Metamizole as the Most Consumed Analgesic in Brazil During the COVID-19 Pandemic: Why Does It Matter?

Abstract

Background: During the COVID-19 pandemic, analgesic use increased significantly, primarily due to self-medication for symptom relief. In Brazil, metamizole (dipyrone) is widely used despite international restrictions, highlighting the importance of evaluating its consumption patterns. Objective: To assess analgesic use during the COVID-19 pandemic. Methods: This cross-sectional study was conducted via a household survey in Alegre, Espírito Santo, Brazil. Structured questionnaires were used to collect data on sociodemographic characteristics, clinical conditions, and medication use. Descriptive statistics included frequency distributions, medians, and interquartile ranges. Factors associated with analgesic use were analyzed using Poisson regression with robust variance. Results: Among 694 participants, 31.6% reported using analgesics, with metamizole being the most frequently used (87.2%), followed by acetaminophen (paracetamol) (24.7%). Analgesic use was more common among individuals with polypharmacy, lower self-reported quality of life, better self-perceived health, and recent dental appointments. Conclusions: A high prevalence of analgesic use was identified, particularly of metamizole. Given its over-the-counter availability and growing evidence of risks such as liver injury and other adverse events, ongoing monitoring is essential. These findings underscore the need for public health strategies and pharmacist involvement to promote the rational and safe use of analgesics.

1. Introduction

Analgesics play a crucial role in managing pain and reducing fever and are among the most widely used medications worldwide. In Brazil, metamizole (dipyrone) and acetaminophen (paracetamol) are the most used analgesics [1]. These drugs are crucial in alleviating pain associated with various conditions, including flu-like symptoms, COVID-19 manifestations, and post-vaccination reactions, thereby reinforcing their importance, particularly during pandemics [2,3].

In the context of rational medicine use, it is essential to distinguish between medications that require a prescription and those classified as over-the-counter (OTC), which can be purchased without a prescription. The wide availability of OTC drugs facilitates self-medication, often guided by prior experience, advice from relatives or friends, or information accessed online [4,5].

While OTC drugs offer convenience and quick relief, their easy access can lead to inappropriate use. Such misuse may pose significant risks, including masking underlying conditions, adverse drug interactions, increased toxicity, and reduced therapeutic effectiveness. Additionally, prolonged use or incorrect dosages can worsen clinical conditions and compromise patient safety. Therefore, self-medication, often driven by the urgency to relieve symptoms, represents a substantial public health concern [6].

This issue became even more pronounced during the COVID-19 pandemic. The overlap between common flu symptoms, such as fever, cough, and body aches, and those of SARS-CoV-2 led many individuals to use analgesics for symptomatic relief [7]. In many cases, this resulted in self-medication before diagnostic confirmation, potentially delaying appropriate treatment [8].

Within this scenario, pharmacists have emerged as key healthcare professionals in promoting the safe use of medications. Over recent decades, their role in public health has expanded significantly. With specialized training, pharmacists provide essential guidance to patients, helping to prevent adverse events and promote the rational use of medicines, especially crucial during health crises [9,10,11].

Therefore, assessing the prevalence and patterns of analgesic use during the COVID-19 pandemic is essential for enhancing pharmaceutical care. These data support the identification of inappropriate use, guide interventions to promote rational medication practices, and reinforce the pharmacist’s role in protecting public health.

2. Results

A total of 694 individuals were interviewed, of whom 72.9% were women and 43.4% were aged 60 years or older. The median age was 56 years (interquartile range [IQR]: 37.0–67.0). Approximately 47% of participants self-identified as White, 69.6% lived in the municipal seat of Alegre, and 43.3% were married. Regarding religion, 49.6% identified as Catholic. In terms of education, 30.7% had completed high school, and 47.1% reported a family income of up to one minimum wage (

Table 1. Sociodemographic characteristics of the sample.

