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Hồ sơ an toàn của thuốc thảo dược được nộp để xin cấp phép tiếp thị tại Tanzania: một nghiên cứu hồi cứu cắt ngang
Tóm tắt
Việc sử dụng thuốc thảo dược ngày càng phổ biến yêu cầu các cơ quan quản lý quốc gia có cơ chế hiệu quả để kiểm soát các sản phẩm này, bao gồm cả việc cấp phép tiếp thị (MA) và theo dõi an toàn. Thuốc thảo dược cũng giống như thuốc thông thường cần phải được đánh giá về hiệu quả, an toàn và chất lượng thông tin trước khi được cấp phép MA. Tuy nhiên, bằng chứng hoàn chỉnh về an toàn chủ yếu dựa vào lịch sử sử dụng truyền thống lâu dài. Thuốc thảo dược có thể gây ra phản ứng bất lợi do nhiều yếu tố và do đó cần có các thử nghiệm lâm sàng để đảm bảo an toàn. Thực hành điều trị bằng thuốc thảo dược liên quan đến việc kết hợp nhiều loại cây khác nhau để đạt được hiệu quả mong muốn, trong khi nhiều thành phần thảo dược được biết là có thể gây độc tính và tương tác giữa các loại thảo dược do sự đa dạng của các thành phần hoạt chất phức tạp trong thực vật. Việc tuân thủ các yêu cầu quy định về thuốc thảo dược đã được chứng minh là khó khăn cho các nhà sản xuất vì các nước khác nhau có yêu cầu quy định khác nhau với sự biến đổi rộng rãi, dẫn đến việc rất ít thuốc thảo dược được cấp phép MA. Rất ít nghiên cứu về hồ sơ xin cấp phép tiếp thị thuốc thảo dược đã được thực hiện ở các nước khác, với không có nghiên cứu nào trong bối cảnh hệ thống quy định của châu Phi. Mục tiêu của nghiên cứu này là xác định loại tài liệu an toàn được nộp trong hồ sơ đăng ký thuốc thảo dược để hỗ trợ MA tại Tanzania. Một nghiên cứu hồi cứu cắt ngang về hồ sơ thuốc thảo dược được nộp tại Cơ quan Thuốc và Thiết bị Y tế Tanzania từ năm 2009 đến 2020 đã được thực hiện. Tới 75% đơn xin sản phẩm thuốc thảo dược là các sản phẩm kết hợp được làm từ hơn một chất thảo dược hoặc cây. Trong số 84 hồ sơ được phân tích, phần lớn không cung cấp bằng chứng về dữ liệu an toàn tiền lâm sàng (55%) và dữ liệu an toàn lâm sàng (68%). Bằng chứng về dữ liệu an toàn ở người chủ yếu đến từ tài liệu (70%) và không phải từ các nghiên cứu lâm sàng của nhà sản xuất. Các tham số chất lượng có tác động đến an toàn không được bao gồm trong 48% và 23% của chỉ tiêu về chất thảo dược hoạt tính và sản phẩm hoàn chỉnh, tương ứng. Phân tích hồ sơ thuốc thảo dược cho thấy sự thiếu sót chính về dữ liệu an toàn để hỗ trợ MA. Các nhà sản xuất cần cung cấp bằng chứng để hỗ trợ an toàn cho sản phẩm của họ để phục vụ cho các quyết định quy định dựa trên bằng chứng và tránh việc xem xét nhiều lần các đơn đăng ký.
Từ khóa
#thuốc thảo dược #cấp phép tiếp thị #an toàn thuốc #hồ sơ thuốc #châu Phi #cơ quan quản lý.Tài liệu tham khảo
World Health Organization. WHO traditional medicine strategy: 2014–2023: World Health Organization; 2013.
World Health Organization. Research guidelines for evaluating the safety and efficacy of herbal medicines: WHO Regional Office for the Western Pacific; 1993.
Qu L, Zou W, Wang Y, Wang M. European regulation model for herbal medicine: the assessment of the EU monograph and the safety and efficacy evaluation in marketing authorization or registration in Member States. Phytomedicine. 2018;42:219–25.
World Health Organization. Guidelines for the regulation of herbal medicines in the South-East Asia Region. WHO Regional Office for South-East Asia; 2004.
