The development of herbal medicinal products: Quality, safety and efficacy as key factors

Pharmaceutical Medicine

Volumn 22, Issue 2, 2008, Pages 107-118

  Cañigueral, Salvador ^a   Tschopp, Roger ^b   Ambrosetti, Lara ^b   Vignutelli, Alberto ^b   Scaglione, Francesco ^c   Petrini, Orlando ^d  

^a UNIVERSITY OF BARCELONA   (Spain)

^b R and D   (Switzerland)

^c UNIVERSITY OF MILAN   (Italy)

^d Cantonal Institute of Microbiology   (Switzerland)

Author keywords

Clinical trial design; Herbal medicines, general; Phytotherapies, general; Research and development

Indexed keywords

ACETYLSALICYLIC ACID; CIMICIFUGA RACEMOSA EXTRACT; CYCLOSPORIN A; DIGOXIN; GINKGO BILOBA EXTRACT; GINSENG EXTRACT; GINSENOSIDE; HERBACEOUS AGENT; HYPERICUM EXTRACT; HYPERICUM PERFORATUM EXTRACT; INDINAVIR; THYMOL; WARFARIN;

ADD ON THERAPY; ALZHEIMER DISEASE; AMENORRHEA; ANTIMICROBIAL ACTIVITY; BLEEDING; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DECREASED APPETITE; DEPRESSION; DIARRHEA; DIZZINESS; DOSE RESPONSE; DRUG EFFICACY; DRUG PURIFICATION; DRUG QUALITY; DRUG RESEARCH; DRUG SAFETY; DRUG SURVEILLANCE PROGRAM; EDEMA; GASTROINTESTINAL TOXICITY; HEADACHE; HUMAN; HYPERTENSION; HYPOTENSION; IDIOPATHIC DISEASE; INSOMNIA; MENOPAUSAL SYNDROME; NERVOUSNESS; PHYTOTHERAPY; PRIORITY JOURNAL; RASH; REVIEW; SIDE EFFECT; UNSPECIFIED SIDE EFFECT; VERTIGO;

EID: 41749101026     PISSN: 11782595     EISSN: None     Source Type: Journal    
DOI: 10.1007/BF03256690     Document Type: Review

References (135)