Variables	Total
Age in years (median. IQR)	56.0 (37.0–67.0)
Age group (n. %)
<60 years	390 (56.6)
60 years or older	299 (43.4)
Sex (n. %)
Female	506 (72.9)
Male	188 (27.1)
Race (n. %)
White	329 (47.5)
Brown	235 (34.0)
Others	128 (18.5)
Marital status (n. %)
Single	183 (26.4)
Married	300 (43.3)
Others	210 (30.3)
Education (n. %)
Up to incomplete primary school	264 (38.0)
Complete primary education	88 (12.7)
High school incomplete	42 (6.1)
Complete high school	213 (30.7)
Technical or higher	87 (12.5)
Income (n. %)
Up to one minimum wage	308 (47.1)
Up to two minimum wages	276 (42.2)
More than two minimum wages	70 (10.7)

Caption: Most participants were women (72.9%) and under 60 years of age, with low income and education levels, reflecting the typical sociodemographic profile of the local population surveyed. IQR: Interquartile range; n: number of interviewees per variable; %: percentage of the variable to the total number of interviewees.

).

Regarding health characteristics (

Table 2. Clinical and health characteristics of the sample.

Variables	Total
Quality of life (median. IQR)	0.884 (0.817–1.000)
Self-rated health (n. %)
Very good/good	363 (52.3)
Regular	276 (39.8)
Bad/very bad	55 (7.9)
Classification BMI (n. %)
Normal weight	200 (31.0)
Underweight	23 (3.6)
Overweight	244 (37.8)
Obesity	178 (27.6)
Do regular physical activity (n. %)
Yes	245 (35.4)
No	448 (64.6)
Use of alcohol (n. %)
Yes	176 (25.4)
No	516 (74.6)
Smoker (n. %)
Yes	94 (13.6)
No	599 (86.4)
Hours of sleep per day (n. %)
<6 h	162 (23.4)
6 to 7 h	189 (27.4)
7 to 8 h	227 (32.8)
>8 h	113 (16.4)
Medical appointments in the last year (n. %)
Yes	550 (79.6)
No	141 (20.4)
Dental appointments in the last year (n. %)
Yes	260 (38.9)
No	409 (61.1)
Consultations with a nutritionist in the last year (n. %)
Yes	61 (9.3)
No	594 (90.7)
Hospitalizations in the last year (n. %)
Yes	91 (13.1)
No	602 (86.9)
Private health insurance (n. %)
Yes	157 (22.6)
No	537 (77.4)
Used Municipal Basic Pharmacy in the last year (n. %)
Yes	367 (53.4)
No	320 (46.6)
Used a private pharmacy in the last year (n. %)
Yes	608 (87.7)
No	85 (12.3)
Self-medication (n. %)
Yes	454 (69.4)
No	200 (30.6)
Polypharmacy (n. %)
No polypharmacy	241 (34.8)
Minor polypharmacy (2 to 4 drugs)	311 (44.9)
Major polypharmacy (5 or more drugs)	140 (20.2)
Medication adherence problem (n. %)
Yes	164 (25.8)
No	471 (74.2)
Use of medicinal plants (n. %)
Yes	269 (39.7)
No	409 (60.3)

Caption: A significant proportion of participants reported good health perception, despite the high prevalence of overweight/obesity and low levels of physical activity, indicating potential risk factors for analgesic use. IQR: Interquartile range; n: number of interviewees per variable; %: percentage of the variable to the total number of interviewees.

), 52.3% of participants rated their health as very good or good, with a median quality of life score of 0.884 (IQR: 0.817–1.000). Based on BMI classification, 38% were overweight and 28% were obese. The majority (65%) reported not engaging in regular physical activity, while 25.4% reported alcohol use and 13.6% identified as smokers. Approximately 32.8% reported sleeping between 7 and 8 h per day.

In the previous year, 79.6% of participants had a medical consultation, 38.9% had visited a dentist, 9.3% had consulted a nutritionist, and 13.1% had been hospitalized. Additionally, 77.4% did not have private health insurance. Use of the Municipal Basic Pharmacy was reported by 53.4%, while 87.7% purchased medications from private pharmacies.

Self-medication was reported by 69.4% of participants. Minor polypharmacy (defined as the use of two to four medications) was observed in 44.9% of the sample, while major polypharmacy (five or more medications) was reported by 20.2%. Furthermore, 25.8% reported difficulties with medication adherence, and 39.7% used medicinal plants. A confirmed diagnosis of COVID-19 was reported by 18.8% of participants (n = 129).

