Deaths and hospitalizations resulting from poisoning by prescription and over-the-counter drugs in Brazil

Fernanda Gross Duarte Marcelo Neubauer de Paula Nelzair Araújo Vianna Maria Conceição Chagas de Almeida Edson Duarte Moreira JuniorAbout the authors

ABSTRACT

OBJECTIVE:

To estimate the incidence of hospitalizations considering drug intoxication and the mortality of these diseases in Brazil, given trends from 2009 to 2018.

METHODS:

Data on hospital admissions and deaths come from DATASUS and demographic data from the Brazilian Institute of Geography and Statistics (IBGE). Hospital admissions with Autorização para Internação Hospitalar (AIH - Authorization for Hospital Admission) indicated as a procedure “treatment of intoxication or poisoning due to exposure to drugs and substances for non-drug use” were selected, with only cases of hospitalization due to drug intoxication being analyzed. The incidence of hospitalization and mortality were calculated separately for intoxications caused by medicamentos com prescrição (MRx - prescription drugs) and medicamentos isentos de prescrição (MIP - over-the-counter drugs). Rates were further stratified by sex, age group, and region of residence in Brazil. Trend analysis was performed by generalized linear regression using the Prais-Winsten method.

RESULTS:

MRx caused most hospitalizations (97%), with mortality approximately 50 times higher when compared to hospitalizations for MIP. The incidence trend in hospitalizations for MRx was stationary and mortality increased during the study period, whereas the trend in mortality and in the incidence of hospitalizations for MIP decreased.

CONCLUSIONS:

Hospitalizations for drug intoxication, especially those caused by MRx, have a great impact and importance on public health considering that prevention is possible.

DESCRITORES:
Medicamentos sem Prescrição, envenenamento; Medicamentos sob Prescrição, envenenamento; Hospitalização; Envenenamento, mortalidade

INTRODUCTION

Drug intoxication results from exposure to a drug at doses higher than those usually used for prophylaxis, diagnosis, treatment, or for modification of physiological functions. This may result in different signs and symptoms, depending on the type of drug and drug metabolism11 Agência Nacional de Vigilância Sanitária. Resolução N° 4, de 10 de fevereiro de 2009. Dispõe sobre as normas de farmacovigilância para os detentores de registro de medicamentos de uso humano. Brasília, DF: Anvisa; 2009 [cited 2021 Mar 16]. Available from: https://bvsms.saude.gov.br/bvs/saudelegis/anvisa/2009/res0004_10_02_2009.html
https://bvsms.saude.gov.br/bvs/saudelegi...
. Intoxication can occur unintentionally or accidentally, when it results from self-medication, dosage error, inadequate therapy, medication change, or involuntary ingestion; or intentional, when related to abuse, misuse, or self-injury22 Amaral DA. Intoxicações por medicamento. In: Seizi O, organizador. Fundamentos de toxicologia. 2.ed. São Paulo: Varella; 2003. p.367-79.. Severe cases of poisoning, leading to hospital admissions and even death, constitute an important public health problem33 World Health Organization (WHO). Guidelines on the prevention of toxic exposures. Education and public awareness activities / International Programme on Chemical Safety.2004. Available from: https://www.who.int/ipcs/features/prevention_guidelines.pdf4.
https://www.who.int/ipcs/features/preven...
.

Between 2009 and 2018, the Sistema Nacional de Informações Tóxico-Farmacológicas (Sinitox - National Toxic-Pharmacological Information System) registered 254,135 cases of poisoning in Brazil, with a total of 710 deaths (0.28%). Medicines were the main cause of intoxication among all the agents notified, or about 29% of cases in the period, followed by venomous animals, household cleaning products, and pesticides44 Sistema Nacional de Informações Tóxico-Farmacológicas: dados de intoxicação: dados nacionais. Rio de Janeiro: Fiocruz; c2009 [cited 2021 Mar 16]. Available from: https://sinitox.icict.fiocruz.br/dados-nacionais
https://sinitox.icict.fiocruz.br/dados-n...
. Since 1994, pharmaceuticals occupy the first place in the ranking of intoxications and the second place in the number of deaths. In 2016, according to data from Sinitox, accidental poisoning was one of the main causes of occurrences with medications, representing about a third of reported cases (32.7%)44 Sistema Nacional de Informações Tóxico-Farmacológicas: dados de intoxicação: dados nacionais. Rio de Janeiro: Fiocruz; c2009 [cited 2021 Mar 16]. Available from: https://sinitox.icict.fiocruz.br/dados-nacionais
https://sinitox.icict.fiocruz.br/dados-n...
.