1. Williamson EM. Synergy and other interactions in phytomedicines. Phytomedicine 2001 Sep; 8 (5): 401-9
2. Attiso M, Bonati A, Concha JA, et al. Réunion OMS sur la sélection et caractérisation des plantes médicinales (drogues végétales). Document DPM/79.1. 1978 Oct 9-13; Geneva. Geneva: WHO, 1978
3. European Directorate for the Quality of Medicines. European pharmacopoeia. 6th ed. Strasbourg: Council of Europe, 2008
4. Directive 2004/24/EC of the European Parliament and of the Council of 31 March 2004 amending, as regards traditional herbal medicinal products, Directive 2001/83/EC on the Community code relating to medicinal products for human use (Official Journal L 136, 30/4/2004, p. 85-90) [online]. Available from URL: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-1/dir_2004_24/ dir_2004_24_en.pdf [Accessed 2008 Feb 27]
5. Herbal Medicinal Products Committee (HMPC). Guideline on specifications: test procedures and acceptance criteria for herbal substances, herbal preparations and herbal medicinal products/traditional herbal medicinal products. CPMP/ QWP/2820/00 Rev 1. London 2006 [online]. Available from URL: http://www.emea.europa.eu/pdfs/human/qwp/282000en.pdf [Accessed 2008 Feb 27]
6. Cañigueral S. Fitoterapia: una terapéutica para el tercer milenio? Revista Fitoterapia 2002; 2 (2): 101-21
7. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 1998 Nov 11; 280 (18): 1569-75
8. World Health Organization. WHO monographs on selected medicinal plants. Volume 1. Geneva: World Health Organization, 1999 [online]. Available from URL: http://whqlibdoc.who.int/publications/1999/9241545178.pdf [Accessed 2008 Feb 12]
9. World Health Organization. WHO monographs on selected medicinal plants. Volume 2. Geneva: World Health Organization, 2002 [online]. Available from URL: http://whqlibdoc.who.int/publications/2002/9241545372.pdf [Accessed 2008 Feb 12]
10. World Health Organization. WHO monographs on selected medicinal plants. Volume 3. Geneva: World Health Organization. 2007 [online]. Available from URL: http://www.who.int/medicines/publications/traditional/MedPlantsMonograph3.pdf [Accessed 2008 Mar 6]
11. World Health Organization. WHO guidelines on good agricultural and collection practices (GACP) for medicinal plants. Geneva: World Health Organization, 2003 [online]. Available from URL: http://whqlibdoc.who.int/ publications/2003/9241546271.pdf [Accessed 2008 Feb 12]
12. World Health Organization. Quality control methods for medicinal plant materials. Geneva: World Health Organization, 1998 [online]. Available from URL: http://whqlibdoc.who.int/publications/1998/9241545100.pdf [Accessed 2008 Feb 12]
13. World Health Organization. WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems. Geneva: World Health Organization, 2004
14. World Health Organization. General guidelines for methodologies on research and evaluation of traditional medicine. Geneva: World Health Organization, 2000 [online]. Available from URL: http://whqlibdoc.who.int/hq/ 2000/WHO_EDM_TRM_2000.1.pdf [Accessed 2008 Feb 12]
15. Herbal Medicinal Products Committee (HMPC). Guideline on good agricultural and collection practice (GACP) for starting materials of herbal origin. EMEA/ HMPC/246816/2005. London, 2006 [online]. Available from URL: http://www.emea.europa.eu/pdfs/human/hmpc/24681605en.pdf [Accessed 2008 Mar 6]
16. Working Party on Herbal Medicinal Products (HMPWP). Updated draft points to consider on the evidence of safety and efficacy required for well-established herbal medicinal products in bibliographic applications. EMEA/HMPWG/23/ 99. Draft 1999 Jan 21 [online]. Available from URL: http://www.emea.europa.eu/pdfs/ human/hmpc/002399en.pdf [Accessed 2008 Mar 6]