Among the 694 respondents, 219 (31.6%) reported using analgesics (ATC code: N02), while 36 individuals (5.2%) reported using anti-inflammatory and anti-rheumatic drugs (ATC code: M01) (Supplemental Table S1). Metamizole was the most frequently used analgesic, accounting for 27.5% of total consumption, followed by acetaminophen at 7.8%. Both metamizole and acetaminophen were also commonly used in combination with other active ingredients (

Table 3. Analgesics most consumed during the COVID-19 pandemic.

Analgesic Medicines (N02)	Total	(%) Total n = 694	(%) Analgesics n = 219
Metamizole (dipyrone)	191	27.5%	87.2%
Acetaminophen (paracetamol)	54	7.8%	24.7%
Metamizole monohydrate + orphenadrine citrate + caffeine anhydrous	25	3.6%	11.4%
Phenylephrine hydrochloride + acetaminophen + chlorpheniramine maleate	18	2.6%	8.2%
Caffeine + carisoprodol + diclofenac sodium + acetaminophen	17	2.4%	7.8%

Caption: Among participants who used analgesics, 87.2% reported using metamizole (dipyrone), highlighting its predominant role in pain management in Brazil, despite its restriction or ban in several countries due to safety concerns. Metamizole = dipyrone; Acetaminophen = paracetamol.

).

During the COVID-19 pandemic, several factors were significantly associated with analgesic use (

Table 4. Factors associated with analgesic consumption during the COVID-19 pandemic.

Variables	PR	(95% CI)	p-Value
Self-rated health
Bad/very bad	1
Regular	1.29	(0.82–2.03)	0.263
Very good/good	1.94	(1.24–3.02)	0.004
Dentist appointment
No	1
Yes	1.32	(1.06–1.63)	0.011
Polypharmacy
No	1
Yes–Minor	1.82	(1.36–2.45)	<0.001
Yes–Major	2.43	(1.76–3.34)	<0.001
Quality of life
0.885 a 1.000	1
−0.2 a 0.884	1.52	(1.19–1.93)	0.001

Caption: Positive associations were observed with polypharmacy, better self-rated health, dental consultations, and lower quality of life scores, suggesting that both clinical and behavioral factors influence analgesic use. PR: prevalence ratio; CI: confidence interval.

). Participants who rated their health as very good or good had a higher prevalence of analgesic use compared to those who rated their health as poor or very poor (Prevalence Ratio [PR] = 1.94; 95% CI: 1.24–3.02; p = 0.004). Those who had visited a dentist in the previous year were also more likely to use analgesics (PR = 1.32; 95% CI: 1.06–1.63; p = 0.011).

Polypharmacy was strongly associated with analgesic use. Participants with major polypharmacy (five or more medications) had 2.43 times the prevalence of analgesic use compared to those without polypharmacy (95% CI: 1.76–3.34; p < 0.001). Minor polypharmacy was also associated with increased use (PR = 1.82; 95% CI: 1.36–2.45; p < 0.001).

Additionally, quality of life was inversely associated with analgesic use: individuals with EQ-5D scores below 0.885 had a higher prevalence of analgesic consumption (PR = 1.52; 95% CI: 1.19–1.93; p = 0.001), suggesting that lower perceived quality of life may be linked to greater need for pain management.

3. Discussion

Among the 694 participants surveyed, 219 (31.5%) reported using analgesics, indicating a considerable prevalence of consumption. Metamizole was the most frequently used analgesic, with 191 participants (87.2%) reporting its use as a single agent. When including combinations containing metamizole, such as metamizole monohydrate with orphenadrine citrate and caffeine anhydrous (25 reports), the total number of users rises to 215, representing 98.1% of all analgesic users. Acetaminophen ranked second, with 54 reports (24.7%) as a single drug. When combinations such as phenylephrine hydrochloride + acetaminophen + chlorpheniramine maleate (18 cases) and caffeine + carisoprodol + diclofenac sodium + acetaminophen (17 cases) are included, total use reaches 89, or 40.6% of all analgesic consumption. These findings highlight the predominance of analgesic use in the population, particularly of metamizole and acetaminophen, both widely used to relieve pain and fever.