In most developed countries, the situation is similar to that in Brazil, with medicines leading the causes of exogenous intoxication55 National Poisons Information Service (NPIS). National Poisons Information Service Report 2018/19. Available from: https://www.npis.org/Download/NPISAnnualReport2018-19.pdf
https://www.npis.org/Download/NPISAnnual...
. In the United States of America (USA), national data from 2018 indicate that more than two million cases of intoxication were caused by medicines66 Gummin DD, Mowry JB, Spyker DA, Brooks DE, Beuhler MC, Rivers LJ, et al. 2018 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 36th Annual Report. Clin Toxicol (Phila). 2019;57(12):1220-413. https://doi.org/10.1080/15563650.2019.1677022
https://doi.org/10.1080/15563650.2019.16...
. Additionally, there was an increasing trend in mortality rates from drug poisoning between 1994 and 2010, in all regions and demographic groups in the USA, with accidental poisoning being the main cause (71%)77 Richardson R, Charters T, King N, Harper S. Trends in educational inequalities in drug poisoning mortality: United States, 1994-2010. Am J Public Health. 2015;105(9):1859-65. https://doi.org/10.2105/AJPH.2015.302697
https://doi.org/10.2105/AJPH.2015.302697...
.

In Brazil, drugs can be classified as Medicamentos com prescrição (MRx - prescription drugs) or Medicamentos sentos de prescrição (MIP - over-the-counter drugs). This classification was established for the first time in Brazilian sanitary legislation, in 1973, when the sanitary control of the medicine trade was regulated. In this case, the concept of over-the-counter drugs relates to not depend on prescription drugs, establishing differences regarding the labeling and advertising of prescribed products88 Brasil. Lei N° 5991, de 17 de dezembro de 1973. Dispõe sobre o Controle Sanitário do Comércio de Drogas, Medicamentos, Insumos Farmacêuticos e Correlatos, e dá outras Providências. Brasíla, DF; 1973 [cited 2021 Mar 16]. Available from: http://www.planalto.gov.br/ccivil_03/leis/l5991.htm
http://www.planalto.gov.br/ccivil_03/lei...
. In 2016, the Agência Nacional de Vigilância Sanitária (Anvisa - National Health Surveillance Agency) more clearly defined the criteria for a drug to be classified as “prescription-free”, including 33 therapeutic groups, with exceptions99 Agência Nacional de Vigilância Sanitária. Instrução Normativa N° 11, de 29 de setembro de 2016. Dispõe sobre a lista de medicamentos isentos de prescrição. Diário Oficial da União. 30 set 2016 [cited 2020 Dec 28]; Seção 1:99. Available from: https://www.in.gov.br/materia/-/asset_publisher/Kujrw0TZC2Mb/content/id/23376708/do1-2016-08-03-resolucao-rdc-n-98-de-1-de-agosto-de-2016-23376586
https://www.in.gov.br/materia/-/asset_pu...
. The criteria for the inclusion of drugs in the MIP list take into account the following aspects: marketing time, drug safety, identifiable symptoms, use for a short period of time, being manageable by the patient, presenting low-risk potential, and not presenting dependence99 Agência Nacional de Vigilância Sanitária. Instrução Normativa N° 11, de 29 de setembro de 2016. Dispõe sobre a lista de medicamentos isentos de prescrição. Diário Oficial da União. 30 set 2016 [cited 2020 Dec 28]; Seção 1:99. Available from: https://www.in.gov.br/materia/-/asset_publisher/Kujrw0TZC2Mb/content/id/23376708/do1-2016-08-03-resolucao-rdc-n-98-de-1-de-agosto-de-2016-23376586
https://www.in.gov.br/materia/-/asset_pu...
.

We intend to estimate the incidence of hospitalizations for drug intoxication, generally and according to the type of drug (prescription or exempt), as well as the mortality of these diseases in Brazil, describing the trends observed in these estimates in the period between 2009 and 2018.

METHODS

This is a retrospective study to determine the rates of hospital admissions and deaths caused by drug intoxication in Brazil. A review of data on drug poisoning was carried out in the Base do Sistema Único de Saúde (Datasus - Unified Health System Database) during 10 years (date of exit: 2009 to 2018), including information such as gender, age, place of residence, and type of drug intoxication. Results for intoxications caused by prescription drugs are presented separately from those caused by over-the-counter drugs.

Data on admissions and deaths are from the DATASUS portal and were extracted by the TabWin software, provided by DATASUS. Demographic data were obtained from the 2010 Census and from inter-census estimates for other years, made available through the data portal of the Brazilian Institute of Geography and Statistics (IBGE)1010 Instituto Brasileiro de Geografia e Estatística. Estimativas da População. Rio de Janeiro: IBGE; 2020 [cited 2020 Dec 28]. Available from: https://www.ibge.gov.br/estatisticas/sociais/populacao.html
https://www.ibge.gov.br/estatisticas/soc...
.

Initially, hospital admissions reported between 2009 and 2018, which the Autorização para Internação Hospitalar (AIH - Authorization for Hospital Admission) requested as a procedure, were selected for “Treatment of intoxication or poisoning due to exposure to medication and substances for non-drug use”. Subsequently, only confirmed admissions in this procedure were kept; admissions considered for another purpose in the discharge/death report were excluded. Cases of drug intoxication were classified according to therapeutic groups and set apart by prescription or over-the-counter, using information from the primary and secondary International Classification of Diseases (ICD). We analyzed cases resulting from drug intoxication in this article.

