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Medication shortages during the COVID-19 pandemic: Saving more than COVID lives

      In the United States (US) alone, 3,302,194 cases and 135,171 deaths due to COVID-19 have been confirmed as of July 12th, 2020 [
      ]. To put this in perspective, from 2018–2019, the CDC estimated there were approximately 35,500,000 cases and 34,200 deaths due to influenza [
      ]. These statistics correspond to a case-fatality ratio (CFR), the number of deaths divided by the total number of confirmed cases, that is nearly 40 times that of influenza in the case of COVID-19 (CFR 0.1% and 4.0%, respectively). Over the course of the pandemic, hospital resources have become scarce. Shortages of PPE, healthcare personnel, and ventilators have been reported nationwide, now add medications to the list of shortages [
      ,
      ,
      ].
      From 2015–2019, annual medication shortages have increased consistently from 5 to 31 (Fig. 1). However, over the span of only 6 months, 27 new shortages were announced in 2020 [
      ]. Medication shortages in 2020 have reached 87% that of the shortages reported in 2019 in half of the time. When considering the effect of the second wave of COVID-19 cases it is likely that medication shortages will continue to escalate.
      Fig. 1
      Fig. 1Current Drug Shortages initially reported from January 2016 – July 12th, 2020.
      The number of drug shortages increased from 4 in 2016 to 17 in 2017. This represents a 325% increase in the number of drug shortages. Furthermore, the number of drug shortages increased to 23 in 2018, corresponding to a 35% increase. Moreover, there were 31 drug shortages initially reported in 2019, a 35% increase from 2018. Finally, 27 drug shortages were first reported from January 2020 – July 2020.
      One report of 44,672 confirmed cases of COVID-19 suggests 6168 (14%) patients suffer from severe hypoxic respiratory failure and 2087 (5%) required mechanical ventilation [
      • Wu Z.
      • McGoogan J.M.
      Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention.
      ]. In the case of ventilation, patients often require varying amounts of sedation and/or analgesia depending on their status. For example, fentanyl is a commonly used drug for analgesia, whereas propofol is used for sedation. In addition, midazolam can be infused if heavy sedation is required [

      Vizient. COVID-19 Impact on drugs essential for ventilator use. Published April 7th, 2020. https://newsroom.vizientinc.com/sites/vha.newshq.businesswire.com/files/doc_library/file/COVID-19_impact_upon_ventilator_products_UPDATED2.1_040720.pdf. Accessed July 12th, 2020, 2020.

