INTRODUCTION Chemical reaction occurs continuously in the atmosphere, in factories, in vehicles, in the environment and in our bodies. In a chemical reaction, one or more kinds of matter are changed in a new kind – or several new kinds – of matter. Life as we know it, could not exist without these processes: plants could not photosynthesize, cars could not more, pudding could thicken
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Acupuncture.org.au2Chun Guang Li*1 Phd
Liping Yang1 MPharm
Shu-Feng Zhou2 Phd
1. The Chinese Medicine Research Group, division of Chinese Medicine, RMIT University, Melbourne, Australia2. division of Pharmacy, School of Life Sciences, Queensland University of Technology, Brisbane, Australia A B S T R A C TThe popular use of herbal products in the general community raises concerns for potential herb–drug interactions. The risk of herb–drug interactions is increased if the herbal medicines are used concurrently with drugs which have a narrow therapeutic range, or are used in certain groups of patients, such as the elderly or those with impaired liver and renal functions. This short paper reviews some important concepts in herb–drug interactions and cases involving Chinese herbal medicines. It is important for Chinese medicine practitioners to understand, monitor and report potential herb–drug interactions. K e y W o R d S herb–drug interactions, Chinese herbal medicine, efficacy, safety, adverse reactions, cytochrome P450.
report to the Parliamentary Secretary to the Minister for Health Chinese herbal medicine, as one of the most developed and Ageing of Australia, prepared by the expert Committee on remedies in traditional Chinese medicine, has been widely Complementary Medicines, has identified potential herb–drug used by Chinese medicine practitioners for the treatment interactions as an important area, and encourages more research of a variety of acute and chronic diseases and conditions for on the safety of herbal and other complementary therapies.2 thousands of years. Generally speaking, most Chinese herbal medicine practitioners are familiar with the concept of herb– In this short paper, we have outlined some important aspects herb interactions according to Chinese medicine theory, of herb–drug interactions in the context of Chinese herbal such as the synergistic/additive and/or antagonistic actions medicines. It is important for Chinese herbal medicine of some Chinese herbs under certain clinical conditions. practitioners to understand these concepts in order to optimise However, many practitioners are less familiar with herb–drug clinical therapies and to avoid potential adverse reactions related interactions, possibly due to a limited understanding of the mechanisms underlying herb–drug interactions or difficulties in accessing existing data in this area. The significant increase in the use of herbal medicines in the Australian community also raises concerns of potential toxicity of herbal products, including Chinese herbal medicines.1 A herb–drug interaction is defined as any pharmacological Such concerns are valid, considering some consumers or modification caused by a herbal substance(s) to another patients may take these products concomitantly with multiple exogenous chemical (e.g. a prescription medication) in the conventional drugs for various conditions (particularly for diagnostic, therapeutic, or other action of a drug in or on chronic diseases and conditions in the elderly). The recent the body.3 This relates to so called drug–drug interactions * Correspondent author; e-mail: [email protected] Aust J Acupunct Chin Med 2007;2(1):17–24.