We reckoned the incidence of hospitalization by dividing the number of hospitalizations that occurred in the study population by the number of inhabitants corresponding to the period and place analyzed. Similarly, mortality rates were calculated by dividing the number of deaths by the total population in each study period. Since the crude rates can be influenced by the age structure of populations from different regions and at different time periods, the estimated rates were standardized by age group and direct method, using a the standard population suggested by the World Health Organization (WHO 2000–2025), thus allowing the analysis of trends and comparisons of these data1111 Ahmad OB, Boschi-Pinto C, Lopez AD, Murray CJL, Lozano R, Inoue M. Age standardization of rates: a new WHO standard. Geneva (CH): WHO; 2001 [cited 2021 Mar 16]. (GPE Discussion Paper Series; n° 31). Available from: http://www.who.int/healthinfo/paper31.pdf
http://www.who.int/healthinfo/paper31.pd...
. The analysis of frequencies, rates of hospitalizations, and deaths was performed according to the type of drug intoxication classified as caused by prescription drugs (MRx) or over-the-counter drugs (MIP). We stratified the rates by sex, age group, and region of residence in Brazil. Generalized linear regression performed the trend analysis of the time series by using the Prais-Winsten method1212 Becketti S. Prais-Winsten regression. Stata Tech Bull. 1995 [cited 2021 Mar 16];(25):26-9. Available from: https://www.stata-press.com/journals/stbcontents/stb25.pdf
https://www.stata-press.com/journals/stb...
, with correction for the first-order autocorrelation effect1313 Park RE, Mitchell BM. Estimating the autocorrelated error model with trended data. J Econom. 1980;13(2):185-201.. We considered the stationary trend of hospital admissions/deaths when p > 0.05; declining when p < 0.05 and negative regression coefficient; or ascending when p < 0.05 and positive regression coefficient1414 Gaynor PE, Kirkpatrick RC. Introduction to time-series modeling and forecasting in business and economics. New York: McGraw-Hill; 1993. (McGraw-Hill economic series); (Wiley series in probability and mathematical statistics).. Statistical analyzes were performed using the Stata statistical program (Stata Statistical Software: Release 16. College Station, TX: StataCorp LLC).

RESULTS

Between 2009 and 2018, Brazil had 85,811 hospital admissions due to drug poisoning; MRx poisoning caused 97% of them and MIP caused 3%. The mean incidence of hospitalizations for MRx (4.16 per 100 thousand inhabitants) was much higher than that for MIP (0.13 per 100 thousand inhabitants), RR = 32.8 (95%CI 28.9–37.1). Hospitalizations accounted for 2,644 deaths (3.08%) during the study period. The mortality rate was higher for MRx poisoning (3.11%) than for MIP poisoning (1.93%).

Table 1 shows the frequency of hospital admissions and deaths caused by drug intoxication according to the region and other sociodemographic characteristics. The majority of hospitalizations occurred in females both in MRx poisoning (56.7%) and in those by MIP (54.9%). MRx hospitalizations had a higher mean incidence in females (4.61 per 100,000) compared to males (3.67 per 100,000), but this difference was lower in hospitalizations for MIP. In contrast, females accounted for only a quarter of deaths in admissions for MIP and just under half of those in admissions for MRx. White people were most commonly reported in admissions for MRx and MIP and in almost a third of cases had no information of color reported. The Southeast region had the highest number of hospitalizations for MRx, followed by the South and Midwest regions. The regional distribution of admissions for MIP was similar (Table 1).

Table 1
Frequency of hospitalizations and deaths by type of drug intoxication, Brazil, 2009–2018.

The incidence of hospitalization and mortality by age group are shown in Table 2. Poisonings by MRx and MIP had a higher incidence of hospitalizations in children under 5 years of age, decreasing in frequency with increasing age, especially in hospitalizations for MIP. Mean mortality in the period studied was higher in hospitalizations for MRx than for MIP, RR = 52.0 (95%CI 21.5–126.0). 60 years or older individuals had the highest mortality rate in MRx and MIP poisonings, followed by the under-5 group in admissions for MIP.

Table 2
Incidence of hospitalization and mortality from drug intoxication by age group, Brazil, 2009–2018.

Table 3 shows the incidence of hospitalization and mortality, standardized for the distribution of the world population (WHO 2000–2025), according to the regions of Brazil. During the study period, the highest mean incidence of hospitalizations for MRx occurred in the south and southeast regions, while the north and northeast regions had the lowest rates. In hospitalizations for MIP, the mean incidence was higher in the midwest and south regions. Similarly, the north and northeast regions had the lowest rates. We observed higher mortality for MRx poisonings in the southeast and south regions, whereas MIP had a higher rate in the northeast region.

