Herbal pharmacovigilance in Nepal: challenges and recommendations

Introduction

Based on indigenous knowledge, the traditional practice of herbal medicines is widely prevalent in the world for preventive and therapeutic purposes to maintain good health and wellness of an individual¹. The use of traditional medicine from natural sources is a common phenomenon in South Asia, and uses of traditional medicine, mostly of plant origin, have been widely reported among south Asian countries. The Indian system of medicines, such as the Siddha and Ayurveda, relies heavily on the products derived from plants². Likewise, individuals in Pakistan have been using alternative therapies that are practiced by healers, clergymen, hakims, homeopaths and even quacks³

However, none of these South Asian countries, such as Nepal, India and Pakistan, has a proper system for herbal pharmacovigilance, nor is there proper regulation and research to regulate and standardize the production and use of herbal medicinal products. Lack of stringent regulation and reporting mechanisms may have missed many reports of toxicity in the country. This article aims to discuss the use of herbal products in Nepal, the challenges associated with the adverse reaction due to herbal medicines, and recommendations to overcome these challenges.

Herbal product use in Nepal

Nepal is a biodiversity-rich country because of its variation in the natural topography. Herbal medicines are widely used in Nepal, sometimes as an alternative to allopathic medicines or concomitantly with allopathic medicines. There is a general belief that traditional medicines are safe, effective and less costly compared to allopathic medicines. Nepal is also rich in culture and tradition where different ethnic groups celebrate different festivals and different medicinal plants are used on those occasions. For instance, in one of the biggest festivals, Dashain (celebrated in September-October), devotees use yellowish plant shoots called Jamara in Nepalese vernacular language (germinated from the seedlings of maize, barley, wheat, etc.)⁴. Wheatgrass (Tritcumaestivum linn) juice is used in Nepalese society as it contains a number of vitamins, minerals, amino acids, and vital enzymes, which play an important anticancer role⁵. Recently senior hepatologist in Nepal have claimed that there are severe side effects of drinking wheatgrass juice in patients⁶. Herbal cough syrup containing ginger, Adhatoda vasica, Glycyrrhiza glabra and Ocimum sanctum, are also commonly used in Nepal. A phase IV comparative randomized trial from Pakistan showed that cough syrup containing Adhatoda vasica has a favourable impact on cough and associated symptoms in children⁷.

In Nepal and elsewhere, the use of wild plants for producing herbal medicines is quite common, especially among traditional communities and tribal people. Nepal is one major supplier of wild medicinal plants in the world. Nepalese wild plants, such as Swertia chirata, Astilbe rivularis, Bergenia ciliata, Acorus calamus, Nardostachys grandiflora and Valeriana jatamansi are used by local people, traditional healers and herbal medicinal companies to prepare different types of herbal medicines⁸. More studies are needed to know about side effects of these herbal drug products.

Herbal pharmacovigilance globally

Pharmacovigilance is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other possible drug-related problem⁹. No medicine is free from side effects, be it allopathic or ayurvedic. Therefore, it is clear that besides therapeutic effects there may be systemic and/or topical side effects of herbal medicines in various body systems^10–13. This is of great concern for health regulatory authorities, like the World Health Organization (WHO), to ensure the safe and effective use of traditional herbal medicines, which covers herbs, herbal materials, herbal preparations, and finished herbal products^9,12.

In developed nations, the use of herbal medicines as a dietary supplement is gaining momentum in the neutraceuticals market, making standardization, quality control and clinical trials of herbal medicines mandatory¹⁴. However, even for the USA and European countries, setting up and maintaining a pharmacovigilance system has been a challenge because current pharmacovigilance systems are mostly focused on allopathic medicines, and herbal medicines come from countries of different origins than the country in which they are used, e.g. the USA and Europe¹⁵. Nevertheless, various tools exist to aid individuals to carry out herbal pharmacovigilance. For example, RUCMAS (Roussel Uclaf Causality Assessment Method) is a standard tool that has been widely used in many countries for assessing drug-induced and herb-induced liver injury¹⁶.

The distinction in the regulation of herbal medicines in developed and developing nations have sensitized the WHO to include traditional herbal medicines in pharmacovigilance programs for their safe and effective use, and quality control¹⁷.