World Health Organization. WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems: World Health Organization; 2004.
World Health Organization. Guidelines for the assessment of herbal medicines. World Health Organization; 1991.
Calixto JB. Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents). Braz J Med Biol Res. 2000;33:179–89.
Moreira DL, Teixeira SS, Monteiro MH, De-Oliveira AC, Paumgartten FJ. Traditional use and safety of herbal medicines. Rev Bras Farmacogn. 2014;24(2):248–57.
Teng L, Zu Q, Li G, Yu T, Job KM, Yang X, et al. Herbal medicines: challenges in the modern world. Part 3. China and Japan. Expert Rev Clin Pharmacol. 2016;9(9):1225–33.
European Medicines Agency. Herbal medicinal products European Union: European Medicines Agency; 2022. Available from: https://www.ema.europa.eu/en/human-regulatory/herbal-medicinal-products.
Toklu HZ. Pharmacovigilance of Herbal Medicine: Herbavigilance. Adv Pharmacoepidemiol Drug Saf. 2016;5(4).
Kim M, Woo Y, Han C-h. Current status of the spontaneous reporting and classification/coding system for herbal and traditional medicine in pharmacovigilance. Integr Med Res. 2021;10(1): 100467.
Kamsu-Foguem B, Foguem C. Adverse drug reactions in some African herbal medicine: literature review and stakeholders’ interview. Integr Med Res. 2014;3(3):126–32.
Han J, Xian Z, Zhang Y, Liu J, Liang AJFiP. Systematic overview of aristolochic acids: nephrotoxicity, carcinogenicity, and underlying mechanisms. Front Pharmacol. 2019;10:648.
Martin KW, Ernst E. Herbal medicines for treatment of bacterial infections: a review of controlled clinical trials. J Complement Ther Med. 2003;51(2):241–6.
Martin KW, Ernst E. Herbal medicines for treatment of fungal infections: a systematic review of controlled clinical trials. Mycoses. 2004;47(3–4):87–92.
World Health Organization. General guidelines for methodologies on research and evaluation of traditional medicine. World Health Organization; 2000.
Govindaraghavan S, Sucher NJ. Quality assessment of medicinal herbs and their extracts: criteria and prerequisites for consistent safety and efficacy of herbal medicines. Epilepsy Behav. 2015;52:363–71.
Che C-T, Wang ZJ, Chow MSS, Lam CWK. Herb-herb combination for therapeutic enhancement and advancement: theory, practice and future perspectives. Molecules. 2013;18(5):5125–41.
Gromek K, Drumond N, Simas P. Pharmacovigilance of herbal medicines. Int J Risk Saf Med. 2015;27(2):55–65.
Thakkar S, Anklam E, Xu A, Ulberth F, Li J, Li B, et al. Regulatory landscape of dietary supplements and herbal medicines from a global perspective. Regul Toxicol Pharmacol. 2020;114: 104647.
Dou J, Beitz J, Temple R. Development of plant-derived mixtures as botanical drugs: clinical considerations. In: Ram Sasisekharan SLL, Amy Rosenberg, Larry A. Walker, editor. The science and regulations of naturally derived complex drugs. AAPS Series 32. Cham, Switzerland: Springer 2019. p. 245–64.
Fisher AC, Lee SL. Evolving challenges in developing naturally-derived complex mixtures into drugs: US experience and perspective. In: Ram Sasisekharan SLL, Amy Rosenberg, Larry A. Walker, editor. The science and regulations of naturally derived complex drugs. AAPS Series 32. Cham, Switzerland: Springer; 2019. p. 1–15.
Wu LC, Raw A, Knöss W, Smith M, Zhang W-D, Bedi YS, et al. Regulatory landscapes for approval of naturally-derived complex mixture drugs. In: Ram Sasisekharan SLL, Amy Rosenberg, Larry A. Walker, editor. The science and regulations of naturally derived complex drugs. AAPS Series 32. Cham, Switzerland: Springer; 2019. p. 17–44.
Sahoo N, Manchikanti P. Herbal drug regulation and commercialization: an Indian industry perspective. J Altern Complement Med. 2013;19(12):957–63.
World Health Organization. National policy on traditional medicine and regulation of herbal medicines: Report of a WHO global survey: World Health Organization; 2005.