Table 3
Incidence of hospitalization and mortality from drug intoxication by region, Brazil, 2009–2018.

The total number of hospitalizations and deaths, the regression coefficients, and the trend of hospitalizations and mortality by type of drug intoxication by region are presented in Table 4. In the period from 2009 to 2018, the trend in the incidence of hospitalizations due to MRx drug poisoning was stationary, ascending in the Southern region and decreasing in the Midwest and Northeast regions. While the incidence of hospitalizations for MIP had a decreasing trend in Brazil, especially in the Midwest and Northeast regions. The MRx poisoning mortality tended to ascended in Brazil, including in the South and Southeast regions. The mortality of poisoning by MIP, on the other hand, showed a decreasing trend in the country.

Table 4
Hospitalizations and deaths, regression coefficient and trend of hospitalizations and mortality from drug intoxication by region, Brazil, 2009–2018.

DISCUSSION

In the decade evaluated in this study (2009–2018), MRx caused most hospitalizations (97%) for drug intoxication, an incidence 32 times greater than that of hospitalizations for MIP. Despite the large difference indicating the preponderant role of MRx compared to MIP in severe cases, commerce data during the second half of the studied decade (2014–2018) showed that fewer doses of MRx (7.2 billion) were sold than of MIP (7.7 billion)1515 Pharma, Sales and Marketing Terms - IMS Health - PMB - Pharmaceutical Market Brasil. [cited 30 Jul 2021]. Available from: https://brazilsfe.blogspot.com/2015/12/pharma-terms-ims-o-que-e-pmb-pharmaceutical-market-brasil.html
https://brazilsfe.blogspot.com/2015/12/p...
. Prescription exceptions are mainly based on the low toxicity potential of these products, which have reversible adverse reactions after discontinuation of use and serious reactions only with the administration of large amounts of the product, outside the safe therapeutic window1616 Agência Nacional de Vigilância Sanitária. Resolução - RDC N° 98, de 1° de agosto de 2016. Dispõe sobre os critérios e procedimentos para o enquadramento de medicamentos como isentos de prescrição e o reenquadramento como medicamentos sob prescrição, e dá outras providências. Diário Oficial da União. 3 ago 2016 [cited 2021 Mar 16]; Seção 1:32. Available from: https://www.in.gov.br/materia/-/asset_publisher/Kujrw0TZC2Mb/content/id/23376708/do1-2016-08-03-resolucao-rdc-n-98-de-1-de-agosto-de-2016-23376586
https://www.in.gov.br/materia/-/asset_pu...
. This safety profile is possibly responsible for the lower number of serious poisonings and hospitalizations caused by MIP. The much higher mortality observed in hospitalizations for MRx, about 50 times higher, supports this argument.

ANVISA is responsible for regulating advertising, publicity, information, and other practices with the purpose of disclosing or commercially promoting medicines1717 Agência Nacional de Vigilância Sanitária. Resolução-RDC N° 96, de 17 de dezembro de 2008. Dispõe sobre a propaganda, publicidade, informação e outras práticas cujo objetivo seja a divulgação ou promoção comercial de medicamentos. Brasília, DF: Anvisa; 2008 [cited 2021 Mar 16]. Available from: http://bvsms.saude.gov.br/bvs/saudelegis/anvisa/2008/rdc0096_17_12_2008.html
http://bvsms.saude.gov.br/bvs/saudelegis...
. The agency includes materials prepared by the pharmaceutical industry for prescribers and dispensers. The results of this research, indicating much higher mortality in the use of prescription drugs, have important implications that justify the improvement of this regulation to prevent self-medication and the use of drugs in a non-rational way.