CG Li, LP Yang and SF Zhou
(interactions between drugs), herb–herb interactions disclose the use of herbal products to their physicians,10 and (interactions between herbs) or drug–food interactions most physicians have relatively limited knowledge of various (interactions between drugs and food). Broadly speaking, herbal products, the risk of potential herb–drug interactions is the herb–drug interaction is also a kind of drug interaction, increased. Thus, there have been efforts for implementation of considering that the action of a herbal substance is eventually co-ordinated toxicity-monitoring systems by the World Health caused by chemical ingredients which may be known or organization (WHo) (e.g. WHo Collaborating Centre for unknown. For example, St John’s Wort (Hypericum perforatum), International drug Monitoring, www.who-umc.org), and by a commonly used antidepressant herb, has been reported to various governments, including those of Australia, the United cause significant changes in the action of cyclosporine A in Kingdom, the United States, Singapore and China, aimed at transplant patients (for references, see Table 1). It also decreased improving monitoring and timely reporting of potential herb– plasma concentrations of a range of drugs including digoxin,4 warfarin5 and theophylline.6 It should be pointed out that some herb–drug interactions may be beneficial, e.g. enhancing the efficacy or reducing the adverse reactions of an anti-cancer agent. Recently, a randomised clinical trial has demonstrated that Chinese herbal medicine reduces chemotherapy-induced nausea.7 However, many herb–drug interactions can also be Herb–drug interactions can be caused by various factors. They harmful, e.g. causing adverse reactions or therapeutic failure. may result from chemical reactions between different ingredients, or from changes or modifications to specific biochemical pathways involved in the metabolism or actions of related drugs or herbs. For example, certain Chinese herbs may interfere with the body’s drug transporters and metabolism enzymes, resulting in changes of the metabolism and consequently the actions of The main reason for concern is that herb–drug interactions may potentially affect the clinical safety and efficacy of related drugs or herbs. Although many interactions between herbs and Most herb–drug interactions are mediated by pharmacodynamic drugs may be too minor (in terms of pharmacokinetic and/or and/or pharmacokinetic mechanisms. Pharmacodynamic pharmacodynamic changes) to have any clinical significance, in interactions involve synergistic or antagonistic interactions some cases, these interactions may alter the clinical outcomes or on the same drug targets, e.g. receptors, which can often be the safety of the treatment involved. The risk of harmful herb– predicted and avoided. For example, Ma Huang (Ephedra drug interactions is of particular concern to both consumers species) contains ephedrine-like alkaloids which exhibit and practitioners of herbal and conventional medicines. There sympathomimetic activities. Thus, Ma Huang may interact has been an increasing number of reports on harmful herb– with other sympathomimetic agents, resulting in increased drug interactions globally, partly due to the popularity of using actions of monamine oxidase inhibitors and adrenergic agonists herbal products in the general population.8 such as clonidine, and decreased actions of bethanidine and guanethidine.11 Pharmacokinetic interactions are much It is important to note that the use of multiple medicines will more difficult to anticipate, as they occur through multiple significantly increase the risk of potential herb–drug interactions, mechanisms, including alterations of the drug’s absorption, especially in the elderly or certain groups of consumers, such distribution, metabolism and excretion. Most reported as cancer patients. The risk for drug interactions increases herb–drug interactions are pharmacokinetic interactions. For with the number of products consumed. For example, the example, certain herbal ingredients may inhibit P-glycoprotein- risk for potential interactions when consuming two products mediated drug transport in the liver and intestinal tract, is 6%; five products, 50%; the risk increases to 100% when resulting in changes of absorptions and actions of drugs which consuming eight or more products.9 The likelihood of herb– drug interactions is therefore theoretically higher than drug–drug interactions since most synthetic drugs usually contain a Cytochrome P450 (CyP450) enzymes are the most important drug-metabolising enzymes in the body and are responsible for the metabolism of more than 50% of therapeutic drugs.14 It should be pointed out, however, that our understanding of the Herb–drug interactions often occur when CyP450 enzymes interactions between herbs and drugs is still limited. It is difficult are affected. In humans, there are 57 CyP450 isoenzymes, to characterise and identify definitely a herb–drug interaction and these are grouped into different classes or families. The based only on case reports or case series studies. Considering nomenclature of CyP450s employs a three-tiered classification a significant number of patients or herbal consumers fail to based on the conventions of molecular biology, indicated by CG Li, LP Yang and SF Zhou
an Arabic numeral (family), a capital letter (subfamily) and interact with ibuprofen, trazodone, fluoxetine, buspirone and another Arabic numeral (gene), e.g. CyP1A2.15 Most drug phenytoin (Table 1). It is interesting to note that both warfarin oxidations are catalysed primarily by six CyP450 enzymes and cyclosporine are well-known subtracts of CyP2C9 and (CyP1A2, 2C9, 2C19, 2d6, 2e1 and 3A4/5). Among these, CyP3A4 respectively. St John’s Wort is a potent inducer of CyP3A4 is responsible for metabolising more than 50% of Another example is Gancao (licorice, Glycyrrhiza glabra), The actions of CyP450 may be changed by herbal ingredients which was reported to increase the plasma concentrations through two different mechanisms: induction and inhibition. of prednisolone28,29 by inhibiting the metabolism of The induction of CyP450 usually requires a longer period prednisolone, and also potentiating the skin vasoconstrictive of time (e.g. several days), which may lead to decreased drug action of hydrocortisone.30 Thus, it may potentially modify the plasma levels (through increased drug metabolism), and pharmacological effects of prednisolone and hydrocortisone.
