Abstract
Metamizole is an analgesic widely used after its introduction but later withdrawn in several countries due to the risk of agranulocytosis. Despite this, it remains frequently used worldwide. In June 2024, the Pharmacovigilance Risk Assessment Committee began reviewing metamizole-containing medicines. To assess the current evidence on this risk, we conducted a systematic review and a pharmacovigilance study using EudraVigilance to analyze data cases of agranulocytosis potentially associated with metamizole. In the systematic review, only 14 studies met our inclusion criteria, comprising case-control studies, registry-based descriptive analyses, and two pharmacovigilance studies. Current evidence on metamizole-induced agranulocytosis remains inconclusive. In our pharmacovigilance analysis (from 2003 to 2024), a total of 2244 reports were related to cases of agranulocytosis, of which 1397 (62.3%) related to female and adult patients 1148 (51.2%). The reporting odds ratio (ROR) with a 95% confidence interval (95% CI) showed a higher likelihood of reporting agranulocytosis with metamizole compared to clozapine (ROR: 5.50, 95% CI 5.18–5.82), sulfasalazine (ROR: 7.31, 95% CI 6.58–8.14), penicillamine (ROR: 34.4, 95% CI 11.70–167.89), and NSAIDs (ROR: 41.7, 95% CI 38.24–45.52). Our results confirm an increased likelihood of reporting agranulocytosis with metamizole. Given this risk and the availability of safer, effective alternatives, further research is needed.
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-025-27009-6.
Keywords: Metamizole, Dipyrone, Agranulocytosis, Systematic review, Safety, Pharmacovigilance
Subject terms: Adverse effects, Drug safety, Leukopoiesis
Introduction
Metamizole, introduced clinically in the 1920s, was widely used worldwide in subsequent decades, despite varying national approval timelines across countries1. The first reported case of agranulocytosis dates back to 19362. Although rare, agranulocytosis – defined as a drop in neutrophilic granulocytes below < 500µL/µl blood – is a well-known adverse reaction associated to metamizole and has led to its market withdrawal starting in the 1960s in several countries, including Australia, Canada, France, India, Japan, the Scandinavian countries, the United Kingdom, and the United States.
The metamizole-induced agranulocytosis (MIA) typically presents with nonspecific symptoms such as fever, sore throat, or fatigue, often accompanied by additional mucosal inflammation, including aphthous stomatitis, pharyngitis, tonsillitis, or proctitis, which may worsen as the condition progresses. Moreover, clinical manifestations and complications such as sepsis, tonsillitis, pneumonia, and fever have been documented in approximately 60% of reported cases3.
Despite the known risk, metamizole remains a frequently used medication worldwide, both as a prescription and over-the-counter drug. For instance, it was the third most prescribed analgesic in Switzerland between 2006 and 2013 and the most prescribed analgesic in Germany in 20124,5. In countries where metamizole is available over the counter, it is commonly used for self-medication and is the most utilized analgesic among patients with chronic pain6.
Metamizole-containing medicines are authorized in several European Union countries for the treatment of moderate to severe pain and fever. Approved uses vary between countries, ranging from pain following surgery and injuries to cancer-related pain and fever. Risk minimization measures for agranulocytosis also differ across countries. Consequently, on June 13, 2024, the Pharmacovigilance Risk Assessment Committee (PRAC) initiated a review of metamizole-containing medicines7. This review was requested by the Finnish regulatory agency following reports of agranulocytosis associated with metamizole, despite recent efforts to strengthen risk minimization measures (e.g., updated product information with strengthened warnings, and PRAC-recommended educational materials for prescribers).
To date, the Finnish regulatory agency has decided to withdraw the marketing authorization for the only metamizole-containing medicine available in the country. Figure 1 illustrates the current regulatory status of metamizole-containing medicines (marketed with or without prescription, or withdrawn) across European Union countries.
Fig. 1.
Authorization status of metamizole in European Union countries, updated to reflect the latest review by the Pharmacovigilance Risk Assessment Committee (PRAC) on June 13, 2024, which led the Finnish regulatory agency to withdraw (in red) the marketing authorization for metamizole-containing medicines. This map was generated using R Statistical Software (version 4.4.0; R Foundation for Statistical Computing, Wien, Austria. URL: https://www.R-project.org/).