      ]. These medications are essential not patient comfort and to minimize the risk of self extubation. Yet, all 3 of these medications are currently in shortage (Table 1).
      Table 1Selected FDA Medication Shortages.
      Selected medication shortages during the COVID-19 pandemic
      Date first announcedDrugTherapeutic category
      2016September 19thKetoprofen CapsulesAnalgesia
      2017November 6thDopamine Hydrochloride InjectionCardiovascular
      November 6thDobutamine Hydrochloride InjectionCardiovascular, Renal
      November 14thHeparin Sodium and Sodium Chloride 0.9% InjectionHematology
      March 1stLabetalol Hydrochloride InjectionCardiovascular
      2018March 23rdRopivacaine Hydrochloride InjectionAnesthesia
      May 3rdLorazepam Injection, USPNeurology
      2019September 12thAmphetamine Aspartate; Amphetamine Sulfate; Dextroamphetamine Saccharate; Dextroamphetamine Sulfate TabletsPsychiatry
      February 8thDexamethasone Sodium Phosphate InjectionDermatology, Gastroenterology, Oncology, Ophthalmology, Pulmonary/Allergy, Rheumatology
      March 14thFlurazepam Hydrochloride CapsulesPsychiatry
      April 2ndMetoprolol Tartrate Injection, USPCardiovascular
      August 7thTechnetium Tc99m Succimer Injection (DMSA)Medical Imaging
      February 26thAVYCAZ (ceftazidime and avibactam) for Injection, 2 g/0.5 gAnti-infective
      2020April 2ndHydrocortisone Tablets, USPEndocrinology/Metabolism
      April 2ndMidazolam Injection, USPAnesthesia
      April 7thFurosemide Injection, USPCardiovascular
      April 8thCisatracurium Besylate InjectionAnesthesia
      April 10thDexmedetomidine InjectionAnesthesia
      April 10thEtomidate InjectionAnesthesia
      April 10thPropofol Injectable EmulsionAnesthesia
      April 14thAzithromycin TabletsAnti-infective
      April 22ndContinuous Renal Replacement Therapy (CRRT) SolutionsRenal
      May 5thFamotidine InjectionGastroenterology
      May 6thVecuronium Bromide for InjectionPulmonary/Allergy
      May 11thDimercaprol (Bal in Oil) Injection USPHematology
      May 21stAmifostine InjectionOncology
      July 10thDoxycycline Hyclate InjectionAnti-infective
      N/AFentanyl Citrate (Sublimaze) InjectionAnalgesia
      Source: FDA Drug Shortages. U.S. Food & Drug Administration. https://www.accessdata.fda.gov/scripts/drugshortages/default.cfm. Accessed July 12th, 2020.
      There is concern for additional patients presenting to emergency departments as states commit to reopening. One analysis suggests that the number of motor vehicle collisions (MVCs) decreased during the pandemic [
      • Sutherland M.
      • McKenney M.
      • Elkbuli A.
      Vehicle related injury patterns during the COVID-19 pandemic: what has changed?.
      ]. It is likely that the number of MVCs will return to baseline levels as additional states commit to reopening. The additional stress from trauma-related cases on the healthcare system in the midst of preexisting medication shortages could result in deaths that may have been preventable if ample medications were available.
      Furthermore, medication shortages pose a threat to many more patients beyond those infected with COVID-19. For example, hydroxychloroquine and chloroquine are used for many autoimmune diseases such as rheumatoid arthritis. Although the shortages of these medications have recently resolved [
      ], other drugs such as dexamethasone used to treat both COVID-19 and many other diseases is depleting (Table 1).
      With so much coverage on the pandemic, it is easy to forget about patients presenting with other common diseases. For example, heart disease remains the leading cause of death in the US and translates to 1 in every 4 deaths [
      ]. There is a shortage of medications used to treat those with cardiovascular disease, such as furosemide and labetalol injections (Table 1). Similarly, drugs used to prevent blood clots, such as heparin, are also currently in shortage (Table 1).
      In addition, medication shortages will likely have an effect on cancer patients. Shortages of drugs used for medical imaging of cancer, such as Technetium, have the potential to compound the decrease in diagnoses due to the pandemic (Table 1). Furthermore, shortages of oncology medications that provide a protective effect from other chemotherapy agents, such as amifostine, may increase the risk for adverse events and worsen patient outcomes.
      It is possible that as some medication shortages resolve, other shortages will arise and increase mortality. In 2017, over 1.7 million deaths were due to the top 5 causes of death: heart disease, cancer, unintentional injuries, chronic lower respiratory diseases, and stroke [
      ]. The medication shortages reported by the FDA thus far impact all 5 leading causes of death and could have a significant impact on the mortality rate. It is important for us to take proactive measures in order to minimize the negative effects on the nation.
      In the same way manufactures of ventilators are increasing production, the manufacture of medications is a viable option. In addition, if companies such as Ford, Dyson and Tesla were able to create ventilators, large pharmaceutical companies could focus on producing drugs in shortage [
      ]. In addition to increased manufacturing, domestic production of the active ingredient of essential drugs can aid in the shortage, as some drugs are scarce for this reason. The consequences may be dire for those whose life relies on these medications. Although it is still a long road back to normalcy, when the pandemic is over, we may never know if our efforts reached the point of overkill, however, it will be very obvious to us if we did not do enough.

      References

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        • Wu Z.
        • McGoogan J.M.
        Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention.
        JAMA. 2020; 323: 1239-1242https://doi.org/10.1001/jama.2020.2648
      7. Vizient. COVID-19 Impact on drugs essential for ventilator use. Published April 7th, 2020. https://newsroom.vizientinc.com/sites/vha.newshq.businesswire.com/files/doc_library/file/COVID-19_impact_upon_ventilator_products_UPDATED2.1_040720.pdf. Accessed July 12th, 2020, 2020.

        • Sutherland M.
        • McKenney M.
        • Elkbuli A.
        Vehicle related injury patterns during the COVID-19 pandemic: what has changed?.
        Am J Emerg Med. 2020; 38 (Online ahead of print. PMID: 32721782): 1710-1714https://doi.org/10.1016/j.ajem.2020.06.006
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