consequently reduced drug effects. Conversely, the inhibition of CyP450 is usually immediate and may lead to increased drug plasma levels (through decreased drug metabolism), and thus increased drug effects, which may result in significant adverse reactions or toxicities. Many clinical adverse events have been associated with CyP450 inhibitions.
Generally speaking, herb–drug interactions are difficult to predict as they depend on a number of factors, including the In addition to P450s, there are also other drug metabolism conditions of a patient, dose and time of administration of enzymes and transport proteins which may be modulated drugs and herbs, and quality of herbal substances. often the by herbal substances, such as UdP-glucuronosyltransferase individual differences may determine the consequences of a (UGT) enzymes and breast-cancer resistance proteins.
Given the chemical complexity of herbal compositions, it may be easier to predict the potential interactions based on the pharmacological properties of the drug or herb involved (e.g. if the drug or herb has similar or different pharmacodynamic A number of herb–drug interactions have been identified in actions, or acts as the substrate or inhibitor/inducer of certain humans,12,16 as shown in Table 1. The reported drugs include CyP450s or P-glycoprotein). Certain models have been warfarin, aspirin, phenprocoumon, midazolam, alprazolam, developed to predict potential herb–drug interactions, using amitriptyline, oral contraceptives, indinavir, ritonavir, saquinavir, digoxin, cyclosporine, tacrolimus, imatinib and irinotecan.12 There are also numerous studies on animals or It is important to note that herb–drug interactions are likely cells indicating potential herb–drug interactions, although the to be under-reported. Currently, only a small number of relevance of the evidence to humans has yet to be established. drugs and herbs have been tested in clinical trials for potential interactions. Chinese medicine practitioners and physicians one of the most commonly reported drugs involved in herb– should examine prescribed drugs and herbal formulations/ drug interactions is warfarin. More than 15 different herbs products to identify whether any ingredients of concern are were reported to interfere with warfarin (and related drugs, involved. They should also monitor clinical signs of the patients such as heparin, aspirin, and coumarin derivatives). A number for any changes in responses or side effects of administered of Chinese herbs may potentially interact with warfarin, to drugs after taking herbal medicines. The general advice is to cause bleeding. Such herbs include Ginger (Zingiber officinale), avoid the concurrent use of drugs and herbal medicines in Ginseng (Panax species), danshen (Salvia miltiorrhiza) and dang gui (Angelica sinensis)17,18 (Table 1). one of the most commonly reported herbs involved is St John’s Wort (Hypericum perforatum), which has been reported to interfere with cyclosporine, digoxin, theophylline, oral contraceptives, methadone, fluoxetine and buspirone (Table In Australia, all suspected drug interactions, including suspected 1). For example, a number of cases have been reported adverse reactions to prescription medicines, vaccines, over-the- showing that St John’s Wort decreased cyclosporine blood counter and complementary medicines, should be reported to concentrations.19-27 Gingko biloba was also reported to the Adverse drug Reactions Unit at the Therapeutic Goods CG Li, LP Yang and SF Zhou
TABLe 1 Reported Herb–Drug Interactions in Humans St John’s Wort (Hypericum perforatum) Siberian ginseng (Eleutherococcus senticosis) devil’s claw (Harpagophytum procumbens) CG Li, LP Yang and SF Zhou
Notes: All clinical trials included in the table demonstrated significant herb–drug interactions, except the one marked with *, which showed no significant interaction between Warfarin and Ginkgo. ** Indicates that the Latin name was not given in the relevant study, meaning that the herb species could not be identified with certainty by the authors of this review.
