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Drug Shortages in Pediatrics in Europe: The Position of the European Pediatric Societies

2023; Elsevier BV; Volume: 261; Linguagem: Inglês

10.1016/j.jpeds.2023.113472

1097-6833

Gottfried Huss, Shimon Barak, Laura Reali, Christine Magendie, Angel Carrasco-Sanz, Eli Somekh, Robert Cohen, Yaël Levy, Leyla S. Namazova-Baranova, Mehmet Vural, Massimo Pettoello‐Mantovani,

Adolescent and Pediatric Healthcare

Prescription and nonprescription drug shortages are not a new phenomenon.1Donnelly K.A. Zocchi M.S. Katy T.A. Fox E.R. Pines J.M. van den Anker J.N. et al.Prescription drug shortages: pediatric emergency and critical care medications.Pediatr Emerg Care. 2021; 37: e726-e731PubMed Google Scholar The recent health crisis caused by the COVID-19 pandemic has further highlighted a chronic shortage of drugs and medical equipment in many western countries. This is a growing problem for Europe's national health systems. In recent years, shortages of all types of drugs have become increasingly common in hospital pediatrics and primary care and pose a threat to the health of adults and children in Europe and the US.1Donnelly K.A. Zocchi M.S. Katy T.A. Fox E.R. Pines J.M. van den Anker J.N. et al.Prescription drug shortages: pediatric emergency and critical care medications.Pediatr Emerg Care. 2021; 37: e726-e731PubMed Google Scholar, 2Banerjee R. Thurm C.W. Fox R. Hersh A.L. Antibiotic Shortages in Pediatrics.Pediatrics. 2018; 142e20180858Crossref PubMed Scopus (4) Google Scholar, 3European Civic University AllianceCIVIS member universities united against COVID-19.https://civis.eu/en/news/civis-member-universities-united-against-covid-19Date accessed: February 8, 2023Google Scholar As early as April 2020, the Alliance of European University Hospitals warned that the increasing demand from intensive care units for anesthetics, antibiotics, muscle relaxants, and "off-label" drugs for the treatment of COVID-19 could lead to stock-outs.3European Civic University AllianceCIVIS member universities united against COVID-19.https://civis.eu/en/news/civis-member-universities-united-against-covid-19Date accessed: February 8, 2023Google Scholar However, after 2020, with declining production, logistical problems, and export and storage bans due to the current pandemic-related health crisis, the risk of shortage has increased.4Cohen R. Pettoello-Mantovani M. Giardino I. Carrasco-Sanz A. Somekh E. Levy C. The shortage of amoxicillin: an escalating public health crisis in pediatrics faced by several western countries.J Pediatr. 2023; https://doi.org/10.1016/j.jpeds.2023.01.001Abstract Full Text Full Text PDF Scopus (1) Google Scholar In September 2020, the European Union (EU) Parliament voted on a resolution calling for the EU to become more self-sufficient in health care.5European UnionEuropean parliament resolution of 17 September 2020 on the shortage of medicines.https://www.europarl.europa.eu/doceo/document/TA-9-2020-0228_EN.htmlDate accessed: February 8, 2023Google Scholar In the text, the members of the European Parliament called for securing stocks, restoring local production of medicines, and ensuring better European coordination of national health strategies. Unfortunately, 2 years later, the problem has not been solved, but to the contrary has worsened. Currently, public health systems are facing a drug shortage crisis of unforeseen magnitude, one, ie, seriously undermining the public health of European nations.3European Civic University AllianceCIVIS member universities united against COVID-19.https://civis.eu/en/news/civis-member-universities-united-against-covid-19Date accessed: February 8, 2023Google Scholar In particular, primary care pediatrics is in great distress6Tufts L. Worthy M. Putty K. Wallace T. Waldeck K. Waldeck J.M. et al.Improving resident experience during the pediatric intensive care unit rotation.Global Pediatrics. 2023; 3100029https://doi.org/10.1016/j.gpeds.2022.100029Crossref Google Scholar due to the shortage of essential drugs to ensure the health of the pediatric population. Between 2000 and 2018, drug shortages in the EU grew up to 20 times.7European UnionREPORT on the shortage of medicines – how to address an emerging problem.https://www.europarl.europa.eu/doceo/document/A-9-2020-0142_EN.htmlDate accessed: February 8, 2023Google Scholar However, according to a note from the European Commission, the availability of widely used essential products continued to decline significantly after that date.7European UnionREPORT on the shortage of medicines – how to address an emerging problem.https://www.europarl.europa.eu/doceo/document/A-9-2020-0142_EN.htmlDate accessed: February 8, 2023Google Scholar As discussed by the EU report, the causes are complex