Hospitalizations were more common in females, while mortality was higher in males, both for MIP and MRx poisoning. Mota et al. (2012) analyzed the 1996 to 2005 period and also observed a higher prevalence of deaths from drug poisoning in men1818 Mota DM, Melo JRR, Freitas DRC, Machado M. Perfil da mortalidade por intoxicação com medicamentos no Brasil, 1996-2005: retrato de uma década. Cienc Saude Coletiva. 2012;17(1):61-70. https://doi.org/10.1590/S1413-8123201200010000
https://doi.org/10.1590/S1413-8123201200...
. Children had more hospitalizations for drug intoxication in under 5 years of age, regardless of the type of medication. Accidental drug ingestion is more common in this age group1919 Lee J, Fan NC, Yao TC, Hsia SH, Lee EP, Huang JL, et al. Clinical spectrum of acute poisoning in children admitted to the pediatric emergency department. Pediatr Neonatol. 2019;60(1):59-67. https://doi.org/10.1016/j.pedneo.2018.04.001
https://doi.org/10.1016/j.pedneo.2018.04...
,2020 Lessa MA, Bochner R. Analysis of hospitalizations of children under one year of age due to drug intoxication and adverse events in Brazil. Rev Bras Epidemiol. 2008;11(4):1-15. https://doi.org/10.1590/S1415-790X2008000400013
https://doi.org/10.1590/S1415-790X200800...
. Moreover, the lower body weight in this group makes them more vulnerable to intoxication with relatively lower doses2121 Lacroix J, Gaudreault P, Gauthier M. Admission to a pediatric intensive care unit for poisoning: a review of 105 cases. Crit Care Med. 1989;17(8):748-50. https://doi.org/10.1097/00003246-198908000-00005
https://doi.org/10.1097/00003246-1989080...
,2222 Toce MS, Burns MM. The poisoned pediatric patient. Pediatr Rev. 2017;38(5):207-20. https://doi.org/10.1542/pir.2016-0130
https://doi.org/10.1542/pir.2016-0130...
. Mortality rates were higher in the older adults, similar to what was observed in other studies2323 Santos GAS, Boing AC. Mortalidade e internações hospitalares por intoxicações e reações adversas a medicamentos no Brasil: análise de 2000 a 2014. Cad Saude Publica. 2018;34(6):e00100917. https://doi.org/10.1590/0102-311X00100917
https://doi.org/10.1590/0102-311X0010091...
,2424 Ramos LR, Tavares NUL, Bertoldi AD, Farias MR, Oliveira MA, Luiza VL, et al. Polypharmacy and polymorbidity in older adults in Brazil: a public health challenge. Rev Saude Publica. 2016;50 Suppl 2:1s-12s. https://doi.org/10.1590/S1518-8787.2016050006145
https://doi.org/10.1590/S1518-8787.20160...
. It is possible that the more frequent use of drugs and the increased susceptibility to toxicity, associated with the decrease in the ability to metabolize and excrete drugs due to advancing age, may have contributed to the higher mortality observed in older adults2424 Ramos LR, Tavares NUL, Bertoldi AD, Farias MR, Oliveira MA, Luiza VL, et al. Polypharmacy and polymorbidity in older adults in Brazil: a public health challenge. Rev Saude Publica. 2016;50 Suppl 2:1s-12s. https://doi.org/10.1590/S1518-8787.2016050006145
https://doi.org/10.1590/S1518-8787.20160...
,2525 Baldoni AO, Chequer FMD, Ferraz ERA Oliveira DP, Pereira LRL, Dorta DJ. Elderly and drugs: risks and necessity of rational use. Braz J Pharm Sci. 2010;46(4):617-32. https://doi.org/10.1590/S1984-82502010000400003
https://doi.org/10.1590/S1984-8250201000...
.

The incidence of hospitalizations for MIP and MRx varied in Brazil, wherein the South, Midwest, and Southeast regions had the highest rates and the North and Northeast regions the lowest. Mortality from poisonings varied according to the region of Brazil. In the southeast and south there were the highest mortality rates for MRx, while the Northeast and Midwest regions had the highest mortality for MIP. There is evidence in Brazil of the association between greater purchasing power and greater use of medicines2626 Bertoldi AD, Dal Pizzol TS, Ramos LR, Mengue SS, Luiza VL, Tavares NUL, et al. Sociodemographic profile of medicines users in Brazil: results from the 2014 PNAUM survey. Rev Saude Publica. 2016;50 Suppl 2:1s-10s. https://doi.org/10.1590/S1518-8787.2016050006119
https://doi.org/10.1590/S1518-8787.20160...
. This may explain the higher and growing rates of drug intoxication in the south and southeast regions, where the per capita income of the population is higher than in other regions of the country2727 Agência IBGE Notícias. IBGE divulga o rendimento per capita 2017. Rio de Janeiro: IBGE; 2018 [cited 2021 Mar 16]. Available from: https://agenciadenoticias.ibge.gov.br/agencia-sala-de-imprensa/2013-agencia-de-noticias/releases/20154-ibge-divulga-o-rendimento-domiciliar-per-capita-2017
https://agenciadenoticias.ibge.gov.br/ag...
. Thus, the differences observed may be consequences of inequalities in the availability and access to drugs. They can also be consequences of differences in the coverage of health services responsible for reporting cases and deaths from drug poisoning in different regions in Brazil.