Administration (TGA) (www.tga.gov.au/adr). Reports can be made electronically at www.tgasime.health.gov.au, or by using Herb–drug interaction is an important issue affecting the the ‘Blue Card’ pre-paid reporting form (available from www.
efficacy and safety of therapeutic treatments. Chinese herbal tga.gov.au/adr), or by calling the Consumer Adverse Medication medicine practitioners should have adequate knowledge in events Line (telephone: 1300 134 237). The information to this area and adopt proper strategies to monitor and report be included in a report is the patient’s details, a description potential herb–drug interactions in order to minimise harmful of the suspected reaction and medicines involved, as well as adverse reactions and improve the efficacy of Chinese herbal any treatment and outcome details (refer to the Blue Card for an information check-list). For complementary medicines, it will be useful to include product information such as AUST L number if possible. CG Li, LP Yang and SF Zhou
20. Mai I, Kruger H, Budde K, Johne A, Brockmoller J, Neumayer HH et al. Hazardous pharmacokinetic interaction of Saint John’s wort 1. MacLennan AH, Myers SP, Taylor AW. The continuing use of (Hypericum perforatum) with the immunosuppressant cyclosporin. complementary and alternative medicine in South Australia: costs Int J Clin Pharmacol Ther 2000;38(10):500–2.
and beliefs in 2004. Med J Aust 2006;184(1):27–31.
21. Karliova M, Treichel U, Malago M, Frilling A, Gerken G, Broelsch 2. expert Committee on Complementary Medicines in the Health Ce. Interaction of Hypericum perforatum (St John’s wort) with System. Complementary Medicines in the Australian Health cyclosporin A metabolism in a patient after liver transplantation. J System. Canberra: Commonwealth of Australia; 2003.
3. Kuhn MA. Herbal remedies: drug–herb interactions. Crit Care 22. Ruschitzka F, Meier PJ, Turina M, Luscher TF, Noll G. Acute heart transplant rejection due to Saint John’s wort. Lancet 2000;355(9203):548–9.
4. Johne A, Brockmoller J, Bauer S, Maurer A, Langheinrich M, Roots I. Pharmacokinetic interaction of digoxin with an herbal extract 23. Moschella C, Jaber BL. Interaction between cyclosporine and from St John’s wort (Hypericum perforatum). Clin Pharmacol Ther Hypericum perforatum (St John’s wort) after organ transplantation. Am J Kidney dis 2001;38(5):1105–7.
5. yue Qy, Bergquist C, Gerden B. Safety of St John’s wort (Hypericum 24. Turton-Weeks SM, Barone GW, Gurley BJ, Ketel BL, Lightfoot perforatum). Lancet 2000;355(9203):576–7.
ML, Abul-ezz SR. St John’s wort: a hidden risk for transplant patients. Prog Transplant 2001;11(2):116–20.
6. Nebel A, Schneider BJ, Baker RK, Kroll dJ. Potential metabolic interaction between St John’s wort and theophylline. Ann 25. Ahmed SM, Banner NR, dubrey SW. Low cyclosporin: a level due to Saint John’s wort in heart transplant patients. J Heart Lung Transplant 2001;20(7):795.
7. Mok T, yeo W, Johnson P, Hui P, Ho W, Lam K et al. A double-blind placebo-controlled randomized study of Chinese herbal medicine 26. Beer AM, ostermann T. [St John’s wort: interaction with cyclosporine as complementary therapy for reduction of chemotherapy-induced increases risk of rejection for the kidney transplant and raises daily toxicity. Ann oncol 2007;18(4):768–74.
cost of medication]. Med Klin (Munich) 2001;96(8):480–3.