Challenges to herbal pharmacovigilance in Nepal

In Nepal, the Department of Drug Administration (DDA) has been nominated as the national pharmacovigilance center by the Uppsala Monitoring Center (UMC), Sweden, for reporting of adverse drug reactions¹⁸. Herbal (Ayurvedic) medicines in the market possess variation in quality control due to a lack quality standards and stringent regulatory environment¹⁹. The DDA raised the issue of significant heavy metal content in herbal products being marketed by street vendors in its bulletin ‘Drug Bulletin of Nepal’²⁰; however, regulation and monitoring aspects are at a very early stage. Self-medication of traditional herbal medicines is also very common among Nepalese individuals²¹, and additionally, it is unknown if the concomitant use of both herbal and allopathic drugs may interact resulting in adverse drug events^22,23. The public also have a general belief that these herbal medicines are safe.

Though the DDA acts as a national pharmacovigilance center, there are no reports of adverse events so far due to traditional herbal medicines in Nepal. The Department of Ayurveda (DoAy) under the Ayurveda Health Policy, 1996, was developed to regulate herbal medicines in Nepal. The central Ayurvedic hospital established at Nardevi, Kathmandu in 1933, and Midwestern Regional Ayurvedic hospital established in Dang contributed to the promotion of the use of Ayurvedic herbal medicines. There are more than 216 zonal Ayurvedic dispensaries throughout the country. Herbs Production and Processing Company Ltd. was also established at Jadibudi, Kathmandu to produce herbal products. National Ayurveda Formulary has been published by DoAy²⁴. Yet, there is no such effective implementation of policy, investigations and quality control of herbal products^19,25. Stringent implementation of the policy is yet to be seen in the country.

There is a necessity for herbal pharmacovigilance in Nepal. However, several challenges exist for the development of herbal pharmacovigilance system in Nepal. Standardization of herbal products with respect to active ingredients is a tedious process that are yet to be performed in Nepal²⁶. Reporting of adverse events of herbal medicines is not mandatory in Nepal^27,28. The challenge remains the same for drugs other than Ayurvedic drugs. Underreporting of adverse drug reactions is common in Nepal as well. There are many factors that can affect the reporting of adverse drug reactions like lack of knowledge and perception among healthcare professionals, shown by a systematic review²⁹. A study done in Nepal also suggests that there are reasons like availability of less time for these activities. Also, a lack of confidence to certify the occurrence of any adverse drug reactions has been listed as a reason for underreporting^30,31.

There is an adulteration of heavy metals in herbal medicines and chances of microbial contamination, which may deteriorate the quality of herbal products³². Most herbal medicines are provided by traditional herbal practitioners in different regions of the nation, which makes it difficult to assesses severe effects of easily accessible herbal medicines in every corner of the nation. In addition, there may be problems in the identification of medicinal plants, since all the medicinal herbs present in Nepal are yet to be explored.

The study done by Poudel et al. has proposed that there is an enormous requirement for the advancement of regulations for the screening of herbal fixed dose combinations (FDCs) to ensure their safety, efficacy and optimum utilization³³. Regardless of the uncertain health advantages of the herbal FDC products, these have become common practice in developing countries³⁴.

Recommendations to overcome challenges

To overcoming existing challenges in Nepal, we suggest the following recommendations for herbal pharmacovigilance:

The proposed implementation of herbal pharmacovigilance centers can be conducted in a similar way to already existing pharmacovigilance centers that deal with allopathic medicines. Their implementation can be conducted via the DDA in collaboration with regional Ayurvedic centers, such as Naradevi Ayurvedic Hospital, Tribhuvan University Ayurvedic Hospital, and District Ayurvedic Hospitals. We recommend that Vigiflow software can be used³⁸, as per usual pharmacovigilance reporting practice, as this may be linked to the UMC. Pharmacists and Ayurvedic doctors can be mobilized for reporting and management of the software. The scope of the proposed herbal pharmacovigilance center can be expanded to consumer levels in households via consumer awareness programs, such as MedWatch³⁹ in the USA. This may help address the concerns of consumers’ non-prescriptive Ayurvedic medications at the community level.

The way forward

Globally, herbal medicines are extensively used in health care. Regardless of whether upheld by therapeutic science or basically by many years of use, treatment with herbal medicines will stay prominent. In the quest for an alternative to allopathic medicines and with more evidence-based findings, the use of herbal medicine will increase in the future. Successful implementation of herbal pharmacovigilance is essential for developing reliable information/database on the safety of herbal medicines. It is also essential for the improvement of appropriate guidelines to ensure their safety and effective use. There is an urgent need for educational intervention on adverse reactions with regard to herbal medicine. Continuing education programs are recommended to provide the clinical practitioner's environment to redesign their insight in this quickly growing public health concern.

Data availability

No data is associated with this article.