The trend in the incidence of hospitalizations for MRx was stationary, but mortality increased during the decade, whereas we observed a decreasing trend in mortality and in the incidence of hospitalizations for MIP in the same period. The epidemiological profile of the Brazilian population has been changing with an increase in the prevalence of chronic diseases related to the more frequent use of medications2828 Schramm JMA, Oliveira AF, Leite IC, Valente JG, Gadelha AMJ, Portela MC, et al. Transição epidemiológica e o estudo de carga de doença no Brasil. Cienc Saude Coletiva. 2004;9(4):897-908. https://doi.org/10.1590/S1413-81232004000400011
https://doi.org/10.1590/S1413-8123200400...
,2929 Marinho F, Passos VMA, França EB. Novo século, novos desafios: mudança no perfil da carga de doença no Brasil de 1990 a 2010. Epidemiol Serv Saude. 2016;25(4):713-24. https://doi.org/10.5123/S1679-49742016000400005
https://doi.org/10.5123/S1679-4974201600...
. Polypharmacy has become a problem among older adults. In Brazil, it is estimated that 82% of people over 60 years old use at least one medication3030 Bezerra TA, Brito MAA, Costa KNFM. Characterization of medication use among elderly people attended at a family health care service. Cogitare Enferm. 2016;21(1):1-10.. Although these drugs can increase quality and life expectancy, they can also pose risks to this population due to drug interactions and the change in physiology caused by senescence3131 Pagno AR, Gross CB, Gewehr DM, Colet CF, Berlezi EM. A terapêutica medicamentosa, interações potenciais e iatrogenia como fatores relacionados à fragilidade em idosos. Rev Bras Geriatr Gerontol. 2018;21(5):610-9. https://doi.org/10.1590/1981-22562018021.180085
https://doi.org/10.1590/1981-22562018021...
. This may be one of the factors responsible for maintaining the incidence of hospitalizations and the increase in mortality in cases of MRx poisoning.

Limitations and Merits

The retrospective nature of this study, based on a pre-existing database whose available information is limited, hampered the investigation of certain characteristics related to the circumstances, causes, and treatment of hospitalizations for drug intoxication. Moreover, the information refers only to public health services, not covering private services. Therefore, the rates produced are underestimated. However, national coverage of the data, including a period of several years, allowed for comparisons between different regions and provided trend measures for the incidence of hospitalizations for drug intoxication, as well as for mortality.

CONCLUSIONS

Hospitalizations for drug intoxication have a great impact and importance on public health, deserving attention especially for its potentially preventable nature. Despite greater access to prescription-free medicines, almost all hospitalizations and deaths in Brazil between 2009 and 2018 occurred as a result of intoxication caused by prescription-only medicines. Our results reinforce the need for analytical studies to identify the determinants and prevent the occurrence of drug intoxications.

  • Funding: This study protocol was independently developed by the investigators and had unconditional financial support from the Associação Brasileira da Indústria de Medicamentos Isentos de Prescrição (ABIMIP - Brazilian Association of Over-the-Counter Medicines Industry).