Despite this well-documented safety risk, the magnitude and consistency of MIA risk remain unclear. Existing studies report widely varying incidence rates, and no recent synthesis has systematically compared these literature findings with real-world post-marketing pharmacovigilance data.
To address this uncertainty, we conducted a systematic review of the literature to gather current evidence on the risk of MIA. Additionally, we performed a pharmacovigilance study to analyze data on reports of suspected adverse drug reactions (ADRs), aiming to characterize MIA cases and determine whether there is a disproportionality in the reporting of metamizole-induced agranulocytosis compared to agranulocytosis associated with other drugs known to carry this risk.
Methods
Study design
Our study consisted of two main components: a systematic review and an analysis of pharmacovigilance data. The systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure methodological rigor and transparency8. Additionally, we performed an analysis of pharmacovigilance data obtained from the European pharmacovigilance database, EudraVigilance, to provide complementary insights9.
Systematic review strategy and selection criteria
We conducted a systematic search of the electronic bibliographic databases MEDLINE (via PubMed) and Embase. The search query used for PubMed, which was adapted for Embase, is detailed in Supplementary Table 1.
We included only observational studies, such as cohort studies, case-control studies, and cross-sectional studies, while excluding clinical trials, reviews, case reports, study protocols, abstracts, book chapters, and editorials. Eligible studies focused on patients aged ≥ 16 years treated with metamizole, regardless of its formulation or indication. Additionally, we selected only studies reporting agranulocytosis as an adverse event potentially associated with metamizole use. Given the heterogeneity of included studies in terms of design, populations, and outcome reporting, a formal quality assessment or risk-of-bias evaluation was not performed.
After removing duplicate studies, two researchers independently screened the titles and abstracts of all identified studies to determine their eligibility for further evaluation. Any disagreements between the two researchers were resolved by consulting a third researcher. Studies that did not meet the inclusion criteria were excluded, and the full texts of the remaining studies were reviewed to ensure the availability of complete data.
Data were extracted using a standardized form, which included the following information: study characteristics (e.g., first author, publication year, study design, geographical region); patient characteristics (e.g., number of enrolled patients, mean or median age, sex); data source; duration of follow-up; and any comparator drugs used.
Pharmacovigilance analysis
All individual case safety reports (ICSRs) of suspected adverse drug reactions (ADRs) associated with metamizole as the active substance were extracted from EudraVigilance, starting from the first reported case involving metamizole. The ICSRs retrieved from EudraVigilance provide detailed information for each case, including patient characteristics (i.e., age group and sex), suspected ADRs (i.e., duration, outcome, and severity), drug-related details (i.e., role—suspected, interacting, or concomitant—; active substance and/or medicinal product name; indication; pharmaceutical form; and route of administration), and other relevant data such as the type of report (i.e., spontaneous or non-spontaneous) and the reporter’s qualification (i.e. healthcare professional or patient/citizen). All extracted ICSRs underwent deduplication to eliminate potential duplicate reports prior to analysis.
Data analysis
Cases of suspected metamizole-induced agranulocytosis (MIA) were identified by selecting all ICSRs that included at least one of the following events coded as Preferred Terms (PTs) from the Medical Dictionary for Regulatory Activities’ (MedDRA) Standardised MedDRA Query (SMQ) “Agranulocytosis” (narrow scope): Agranulocytosis, Aplastic anaemia, Autoimmune aplastic anaemia, Bone marrow failure, Clonal cytopenia of undetermined significance, Cytopenia, Febrile bone marrow aplasia, Febrile neutropenia, Idiopathic cytopenia of undetermined significance, Immune-mediated cytopenia, Immune-mediated pancytopenia, Myelosuppression, Neutropenic colitis, Neutropenic infection, Neutropenic sepsis, Pancytopenia, Panmyelopathy, and Pure white cell aplasia10.
For the disproportionality analysis, comparator drugs were selected based on their well-documented association with agranulocytosis in the literature, and sufficient reporting frequency in EudraVigilance to ensure stable comparisons. These comparator drugs included clozapine, sulfasalazine, antithyroid drugs (i.e., carbimazole and propylthiouracil), penicillamine, and non-steroidal anti-inflammatory drugs (NSAIDs). The analysis was conducted by calculating the reporting odds ratio (ROR) with a 95% confidence interval (95% CI) to compare the likelihood of agranulocytosis reporting between metamizole and these reference drugs.