Liu Y, Yang Z, Cheng J, Fan D. Barriers and countermeasures in developing traditional Chinese medicine in Europe. Front Med. 2016;10(3):360–76.
Complementary medicines—use of the ZA-CTD format in the preparation of a registration application [Internet]. SAHPRA. 2020. Available from: https://www.sahpra.org.za/wp-content/uploads/2020/07/7.03_CMs_ZACTD_Jun20_v3_2.pdf.
CTD modules 2, 3, 4 and 5 for registered complementary medicine applications Australian Regulatory guidelines [Internet]. Therapeutic Goods Administration. 2020 [cited October 2023]. Available from: https://www.tga.gov.au/sites/default/files/ctd_modules_2_3_4_and_5_for_registered_complementary_medicine_applications_0.pdf.
Peschel W. The Traditional Herbal Medicine Directive within the European regulatory framework for herbal products. Bol Latinoam Caribe Plantas Med Aromat. 2007;6(4):102–11.
Natural Health products ingredients database: Pre-Cleared Information [Internet]. Government of Canada. 2023. Available from: https://webprod.hc-sc.gc.ca/nhpid-bdipsn/search-rechercheReq.do.
United Republic of Tanzania. Tanzania Medicines and Medical Device Act Chapter 219. Revised 2021 ed. Dar-Es Salaam, Tanzania: Government Printer 2021.
Tanzania Medicines and medical devices Authority. The Tanzania Food, Drugs and Cosmetics (Registration of Medicinal Products) Regulations, 2015 Dar Es Salaam Tanzania: Tanzania Medicines and medical devices Authority; 2015.
Tanzania Medicines and Medical Devices Authority. Guidelines on submission of documentation for marketing authorization of herbal medicinal products. Dar Es Salaam: TMDA; 2020.
Carvalho AC, Balbino EE, Maciel A, Perfeito JP. Situation of herbal medicines register in Brazil. Rev Bras Farmacogn. 2008;18:314–9.
Scholten WK, Halkes SBA. Introducing a system for the assessment of quality, safety, and efficacy of herbal medicinal products in the Netherlands. Drug Inf J. 2001;35(2):461–8.
Peschel W. The use of community herbal monographs to facilitate registrations and authorisations of herbal medicinal products in the European Union 2004–2012. J Ethnopharmacol. 2014;158:471–86.
Tanzania Food and Drugs Authority. Guidelines for application for registration of Herbal Medicines in Tanzania. Dar Es Salaam: TFDA; 2004.
Microsoft Corporation. Microsoft Excel [Internet] 2018 [Available from: https://office.microsoft.com/excel.
IBM Corp. IBM SPSS Statistics for Windows, Version 28.0 [Internet]: Armonk NY; 2021 [cited 2021. Available from: https://www.ibm.com/se-en/products/spss-statistics?lnk=sehpv18ct7.
Huntley AL, Coon JT, Ernst E. The safety of herbal medicinal products derived from Echinacea species. Drug Saf. 2005;28(5):387–400.
Ernst E. Serious psychiatric and neurological adverse effects of herbal medicines-a systematic review. Acta Psychiatr Scand. 2003;108(2):83–91.
Bilgi N, Bell K, Ananthakrishnan AN, Atallah E. Imatinib and Panax ginseng: a potential interaction resulting in liver toxicity. Ann Pharmacother. 2010;44(5):926–8.
Bos R, Hendriks H, Scheffer J, Woerdenbag H. Cytotoxic potential of valerian constituents and valerian tinctures. Phytomedicine. 1998;5(3):219–25.
Dalla Corte C, Fachinetto R, Colle D, Pereira R, Avila D, Villarinho J, et al. Potentially adverse interactions between haloperidol and valerian. Food Chem Toxicol. 2008;46(7):2369–75.
Berdai MA, Labib S, Chetouani K, Harandou M. Case report—Atropa Belladonna intoxication: a case report. Pan Afr Med J. 2012;11(1):72.
Çaksen H, Odabaş D, Akbayram S, Cesur Y, Arslan Ş, Üner A, et al. Deadly nightshade (Atropa belladonna) intoxication: an analysis of 49 children. Hum Exp Toxicol. 2003;22(12):665–8.