and include production problems, industry quotas, and legal parallel trade, ie, the import of medicines from other member states where the price is lower.7European UnionREPORT on the shortage of medicines – how to address an emerging problem.https://www.europarl.europa.eu/doceo/document/A-9-2020-0142_EN.htmlDate accessed: February 8, 2023Google Scholar Other causes are epidemics and natural disasters, which cause unforeseen increases in demand, and the cost of medicines, which is set at the national level.7European UnionREPORT on the shortage of medicines – how to address an emerging problem.https://www.europarl.europa.eu/doceo/document/A-9-2020-0142_EN.htmlDate accessed: February 8, 2023Google Scholar The EU is increasingly dependent on third countries, particularly India and China, for the production of active pharmaceutical ingredients, chemical raw materials, and drugs.7European UnionREPORT on the shortage of medicines – how to address an emerging problem.https://www.europarl.europa.eu/doceo/document/A-9-2020-0142_EN.htmlDate accessed: February 8, 2023Google Scholar,8D'Apolito M. Colia A.L. Lasalvia M. Capozzi V. Falcone M.P. Pettoello-Mantovani M. et al.Urea-induced ROS accelerate senescence in endothelial progenitor cells.Atherosclerosis. 2017; 263: 127-136Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Unfortunately, the solutions adopted by the EU do not seem to have succeeded in mitigating the problem of drug shortages, despite the fact that the European Parliament had called for strengthening the production of medicines in Europe and setting minimum quality standards for health care, adopting best practices for stockpile management, increasing joint purchasing of medicines, and simplifying the transfer of medicines between member states. In its 2017 resolution, the European Parliament called for better tracking of research and development costs, public funding, and market expenditures to make medicines more affordable.9European UnionREPORT on EU options for improving access to medicines.https://www.europarl.europa.eu/doceo/document/A-8-2017-0040_EN.htmlDate accessed: February 8, 2023Google Scholar In April 2020, the European Commission issued guidelines to counter drug shortages due to the coronavirus pandemic,10European Union ParliamentAddressing shortages of medicines. commission guidelines to avoid shortages of medicines during the pandemic and establish a coordinated approach across Europe.https://www.europarl.europa.eu/RegData/etudes/BRIE/2020/649402/EPRS_BRI(2020)649402_EN.pdfDate accessed: February 8, 2023Google Scholar calling on member states to suspend export bans, avoid national stockpiles, and increase and reorganize production.11Pettoello-Mantovani C. Olivieri B. Food safety and public health within the frame of the EU legislation.Global Pediatrics. 2022; 2100020https://doi.org/10.1016/j.gpeds.2022.100020Crossref Google Scholar However, the problem of drug shortages still seems to be unresolved and a threat to the health of children. This commentary, jointly authored by the European Confederation of Primary Care Pediatricians and the European Paediatric Association/Union of National European Paediatric Societies and Associations, highlights a joint statement issued by the 2 leading European pediatric societies addressing the serious problem of drug shortages in primary care pediatrics in Europe (Table).TableAddressing drug shortages in primary care pediatrics in EuropeJoint statement by• ECPCP• EPA-UNEPSADrug shortages challenge health care systems around the world. Authorities and public agencies in Europe and the US are now reporting shortages of commonly prescribed medications in pediatric settings. This situation raises fears that most of the drugs used to treat various pediatric conditions will be in short supply for the current winter season and for months to come.ECPCP and EPA-UNEPSA emphasize that drug shortages can pose health risks to patients through undertreatment, medication errors, increased length of hospital stay, and adverse reactions due to attempts to replace unavailable drugs. Populations around the globe are in the transition phase from pandemic COVID to endemic COVID. The unseasonably early increase in respiratory infections in Europe during the winter 2022-23 is caused by unusual immunologic gaps. The early winter flu wave in children places an unexpected burden on pediatric primary care and increased demand for specialty anti-infective drugs. Children are a particularly vulnerable patient group with very limited pharmaceutical treatment options. This exposed them to adverse outcomes caused by shortages of essential medications. Problems with production and supply of existing drugs reduce the availability of critical products and preparations.ECPCP and