8. Li CG, Monyle K, Xue C. Problems and challenges with 27. Alscher dM, Klotz U. drug interaction of herbal tea containing St Chinese herbal medicine. In: Leung P, Xue C, Cheng y, editors. John’s wort with cyclosporine. Transpl Int 2003;16(7):543–4.
A comprehensive guide to Chinese medicine. Singapore: World 28. Chen MF, Shimada F, Kato H, yano S, Kanaoka M. effect of oral administration of glycyrrhizin on the pharmacokinetics of 9. Mathewson Kuhn M. Pharmacotherapeutics: a nursing process prednisolone. endocrinol Jpn 1991;38(2):167–74.
approach. 4th ed. Philadelphia: FA davis; 1998.
29. Chen MF, Shimada F, Kato H, yano S, Kanaoka M. effect of 10. Klepser TB, doucette WR, Horton MR, Buys LM, ernst Me, glycyrrhizin on the pharmacokinetics of prednisolone following Ford JK et al. Assessment of patients’ perceptions and beliefs low dosage of prednisolone hemisuccinate. endocrinol Jpn regarding herbal therapies. Pharmacotherapy 2000;20(1):83–7.
11. Wooltorton e, Sibbald B. ephedra/ephedrine: cardiovascular and 30. Teelucksingh S, Mackie Ad, Burt d, McIntyre MA, Brett L, edwards CR. Potentiation of hydrocortisone activity in skin by glycyrrhetinic acid. Lancet 1990;335(8697):1060–3.
12. yang XX, Hu ZP, duan W, Zhu yZ, Zhou SF. drug–herb interactions: eliminating toxicity with hard drug design. Curr 31. Barone GW, Gurley BJ, Ketel BL, Abul-ezz SR. Herbal supplements: a potential for drug interactions in transplant recipients. Transplantation 2001;71(2):239–41.
13. yoshida N, Koizumi M, Adachi I, Kawakami J. Inhibition of P-glycoprotein-mediated transport by terpenoids contained in 32. Rey JM, Walter G. Hypericum perforatum (St John’s wort) in herbal medicines and natural products. Food Chem Toxicol depression: pest or blessing? Med J Aust 1998;169(11–12):583–6.
33. Bon S, Hartmann K, Johanniskraut KM. ein enzyminduktor? 14. Block KI, Gyllenhaal C. Clinical corner: herb–drug interactions in cancer chemotherapy: theoretical concerns regarding drug 34. Gordon JB. SSRIs and St John’s wort: possible toxicity? Am Fam metabolizing enzymes. Integr Cancer Ther 2002;1(1):83–9.
15. Nebert dW, Nelson dR, Coon MJ, estabrook RW, Feyereisen 35. Breidenbach T, Hoffmann MW, Becker T, Schlitt H, Klempnauer R, Fujii-Kuriyama y et al. The P450 superfamily: update on new J. drug interaction of St John’s wort with cyclosporin. Lancet sequences, gene mapping, and recommended nomenclature. dNA 36. Breidenbach T, Kliem V, Burg M, Radermacher J, Hoffmann 16. Zhou S, Huang M, Xu A, yang H, duan W, Paxton JW. Prediction MW, Klempnauer J. Profound drop of cyclosporin A whole blood of herb–drug metabolic interactions: a simulation study. Phytother trough levels caused by St John’s wort (Hypericum perforatum). Transplantation 2000;69(10):2229–30.