According to the Pharmaceutical Market Statistical Yearbook, published by the National Health Surveillance Agency (ANVISA) through the Medicines Market Regulation Chamber (CMED), the most commonly used analgesics in Brazil between 2020 and 2023 were metamizole, acetaminophen, and ibuprofen. Metamizole stands out as one of the most widely consumed drugs in the country, available in various formulations and used both as a single agent and in combination with other compounds. Acetaminophen is also a popular choice, particularly for managing mild to moderate pain and fever, and is commonly prescribed to both adults and children. Ibuprofen, which has both analgesic and anti-inflammatory properties, is mainly indicated for musculoskeletal and febrile conditions. The widespread availability of these drugs reflects a population seeking effective and accessible options for managing pain and fever [12,13,14,15].

Metamizole and acetaminophen are available by prescription through public primary healthcare pharmacies in Brazil. Both are included in the National List of Essential Medicines (RENAME), which guides the provision of safe, effective, and essential treatments within the Brazilian Unified Health System (SUS). Their inclusion ensures access to widely used analgesics for managing pain and fever, while also promoting rational use under professional supervision [16]. In addition to their public-sector distribution, these medications are widely available over the counter in community pharmacies, further enhancing access. This widespread availability underscores the importance of pharmacist supervision to ensure the safe and appropriate use of these drugs [12,13,14,15,16].

During the COVID-19 pandemic, the widespread availability of metamizole and acetaminophen was accompanied by significant self-medication practices. Both medications were frequently used without professional supervision, often in response to common symptoms such as fever, headache, and musculoskeletal pain. This pattern likely reflects the population’s attempt to manage symptoms at home while avoiding healthcare facilities during periods of social distancing and system overload. The over-the-counter status of these drugs facilitated access but also underscored the need for greater guidance and pharmacovigilance regarding their use in the context of public health emergencies [7].

Despite being restricted in several countries due to rare but serious adverse effects, such as neutropenia and agranulocytosis [17,18], metamizole remains the most frequently used analgesic in Brazil [7,19]. Studies have consistently documented its extensive use for headache, muscle pain, and fever across different age groups [7,19]. In contrast to countries such as the United States, the United Kingdom, France, Canada, India, Japan, and Australia, where metamizole is banned or heavily restricted, it remains available and widely used in nations like Germany, Russia, Mexico, South America, and China. In these settings, health authorities consider its benefits to outweigh its risks when used under medical supervision. This regulatory divergence reflects differences in pharmacovigilance systems, cultural norms, and levels of risk tolerance [19,20].

More recently, metamizole has also been associated with an increased risk of liver injury compared to other non-narcotic analgesics, particularly acetaminophen (adjusted HR 1.69; 95% CI: 1.46–1.97), with consistent findings across sensitivity analyses using comparators such as naproxen [18]. Although cases of metamizole-induced liver injury were rarely reported prior to 2019, more than 50 cases have since been documented, including fatalities and liver transplants, prompting reassessments by regulatory agencies. Clinical presentations vary, ranging from hyperacute, hypersensitivity-like reactions to delayed hepatocellular or mixed injury after prolonged use. While most cases resolve upon drug withdrawal, hepatocellular injury with jaundice has been associated with a fatality rate of at least 10%. These findings highlight the need for caution, further research to better quantify the risk, and immediate drug discontinuation when liver toxicity is suspected [20].

Additionally, a review of 22 studies found that metamizole is consistently associated with an increased risk of agranulocytosis, although the magnitude of relative risk varied widely. While no significant association was identified with aplastic anemia, most case-control studies reported a higher risk of upper gastrointestinal bleeding. Overall, the literature shows variability in risk estimates and notable methodological limitations, underscoring the need for more rigorous research to accurately assess the safety profile of metamizole in comparison to other non-narcotic analgesics [17].

Acetaminophen also showed high prevalence in this study, with 54 instances reported as monotherapy and 89 in combination with other drugs, accounting for 40.6% of all analgesic use. Internationally, acetaminophen is among the most frequently used analgesics, particularly in countries where metamizole is unavailable. Its use for managing pain and fever, including post-COVID-19 symptoms such as muscle and joint pain, is well documented. However, excessive or prolonged use may lead to hepatotoxicity, emphasizing the need for clinical monitoring and careful administration [21].