EPA-UNEPSA stress that a joint effort to understand the source of the problem can help resolve the current emergency and strengthen the preparedness of public health systems to deal with the next inevitable crisis.Finally, the 2 leading European pediatric societies raise awareness among stakeholders, including health care professionals, legislators, and public health administrators, of the problem of drug shortages in primary care pediatrics and emphasize the importance of their close and effective interaction and collaboration to adequately address the recurring problem of drug shortages in this key public health area.The appendix to this statement briefly discusses the general issue of drug shortages, its implications for primary care pediatrics, and possible useful measures to address this problem at the international, national, and local levels.APPENDIX• Global geopolitical dimension of medicine shortageDrug shortages have taken on a global geopolitical dimension. The COVID-19 crisis has made the geopolitical dimension of drug shortages evident, highlighting the dependence of the European Union and the US on countries outside their borders for the production of active pharmaceutical ingredients (APIs) and drugs. According to information from the generic drug industry, China is a major producer of pharmaceutical inputs, particularly raw materials, intermediates, and APIs. The country is also considered by far the largest supplier of APIs or key intermediates for some essential drugs, such as analgesics (painkillers) or anti-infectives.• Challenges by new seasonal epidemiological featuresAn unusually rapid onset of the annual flu season, caused by respiratory syncytial virus, influenza A and B, and many other viruses, has created a surge in demand for prescribed amoxicillin and pain relievers that parents can purchase without a prescription. Because these epidemiological features were unexpected, they could not be predicted and the increase in demand could not be anticipated.• Medicines fall short in pediatric primary care.More than 86% of European hospital pharmacists are experiencing difficulties in sourcing different types of medicines, and 66% report this as a daily or weekly problem. These shortages in Europe involve originator drugs in 51.8% of cases, and while the percentage rises to about 60% if we include generic formulations.1Donnelly K.A. Zocchi M.S. Katy T.A. Fox E.R. Pines J.M. van den Anker J.N. et al.Prescription drug shortages: pediatric emergency and critical care medications.Pediatr Emerg Care. 2021; 37: e726-e731PubMed Google Scholar In particular, the prescription antibiotic amoxicillin is in short supply due to increased demand. Certain liquid formulations and suppositories of paracetamol (US: acetaminophen) and ibuprofen which are frequently recommended as fever-medicine and painkillers fall short in 26 European countries (as reported by the European Medicines Agency) and in the US.• Missing priority for pediatric medicine.Child-friendly medicines are neglected when measuring accessibility to medicines. There is no comprehensive overview of available data on children's medications. Children do not have a voice and cannot advocate for themselves by demanding more attention and investment in the production of children's medicines, which is currently limited probably because of limited earnings. Children need advocates on their behalf to obtain adequate data and improve access to child-friendly medicines.Tackling children's medicine shortage in primary care pediatrics:There is no magic solution to avoid the shortage of children's medicines in primary care. However, actions are needed to respond to the shortage at different international, national, and local levels with different stakeholders.• Actions expected by international organizations and agencies (European Commission, European Union, European Medicines Agency, World Health Organization).Ensure the production and supply of essential medicines for children in all countries. Proposed changes to European Union pharmaceutical law should include more stringent obligations for the supply of medicines and more timely notifications of shortages. Improve communications among different countries regarding medications supply and stock files to better balance between demand and supply• Actions expected by the national governments and public health authorities.Protection of children's health through improved monitoring of causes of drug shortages and consideration of new regulations and legislation to ensure sufficient production and supply of essential medicines for children in hospitals and primary pediatric care. Promotion of healthy lifestyle for children and adolescents. Assure the prevention of infections with public promotion of vaccines and nonpharmaceutical personal protection to interrupt transmissions.