Data management and all statistical analysis were performed using the R Statistical Software (version 4.4.0; R Foundation for Statistical Computing, Wien, Austria. URL: https://www.R-project.org/).
Results
Systematic review
The search returned a total of 634 publications (MEDLINE: n = 132, 20.8%; EMBASE: n = 502, 79.2%). Of these, 242 duplicates were removed, leaving 392 records to be screened based on titles and abstracts. During the second screening phase, 22 publications were assessed in full text, and only 14 met the inclusion criteria and were included in the systematic review (Fig. 2).
Fig. 2.
Flow diagram of the study selection process.
The characteristics of the included studies are summarized in Table 1.
Table 1.
Characteristics of the studies included.
| First author, year | Geographical Region | Study design | Data source | Time of follow-up |
Other treatments |
|---|---|---|---|---|---|
| Arneborn, 198217 | Sweden (Stockholm County) | Case-control study | Electronic health records |
5 years (1973–1978) |
Sulfamides, antithyroid drugs, antihistamines, phenothiazines, diuretics, NSAIDs, antibiotics, antimalarial combination therapy, penicillamine, tolbutamide, aurothioglucose, unspecified purgative, phenytoin |
| Blaser, 201522 | International | Pharmacovigilance study | Pharmacovigilance database (national: Switzerland, international: VigiBase) |
45 years (1968–2013) |
No |
| Gonzalez-Cardenas, 201811 | Colombia | Descriptive analysis | Electronic health records | Not available | No |
| Huber, 201412 | Germany (Berlin) | Case-control study | Electronic health records |
10 years (2000–2010) |
Clozapine, sulfasalazine, thiamazole, carbamazepine |
| Ibanez, 200516 | Spain (Barcelona) | Case-control study (population-based) | Electronic health records |
21 years (1980–2001) |
Acetylsalicylic acid, propifenazone, acetaminophen, diclofenac, indomethacin, other NSAIDs, carbamazepine, spironolactone, others |
| Klose, 202020 | Germany | Cohort study | German health insurance | 4 years (2010–2013) | All other treatments |
| Maciá‑Martínez, 202321 | Spain | Cohort study | Electronic health records |
17 years (2005–2022) |
Non-steroidal anti-inflammatory drugs, opioids-paracetamol |
| Maj, 200218 | Poland | Descriptive analysis | Electronic health records |
4 years (1997–2001) |
No |
| Maj, 200419 | Poland | Descriptive analysis (population-based) | Electronic health records |
1 years (2002–2003) |
No |
| Navarro-Martinez, 201513 | Spain (Valencia) | Descriptive analysis | Electronic health records |
14 years (1996–2010) |
No |
| Revuelta-Herrero, 201914 | Spain | Pharmacovigilance study | Electronic health records |
1,5 years (2015–2017) |
Piperacillin/tazobactam, dexketoprofen, linezolid |
| Van Der Klauw, 199824 | Netherlands | Descriptive study | Drug Safety Unit of Dutch Inspectorate for Health Care |
20 years (1974–1994) |
Mianserin, sulfasalazina, sulfametossazolo, penicilline, cimetidina, altri |
| Van Der Klauw, 199915 | Netherlands | Case-control study (population-based) | Electronic health records |
3 years (1987–1990) |
Mianserin, sulfasalazine, sulfamethoxazole, penicillins, cimetidine, others |
| Zahn, 200123 | Germany | Descriptive study | Electronic health records |
5 years (2015–2020) |
No |
Given the rarity of the event, descriptive studies based on hospital registries from single hospitals have not shown cases of MIA11. The most significant evidence on MIA comes from case-control studies with long follow-up periods. A study using data from hospital registries in Berlin, with a 10-year follow-up, identified 63 cases of drug-induced agranulocytosis, of which ten were associated with metamizole, followed by clozapine, sulfasalazine, thiamazole, and carbamazepine12. Two studies based on Spanish hospital registries and one study from Dutch hospital registries showed that the drug most commonly associated with agranulocytosis was metamizole13–15. Another case-control study found that the drug with the highest risk of agranulocytosis was ticlopidine, followed by calcium dobesilate, antithyroid drugs, metamizole, and spironolactone16. Another study showed that the drugs most frequently involved in agranulocytosis cases were those used for hyperthyroidism, penicillamine, and sulfonamides17. In this study, it was observed that about 11% of patients with drug-induced agranulocytosis had a fatal outcome17. However, the few cases of MIA in some studies are influenced by the fact that they were conducted in countries where metamizole had been withdrawn from the market (e.g., metamizole was withdrawn in Sweden in 1973). For instance, in the study conducted by Arneborn et al., the agranulocytosis was induced by metamizole imported from another country17. Two studies based on data from hospital registries in Poland showed a very low incidence of MIA (0.2 cases per million person-days of use)18,19.