17. Working Party on Herbal Medicinal Products. Final concept paper on the implementation of different levels of scientific evidence in core-data for herbal drugs. EMEA/HMPWP/1156/03. London 2004 [online]. Available from URL: http://www.emea.europa.eu/pdfs/human/hmpc/115603en.pdf [Accessed 2008 Feb 12]
18. European Scientific Cooperative on Phytotherapy (ESCOP). ESCOP monographs: the scientific foundation for herbal medicinal products. Stuttgart: Thieme, 2003
19. Bauer R. Quality criteria and standardization of phytopharmaceuticals: can acceptable drug standards be achieved. Drug Inf J 1998; 32: 101-10
20. Bauer R, Tittel G. Quality assessment of herbal preparations as a precondition of pharmacological and clinical studies. Phytomedicine 1996; 2 (3): 193-8
21. Busse W. The significance of quality for efficacy and safety of herbal medicinal products. Drug Inf J 2000; 34: 15-23
22. Mrlianova M, Tekel'ova D, Felklova M, et al. The influence of the harvest cut height on the quality of the herbal drugs Melissae folium and Melissae herba. Planta Med 2002 Feb; 68 (2): 178-80
23. Soldati F, Tanaka O. Panax ginseng: relation between age of plant and content of ginsenosides. Planta Med 1984 Aug; 50 (4): 351-2
24. Sprecher E. Ginseng: miracle drug or phytopharmacon? Apoth J 1987; 9: 52-61
25. Kitagawa I, Taniyama T, Shibuya H, et al. Chemical studies on crude drug processing: V. On the constituents of ginseng radix rubra (2). Comparison of the constituents of white ginseng and red red ginseng prepared from the same Panax ginseng root. J Pharm Soc Jpn 1987; 107: 495-505
26. Lemli J, Cuveele J. Les transformations des hétérosides anthroniques pendant le séchage des feuilles de Cassia senna et de Rhamnus frangula. Planta Med 1978; 34: 311-8
27. Stahl-Biskup E. Essential oil chemistry of the genus Thymus: a global view. In: Bussing A, editor. Medicinal and aromatic plants: industrial profiles. Amsterdam: Harwood Academic Publishers, 2002: 75-124
28. Stahl-Biskup E, Laakso I. Essential oil polymorphism in Finnish Thymus species. Planta Med 1990 Oct; 56 (5): 464-8
29. DeFeudis FV. Ginkgo biloba extract (EGb 761): pharmacological activities and clinical applications. Amsterdam: Elsevier Science Publishers, 1991: 24
30. Kennedy DO, Scholey AB. Ginseng: potential for the enhancement of cognitive performance and mood. Pharmacol Biochem Behav 2003 Jun; 75 (3): 687-700
31. Sünram-Lea SI, Birchall RJ, Wesnes KA, et al. The effect of acute administration of 400 mg of Panax ginseng on cognitive performance and mood in healthy young volunteers. Curr Top Nutraceut Res 2005; 3 (1): 65-74
32. Scaglione F, Pannacci M, Petrini O. The standardised G115 Panax ginseng C.A. Meyer extract: a review of its properties and usage. Evid Based Integr Med 2005; 2 (4): 195-206
33. Van Schepdael P. Les effets du ginseng G115 sur la capacité physique de sportifs d'endurance. Acta Ther 1993; 19 (4): 337-47
34. Rosenfeld MS, Nachtajler SP, Schwartz GT, et al. Evaluation of the efficacy of a standardized ginseng extract in patients with psychophysical asthenia and neurological disorders. Semana Med 1989, 173 (9): 148-54
35. D'Angelo L, Grimaldi R, Caravaggi M, et al. A double-blind, placebo-controlled clinical study on the effect of a standardized Ginseng extract on psychomotor performance in healthy volunteers. J Ethnopharmacol 1986; 16 (1): 15-22
36. Dörling E, Kirchdorfer AM, Rückert KH. Do ginsenosides influence the performance? Results of a double-blind study. Notabene Med 1980; 10 (5): 241-6
37. Fuzzati N, Gabetta B, Jayakar K, et al. Liquid chromatography- electrospray mass spectrometric identification of ginsenosides in Panax ginseng roots. J Chromatogr A 1999 Aug 27; 854 (1-2): 69-79