• Actions expected from the pharmaceutical industry.Avoid production shortages, which often recognize internal problems within pharmaceutical companies, and poor or temporary unavailability of distribution. Promote independent national production and storage of primary substances for essential drugs.• Actions expected by pharmacies.Improve frequent communication with prescribers and providers about available medications. Advise parents on over-the-counter medications and alternatives. Check in-store alternatives first if some products are not available. Improve promotion of the use of generic versions of brand-name products, which are perfectly safe and often a much more convenient option.• Actions expected of pediatricians.Ambulatory pediatric care providers must be advocates for the safety of patients and protect children from drug shortages. They must be aware of current shortages and implement mitigation strategies. Implementing resilience strategies. Avoid unnecessary treatment of fever and viral infections. In cases of nonsevere otitis media, upper respiratory tract infections, and sinusitis, waiting is an option. Patients will be satisfied if the reasons for forgoing antibiotic treatment are explained. If amoxicillin is indicated and liquid formulations are not available, prescribe drugs that have not been affected by the shortage, including amoxicillin in tablets, chewable tablets, or dispersible formulations that are able to take. When amoxicillin cannot be used, consider the following alternatives: amoxicillin/clavulanate. Avoid cephalosporins, as resistance problems are becoming more important. If antipyretics/analgesics are indicated, including acetaminophen, paracetamol, or ibuprofen, and liquid formulations are not available, prescribe tablets, chewable tablets, or dispersible formulations for children who are able to take these formulations. The latter have been affected by the shortage to a lesser extent. Consider prescribing alternative drugs. Advise parents and caregivers that most tablets can be split/shredded and capsules can be opened. Both can be mixed with any tasty liquid. Chewable tablets can also be divided. Consider using complementary and alternative medicine, when possible. Follow guidelines regarding judicious usage of antibiotics, antipyretics, and other medications• Actions expected from parents.Avoid wasting medicines (disposing medicines before their expiration date). Avoid pressuring doctors to prescribe antibiotics for minor illnesses. Strengthen the ability to cope with infectious symptoms. Use natural methods and medicine whenever it is safe, applicable, and advisable.ECPCP, European Confederation of Primary Care Pediatricians; EPA-UNEPSA, European Paediatric Association-Union of National European Paediatric Societies and Association. Open table in a new tab ECPCP, European Confederation of Primary Care Pediatricians; EPA-UNEPSA, European Paediatric Association-Union of National European Paediatric Societies and Association. Children are a particularly vulnerable patient group12Petito A. Pop T.L. Namazova-Baranova L. Mestrovic J. Nigri L. Vural M. et al.The burden of depression in adolescents and the importance of early recognition.J Pediatr. 2020; 218: 265-267.e1Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar with very limited pharmaceutical treatment options.12Petito A. Pop T.L. Namazova-Baranova L. Mestrovic J. Nigri L. Vural M. et al.The burden of depression in adolescents and the importance of early recognition.J Pediatr. 2020; 218: 265-267.e1Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar This limitation exposed them to adverse outcomes caused by shortages of essential medications. The European Confederation of Primary Care Pediatricians and European Paediatric Association/Union of European National Paediatric Societies and Associations emphasize the importance of ensuring optimal use of pediatric drugs in hospitals and ambulatory settings, through stock redistribution, consideration of alternative drugs, and optimization of pharmacy sales. Finally, the 2 societies jointly emphasize the dual need, on the one hand, to strengthen the EU production and supply resilience and, on the other hand, to increase price transparency and public funding for research and development.7European UnionREPORT on the shortage of medicines – how to address an emerging problem.https://www.europarl.europa.eu/doceo/document/A-9-2020-0142_EN.htmlDate accessed: February 8, 2023Google Scholar,9European UnionREPORT on EU options for improving access to medicines.https://www.europarl.europa.eu/doceo/document/A-8-2017-0040_EN.htmlDate accessed: February 8, 2023Google Scholar The authors declare no conflicts of interest.