Lapi F, Gallo E, Giocaliere E, Vietri M, Baronti R, Pieraccini G, et al. Acute liver damage due to Serenoa repens: a case report. Br J Clin Pharmacol. 2010;69(5):558.
Agbabiaka TB, Pittler MH, Wider B, Ernst E. Serenoa repens (Saw Palmetto) a systematic review of adverse events. Drug Saf. 2009;32:637–47.
Rahman N, Fazilah A, Effarizah M. Toxicity of nutmeg (myristicin): a review. Int J Adv Sci Eng Inf Technol. 2015;5(3):61–4.
Arumugam G, Purushotham B, Swamy MK. Myristica fragrans Houtt.: botanical, pharmacological, and toxicological aspects. Natural Bio-active Compounds: Volume 2: Chemistry, Pharmacology Health Care Practices. 2019:81–106.
Jain R, Sharma A, Gupta S, Sarethy IP, Gabrani R. Solanum nigrum: current perspectives on therapeutic properties. Altern Med Rev. 2011;16(1):78–85.
The East African Community (EAC). Compendium of Good Manufacturing Practices (GMP) technical documents for harmonization of medicines regulation in the East African community. EAC; 2014.
European Medicines Agency. Uptake of the traditional use registration scheme and implementation of the provisions of Directive 2004/24/EC (Status: 31 December 2016) London: European Medicines Agency; 2017. Report No.: EMA/HMPC/322570/2011 Rev. 7.
Ghana Food and Drugs Authority. List of all registered Products: GhanaFDA; 2023. Available from: https://fdaghana.gov.gh/registered-products.php.
National Agency for Food and Drug Administration and Control. NAFDAC Green Book: Registered Products: NAFDAC; 2023. Available from: https://greenbook.nafdac.gov.ng/.
Zhou X, Li C-G, Chang D, Bensoussan A. Current status and major challenges to the safety and efficacy presented by Chinese herbal medicine. J Medicines. 2019;6(1):14.
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;17(1):35–44.
Zhang M, Long Y, Sun Y, Wang Y, Li Q, Wu H, et al. Evidence for the complementary and synergistic effects of the three-alkaloid combination regimen containing berberine, hypaconitine and skimmianine on the ulcerative colitis rats induced by trinitrobenzene-sulfonic acid. Eur J Pharmacol. 2011;651(1–3):187–96.
Zhang A, Sun H, Wang X. Potentiating therapeutic effects by enhancing synergism based on active constituents from traditional medicine. Phytother Res. 2014;28(4):526–33.
Yuan X, Sun Y, Miao N, Sun S, Wang Y, Hu Z, et al. The synergistic anti-inflammatory effect of the combination of sodium ferulate and oxymatrine and its modulation on inflammation-associated mediators in RAW 264.7 cells. J Ethnopharmacol. 2011;137(3):1477–85.
Ness J, Johnson D, Nisly N. “Polyherbacy”: herbal supplements as a form of polypharmacy in older adults. J Gerontol A Biol Sci Med Sci. 2003;58(5):478.
Baxter K, Driver S, Williamson E. Stockley's herbal medicines interactions: Pharmaceutical Press London, UK; 2013.
Johri R, Zutshi U. An ayurvedic formulation ‘Trikatu’ and its constituents. J Ethnopharmacol. 1992;37(2):85–91.
Darben T, Cominos B, Lee C. Topical eucalyptus oil poisoning. Australas J Dermatol. 1998;39(4):265–7.
Webb N, Pitt W, Health C. Eucalyptus oil poisoning in childhood: 41 cases in south-east Queensland. J Pediatr. 1993;29(5):368–71.
Aydιn A, Aktay G, Yesilada E. A guidance manual for the toxicity assessment of traditional herbal medicines. Nat Prod Commun. 2016;11(11):1934578X1601101131.
Rider CV, Nyska A, Cora MC, Kissling GE, Smith C, Travlos GS, et al. Toxicity and carcinogenicity studies of Ginkgo biloba extract in rat and mouse: liver, thyroid, and nose are targets. J Toxicol Pathol. 2014;42(5):830–43.
Mei N, Guo X, Ren Z, Kobayashi D, Wada K, Guo L, et al. Review of Ginkgo biloba-induced toxicity, from experimental studies to human case reports. J Environ Sci. 2017;35(1):1–28.