38. Soldati F. Panax ginseng: standardization and biological activity. In: Cutler SJ, Cutler HG, editors. Biologically active natural products: pharmaceuticals. Boca Raton (FL): CRC Press, 2000: 209-32
39. Shin JY, Song JY, Yun YS, et al. Immunostimulating effects of acidic polysacchar-ides extract of Panax ginseng on macrophage function. Immunopharmacol Immunotoxicol 2002; 24 (3): 469-82
40. Song JY, Akhalaia M, Platonov A, et al. Effects of polysaccharide ginsan from Panax ginseng on liver function. Arch Pharm Res 2004; 27 (5): 531-8
41. Mahady GB, Fabricant D, Chadwick LR, et al. Black cohosh: an alternative therapy for menopause? Nutr Clin Care 2002; 5: 283-9
42. American Botanical Council. Ginseng evaluation program [online]. Available from URL:http://abc.herbalgram.org/site/DocServer/ Ginseng_Evaluation_Program.pdf?docID=241 [Accessed 2008 Feb 20]
43. Hall T, Lu Z, Yat PN, et al. Evaluation of consistency of standardized Asian ginseng products in the Ginseng Evaluation Program. Herbalgram 2001; 52: 31-45
44. Ernst E. A reevaluation of kava. Br J Clin Pharmacol 2007; 64: 415-7
45. Whittona PA, Laua A, Salisburyb A, et al. Kava lactones and the kava-kava controversy. Phytochemistry 2003; 64: 673-9
46. Boerner RJ, Sommer H, Berger W, et al. Kava-Kava extract LI 150 is as effective as opipramol and buspirone in generalised anxiety disorder: an 8-week randomized, double-blind, multi-centre clinical trial in 129 out-patients. Phytomedicine 2003; 10: 38-49
47. Chan K. Some aspects of toxic contaminants in herbal medicines. Chemosphere 2003 Sep; 52 (9): 1361-71
48. De Smet P. Overview of herbal quality control. Drug Inf J 1999; 33 (3): 717-24
49. United States Pharmacopoeia [online]. Available from URL: http://www.usp.org/aboutUSP/contactUs.html [Accessed 2008 Feb 26]
50. World Health Organization, Regional Office for the Western Pacific, Manila. Research guidelines for evaluating the safety and efficacy of herbal medicines. 1993 [online]. Available from URL: http://www.wpro.who.int/ publications/pub_9290611103.htm [Accessed 2008 Feb 12]
51. Committee on Herbal Medicinal Products. Guideline on non-clinical documentation for herbal medicinal products in applications for marketing authorization (bibliographical and mixed applications) and in applications for simplified registration. EMEA/HMPC/32116/2005. 2006 [online]. Available from URL: http://www.emea.europa.eu/pdfs/human/hmpc/3211605en.pdf [Accessed 2008 Feb 12]
52. Loew D, Kaszkin M. Approaching the problem of bioequivalence of herbal medicinal products. Phytoyher Res 2002; 16: 705-11
53. Westerhoff K, Kaunzinger A, Wurglics M, et al. Biorelevant dissolution testing of St John's wort products. J Pharm Pharmacol 2002 Dec; 54 (12): 1615-21
54. Barnes J. Quality, efficacy and safety of complementary medicines: fashions, facts and the future: part I. Regulation and quality. Br J Clin Pharmacol 2003 Mar; 55 (3): 226-33
55. Barnes J. Quality, efficacy and safety of complementary medicines: fashions, facts and the future: part II. Efficacy and safety. Br J Clin Pharmacol 2003 Apr; 55 (4): 331-40
56. Schulz V, Hansel R, Blumenthal M, et al. Rational phytotherapy: a reference guide for physicians and pharmacists. 5th ed. Berlin: Springer Verlag, 2004
57. Ernst E. Jumping to conclusions. Phytomedicine 2003; 10 (8): 708-9
58. Petrini O. Klinische Entwicklung von Phytopharmaka. Wien Med Wochenschr 2002; 152 (7-8): 204-8
59. Szanto E, Gruber D, Sator M, et al. Placebo-controlled study of Melbrosia in treatment of climacteric symptoms [in German]. Wien Med Wochenschr 1994; 144 (7): 130-3
