PHARMACOVIGILANCE IN THE ERA OF COVID-19: A CONCISE REVIEW OF THE CURRENT SCENARIO, IMPLICATIONS, AND CHALLENGES
Keywords:Pharmacovigilance, ADR reporting, COVID-19, Drug repurposing, Hydroxychloroquine
The pandemic of Coronavirus Disease 2019 (COVID-19) has now affected the entire globe which was first surfaced in China in December 2019. In absence of effective therapy to manage COVID-19, repurposed therapies were being used to manage the condition. In view of an urgent need for definitive therapy, multiple repurposed drugs, and investigational drug candidates are being tried in clinical trials which may lead to the emergence of unknown short term and long term adverse drug reactions (ADRs), and hence it is crucial to assess the safety of the tried therapeutic interventions. The lag in the pharmacovigilance activities in the midst of this pandemic fosters under-reporting of ADRs. Difficulty in causality assessment due to factors like wide variations in clinical presentation, concomitant use of multiple drugs, associated comorbidities, drug-drug and drug-disease interaction which forestalls the appropriate causality assessment. Hydroxychloroquine, a repurposed antimalarial drug has been a part of hue and cry at present because of its in-question safety in patients with cardiac disorders. National and International Drug monitoring centers have stressed upon reporting of ADRs and to boost up the process and come up with various recommendations. We can overcome these issues by working cohesively, motivating HCPs and patients to report ADRs electronically, and by setting up dedicated pharmacovigilance rapid response team to tackle the issues at the earliest.
Jin YH, Cai L, Cheng ZS, Cheng H, Deng T, Fan YP, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res 2020;7:4.
World Health Organization (WHO)[internet]. Coronavirus (COVID-19) events as they happen. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen. [Last accessed on 16 Jul 2020]
Niharika D, Niharika B, Aishwarya T, Nikitha A, Butool R, Ibrahim M, et al. Coronavirus-a virus in learning. Int J Curr Pharm Res 2020;12:7–10.
World Health Organization. WHO Coronavirus Disease (COVID-19) Dashboard. Available from: https://covid19.who.int/ [Last accessed on 16 Jul 2020]
World Health Organization. What are the symptoms of COVID-19? Q and A on coronaviruses (COVID-19): WHO TEAM health emergencies preparedness and response. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub/q-a-detail/coronavirus-disease-covid-19 [Last accessed on 18 Jul 2020]
Navdeep K, Simranpreet K, Manjinder K. A review on the fifth pandemic: coronavirus. Asian J Pharm Clin Res 2020;13:25–31.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, China. JAMA 2020;323:1061–9.
Kumar T, Dutta S, Sahai R, Khasbage S, Kumar R, Banerjee S. Dermatological manifestations of COVID-19: a review based on existing reports. Int J Curr Res Rev 2020;12:65–8.
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579:270-3.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult in patients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054–62.
Chung M, Bernheim A, Mei X, Zhang N, Huang M, Zeng X, et al. CT imaging features of 2019 novel coronavirus (2019-nCoV). Radiology 2020;295:202–7.
Shi H, Han X, Zheng C. Evolution of CT manifestations in a patient recovered from 2019 novel coronavirus (2019-nCoV) pneumonia in Wuhan, China. Radiology 2020;295:20.
Clinicaltrialsarena.com. [Homepage in internet]. Coronavirus treatment: Vaccines/drugs in the pipeline for COVID-19. Available from: https://www.clinicaltrialsarena.com/analysis/coronavirus-mers-cov-drugs/ [Last accessed on 20 Jul 2020]
World Health Organization [Internet]. Pharmacovigilance; Essential medicines and health products. Available from: https://www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/ [Last accessed on 20 Jul 2020]
WHO pharmacovigilance indicators: a practical manual for the assessment of pharmacovigilance systems. World Health Organization; 2015. Available from: https://www.who.int/medicines/areas/quality_safety/safety_efficacy/EMP_PV_Indicators_web_ready_v2.pdf [Last accessed on 20 Jul 2020]
Kumar L. Pharmacovigilance/Reporting adverse drug reactions: an approach to enhance health surveillance and extending market share by minimizing the chances of drug withdrawals. Int J Pharm Pharm Sci 2015;7:1–7.
Dutta S. Pharmacovigilance in India: Evolution and change in scenario in India. Int J Sci Res 2018;7:976-8.
Indian Pharmacopoeia Commission. Pharmacovigilance Programme of India; Network: Data Flow. Available from: https://www.ipc.gov.in/PvPI/about.html [Last accessed on 22 Jul 2020]
Uppsala Reports. Pharmacovigilance in the age of covid-19; Uppsala Monitoring Centre. Available from: https://www.uppsalareports.org/articles/pharmacovigilance-in-the-age-of-covid-19/ [Last accessed on 24 Jul 2020]
Kalaiselvan V, Thota P, Singh GN. Pharmacovigilance programme of India: recent developments and future perspectives. Indian J Pharmacol 2016;48:624-8.
Masurkar P. A need of better pharmacovigilance system in India. Asian J Pharm Clin Res 2017;10:22–4.