The first cohort claims-based study aimed at estimating the risk of metamizole-induced agranulocytosis (MIA) analyzed data from a large German health insurance fund covering the period from 2010 to 201320. The study reported a relative risk of 3.03 (95% CI 2.49–3.69) for MIA and metamizole-induced neutropenia. Additionally, the estimated risk of developing agranulocytosis or neutropenia following metamizole prescription was approximately 1 in 1,602 patients (95% CI 1:1,926–1:1,371). Another cohort study compared the incidence rate and risk of agranulocytosis associated with metamizole versus nonsteroidal anti-inflammatory drugs (NSAIDs)21. Although agranulocytosis was found to be very rare, its occurrence was over four times more frequent in patients exposed to metamizole compared to those treated with other analgesics. Specifically, the crude incidence rate of agranulocytosis in the metamizole cohort was 8.52 cases per 10,000,000 person-weeks of treatment (95% CI 2.75–26.42), compared to 1.62 cases per 10,000,000 person-weeks (95% CI 0.68–3.90) in the NSAID cohort.
Pharmacovigilance studies using international (e.g., Vigibase) and national (e.g., Swiss national pharmacovigilance network) databases have highlighted that female sex, advanced age, and methotrexate as a concomitant drug are common characteristics in MIA-fatal cases22. A pharmacovigilance project involving 7809 patients admitted to a German University Hospital, with almost 32% of patients exposed to metamizole, identified cases of MIA that resolved without sequelae23. Finally, data analysis from the Drug Safety Unit of the Dutch Inspectorate for Health Care did not reveal any MIA cases with a clear drug/event causal relationship24.
Pharmacovigilance analysis
From 2003 (the year of the first reported suspected ADR associated with metamizole) to October 2024, a total of 15,006 ICSRs where metamizole was reported as suspected drug were extracted from the EudraVigilance database. Of these, 2,244 ICSRs were related to cases of agranulocytosis. In general, aside from a peak in 2008, reports mentioning metamizole as the suspected drug remained below 1,000 until 2017, while from 2018 to 2024, they remained relatively high, with a peak in reports of metamizole-induced agranulocytosis in 2024 (January-October) (Fig. 3).
Fig. 3.
Trend of suspected adverse drug reactions from metamizole (January 2003 – October 2024) (red curve) and agranulocytosis associated with metamizole (blue bars).
More than half of the ICSRs were associated with female patients (N = 1397, 62.3%) aged between 18 and 64 years (N = 1148, 51.2%). All ICSRs were spontaneous in nature, and the suspected ADRs were primarily reported by healthcare professionals (N = 2109, 94%). The majority of the reports came from countries within the European Economic Area (N = 1720, 76.6%) (Table 2).
Table 2.
Characteristics of the individual case safety reports (ICSRs) associated with metamizole-induced agranulocytosis (MIA).
| N. of ICSR | |
|---|---|
| 2244 (100.0) | |
| Sex (%) | |
| Female | 1397 (62.3) |
| Male | 797 (35.5) |
| Not available | 50 (2.2) |
| Age category (%) | |
| 0–1 month | 1 (< 0.1) |
| 2 months − 2 years | 13 (0.6) |
| 3–11 years | 24 (1.1) |
| 12–17 years | 90 (4.0) |
| 18–64 years | 1148 (51.2) |
| 65–85 years | 683 (30.4) |
| >85 years | 119 (5.3) |
| Not available | 166 (7.4) |
| Type of report (%) = Spontaneaus | 2244 (100.0) |
| Primary source qualification (%) | |
| Healthcare professional | 2109 (94.0) |
| Non-healthcare professional | 115 (5.1) |
| Not available | 20 (0.9) |
| Country (%) = Economic European Area | 1720 (76.6) |
Of the 2244 ICSRs reporting a suspected case of metamizole-induced agranulocytosis, the adverse co-reported reactions of agranulocytosis were mainly fever (N = 305, 7.0%), leukopenia (N = 212, 4.9%), sepsis (N = 183, 4.2%), neutropenia (N = 121, 2.8%), thrombocytopenia (N = 116, 2.7%), pneumonia (N = 99, 2.3%), oropharyngeal pain (N = 84, 1.9%), septic shock (N = 76, 1.8%), tonsillitis (N = 73, 1.7%), and anemia (N = 66, 1.5%) (Fig. 4).