60. Kennedy DO, Scholey AB, Wesnes KA. Differential, dose dependent changes in cognitive performance following acute administration of a Ginkgo biloba/ Panax ginseng combination to healthy young volunteers. Nutr Neurosci 2001; 4 (5): 399-412
61. Kennedy DO, Scholey AB, Wesnes KA. Modulation of cognition and mood following administration of single doses of Ginkgo biloba, ginseng, and a ginkgo/ginseng combination to healthy young adults. Physiol Behav 2002 Apr 15; 75 (5): 739-51
62. Reay JL, Kennedy DO, Scholey AB. Single doses of Panax ginseng (G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity. J Psychopharmacol 2005 Jul; 19 (4): 357-65
63. Reay JL, Kennedy DO, Scholey AB. The glycaemic effects of single doses of Panax ginseng in young healthy volunteers. Br J Nutr 2006 Oct; 96 (4): 639-42
64. Reay JL, Kennedy DO, Scholey AB. Effects of Panax ginseng, consumed with and without glucose, on blood glucose levels and cognitive performance during sustained 'mentally demanding' tasks. J Psychopharmacol 2006 Nov; 20 (6): 771-81
65. Scaglione F, Cattaneo G, Alessandria M, et al. Efficacy and safety of the standardised ginseng extract G115 for potentiating vaccination against the influenza syndrome and protection against the common cold [corrected]. Drugs Exp Clin Res 1996; 22 (2): 65-72
66. Scaglione F, Cogo R, Cocuzza C, et al. Immunomodulatory effects of Panax ginseng C. A. Meyer(G 115) on alveolar macrophages from patients suffering with chronic bronchitis. Int J Immunother 1994; 10 (1): 21-4
67. Scaglione F, Ferrara F, Dugnani S, et al. Immunomodulatory effects of two extracts of Panax ginseng C.A. Meyer. Drugs Exp Clin Res 1990; 16 (10): 537-42
68. Scaglione F, Weiser K, Alessandria M. Effects of the standardised ginseng extract G115® in patients with chronic bronchitis: a nonblinded, randomised, comparative pilot study. Clin Drug Invest 2001; 21 (1): 41-5
69. Scholey AB, Kennedy DO. Acute, dose-dependent cognitive effects of Ginkgo biloba, Panax ginseng and their combination in healthy young volunteers: differential interactions with cognitive demand. Hum Psychopharmacol 2002 Jan; 17 (1): 35-44
70. Bars PLI, Katz MM, Berman N, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. JAMA 1997; 278: 1327-32
71. Bars PLI, Kieser M, Itil KZ. A 26-week analysis of a double-blind, placebo-controlled trial of the Ginkgo biloba extract EGb 761 in dementia. Dement Geriatr Cogn Disord 2000; 11: 230-7
72. Bars PLI, Velasco FM, Ferguson JM, et al. Influence of the severity of cognitive impairment on the effect of the Ginkgo biloba extract EGb 761 in Alzheimer's disease. Neuropsychobiology 2002; 45: 19-26
73. Cockle SM, Kimber S, Hindmarch I. The effects of four months supplementation with Ginkgo biloba extract (LI 1370) on activities of daily living in an older population: a postal survey. Phytomedicine 2000; 7: 21
74. Cohen AJ, Bartlik B. Ginkgo biloba for antidepressant-induced sexual dysfunction. J Sex Marital Ther 1998; 24: 139-43
75. Dongen MV, Rossum EV, Kessels AGH, et al. The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment: new results of a randomized clinical trial. J Am Geriatr Soc 2000; 48: 1183-94
76. Elsabagh S, Hartley DE, Ali O, et al. Effects of 6 weeks' treatment with Ginkgo biloba on cognitive function and mood in a young healthy population. J Psychopharmacol 2003; 17: A61
77. Elsabagh S, Hartley DE, File SE. Limited cognitive benefits in stage +2 postmenopausal women after 6 weeks of treatment with Ginkgo biloba. J Psychopharmacol 2005; 19: 173-81
78. Kanowski S, Herrmann WM, Stephan K, et al. Proof of efficacy of the Ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry 1996; 29: 47-56
