ADRs (Adverse Drug Reactions) related to ayurvedic medicine used in COVID-19

: Background: Adverse Drug Reaction (ADR) is a response to a drug which is noxious and unintended, and which occurs at therapeutic doses. Due to a lack of systematic documentation regarding the occurrence of ADR and other issues to the safety of Ayurvedic medicines, concern about the traditional medical system has recently been increased. This is seen by a rise in safety reports and misunderstandings, especially in the recent pandemic. Objective: To monitor and analyse the suspected ADR to Ayurvedic medicines used in COVID-19. Materials and Methods : ADR monitoring data was collected through spontaneous and intensive method for a span of 2-year (April 2020 to April 2022) during the peak days of COVID-19 from the IPvCC of the National Institute of Ayurveda, Jaipur, India. The IPvCC Program is governed by NPvCC under the supervision of Ministry of AYUSH, Govt. of India, New Delhi. NPvCC is ultimately responsible to monitor and recommend regulatory interventions on the generated national ADR data. Result : In a span of two-year, 142 adverse drug events were reported out of which 17 were confirmed as ADR due to suspected Ayurvedic drugs. Conclusion: Overall review demonstrated that Ayurveda has traditionally been placed a strong emphasis on treatments that aim to heal the underlying illness while preventing the development of new illnesses.


Introduction:
Coronavirus disease (COVID-19) is a contagious illness caused by the SARS-CoV-2 virus.This virus was previously unknown to medical science. 1 The first case of COVID-19 in India was reported on January 30, 2020, and it quickly spread throughout the country. 2 The severity of COVID-19 had brought attention to the challenges facing the healthcare system, the same rapid disease outbreaks called for the fusion of traditional knowledge systems and modern medicine.The World Health Organisation (WHO) was constantly monitoring the disease pandemic and updating the information available regarding its spread, mortality, and morbidity. 3om the Ayurvedic point of view, COVID-19 comes under janapadodhwamsa vikara (epidemic disease).The concept of an epidemic diseases is described in Charaka Samhita .4With recommended guidelines of AYUSH Ministry, Govt. of India, the use of Ayurvedic medicine for Covid-19 was increased.However, the widespread misconception about herbal medications is that they are fully risk-free. 5This delusion has encouraged widespread self-medication worldwide, frequently with unfavorable outcomes and side-effect consequences.Consumers may have negative repercussions including adverse drug reactions (ADRs) and drug-drug interactions if they are not informed about how to use medicine properly.In order to protect the public's health, practitioners and healthcare professionals in ASU&H hospitals must now use extreme caution when it comes to drug safety monitoring. 6Since pharmacovigilance is all about the science and activities relating to the detection, assessment, understanding and prevention of adverse effects of drugs or any other possible drug related problem 7 and ADR are the reaction that may be due to the drug itself or one of its metabolites, from an interaction between two or more drugs or between a drug and food.According to WHO "ADR is defined as a response to a drug that is noxious and unintended, and that occurs at doses normally used in human for the prophylaxis's, diagnosis or therapy of disease or for the modification of physiological function" 6,7 .Suspected ADR means that while a causal relationship in the individual case has not been proven, a relationship is initially assumed to exist between the medicine taken and the symptoms or diagnosis. 7

Material and Methods:
The Ministry of AYUSH, Govt. of India, began the clinical trials of Ayurvedic medicines for treating and preventing the novel coronavirus that causes COVID-19.The clinical trials of Ayush medicines for COVID-19 was a joint initiative of three organisations viz. the Ministry of AYUSH, the Ministry of Health & Family Welfare and Council of Scientific and Industrial Research (CSIR) with technical support of Indian Council of Medical Research (ICMR). 8,9,10yurvedic medicines such as Ashwagandha, Yashtimadhu, Guduchi Pippali, Guduchi Ghanavati (Samshamani Vati), Ayush kwath, and a poly herbal formulation (Ayush-64) are being used in the clinical trials involving health workers and those working in COVID-19 high-risk areas. 11,12 the current study, ADR monitoring data was collected through spontaneous and intensive method for a span of 2-year (April 2020 to April 2022) during the peak days of COVID-19 from the Intermediary Pharmacovigilance Coordination Centre (IPvCC) of the National Institute of Ayurveda, Jaipur, India.The IPvCC Program is governed by National Pharmacovigilance Coordination Centre (NPvCC) under the supervision of Ministry of AYUSH, Govt.
of India, New Delhi.NPvCC is ultimately responsible to monitor and recommend regulatory interventions on the generated national ADR data. 13,14sult: The incidence and characteristics of ADR to Ayurvedic medication have been recorded in the current data during the period of COVID-19.This would assist in creating a number of measures to increase pharmacovigilance in Ayurveda.One year's worth of 142 reported adverse medication reactions, resulted in 17 identified as suspected drug-related ADRs (Table 1).These cases involve three ADRs reported from AYUSH-64 with complaints of headache, nausea, and dizziness.One ADR with complaints of elation, flatulence, and headache was recorded from Samsamni vati.Four ADRs were reported from Ashwagandha Churna with the typical complaints of headache, bloating in the abdomen, and loose motion.One ADR recorded from Chyavanprash, Five ADRs reported from homemade decoction, and Ayush kwath.Two ADRs reported from yashtimadhu churna.The suspected drug ADR was assessed using contemporary criteria.