Lee M, Cheng B, Che C, Hsieh D. Cytotoxicity assessment of Ma-huang (Ephedra) under different conditions of preparation. J Toxicol Sci. 2000;56(2):424–30.
Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. NEJM. 2000;343(25):1833–8.
European Medicines Agency. Guideline on non-clinical documentation in applications for marketing authorisation/registration of well-established and traditional herbal medicinal products. European Union: European Medicines Agency; 2017.
Dosoky NS, Setzer WN. Maternal reproductive toxicity of some essential oils and their constituents. Int J Mol Sci. 2021;22(5):2380.
Busse W. The significance of quality for efficacy and safety of herbal medicinal products. Drug Inf J. 2000;34(1):15–23.
Ernst E. Toxic heavy metals and undeclared drugs in Asian herbal medicines. Trends Pharmacol Sci. 2002;23(3):136–9.
Nagajyoti PC, Lee KD, Sreekanth T. Heavy metals, occurrence and toxicity for plants: a review. Environ Chem Lett. 2010;8(3):199–216.
Ang H. Lead contamination in Eugenia dyeriana herbal preparations from different commercial sources in Malaysia. Food Chem Toxicol. 2008;46(6):1969–75.
Ałtyn I, Twarużek M. Mycotoxin contamination concerns of herbs and medicinal plants. J Toxins. 2020;12(3):182.
World Health Organization. WHO guidelines for assessing quality of herbal medicines with reference to contaminants and residues: World Health Organization; 2007.
European Medicines Agency. Guidelines on specification: Test procedures and acceptance criteria for herbal substances, herbal preparations and herbal medicinal products. European Union: European Medicines Agency; 2006.
Santos L, Marín S, Sanchis V, Ramos AJ. Agriculture. Screening of mycotoxin multicontamination in medicinal and aromatic herbs sampled in Spain. J Sci Food. 2009;89(10):1802–7.
Chourasia HK. Mycobiota and mycotoxins in herbal drugs of Indian pharmaceutical industries. Mycol Res. 1995;99(6):697–703.
Harris ES, Cao S, Littlefield BA, Craycroft JA, Scholten R, Kaptchuk T, et al. Heavy metal and pesticide content in commonly prescribed individual raw Chinese Herbal Medicines. Sci Total Environ. 2011;409(20):4297–305.
Zhi-guang H, Yue-ru L, Yu Z, Xiu-mei W, Dan C, Zhong-bin L, et al. Distribution of 19 organochlorinated pesticides residues in ginseng and soils in Jilin Province. China Afr J Biotechnol. 2011;10(85):19764–70.
de Sousa Lima CM, Fujishima MAT, de Paula LB, Mastroianni PC, de Sousa FFO, da Silva JO. Microbial contamination in herbal medicines: a serious health hazard to elderly consumers. BMC Complement Med Ther. 2020;20(1):1–9.
Rajeshwari P, Raveesha KA. Mycological analysis and aflatoxin B1 contaminant estimation of herbal drug raw materials. AJTCAM. 2016;13(5):123–31.
Russo S, Mastropasqua M, Mosetti M, Persegani C, Paggi A. Low doses of liquorice can induce hypertension encephalopathy. Am J Nephrol. 2000;20(2):145–8.
Seeff LB, Bonkovsky HL, Navarro VJ, Wang G. Herbal products and the liver: a review of adverse effects and mechanisms. Gastroenterology. 2015;148(3):517-32e3.
Tovar RT, Petzel RM. Herbal toxicity. Dis Mon. 2009;55(10):592–641.
Raynor DK, Dickinson R, Knapp P, Long AF, Nicolson DJ. Buyer beware? Does the information provided with herbal products available over the counter enable safe use? BMC Med. 2011;9(1):1–9.
Maat HP, Lentz L. Improving the usability of patient information leaflets. Patient Educ Couns. 2010;80(1):113–9.
UK Herbal Medicines Advisory Committee (HMAC) for the Herbal Medicines and Practitioners Working Group (HMPWG). Safety, regulation and herbal medicines: a review of the evidence. United Kingdom Government; 2014. https://www.gov.uk/government/publications/advice-on-regulating-herbal-medicines-and-practitioners. Accessed 09 July 2023.