Although both metamizole and acetaminophen are effective for symptom management, their use in infectious disease contexts, such as COVID-19, should be carefully monitored. Ongoing studies continue to evaluate the safety of metamizole, particularly due to its potential to cause neutropenia [19]. In the post-acute phase of COVID-19, analgesics such as acetaminophen remain commonly used to relieve persistent symptoms, including headache and myalgia [2].

This study also identified key factors associated with analgesic use during the COVID-19 pandemic, including polypharmacy, lower self-reported quality of life, dental consultations, and better self-perceived health. Individuals who used multiple medications, had lower EQ-5D scores, or underwent dental procedures were more likely to report analgesic use. Interestingly, a better self-perceived health status was also associated with increased analgesic use.

Although the observed association between better self-rated health and increased analgesic use may seem counterintuitive, it can be explained by the distinction between subjective health perception and objective health status. Self-rated health reflects a broad, personal appraisal of one’s condition, often shaped by cultural norms, expectations, and perceived symptom relief. In contrast, the EQ-5D instrument assesses specific domains, such as mobility, pain/discomfort, and anxiety/depression, that more directly capture functional limitations and disease burden. Previous studies have shown that individuals may report good health even when experiencing chronic symptoms or impairments, provided these are effectively managed with medication or other treatments [21,22,23]. In Brazil, analgesics such as metamizole and acetaminophen are low-cost, widely accessible, over-the-counter drugs and available in the public health system. Their availability and effectiveness in controlling pain may help individuals maintain functional capacity and carry out daily activities, contributing to a more favorable perception of health. Thus, the observed association likely reflects the role of analgesics in supporting symptom management and preserving autonomy, even in the presence of underlying health conditions [7,12,13,14,15,16,17].

Polypharmacy often reflects the management of multiple comorbidities, where pain control is a common therapeutic goal, helping to explain the higher prevalence of analgesic use [24]. Lower quality of life scores are typically associated with increased discomfort or pain, reinforcing the observed link to greater medication use [25]. The positive association between self-rated health and analgesic use may suggest that effective symptom control contributes to a more favorable health perception, an association previously reported in other conditions [23]. Furthermore, the association with dental consultations may reflect both the treatment of orofacial pain and improved access to healthcare services, which can facilitate appropriate analgesic prescribing [26].

Collectively, these findings underscore the importance of understanding the behavioral and clinical context surrounding analgesic use, particularly in pandemic settings, where health systems are strained and self-medication becomes more common.

The clinical relevance of our study lies in documenting the high consumption of metamizole in Brazil during the COVID-19 pandemic, a drug that is banned or restricted in many countries due to its potential for serious adverse effects. Understanding consumption patterns is crucial for pharmacovigilance and for informing public health strategies, particularly given the rise in self-medication observed during the pandemic [7,17,18,19,20].

This study has some limitations that should be acknowledged. First, as a cross-sectional analysis, it does not provide information on analgesic use trends before or after the COVID-19 pandemic, limiting conclusions about temporal changes in consumption patterns. Second, we lacked detailed data on the specific reasons for analgesic use, such as the types of pain or symptoms that prompted consumption. Additionally, we did not evaluate clinical outcomes related to analgesic use, including potential adverse effects such as liver or kidney dysfunction or gastrointestinal complications. These limitations restrict a more comprehensive understanding of both the determinants and consequences of analgesic use. Future research should address these gaps by exploring longitudinal trends, specific indications for use, and potential health outcomes to support informed public health strategies.

4. Materials and Methods

4.1. Study Design and Setting

This was a cross-sectional epidemiological study conducted through a household survey in the municipality of Alegre (Espírito Santo, Brazil) between November and December 2021, during the COVID-19 pandemic.

4.2. Study Population and Sample Selection

The study population consisted of residents from both central and peripheral urban areas of Alegre, aged 18 years or older, who agreed to participate by signing the Informed Consent Form. The sampling process included only the urban population of the municipality. According to the most recent census, Alegre’s urban population totaled 21,512, with 16,179 residents living in the municipal seat [27].