79. Kanowski S, Hoerr R. Ginkgo biloba extract EGb 761 in dementia: intent-to-treat analyses of a 24-week, multi-center, double-blind, placebo-controlled, randomized trial. Pharmacopsychiatry 2003; 36: 297-303
80. Wesnes KA, Ward T, McGinty A, et al. The memory enhancing effects of a Ginkgo biloba/Panax ginseng combination in healthy middle-aged volunteers. Psychopharmacology 2000; 152: 353-61
81. Schrader E. Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. Int Clin Psychopharmacol 2000; 15: 61-8
82. Sommer H. Improvement in psychovegetative symptoms by Hypericum in a multicenter double-blind study. Nervenheilkunde 1991; 10: 308-10
83. Taylor LV, Kobak KA. An open-label trial of St. John's wort (Hypericum perforatum) in obsessive-compulsive disorder. J Clin Psychiatry 2000; 61: 575-8
84. Vorbach EU, Huebner WD, Arnoldt KH. Effectiveness and tolerance of the hypericum extract LI 160 in comparison with imipramine: randomized double blind study with 135 out-patients. Nervenheilkunde 1993; 12: 290-6
85. Woelk H. Comparison of St John's wort and imipramine for treating depression: randomised controlled trial. BMJ 2000; 321: 536-9
86. Woelk H, Beneke M, Gebert I, et al. Hypericum extract Ze 117 versus imipramine: a randomised, controlled study in mild-moderate depression. Phytomedicine 2000; 7: 108
87. Birks J, Grimley EV, Van Dongen M. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2002; (4): CD003120
88. Ernst E. The risk-benefit profile of commonly used herbal therapies: ginkgo, St John's wort, ginseng, echinacea, saw palmetto, and kava. Ann Intern Med 2002 Jan 1; 136 (1): 42-53
89. Ernst E, Pittler MH. Ginkgo biloba for dementia: a systematic review of double-blind, placebo-controlled trials. Clinical Drug Invest 1999; 17 (4): 301-8
90. Foster S. Black cohosh: Cimicifuga racemosa, a literature review. Herbalgram 1999; 45: 35-50
91. Kennedy DO, Scholey AB. The psychopharmacology of European herbs with cognition-enhancing properties. Curr Pharm Des 2006; 12 (35): 4613-23
92. Oken BS, Storzbach DM, Kaye JA. The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. Arch Neurol 1998 Nov; 55 (11): 1409-15
93. Pittler MH, Vogler BK, Ernst E. Feverfew for preventing migraine. Cochrane Database Syst Rev 2000; (3): CD002286
94. Vogler BK, Pittler MH, Ernst E. The efficacy of ginseng: a systematic review of randomised clinical trials. Eur J Clin Pharmacol 1999 Oct; 55 (8): 567-75
95. Whiskey E, Werneke U, Taylor D. A systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review. Int Clin Psychopharmacol 2001 Sep; 16 (5): 239-52
96. Williams Jr JW, Mulrow CD, Chiquette E, et al. A systematic review of newer pharmacotherapies for depression in adults: evidence report summary. Ann Intern Med 2000 May 2; 132 (9): 743-56
97. Wilt TJ, Ishani A, Stark G, et al. Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. JAMA 1998 Nov 11; 280 (18): 1604-9
98. Wagner H. Futuro en la investigación en Fitoterapia: tendencias y retos. Revista Fitoterapia 2006; 6 (2): 101-17
99. De Smet PA. Herbal remedies. N Engl J Med 2002 Dec 19; 347 (25): 2046-56
100. Newton KM, Reed SD, LaCroix AZ, et al. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med 2006 Dec 19; 145 (12): 869-79
101. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288: 321-33
102. Haynes B. Can it work? Does it work? Is it worth it? The testing of healthcare interventions is evolving. BMJ 1999 Sep 11; 319 (7211): 652-3
103. Ernst E. Risks of herbal medicinal products. Pharmacoepidemiol Drug Saf 2004 Nov; 13 (11): 767-71
104. 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 Oct; 54 (8): 589-94
105. James JS. St. John's wort warning: do not combine with protease inhibitors, NNRTIs. AIDS Treat News 2000 Feb 18; 337: 3-5