Discussion:
It has been noted that only a small number of Ayurvedic medications are used by patients as over the counter (OTC) medications.In a variety of health care facilities, these OTCs are offered for sale as either herbal medications or herbal products.Some adverse events have also been recorded as a result of insufficient regulatory measures, mostly uncontrolled distribution methods, such as mail order or online sales, poor quality control systems, and incorrect administration. 15searchers from reputable national research organisations have discovered that the polyherbal formulation AYUSH-64 can be used as a supplemental treatment for asymptomatic, mild and moderate Covid-19 infection. 16At the National Institute of Nutrition in Hyderabad (NIN-ICMR), a pre-clinical investigation was also carried out to assess the immune-modulatory potential and safety/ toxicity of the AYUSH Kwatha formulation.The Ministry has conducted nationwide communitybased studies through its Research Councils (CCRAS) and instructed these National Institutes for mass distribution of AYUSH-64 to asymptomatic, mild to moderate COVID-19 patients in home isolation during the second COVID-19 outbreak in India based on the potential leads identified through various studies.
A clinical trial comparing the efficacy/safety of Ashwagandha with Hydroxychloroquine Sulphate (HCQ) for COVID-19 Prophylaxis in high-risk healthcare workers showed that Ashwagandha is non-inferior to Hydroxychloroquine in terms of prophylactic effect against COVID-19.Further, it has a superior safety profile as significantly less adverse events were reported in the Ashwagandha group compared to HCQ group.
As seen in clinical experiments conducted during the COVID-19 pandemic, the formulation known as Guduchi Ghana vati or Samshamani Vati, which is made from aqueous extracts of the stem of Tinospora cordifolia, had a favourable impact on people's immune system and general well-being.Most study participants consumed guduchi ghan vati.This satisfactory drug compliance may depend on the dose, dosage form, and palatability of the formula.Gastrointestinal issues were infrequently observed as ADR/AE in patients and were managed with dietary advice, modifications to medication administration schedules, etc.No severe ADRs or serious AEs that necessitated hospitalisation occurred with guduchi.
The results support the prophylaxis potential of Chyawanprash as one of the preventive remedies for COVID-19.It has been found effective and safe among the high-risk health care workers and apparently healthy individuals in reducing the incidence of COVID-19.The current understanding of COVID-19 indicates that good immune status is vital for prevention and safeguard from disease progression.Ayush interventions can certainly play a pivotal role in the modulation of immune system thereby providing prophylaxis against COVID-19 and prevention of disease progression in COVID-19 patients.

Conclusion:
Based on the study outcomes of the clinical trials undertaken during COVID-19 pandemic, these Ayush medicines are proposed for COVID-19 prophylaxis and management.Further, the safety of these interventions is not an issue as such as these interventions are routinely used in the clinical practice since ages.Moreover, there is wide-spread acceptance regarding the effectiveness and safety of Ayush interventions in common ailments among the masses.When a drug is taken in proper form, dose, time and with specific Anupana, then there is less chance of causing any ADR. 16

Source of fund: (if any): Nil
Pharmacovigilance program for Ayush medicine is coordinated by NPvCC under the supervision of Ministry of AYUSH, Govt. of India, New Delhi that monitors the ADRs of traditional medicine and recommend regulatory interventions based on the generated ADR data.NPvCC has also launched specific suspected ADR Reporting Form for Drugs used in Covid-19.

Table 1 :
Data related to ADR