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Drug–Drug Interactions and the Risk of Emergency Hospitalizations: A Nationwide Population-Based Study

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Abstract

Background

Several studies suggest a significant risk of hospitalization because of drug–drug interactions in the general population. However, to our knowledge, this risk has never been measured precisely in a large population.

Objective

We aimed to estimate the risk of emergency hospitalization associated with exposure to the contraindicated concomitant use of interacting drugs in the general population.

Methods

A self-controlled case-series analysis was carried out on a cohort of 150,000 subjects randomly selected from the French national health insurance database, between 01/01/2016 and 31/12/2016. Exposure to the contraindicated concomitant use of interacting drugs was defined as the overlapping period of dispensings of drugs contraindicated because of clinically meaningful drug–drug interactions. The main outcome, incidence rate ratios, comparing the incidence rate of emergency hospitalizations during each category of exposure time periods with that during the reference period, was estimated using the conditional Poisson regression model.

Results

Over the study period, 967 subjects were exposed to at least one contraindicated concomitant use of interacting drug and 177 had been exposed and presented at least one emergency hospitalization. Compared to the unexposed follow-up time, the risk of emergency hospitalization increased during exposure to contraindicated concomitant use of interacting drug periods (incidence rate ratio: 2.41; 95% confidence interval 1.55–3.76). This could translate into 7200 (4500–8900) potentially preventable emergency hospitalizations yearly in France.

Conclusions

We evidenced an almost 2.5-fold increase in the risk of emergency hospitalizations during periods of exposure to contraindicated concomitant use of interacting drugs, with a potential public health impact exceeding 7000 preventable hospitalizations yearly in France. These results confirm the need to reinforce training in prescription practices and tools for prevention concerning contraindicated concomitant use of interacting drugs. These would especially concern drugs involved in an increase in long QT syndrome when associated such as citalopram, and highly prescribed drugs with a risk of overdose if co-prescribed with cytochrome P450 inhibitors, such as antigout and lipid-lowering drugs.

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References

  1. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386:743–800.

  2. Schumock GT, Li EC, Suda KJ, et al. National trends in prescription drug expenditures and projections for 2014. Am J Health Syst Pharm. 2014;71:482–99.

    Article  PubMed  Google Scholar 

  3. Abolhassani N, Castioni J, Marques-Vidal P, Vollenweider P, Waeber G. Determinants of change in polypharmacy status in Switzerland: the population-based CoLaus study. Eur J Clin Pharmacol. 2017;73:1187–94.

    Article  PubMed  Google Scholar 

  4. Wastesson JW, Minguez AC, Fastbom J, Maioli S, Johnell K. The composition of polypharmacy: a register-based study of Swedes aged 75 years and older. PLoS ONE. 2018;13: e0194892.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Guthrie B, Makubate B, Hernandez-Santiago V, Dreischulte T. The rising tide of polypharmacy and drug-drug interactions: population database analysis 1995–2010. BMC Med. 2015;13:74.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kantor ED, Rehm CD, Haas JS, Chan AT, Giovannucci EL. Trends in prescription drug use among adults in the United States from 1999–2012. JAMA. 2015;314:1818–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Qato DM, Wilder J, Schumm LP, Gillet V, Alexander GC. Changes in prescription and over-the-counter medication and dietary supplement use among older adults in the United States, 2005 vs 2011. JAMA Intern Med. 2016;176:473–82.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Guillot J, Maumus-Robert S, Marceron A, Noize P, Pariente A, Bezin J. The burden of potentially inappropriate medications in chronic polypharmacy. J Clin Med. 2020;9:3728.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Létinier L, Cossin S, Mansiaux Y, et al. Risk of drug-drug interactions in out-hospital drug dispensings in France: results from the DRUG-Drug Interaction Prevalence Study. Front Pharmacol. 2019;10:265.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Chatsisvili A, Sapounidis I, Pavlidou G,  et al. Potential drug-drug interactions in prescriptions dispensed in community pharmacies in Greece. Pharm World Sci. 2010;32:187–93.

    Article  PubMed  Google Scholar 

  11. Marzolini C, Elzi L, Gibbons S, et al. Prevalence of comedications and effect of potential drug-drug interactions in the Swiss HIV Cohort Study. Antivir Ther (Lond). 2010;15:413–23.

    Article  CAS  Google Scholar 

  12. van Leeuwen RWF, Brundel DHS, Neef C, et al. Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs. Br J Cancer. 2013;108:1071–8.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Nusair MB, Al-Azzam SI, Arabyat RM, Amawi HA, Alzoubi KH, Rabah AA. The prevalence and severity of potential drug-drug interactions among adult polypharmacy patients at outpatient clinics in Jordan. Saudi Pharm J. 2020;28:155–60.

    Article  CAS  PubMed  Google Scholar 

  14. Ren W, Liu Y, Zhang J, et al. Prevalence of potential drug-drug interactions in outpatients of a general hospital in China: a retrospective investigation. Int J Clin Pharm. 2020;42:1190–6.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Seymour RM, Routledge PA. Important drug-drug interactions in the elderly. Drugs Aging. 1998;12:485–94.

    Article  CAS  PubMed  Google Scholar 

  16. Becker ML, Kallewaard M, Caspers PWJ, Visser LE, Leufkens HGM, Stricker BHC. Hospitalisations and emergency department visits due to drug-drug interactions: a literature review. Pharmacoepidemiol Drug Saf. 2007;16:641–51.

    Article  PubMed  Google Scholar 

  17. Dechanont S, Maphanta S, Butthum B, Kongkaew C. Hospital admissions/visits associated with drug–drug interactions: a systematic review and meta-analysis. Pharmacoepidemiol Drug Saf. 2014;23:489–97.