The sample size was calculated based on the total urban population, adopting a 95% confidence level (α = 0.05), an estimated prevalence of 50% for the outcomes, and a design effect of 1.5. These parameters yielded a minimum sample size of 567 individuals. To account for potential losses, a 10% increase was applied, resulting in a target sample of 624 participants [28].

Participants were selected using probability proportional to size (PPS) sampling. In the first stage, 10 out of 37 urban census tracts were randomly selected. In the second stage, an equal number of individuals were surveyed in each tract [29,30].

4.3. Researcher Training

The research team received theoretical training via Google Meet between October and November 2021. Supplementary training materials, including instructional videos, were provided through the Google Classroom platform (Google LLC, Mountain View, CA, USA) to support learning on the data collection instrument.

Before fieldwork began, practical training was conducted on 21 and 22 November 2021, to reinforce procedures and protocols. A pilot study was also carried out to test the questionnaire and offer researchers hands-on field experience.

A dedicated support committee was established to assist field researchers with questions or issues, providing face-to-face, telephone, and electronic support throughout the data collection process.

4.4. Data Collection

Data were collected using a structured and pre-coded questionnaire organized into thematic sections. Part A included sociodemographic information; Part B addressed general health conditions; Part C focused on COVID-19-specific issues; Part D covered healthcare service utilization; and Part E referred to medication use. Part F assessed the use of teas and medicinal plants, while Part G explored alternative therapies, including homeopathy, phytotherapy, compounded, and homemade medications. Part H collected information on lifestyle habits, and Part I assessed quality of life using the EQ-5D-3L instrument (EuroQol Research Foundation, Rotterdam, The Netherlands) [31].

All procedures were standardized. In cases where direct participation was not feasible (due to health problems, hearing impairments, or cognitive limitations), information was provided by a proxy respondent (a relative or caregiver).

4.5. Variables

The dependent variable was the use of analgesic and antipyretic medications, based on the question: “Do you use medication?” If the answer was affirmative, participants were asked to present a medical prescription, medication packaging, or another form of documentation to confirm medication use.

Independent variables included: age, sex, race/ethnicity, region, marital status, religion, education, income, self-perceived health, quality of life, body mass index (BMI), physical activity, alcohol consumption, smoking status, sleep duration, medical and dental appointments, consultations with a nutritionist, hospitalizations, private health insurance coverage, use of public and private pharmacies in the previous year, treatment-related problems, and use of medicinal plants.

The medications most frequently used by self-medicating individuals were classified according to the Anatomical Therapeutic Chemical (ATC) classification system of the World Health Organization (WHO).

4.6. Data Analysis

Descriptive statistics were performed using frequency distributions for categorical variables and medians with interquartile ranges for continuous variables.

Factors associated with analgesic use were analyzed using Poisson regression with robust variance. Variables with a p-value ≤ 0.20 in the bivariate analysis were included in the multivariate model, and only those with a p-value ≤ 0.05 were retained in the final model.

Self-medication was also examined using bivariate and multivariate analyses. Variables with p ≤ 0.20 in the bivariate analysis were included in the multivariate Poisson regression model, and those with p ≤ 0.05 remained in the final model.

All analyses were conducted using Jamovi (version 2.2.5) and Stata (version 16.1).

4.7. Ethical Considerations

The study was approved by the Research Ethics Committee of the Federal University of Espírito Santo, Alegre campus (approval number 4.732.878). All procedures followed the ethical standards of the Human Research Committee, the 1964 Declaration of Helsinki (revised in 2013), and the biosafety standards established during the COVID-19 pandemic [32,33,34].

5. Conclusions

This study highlights the high prevalence of analgesic use during the COVID-19 pandemic, particularly of metamizole, followed by acetaminophen. Given its over-the-counter availability and widespread use, the findings underscore the need for enhanced public health education and strengthened pharmacovigilance. Monitoring the use of these medications is essential, especially in light of growing evidence linking metamizole to increased risks of liver injury and other adverse events. Strengthening the role of pharmacists and implementing targeted public health interventions are key strategies to promote the rational and safe use of analgesics, ensuring both therapeutic efficacy and patient safety.