REFERENCES

  • 1
    Agência Nacional de Vigilância Sanitária. Resolução N° 4, de 10 de fevereiro de 2009. Dispõe sobre as normas de farmacovigilância para os detentores de registro de medicamentos de uso humano. Brasília, DF: Anvisa; 2009 [cited 2021 Mar 16]. Available from: https://bvsms.saude.gov.br/bvs/saudelegis/anvisa/2009/res0004_10_02_2009.html
    » https://bvsms.saude.gov.br/bvs/saudelegis/anvisa/2009/res0004_10_02_2009.html
  • 2
    Amaral DA. Intoxicações por medicamento. In: Seizi O, organizador. Fundamentos de toxicologia. 2.ed. São Paulo: Varella; 2003. p.367-79.
  • 3
    World Health Organization (WHO). Guidelines on the prevention of toxic exposures. Education and public awareness activities / International Programme on Chemical Safety.2004. Available from: https://www.who.int/ipcs/features/prevention_guidelines.pdf4
    » https://www.who.int/ipcs/features/prevention_guidelines.pdf4
  • 4
    Sistema Nacional de Informações Tóxico-Farmacológicas: dados de intoxicação: dados nacionais. Rio de Janeiro: Fiocruz; c2009 [cited 2021 Mar 16]. Available from: https://sinitox.icict.fiocruz.br/dados-nacionais
    » https://sinitox.icict.fiocruz.br/dados-nacionais
  • 5
    National Poisons Information Service (NPIS). National Poisons Information Service Report 2018/19. Available from: https://www.npis.org/Download/NPISAnnualReport2018-19.pdf
    » https://www.npis.org/Download/NPISAnnualReport2018-19.pdf
  • 6
    Gummin DD, Mowry JB, Spyker DA, Brooks DE, Beuhler MC, Rivers LJ, et al. 2018 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 36th Annual Report. Clin Toxicol (Phila). 2019;57(12):1220-413. https://doi.org/10.1080/15563650.2019.1677022
    » https://doi.org/10.1080/15563650.2019.1677022
  • 7
    Richardson R, Charters T, King N, Harper S. Trends in educational inequalities in drug poisoning mortality: United States, 1994-2010. Am J Public Health. 2015;105(9):1859-65. https://doi.org/10.2105/AJPH.2015.302697
    » https://doi.org/10.2105/AJPH.2015.302697
  • 8
    Brasil. Lei N° 5991, de 17 de dezembro de 1973. Dispõe sobre o Controle Sanitário do Comércio de Drogas, Medicamentos, Insumos Farmacêuticos e Correlatos, e dá outras Providências. Brasíla, DF; 1973 [cited 2021 Mar 16]. Available from: http://www.planalto.gov.br/ccivil_03/leis/l5991.htm
    » http://www.planalto.gov.br/ccivil_03/leis/l5991.htm
  • 9
    Agência Nacional de Vigilância Sanitária. Instrução Normativa N° 11, de 29 de setembro de 2016. Dispõe sobre a lista de medicamentos isentos de prescrição. Diário Oficial da União. 30 set 2016 [cited 2020 Dec 28]; Seção 1:99. Available from: https://www.in.gov.br/materia/-/asset_publisher/Kujrw0TZC2Mb/content/id/23376708/do1-2016-08-03-resolucao-rdc-n-98-de-1-de-agosto-de-2016-23376586
    » https://www.in.gov.br/materia/-/asset_publisher/Kujrw0TZC2Mb/content/id/23376708/do1-2016-08-03-resolucao-rdc-n-98-de-1-de-agosto-de-2016-23376586
  • 10
    Instituto Brasileiro de Geografia e Estatística. Estimativas da População. Rio de Janeiro: IBGE; 2020 [cited 2020 Dec 28]. Available from: https://www.ibge.gov.br/estatisticas/sociais/populacao.html
    » https://www.ibge.gov.br/estatisticas/sociais/populacao.html
  • 11
    Ahmad OB, Boschi-Pinto C, Lopez AD, Murray CJL, Lozano R, Inoue M. Age standardization of rates: a new WHO standard. Geneva (CH): WHO; 2001 [cited 2021 Mar 16]. (GPE Discussion Paper Series; n° 31). Available from: http://www.who.int/healthinfo/paper31.pdf
    » http://www.who.int/healthinfo/paper31.pdf
  • 12
    Becketti S. Prais-Winsten regression. Stata Tech Bull. 1995 [cited 2021 Mar 16];(25):26-9. Available from: https://www.stata-press.com/journals/stbcontents/stb25.pdf
    » https://www.stata-press.com/journals/stbcontents/stb25.pdf
  • 13
    Park RE, Mitchell BM. Estimating the autocorrelated error model with trended data. J Econom. 1980;13(2):185-201.
  • 14
    Gaynor PE, Kirkpatrick RC. Introduction to time-series modeling and forecasting in business and economics. New York: McGraw-Hill; 1993. (McGraw-Hill economic series); (Wiley series in probability and mathematical statistics).
  • 15
    Pharma, Sales and Marketing Terms - IMS Health - PMB - Pharmaceutical Market Brasil. [cited 30 Jul 2021]. Available from: https://brazilsfe.blogspot.com/2015/12/pharma-terms-ims-o-que-e-pmb-pharmaceutical-market-brasil.html
    » https://brazilsfe.blogspot.com/2015/12/pharma-terms-ims-o-que-e-pmb-pharmaceutical-market-brasil.html
  • 16
    Agência Nacional de Vigilância Sanitária. Resolução - RDC N° 98, de 1° de agosto de 2016. Dispõe sobre os critérios e procedimentos para o enquadramento de medicamentos como isentos de prescrição e o reenquadramento como medicamentos sob prescrição, e dá outras providências. Diário Oficial da União. 3 ago 2016 [cited 2021 Mar 16]; Seção 1:32. Available from: https://www.in.gov.br/materia/-/asset_publisher/Kujrw0TZC2Mb/content/id/23376708/do1-2016-08-03-resolucao-rdc-n-98-de-1-de-agosto-de-2016-23376586