Fig. 4.
Frequency of adverse events – coded as Preferred Term – related to agranulocytosis.
In the majority of ICSRs of suspected MIA, a favorable outcome was observed (recovered/resolved: N = 1041, 49.5% and recovering/resolving: N = 274, 13.1%). In 203 cases (9.6%), a fatal outcome was reported.
The disproportionality analysis showed a higher likelihood of reporting agranulocytosis associated with the use of metamizole compared to clozapine, sulfasalazine, penicillamine, and NSAIDs; however, no difference was observed with antithyroid drugs (i.e., carbimazole and propylthiouracil) (Table 3).
Table 3.
Reporting odds ratio (ROR) with a 95% confidence interval (CI 95%) related to the risk of reporting agranulocytosis associated with metamizole, compared to other drugs with known associated risks.
| Metamizole vs. | ROR | 95% CI | p-value |
|---|---|---|---|
| Clozapine | 5.50 | 5.18–5.82 | <<0.05 |
| Sulfasalazine | 7.31 | 6.58–8.14 | <<0.05 |
| Antithyroid drugs | 1.03 | 0.94–1.14 | 0.52 |
| Penicillamine | 34.4 | 11.70–167.89 | <<0.05 |
| NSAIDs | 41.7 | 38.24–45.52 | <<0.05 |
Discussion
In this study, we performed a systematic review and a pharmacovigilance analysis using European data to investigate aspects related to the risk of metamizole-induced agranulocytosis (MIA). Despite being a well-known adverse drug reaction (ADR), the occurrence of MIA remains a significant concern. Our analysis aimed to provide a comprehensive overview of the current evidence on this risk, considering both the clinical literature and real-world pharmacovigilance data. By combining findings from a systematic review and a pharmacovigilance analysis of reports from EudraVigilance, we sought to better understand the extent of this risk and its regulatory implications across different European countries.
The risk and incidence of MIA are yet unknown and vary greatly; depending on the study, taking metamizole increased the likelihood of developing agranulocytosis by 1.5 to 40 times compared to not taking the medication25. Based on the studies included in our systematic review, one study conducted across 51 Berlin hospitals between 2000 and 2010 reported an incidence rate of 0.96 cases per million inhabitants per year12. Another study, which retrospectively analyzed reports from Switzerland, estimated an incidence rate ranging from 0.46 to 1.63 cases per million person-days of use22. Similarly, a study utilizing hospital registry data in Poland reported an incidence rate of 0.2 cases per million person-days of use18,19. The differences in incidence estimates could be explained by variations in study designs, such as differences in data collection methods, timeframes, and population sizes. Alternatively, these discrepancies might support the hypothesis of variability related to genetic factors, suggesting that genetic predisposition could influence the observed incidence rates across different populations26. Another factor that may influence incidence estimates is the prevalence of metamizole use in different countries. In populations with higher drug utilization, the likelihood of detecting cases increases, which may contribute to variations in reported incidence rates. Our systematic review identified substantial geographic variation (0.2–1.63 cases/million person-days across countries) and methodological heterogeneity, explaining the wide risk estimate range.
According to the data extracted from EudraVigilance, the agranulocytosis represents a suspected ADR involved in 15% of all ICSRs (N = 2244). The data showed a fluctuating trend in reports, with a significant increase starting from 2018 and a notable peak in 2024. This recent peak, particularly significant considering it refers to a ten-month period, may reflect renewed attention to this safety issue, which has been revisited by the Pharmacovigilance Risk Assessment Committee (PRAC)7. Additionally, media coverage MIA cases may have contributed to the increased reporting. One particularly widely discussed case involved the death of a British tourist in Spain following an agranulocytosis followed by the use of metamizole27. The case led to the development of patient advocacy groups, such as the Association of Drug Affected Patients (ADAF), which have been actively raising awareness about the risks of drug-induced adverse reactions. The efforts of such organizations, combined with increased public awareness, may have encouraged a higher rate of reporting suspected ADRs.