Uppsala Monitoring Centre. VigiLyze; Get the answers you need. Available from: https://www.who-umc.org/vigibase/vigilyze/ [Last accessed on 25 Jul 2020]
Uppsala Monitoring Centre. Descriptive analysis of COVID-19-related spontaneous reports from VigiBase: interim results. WHO Collaborating Centre for International Drug Monitoring, dated 22 Jul 2020. Available from: https://www.who.int/ medicines/regulation/medicines-safety/COVID19-PV-update9.pdf?ua=1 [Last accessed on 28 Jul 2020]
Uppsala Monitoring Centre. Pharmacovigilance and COVID-19; Medicines safety during COVID-19. Available from: https://www.who-umc.org/global-pharmacovigilance/covid-19/ [Last accessed on 29 Jul 2020]
Indian Pharmacopoeia Commission. Pharmacovigilance Programme of India; National Coordination Centre, Indian Pharmacopoeia Commission: ADR Reporting Form. Available from: https://www.ipc.gov.in/PvPI/adr.html [Last accessed on 29 Jul 2020].
Indian Pharmacopoeia Commission. Pharmacovigilance Programme of India (PvPI) Updates; Suspected ADR Reporting Form for Drugs used in Covid-19. Available from: https://www.ipc.gov.in/images/Suspected_ADR_Reporting_Form-converted_2020.pdf [Last accessed on 30 Jul 2020]
Lee J. Market watch. Trump makes the case for chloroquine as a COVID-19 treatment, though it has not been approved by the FDA for this illness 2020 Mar 22. Available from: https://www.marketwatch.com/story/trump-makes-the-case-for-chloroquine-as-a-covid-19-treatment-though-it-has-not-been-approved-by-the-fda-for-this-illness-2020-03-19 [Last accessed on 01 Aug 2020]
Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020;71:732-9.
Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discovery 2020;6:16.
Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 2020;14:72-3.
Chen Z, Hu J, Zhang Z, Jiang S, Han S, Yan D, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. medRxiv; 2020. https://doi.org/10.1101/2020.03.22.20040758.
Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020;56:105949.
Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Sevestre J, et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: a pilot observational study. Travel Med Infect Dis 2020;34:101663.
Revised advisory on the use of Hydroxychloroquine (HCQ) as prophylaxis for COVID-19 infection (in supersession of the previous advisory dated 23rd March, 2020). Ministry of Health and Family Welfare, GOI. Available from: https://www.mohfw.gov.in/pdf/RevisedadvisoryontheuseofhydroxychloroquineasprophylaxisforSARSCOVID19infection.pdf [Last accessed on 02 Aug 2020]
National Institute of Health. Chloroquine or Hydroxychloroquine. COVID-19 Treatment Guidelines Panel. Available from: https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/chloroquine-or-hydroxychloroquine-with-or-without-azithromycin/ [Last accessed on 02 Mar 2021]
Magagnoli J, Narendran S, Pereira F, Cummings TH, Hardin JW, Sutton SS, et al. Outcomes of hydroxychloroquine usage in united states veterans hospitalized with COVID-19. Med (N Y). 2020. DOI:10.1016/j.medj.2020.06.001
World Health Organization. Q and A: Hydroxychloroquine and COVID-19. Available from: https://www.who.int/news-room/q-a-detail/q-a-hydroxychloroquine-and-covid-19 [Last accessed on 04 Aug 2020]
Institute for Safe Medication Practices. Patient taking hydroxychloroquine right after discontinuing azithromycin develops QTc prolongation and cardiac arrest. ISMP Medication Safety Alert! Acute Care. Available from: https://ismp.org/acute-care/special-edition-medication-safety-alert-april-9-2020/covid-19#paragraph-1478. [Last accessed on 05 Aug 2020]
American College of Cardiology: Ventricular Arrhythmia Risk Due to Hydroxychloroquine-Azithromycin Treatment For COVID-19. Available from: https://www.acc.org/latest-in-cardiology/articles/2020/03/27/14/00/ventricular-arrhythmia-risk-due-to-hydroxychloroquine-azithromycin-treatment-for-covid-19 [Last accessed on 06 Aug 2020]
Chatterjee P, Anand T, Singh KJ, Rasaily R, Singh R, Das S, et al. Healthcare workers and SARS-CoV-2 infection in India: a case-control investigation in the time of COVID-19. Indian J Med Res 2020;151:459-67.
Indian Council of Medical Research. Advisory on the use of Hydroxychloroquine as prophylaxis for SARSCoV2 infection. The national task force for COVID-19; Ministry of Health and Family Welfare, GOI. Available from: https://www.mohfw.gov.in/pdf/AdvisoryontheuseofHydroxychloroquinasprophylaxisforSARSCoV2infection.pdf [Last accessed on 06 Aug 2020]
Desai MK. Pharmacovigilance and assessment of drug safety reports during COVID 19. Perspect Clin Res 2020;11:128-31.
Ayurveda’s immunity boosting measures for self-care during COVID 19 crisis. Ministry of AYUSH; Ministry of Health and Family Welfare, GOI. Available from: https://www.mohfw.gov.in/pdf/ImmunityBoostingAYUSHAdvisory.pdf [Last accessed on 06 Aug 2020]
Roy V, Gupta M, Ghosh RK. Perception, attitude and usage of complementary and alternative medicine among doctors and patients in a tertiary care hospital in India. Indian J Pharmacol 2015;47:137‐42.
Sharma A, Agrawal A. Complementary and alternative medicine (CAM) use among patients presenting in out-patient department at tertiary care teaching hospital in Southern Rajasthan, India-a questionnaire based study. Altern Integ Med 2015;4. DOI:10.4172/2327-5162.1000187.