    » https://www.in.gov.br/materia/-/asset_publisher/Kujrw0TZC2Mb/content/id/23376708/do1-2016-08-03-resolucao-rdc-n-98-de-1-de-agosto-de-2016-23376586
  • 17
    Agência Nacional de Vigilância Sanitária. Resolução-RDC N° 96, de 17 de dezembro de 2008. Dispõe sobre a propaganda, publicidade, informação e outras práticas cujo objetivo seja a divulgação ou promoção comercial de medicamentos. Brasília, DF: Anvisa; 2008 [cited 2021 Mar 16]. Available from: http://bvsms.saude.gov.br/bvs/saudelegis/anvisa/2008/rdc0096_17_12_2008.html
    » http://bvsms.saude.gov.br/bvs/saudelegis/anvisa/2008/rdc0096_17_12_2008.html
  • 18
    Mota DM, Melo JRR, Freitas DRC, Machado M. Perfil da mortalidade por intoxicação com medicamentos no Brasil, 1996-2005: retrato de uma década. Cienc Saude Coletiva. 2012;17(1):61-70. https://doi.org/10.1590/S1413-8123201200010000
    » https://doi.org/10.1590/S1413-8123201200010000
  • 19
    Lee J, Fan NC, Yao TC, Hsia SH, Lee EP, Huang JL, et al. Clinical spectrum of acute poisoning in children admitted to the pediatric emergency department. Pediatr Neonatol. 2019;60(1):59-67. https://doi.org/10.1016/j.pedneo.2018.04.001
    » https://doi.org/10.1016/j.pedneo.2018.04.001
  • 20
    Lessa MA, Bochner R. Analysis of hospitalizations of children under one year of age due to drug intoxication and adverse events in Brazil. Rev Bras Epidemiol. 2008;11(4):1-15. https://doi.org/10.1590/S1415-790X2008000400013
    » https://doi.org/10.1590/S1415-790X2008000400013
  • 21
    Lacroix J, Gaudreault P, Gauthier M. Admission to a pediatric intensive care unit for poisoning: a review of 105 cases. Crit Care Med. 1989;17(8):748-50. https://doi.org/10.1097/00003246-198908000-00005
    » https://doi.org/10.1097/00003246-198908000-00005
  • 22
    Toce MS, Burns MM. The poisoned pediatric patient. Pediatr Rev. 2017;38(5):207-20. https://doi.org/10.1542/pir.2016-0130
    » https://doi.org/10.1542/pir.2016-0130
  • 23
    Santos GAS, Boing AC. Mortalidade e internações hospitalares por intoxicações e reações adversas a medicamentos no Brasil: análise de 2000 a 2014. Cad Saude Publica. 2018;34(6):e00100917. https://doi.org/10.1590/0102-311X00100917
    » https://doi.org/10.1590/0102-311X00100917
  • 24
    Ramos LR, Tavares NUL, Bertoldi AD, Farias MR, Oliveira MA, Luiza VL, et al. Polypharmacy and polymorbidity in older adults in Brazil: a public health challenge. Rev Saude Publica. 2016;50 Suppl 2:1s-12s. https://doi.org/10.1590/S1518-8787.2016050006145
    » https://doi.org/10.1590/S1518-8787.2016050006145
  • 25
    Baldoni AO, Chequer FMD, Ferraz ERA Oliveira DP, Pereira LRL, Dorta DJ. Elderly and drugs: risks and necessity of rational use. Braz J Pharm Sci. 2010;46(4):617-32. https://doi.org/10.1590/S1984-82502010000400003
    » https://doi.org/10.1590/S1984-82502010000400003
  • 26
    Bertoldi AD, Dal Pizzol TS, Ramos LR, Mengue SS, Luiza VL, Tavares NUL, et al. Sociodemographic profile of medicines users in Brazil: results from the 2014 PNAUM survey. Rev Saude Publica. 2016;50 Suppl 2:1s-10s. https://doi.org/10.1590/S1518-8787.2016050006119
    » https://doi.org/10.1590/S1518-8787.2016050006119
  • 27
    Agência IBGE Notícias. IBGE divulga o rendimento per capita 2017. Rio de Janeiro: IBGE; 2018 [cited 2021 Mar 16]. Available from: https://agenciadenoticias.ibge.gov.br/agencia-sala-de-imprensa/2013-agencia-de-noticias/releases/20154-ibge-divulga-o-rendimento-domiciliar-per-capita-2017
    » https://agenciadenoticias.ibge.gov.br/agencia-sala-de-imprensa/2013-agencia-de-noticias/releases/20154-ibge-divulga-o-rendimento-domiciliar-per-capita-2017
  • 28
    Schramm JMA, Oliveira AF, Leite IC, Valente JG, Gadelha AMJ, Portela MC, et al. Transição epidemiológica e o estudo de carga de doença no Brasil. Cienc Saude Coletiva. 2004;9(4):897-908. https://doi.org/10.1590/S1413-81232004000400011
    » https://doi.org/10.1590/S1413-81232004000400011
  • 29
    Marinho F, Passos VMA, França EB. Novo século, novos desafios: mudança no perfil da carga de doença no Brasil de 1990 a 2010. Epidemiol Serv Saude. 2016;25(4):713-24. https://doi.org/10.5123/S1679-49742016000400005
    » https://doi.org/10.5123/S1679-49742016000400005
  • 30
    Bezerra TA, Brito MAA, Costa KNFM. Characterization of medication use among elderly people attended at a family health care service. Cogitare Enferm. 2016;21(1):1-10.
  • 31
    Pagno AR, Gross CB, Gewehr DM, Colet CF, Berlezi EM. A terapêutica medicamentosa, interações potenciais e iatrogenia como fatores relacionados à fragilidade em idosos. Rev Bras Geriatr Gerontol. 2018;21(5):610-9. https://doi.org/10.1590/1981-22562018021.180085
    » https://doi.org/10.1590/1981-22562018021.180085

Publication Dates

  • Publication in this collection
    08 Dec 2021
  • Date of issue
    2021

History

  • Received
    31 Jan 2021
  • Accepted
    06 Apr 2021
Faculdade de Saúde Pública da Universidade de São Paulo São Paulo - SP - Brazil
E-mail: revsp@org.usp.br