17. Heck AM, deWitt BA, Lukes AL. Potential interactions between 37. Bauer S, Stormer e, Johne A, Kruger H, Budde K, Neumayer HH alternative therapies and warfarin. Am J Health Syst Pharm et al. Alterations in cyclosporin A pharmacokinetics and metabolism during treatment with St John’s wort in renal transplant patients. Br 18. yu CM, Chan JC, Sanderson Je. Chinese herbs and warfarin J Clin Pharmacol 2003;55(2):203–11.
potentiation by ‘danshen’. J Intern Med 1997;241(4):337–9.
38. Lantz MS, Buchalter e, Giambanco V. St John’s wort and 19. Barone GW, Gurley BJ, Ketel BL, Lightfoot ML, Abul-ezz SR. antidepressant drug interactions in the elderly. J Geriatr Psychiatry drug interaction between St John’s wort and cyclosporine. Ann CG Li, LP Yang and SF Zhou
39. Barbenel dM, yusufi B, o’Shea d, Bench CJ. Mania in a patient 56. durr d, Stieger B, Kullak-Ublick GA, Rentsch KM, Steinert HC, receiving testosterone replacement postorchidectomy taking St Meier PJ et al. St John’s wort induces intestinal P-glycoprotein/ John’s wort and sertraline. J Psychopharmacol 2000;14(1):84–6.
MdR1 and intestinal and hepatic CyP3A4. Clin Pharmacol Ther 40. Ratz Ae, von Moos M, drewe J. [St John’s wort: a pharmaceutical with potentially dangerous interactions]. Schweiz Rundsch Med 57. Mueller SC, Uehleke B, Woehling H, Petzsch M, Majcher- Peszynska J, Hehl eM et al. effect of St John’s wort dose and 41. Schwarz UI, Buschel B, Kirch W. Unwanted pregnancy on self- preparations on the pharmacokinetics of digoxin. Clin Pharmacol medication with St John’s wort despite hormonal contraception. Br J Clin Pharmacol 2003;55(1):112–3.
58. Wang Z, Hamman MA, Huang SM, Lesko LJ, Hall Sd. effect 42. Hall Sd, Wang Z, Huang SM, Hamman MA, Vasavada N, Adigun of St John’s wort on the pharmacokinetics of fexofenadine. Clin AQ et al. The interaction between St John’s wort and an oral contraceptive. Clin Pharmacol Ther 2003;74(6):525–35.
59. Jiang X, Williams KM, Liauw WS, Ammit AJ, Roufogalis Bd, 43. Murphy PA, Kern Se, Stanczyk FZ, Westhoff CL. Interaction of St duke CC et al. effect of St John’s wort and ginseng on the John’s wort with oral contraceptives: effects on the pharmacokinetics pharmacokinetics and pharmacodynamics of warfarin in healthy of norethindrone and ethinyl estradiol, ovarian activity and subjects. Br J Clin Pharmacol 2004;57(5):592–9.
breakthrough bleeding. Contraception 2005;71(6):402–8.
60. Shader RI, Greenblatt dJ. Phenelzine and the dream machine: 44. Waksman JC, Heard K, Jolliff H, daly FFS, Bogdan GM, dart ramblings and reflections. J Clin Psychopharmacol 1985;5(2):65.
RC. Serotonin syndrome associated with the use of St John’s wort 61. Jones Bd, Runikis AM. Interaction of ginseng with phenelzine. J (Hypericum perforatum) and paroxetine [Abstract]. Clin Toxicol Clin Psychopharmacol 1987;7(3):201–2.
62. Janetzky K, Morreale AP. Probable interaction between warfarin 45. Khawaja IS, Marotta RF, Lippmann S. Herbal medicines as a factor and ginseng. Am J Health Syst Pharm 1997;54(6):692–3.
in delirium. Psychiatr Serv 1999;50(7):969–70.