The demographic analysis of ICSRs related to metamizole-induced agranulocytosis showed a higher involvement of female patients. In general, women are at greater risk of experiencing adverse events compared to men and are more likely to report them28–31. Furthermore, we observed a higher frequency of ICSR related to adult patients (18–64 years). The distribution by sex and age group aligns with current evidence; indeed, women and older patients have a higher incidence of metamizole-induced agranulocytosis, reflecting characteristics related to drug use2. The incidence of MIA in pediatric patients remains unclear, although it is hypothesized to be lower than in adults2. As expected, our data show a relatively low involvement of patients under 18 years old.
In ICSRs related to agranulocytosis, the most commonly reported adverse event was pyrexia, a typical nonspecific symptom of MIA. The occurrence of this and other reported events may be influenced by indication bias, as metamizole is often used for its antipyretic and analgesic properties. All other common symptoms of this condition were reported: stomatitis, tonsillitis, pharyngitis, and sepsis25. Metamizole-induced agranulocytosis can lead to severe infections (local or systemic) and death. Of the 2244 ICSR analyzed, just under than 10% involved fatal agranulocytosis. This aligns with a study included in our systematic review, which observed that approximately 11% of patients with drug-induced agranulocytosis experienced a fatal outcome17. However, due to the nature of the data analyzed, we cannot infer a causal drug/event relationship. In fact, these fatal outcomes cannot be exclusively attributed to metamizole, as spontaneous reports lack data on comorbidities, concomitant medications, or other potential risk factors.
Finally, the disproportionality analysis showed a higher likelihood of reporting agranulocytosis from metamizole compared to other drugs known to be associated with this event, such as clozapine, sulfasalazine, penicillamine, and nonsteroidal anti-inflammatory drugs. Importantly, these pharmacovigilance signals indicate statistical associations rather than established causality, as spontaneous reporting systems lack control for confounding factors. No disproportionality was observed in the reporting of agranulocytosis when compared to antithyroid drugs, which likely present the highest risk of agranulocytosis, or at least a comparable risk to that of metamizole.
Conclusion
Despite the well-known risk of metamizole-induced agranulocytosis, its exact magnitude remains unclear and shows considerable variability across the studies, ranging from 1.5 to 40-fold increased risk compared to non-users. These discrepancies may be attributed to differences in study designs, sample sizes, and genetic factors, thought the latter hypothesis requires further investigation26. Moreover, higher drug utilization in certain populations may lead to increased case detection, potentially influencing incidence estimates. Therefore, the current evidence does not provide a definitive picture of the risk associated with metamizole-induced agranulocytosis, and further international studies are warranted. Such studies should account for differing regulatory frameworks and variations in metamizole use across countries. Given these uncertainties, we strongly advocate for well-designed prospective multinational studies and periodic re-evaluations by regulatory agencies to ensure patient safety while balancing therapeutic needs.
Our pharmacovigilance analysis confirms an increased likelihood of reporting agranulocytosis associated with metamizole compared to other drugs known to carry this risk, such as clozapine, sulfasalazine, penicillamine, and NSAIDs (specifically those with ATC code M01A, e.g., diclofenac, ibuprofen, naproxen, ketoprofen). In conclusion, assessing the safety profile of metamizole, it is also important to consider that, in addition to the risk of agranulocytosis, there are effective and safer therapeutic available alternatives.
Supplementary Information
Below is the link to the electronic supplementary material.
Author contributions
A.Z., M.G., D.R., C.R. (Consiglia Riccardi), C.C., and C.P. wrote the manuscript; A.Z., M.G., A.C., and C.R. (Concetta Rafaniello) designed the research; A.Z., M.G., D.R., C.R. (Consiglia Riccardi), A.C., and C.R. (Concetta Rafaniello) performed the research; A.Z., M.G., C.C., and C.P. analyzed data.
Data availability
The datasets analyzed during the current study are publicly available in the EudraVigilance website, https://www.adrreports.eu/.
Declarations
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
These authors contributed equally: Alessia Zinzi and Mario Gaio.
These authors jointly supervised this work: Annalisa Capuano and Concetta Rafaniello.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets analyzed during the current study are publicly available in the EudraVigilance website, https://www.adrreports.eu/.