    Article  PubMed  Google Scholar 

  18. Bykov K, Schneeweiss S, Glynn RJ, Mittleman MA, Gagne JJ. A case-crossover-based screening approach to identifying clinically relevant drug-drug interactions in electronic healthcare data. Clin Pharmacol Ther. 2019;106:238–44.

    Article  CAS  PubMed  Google Scholar 

  19. De Vincentis A, Gallo P, Finamore P, et al. Potentially inappropriate medications, drug-drug interactions, and anticholinergic burden in elderly hospitalized patients: does an association exist with post-discharge health outcomes? Drugs Aging. 2020;37:585–93.

    Article  PubMed  Google Scholar 

  20. Hochheiser H, Jing X, Garcia EA, et al. A minimal information model for potential drug-drug interactions. Front Pharmacol. 2021;11:2477.

    Article  Google Scholar 

  21. Bezin J, Noize P, Mansiaux Y, Jarne A, Pariente A. Antidopaminergic antiemetics and trauma-related hospitalization: a population-based self-controlled case series study. Br J Clin Pharmacol. 2021;87:1303–9.

    Article  CAS  PubMed  Google Scholar 

  22. Thésaurus des interactions médicamenteuses. ANSM. 2021. Available from: https://ansm.sante.fr/documents/reference/thesaurus-des-interactions-medicamenteuses-1. [Accessed 13 Dec 2022].

  23. Bezin J, et al. The national healthcare system claims databases in France, SNIIRAM and EGB: powerful tools for pharmacoepidemiology. Pharmacoepidemiol Drug Saf. 2017;26:954–62.

    Article  PubMed  Google Scholar 

  24. Farrington P, Pugh S, Colville A, et al. A new method for active surveillance of adverse events from diphtheria/tetanus/pertussis and measles/mumps/rubella vaccines. Lancet. 1995;345:567–9.

    Article  CAS  PubMed  Google Scholar 

  25. Petersen I, Douglas I, Whitaker H. Self controlled case series methods: an alternative to standard epidemiological study designs. BMJ. 2016;354: i4515.

    Article  PubMed  Google Scholar 

  26. Rockhill B, Newman B, Weinberg C. Use and misuse of population attributable fractions. Am J Public Health. 1998;88:15–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Whitaker HJ, Paddy Farrington C, Spiessens B, Musonda P. Tutorial in biostatistics: the self-controlled case series method. Stat Med. 2006;25:1768–97.

    Article  PubMed  Google Scholar 

  28. Jawaro T, Bridgeman PJ, Mele J, Wei G. Descriptive study of drug-drug interactions attributed to prescriptions written upon discharge from the emergency department. Am J Emerg Med. 2019;37:924–7.

    Article  PubMed  Google Scholar 

  29. Guédon-Moreau L, Ducrocq D, Duc MF, et al. Absolute contraindications in relation to potential drug interactions in outpatient prescriptions: analysis of the first five million prescriptions in 1999. Eur J Clin Pharmacol. 2003;59:689–95.

    Article  PubMed  Google Scholar 

  30. Danielsson B, Collin J, Nyman A, et al. Drug use and torsades de pointes cardiac arrhythmias in Sweden: a nationwide register-based cohort study. BMJ Open. 2020;10: e034560.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Bordeaux Population Health Research Center, Team Pharmacoepidemiology, Inserm UMR 1219, University of Bordeaux, Bordeaux, France

    Louis Létinier, Julien Bezin & Ana Jarne

  2. Service de Pharmacologie Médicale, CHU Bordeaux, Université de Bordeaux, 146, rue Léo Saignat, BP36, 33076, Bordeaux Cedex, France

    Louis Létinier, Julien Bezin & Antoine Pariente

Authors
  1. Louis Létinier
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  2. Julien Bezin
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  3. Ana Jarne
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  4. Antoine Pariente
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Corresponding author

Correspondence to Louis Létinier.

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Funding

The present study is part of the Drugs Systematized Assessment in real-liFe Environment (DRUGS-SAFE) research program that is funded in part by the French Medicines Agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM); grant number 2014s029. This program aims at creating an integrated system for the concomitant monitoring of drug use and safety in France. The potential impact of drugs, the frailty of populations, and the seriousness of risks drive the research program. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication. This publication represents the views of the authors and does not necessarily represent the opinion of the French Medicines Agency.

Conflict of interest

All authors declare research grants from the French Medicines Agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM).

Ethical approval

This study received the consent of The National Institute for Health Data.

Consent to participate

Not applicable.

Consent for publications

Not applicable.

Availability of Data and Material

Publicly sharing EGB data is forbidden by law according to the French national data protection agency (Commission Nationale de l’Informatique et des LIbertés, CNIL); regulatory decisions AT/CPZ/SVT/JB/DP/CR05222O of 14 June, 2005 and DP/CR071761 of 28 August, 2007. To request data access, please contact The National Institute for Health Data (Institut National des Données de Santé, INDS; website: http://www.indsante.fr/).

Code availability

Not applicable.

Author contributions

LL, JB, and AP contributed to the conception and design; AJ contributed to data acquisition; LL and AJ contributed to data analysis; LL, JB, AJ, and AP contributed to data interpretation; LL contributed to drafting of the article; JB, AJ, and AP critically revised the article for important intellectual content. All authors read and approved the final version of the article.

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Létinier, L., Bezin, J., Jarne, A. et al. Drug–Drug Interactions and the Risk of Emergency Hospitalizations: A Nationwide Population-Based Study. Drug Saf 46, 449–456 (2023). https://doi.org/10.1007/s40264-023-01283-7

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  • DOI: https://doi.org/10.1007/s40264-023-01283-7

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