63. Rosado MF. Thrombosis of a prosthetic aortic valve disclosing a 46. Prost N, Tichadou L, Rodor F, Nguyen N, david JM, Jean- hazardous interaction between warfarin and a commercial ginseng Pastor MJ. [St Johns wort–venlafaxine interaction]. Presse Med 64. Jiang X, Blair ey, McLachlan AJ. Investigation of the effects 47. Johne A, Schmider J, Brockmoller J, Stadelmann AM, Stormer of herbal medicines on warfarin response in healthy subjects: e, Bauer S et al. decreased plasma levels of amitriptyline a population pharmacokinetic–pharmacodynamic modeling and its metabolites on comedication with an extract from St approach. J Clin Pharmacol 2006;46(11):1370–8.
John’s wort (Hypericum perforatum). J Clin Psychopharmacol 65. yuan CS, Wei G, dey L, Karrison T, Nahlik L, Maleckar S et al. American ginseng reduces warfarin’s effect in healthy patients: a 48. Hebert MF, Park JM, Chen yL, Akhtar S, Larson AM. effects of St randomized, controlled trial [Brief communication]. Ann Intern John’s wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers. J Clin Pharmacol 2004;44(1):89–94.
66. McRae S. elevated serum digoxin levels in a patient taking digoxin 49. Mai I, Stormer e, Bauer S, Kruger H, Budde K, Roots I. Impact and Siberian ginseng. CMAJ 1996;155(3):293–5.
of St John’s wort treatment on the pharmacokinetics of tacrolimus 67. Tam LS, Chan Ty, Leung WK, Critchley JA. Warfarin interactions and mycophenolic acid in renal transplant patients. Nephrol dial with Chinese traditional medicines: danshen and methyl salicylate medicated oil. Aust NZ J Med 1995;25(3):258.
50. Sugimoto K, ohmori M, Tsuruoka S, Nishiki K, Kawaguchi 68. Izzat MB, yim AP, el-Zufari MH. A taste of Chinese medicine! A, Harada K et al. different effects of St John’s wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther 2001;70(6):518–24.
69. Page RL, 2nd, Lawrence Jd. Potentiation of warfarin by dong quai. Pharmacotherapy 1999;19(7):870–6.
51. Frye RF, Fitzgerald SM, Lagattuta TF, Hruska MW, egorin MJ. effect of St John’s wort on imatinib mesylate pharmacokinetics. 70. ellis GR, Stephens MR. Untitled (photograph and brief case Clin Pharmacol Ther 2004;76(4):323–9.
report). In ‘Minerva’. BMJ 1999;319(7210):650.
52. Piscitelli SC, Burstein AH, Chaitt d, Alfaro RM, Falloon 71. Shaw d, Leon C, Kolev S, Murray V. Traditional remedies and J. Indinavir concentrations and St John’s wort. Lancet food supplements: a 5-year toxicological study (1991–1995). drug 53. Mathijssen RH, Verweij J, de Bruijn P, Loos WJ, Sparreboom A. 72. Sunter WH. Warfarin and garlic [Letter]. Pharm J 1991;246:722.
effects of St John’s wort on irinotecan metabolism. J Natl Cancer 73. Piscitelli SC, Burstein AH, Welden N, Gallicano Kd, Falloon J. The effect of garlic supplements on the pharmacokinetics of 54. Tannergren C, engman H, Knutson L, Hedeland M, Bondesson saquinavir. Clin Infect dis 2002;34(2):234–8.
U, Lennernas H. St John’s wort decreases the bioavailability of R- 74. Markowitz JS, devane CL, Chavin Kd, Taylor RM, Ruan y, and S-verapamil through induction of the first-pass metabolism. donovan JL. effects of garlic (Allium sativum L.) supplementation Clin Pharmacol Ther 2004;75(4):298–309.
on cytochrome P450 2d6 and 3A4 activity in healthy volunteers. 55. Mueller SC, Majcher-Peszynska J, Uehleke B, Klammt S, Clin Pharmacol Ther 2003;74(2):170–7.
