 genotypes. Xenobiotica. 2010;40:393–9.PubMedCrossRefPubMedCentralGoogle Scholar
  109. Uchida S, Yamada H, Li XD, Maruyama S, Ohmori Y, Oki T, Watanabe H, Umegaki K, Ohashi K, Yamada S. Effects of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide and midazolam in healthy volunteers. J Clin Pharmacol. 2006;46:1290–8.PubMedCrossRefPubMedCentralGoogle Scholar
  110. Wang L, Sweet DH. Active hydrophilic components of the medicinal herb Salvia miltiorrhiza (Danshen) potently inhibit organic anion transporters 1 (Slc22a6) and 3 (Slc22a8). Evid Based Complement Alternat Med. 2012;2012:872458. Scholar
  111. Wang B, Zhou SF. Synthetic and natural compounds that interact with human cytochromeP4501A2 and implications in drug development. Curr Med Chem. 2009;16:4066–218.PubMedCrossRefPubMedCentralGoogle Scholar
  112. Wang LS, Zhou G, Zhu B, Wu J, Wang JG, Abd El-Aty AM, Li T, Liu J, Yang TL, Wang D, Zhong XY, Zhou HH. St John’s Wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. Clin Pharmacol Ther. 2004a;75:191–7.PubMedCrossRefPubMedCentralGoogle Scholar
  113. Wang LS, Zhu B, Abd El-Aty AM, Zhou G, Li Z, Wu J, Chen GL, Liu J, Tang ZR, An W, Li Q, Wang D, Zhou HH. The influence of St John’s Wort on CYP2C19 activity with respect to genotype. J Clin Pharmacol. 2004b;44:577–81.PubMedCrossRefPubMedCentralGoogle Scholar
  114. Werba JP, Giroli M, Cavalca V, Nava MC, Tremoli E, Dal Bo L. The effect of green tea on simvastatin tolerability. Ann Intern Med. 2008;149:286–7.PubMedCrossRefPubMedCentralGoogle Scholar
  115. WHO. Guidelines for good clinical practice (GCP) for trials on pharmaceutical products. In: The use of essential drugs, Sixth report of the WHO Expert Committee. Geneva: WHO; 1995. Annex 3 (WHO Technical Report Series, No. 850).Google Scholar
  116. WHO. Guidelines for assessing quality of herbal medicines with reference to contaminants and residues. Geneva: WHO; 2004a. Accessed Dec 2018Google Scholar
  117. WHO. Guideline on safety monitoring of herbal medicines in pharmacovigilance system. Geneva: WHO; 2004b. Accessed 24 Dec 2018Google Scholar
  118. Wiegman DJ, Brinkman K, Franssen EJ. Interaction of Ginkgo biloba with efavirenz. AIDS. 2009;23:1184–5.PubMedCrossRefPubMedCentralGoogle Scholar
  119. Williamson EM, Driver S, Baxter K. Stockley’s herbal medicines interactions: a guide to the interactions of herbal medicines, dietary supplements and nutraceuticals with conventional medicines. Chicago: Pharmaceutical Press; 2009.Google Scholar
  120. Wills RB, Bone K, Morgan M. Herbal products: active constituents, modes of action and quality control. Nutr Res Rev. 2000;13:47–77.PubMedCrossRefPubMedCentralGoogle Scholar
  121. World Health Organization (WHO). The importance of pharmacovigilance: safety monitoring of medicinal products. Geneva: World Health Organization; 2002.Google Scholar
  122. Wu X, Li Q, Xin H, Yu A, Zhong M. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol. 2005;61:567–72.PubMedCrossRefPubMedCentralGoogle Scholar
  123. Xie R, Tan LH, Polasek EC, Hong C, Teillol-Foo M, Gordi T, Sharma A, Nickens DJ, Arakawa T, Knuth DW, Antal EJ. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  124. Xin HW, Wu XC, Li Q, Yu AR, Xiong L. Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers. Br J Clin Pharmacol. 2009;67:541–6.PubMedPubMedCentralCrossRefGoogle Scholar
  125. Yin OQ, Tomlinson B, Waye MM, Chow AH, Chow MS. Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Pharmacogenetics. 2004;14:841–50.PubMedCrossRefPubMedCentralGoogle Scholar
  126. Yuan CS, Wei G, Dey L, Karrison T, Nahlik L, Maleckar S, Kasza K, Ang-Lee M, Moss J. Brief communication: American ginseng reduces warfarin’s effect in healthy patients: a randomized, controlled trial. Ann Intern Med. 2004;141:23–7.PubMedCrossRefPubMedCentralGoogle Scholar
  127. Zhang L, Yan J, Liu X, Ye Z, Yang X, Meyboom R, Chan K, Shaw D, Duez P. Pharmacovigilance practice and risk control of traditional Chinese medicine drugs in China: current status and future perspective. J Ethnopharmacol. 2012;140:519–25.PubMedCrossRefPubMedCentralGoogle Scholar
  128. Zhang XL, Chen M, Zhu LL, Zhou Q. Therapeutic risk and benefits of concomitantly using herbal medicines and conventional medicines: from the perspectives of evidence based on randomized controlled trials and clinical risk management. Evid Based Complement Alternat Med. 2017;2017:9296404. doi: Scholar
  129. Zhou SF, Zhou ZW, Li CG, Chen X, Yu X, Xue CC, Herington A. Identification of drugs that interact with herbs in drug development. Drug Discov Today. 2007;12:664–73.PubMedCrossRefPubMedCentralGoogle Scholar
  130. Zhou SF, Liu JP, Chowbay B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev. 2009;41:289–95.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  • Kuppusamy Asokkumar
    • 1
  • Subramaniam Ramachandran
    • 2
  1. 1.Department of Pharmacology, College of PharmacySri Ramakrishna Institute of Paramedical SciencesCoimbatoreIndia
  2. 2.Pharmacology SectionPharmacopoeia Commission for Indian Medicine & Homoeopathy, PLIM Campus, Post Kavi NagarGhaziabadIndia

Personalised recommendations