Adverse drug reaction is defined as "an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration and warrants prevention or specific treatment, or alteration of the dosage regimen, or withdrawal of the product" 1. The Thalidomide disaster in 1961 was the start of establishing the WHO Program for International Drug Monitoring, WHO promotes Pharmacovigilance at the country level by working in collaboration with the Monitoring Centre at Uppsala. More than 135 countries are the part of this program. This program not only enhances patient safety for use of medicines but also gives information about safe use and prevention and treatment of any Adverse Drug Reactions (ADRs). ADRs are responsible for significant morbidity and mortality 2, 3.

An unprecedented outbreak of pneumonia of unknown etiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus was identified as the causative agent 4. WHO declared COVID 19 as PANDEMIC on 12th March 2020 posing a high risk to countries with vulnerable systems 5. Hydroxychloroquine(HCQ) is a 4- aminoquinoline with immunosuppressive, antiautophagy and antimalarial activities. Initially it was used as antimalarial drug and it further extended to use in treatment of chronic rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. HCQ was permitted by US Food and Drug Administration(FDA) and it is also advocated by Indian council of Medical Research (ICMR) as preexposure prophylaxis for health care professional as well as high risk for household contacts who were in directly contact with the positive patient 3, 4.

There were many hotspots of COVID-19 which gave an idea to ICMR to start the strategy of giving HCQ prophylactically to all the high-risk community in COVID-19 positive area. So, whenever we give drug in community setting as prophylaxis, several problems may arise including risk of adverse reactions and its monitoring 6. The data published by ICMR on assessment of HCQ prophylaxis among 1323 HCWs indicated mild adverse effects such as headache, nausea, abdominal pain, vomiting, hypoglycaemia and some cardiovascular effects 7. However, data to support the use of HCQ and CQ for COVID-19 are limited and inconclusive 8. FDA has given HCQ as “Emergency use authorization” (EUA) so it was therefore ideal to document and analyse the adverse reaction after taking HCQ prophylactically. In this study we aimed to study the ADR of HCQ in prophylactic doses for COVID-19 among the health care professionals.

Table 1

Characteristic	Number
Age in years (Median)
<30	26
30-50	103
>50	45
• Gender
Male	112
Female	62
Comorbidities
Hypertension	34
Diabetes	11
Ischaemic heart disease	4
Kidney disease	2
Liver disease	2
Others	6

Table 3

Adverse drug Reaction		Age group		Total	Chi square value	P value
		< 50 years	> 50 years
Headache	Present	35	5	40	4.83	0.027 *
	Absent	94	40	134
Nausea	Present	13	4	17	0.05	0.81
	Absent	116	41	157
Loose stools	Present	10	2	12	0.56	0.45
	Absent	119	43	162
Dizziness	Present	9	2	11	0.36	0.54
	Absent	120	43	163
Abdominal cramps	Present	7	1	8	0.78	0.37
	Absent	122	44	166

*In this table we have taken the age group as <50 years and >50 years of age to determine ADR in relation to the age*

Figure 1

Figure 2

Hydroxychloroquine is widely used antimalarial and autoimmune disease drug. Recently, Chloroquine has been reported as a broad-spectrum antiviral drug. At present no effective treatment or vaccine is available for COVID-19. FDA has given EUA for some of the drugs for its use in pandemic and HCQ was one of them for which WHO gave EUA for its use in preexposure prophylaxis as well as for treatment of positive Covid patient. HCQ was also approved by ICMR for the chemoprophylaxis for COVID-19 for the health care professionals working in COVID-19 cases and also for the high risk contacts. There are very limited clinical trials that studied the possible antiviral effect and efficacy of HCQ in treatment of COVID-19 participants 9, 10, 11. Also, there was insufficient data available in published literature regarding the safety and efficacy of HCQ as preexposure prophylaxis.

The CDC panel did not recommend using a high dosage of the drug (i.e. 600 mg twice daily for ten days), because increasing the dose may have unwanted adverse outcomes that should be carefully monitored. These doses were higher than recommended for malaria chemoprophylaxis, and clinical trials are needed to establish safety and efficacy 12. However, some adverse drug reaction may not be due to the direct effect of the drug. It can be due to the stressful condition of working in COVID or it can be due to the dehydrating condition in PPE or due to some drug-drug interactions. Also, HCQ can cause severe hypoglycemia including loss of consciousness that could be life threatening in participants treated with or without antidiabetic medications. So, blood sugar of such participants and drug-drug interactions should be closely monitored by physicians in such vulnerable individuals. A systematic review study done by Xabier Garcia Albeniz et al showed that a low rate of serious adverse effects comprised mainly of mild gastrointestinal side effects 13. Age more than 50 years and with comorbidities are risk factors for severe adverse drug reactions, so these participants should be closely monitored while giving HCQ. A similar study was done by Elettra Fallani MSc et al. reported that most frequent ADRs reported in 2020 were diarrhea, prolonged QT interval, and hypertransaminasemia which was significantly higher than 2019 and specific for COVID-19 subjects treated with hydroxychloroquine 14.

In our study, as shown in Figure No.1 and Table No. 1, we included 174 participants of age groups <30, 30-50, >50 years of age. Out of this 112 were males and 62 females. Figure No.2 shows the associated comorbidities of the participants. Table No. 2 and 3 showed that headache was the most common adverse drug reaction and it was significant in the age group of less than 50 years of age. There is no such reliable or sufficient data that this headache is due to the HCQ itself due to the limitations of our study which included a small sample size for the adverse drug reactions. Also this study cannot be generalized to the general public even though it may be expected that health care professionals are more aware of the symptoms and are likely to report even the slightest of adverse drug reaction correctly. Some additional staff training on pharmacovigilance, institution of a detailed questionnaire to elicit only relevant adverse drug reactions is needed. So, to ensure the safety and efficacy of HCQ larger studies with big sample size for the preexposure prophylaxis among the health care professionals and with high-risk contacts should be carried out. However, if we take the treatment part of HCQ in COVID-19, many studies have been done to prove its effectiveness in the pandemic time. A study done by Mirjam Hempenius concluded that the quality of observational studies done to prove the effectiveness of HCQ for the treatment of COVID-19 symptoms was heterogeneous. In high unmet medical needs, where the pandemic hits the general public, observational studies have always been the sole tool to provide timely evidence which are valuable but provided that the evidence is of high quality 15.

Almost 1/3rd of the participants reported adverse effects. So utmost care should be taken before using HCQ prophylactically in health care professionals working in COVID-19.