Mundkowski RG, Miekisch W et al. The extent of induction of 75. Jiang X, Williams KM, Liauw WS, Ammit AJ, Roufogalis Bd, CyP3A by St John’s wort varies among products and is linked to duke CC et al. effect of ginkgo and ginger on the pharmacokinetics hyperforin dose. eur J Clin Pharmacol 2006;62(1):29–36.
and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2005;59(4):425–32.
CG Li, LP Yang and SF Zhou
76. engelsen J, Nielsen Jd, Hansen KF. [effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in patients on long-term warfarin 85. Almeida JC, Grimsley eW. Coma from the health food store: treatment. A randomized, double-blind, placebo-controlled cross- interaction between kava and alprazolam. Ann Intern Med over trial]. Ugeskr Laeger 2003;165(18):1868–71.
77. Matthews MK, Jr. Association of Ginkgo biloba with intracerebral 86. Schelosky L, Raffauf C, Jendroska K, Poewe W. Kava and dopamine hemorrhage. Neurology 1998;50(6):1933–4.
antagonism. J Neurol Neurosurg Psychiatry 1995;58(5):639–40.
78. Galluzzi S, Zanetti o, Binetti G, Trabucchi M, Frisoni GB. 87. deahl M. Betel nut-induced extrapyramidal syndrome: an unusual Coma in a patient with Alzheimer’s disease taking low dose drug interaction. Mov disord 1989;4(4):330–2.
trazodone and Gingko biloba. J Neurol Neurosurg Psychiatry 2000;68(5):679–80.
88. Harada T, ohtaki e, Misu K, Sumiyoshi T, Hosoda S. Congestive heart failure caused by digitalis toxicity in an elderly man 79. Chen d, Klesmer J, Giovanniello A, Katz J. Mental status changes taking a licorice-containing Chinese herbal laxative. Cardiology in an alcohol abuser taking valerian and Gingko biloba. Am J 89. Iida R, otsuka y, Matsumoto K, Kuriyama S, Hosoya T. 80. Izzo AA, di Carlo G, Borrelli F, ernst e. Cardiovascular Pseudoaldosteronism due to the concurrent use of two herbal pharmacotherapy and herbal medicines: the risk of drug interaction. medicines containing glycyrrhizin: interaction of glycyrrhizin with angiotensin-converting enzyme inhibitor. Clin exp Nephrol 81. Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N engl J Med 90. Hakas JF, Jr. Topical capsaicin induces cough in patient receiving ACe inhibitor. Ann Allergy 1990;65(4):322–3.
82. Meisel C, Johne A, Roots I. Fatal intracerebral mass bleeding 91. Saruwatari J, Nakagawa K, Shindo J, Nachi S, echizen H, associated with Ginkgo biloba and ibuprofen. Atherosclerosis Ishizaki T. The in-vivo effects of sho-saiko-to, a traditional Chinese herbal medicine, on two cytochrome P450 enzymes 83. Kupiec T, Raj V. Fatal seizures due to potential herb–drug interactions (1A2 and 3A) and xanthine oxidase in man. J Pharm Pharmacol with Ginkgo biloba. J Anal Toxicol 2005;29(7):755–8.
84. yin oQ, Tomlinson B, Waye MM, Chow AH, Chow MS. 92. Homma M, oka K, Ikeshima K, Takahashi N, Niitsuma T, Fukuda Pharmacogenetics and herb–drug interactions: experience T et al. different effects of traditional Chinese medicines containing with Ginkgo biloba and omeprazole. Pharmacogenetics similar herbal constituents on prednisolone pharmacokinetics. J Pharm Pharmacol 1995;47(8):687–92.
2nd Quarter 2002 Published by IUMG Provider Relations Department IU Health Plan HMO Pharmacy Update Congratulations to IUPM !!!! The following information is from Pharmacare, IU Psychiatric Management (IUPM) has been IUHP’s Pharmacy Benefit Manager. These changes awarded a full 3-year accreditation from NCQA!!!! reflect decisions made by the Pharmacare P&T Committee in wh