106. Johne A, Brockmoller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clin Pharmacol Ther 1999 Oct; 66 (4): 338-45
107. Mai I, Kruger 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 Oct; 38 (10): 500-2
108. Castot A, Djezzar S, Deleau N, et al. Pharmacovigilance off the beaten track: herbal surveillance or pharmacovigilance of medicinal plants [in French]. Therapie 1997 Mar-Apr; 52 (2): 97-103
109. Siegel RK. Ginseng abuse syndrome: problems with the panacea. JAMA 1979; 241: 1614-5
110. Blumenthal M. Debunking the ginseng abuse syndrome. Whole Foods 1991 Mar: 89-92
111. Gilbert GJ. Ginkgo biloba. Neurology 1997; 48: 1137
112. Lewis SL, Rowin J. Ginkgo biloba: reply from the authors. Neurology 1997; 48: 1137
113. Lewis SL, Rowin J. Ginkgo biloba: reply from the authors. Neurology 1997; 48: 789-90
114. Lewis SL, Rowin J. Association of Ginkgo biloba with intracerebral hemorrhage: reply from the authors. Neurology 1998; 50: 1933-4
115. Odawara M, Tamaoka A, Yamashita K. Ginkgo biloba. Neurology 1997; 48: 789
116. Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med 1997; 336: 1108
117. Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology 1996; 46: 1775-6
118. Skogh M. Extracts of Ginkgo biloba and bleeding or haemorrhage. Lancet 1998; 352: 1145-6
119. Vale S. Subarachnoid haemorrhage associated with Ginkgo biloba. Lancet 1998; 352: 36
120. Vale S. Extracts of Ginkgo biloba and bleeding or haemorrhage. Lancet 1998; 352: 1146
121. Nortier JL, Martinez M-CM, Schmeiser HH, et al. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N Engl J Med 2000; 342: 1686-92
122. Bailey T, Klepser ME. Unsafe and potentially safe herbal therapies. Am J Health Syst Pharm 1999; 56: 125-38
123. Mahady GB. Ginkgo biloba: a review of quality, safety, and efficacy. Nutr Clin Care 2001; 4: 140-7
124. Kaufman DW, Kelly JP, Rosenberg L, et al. Recent patterns of medication use the ambulatory adult population of the United States: the Slone survey. JAMA 2002 Jan 16; 287 (3): 337-44
125. Cvetkovic RS, Goa KL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs 2003; 63 (8): 769-802
126. Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002; 54(4): 349-56
127. Markowitz JS, De Vane 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 (9): PL133-9
128. Piscitelli S, Burstein A, Chaitt D, et al. Indinavir concentrations and St John's wort. Lancet 2000; 355 (9203): 547-8
129. Yue Q, Bergquist C, Gerdén B. Seven cases of decreased effect of warfarin during concomitant treatment with St John's wort. Lancet 2000; 355 (9203): 576-7
130. 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 Apr; 71 (4): 331-7
131. Hohl K, Gaus W. Bibliography on herb-drug and food-drug interactions [online]. Available from URL: http://www.uni-ulm.de/uni/fak/medizin/biodok/v4/ herb_drug_interactions.html [Accessed 2008 Feb 12]
132. Schmid EF, Smith DA, Ryder SW. Communicating the risks and benefits of medicines. Drug Disc Today 2007 May; 12 (9-10): 355-64
133. Committee on Herbal Medicinal Products. Annex 1. Assessment of case reports connected to herbal medicinal products containing cimicifugae racemosae rhizome (black cohosh, root). London, 8 May 2007. Doc. Ref. EMEA/269258/2006 Rev 1 [online]. Available from URL: http://www.emea.europa.eu/pdfs/human/hmpc/ 26925806en.pdf [Accessed 2008 Feb 12]
134. Vanaclocha B, Cañigueral S. Posible hepatotoxicidad del rizoma de cimicífuga. Revista Fitoterapia 2006; 6 (2): 129-35
135. ClinicalTrials.gov, US National Institute of Health [online]. Available from URL: http://clinicaltrials.gov/ct2/results?term=herbal+AND+herbals [Accessed 2008 Feb 27]