Drug product shortages are currently an epidemic in the USA. Lack of available treatments for emergent medical conditions and poisoning negatively impact drug therapy in a variety of ways. Shortages compromise or delay medical care, result in medication errors, and increase patient mortality and morbidity [1, 2]. Furthermore, the lack of less commonly available antidotes recommended by toxicologists creates additional risk to the patient from precarious hospital transfers that otherwise may have been avoided.

In this issue of JMT, Troger and Burns describe the struggle of managing drug shortages and the effects on medical decisions and provision of necessary antidotal therapies [3]. We believe their review, entitled “Pharmaceutical Purchasing: a review of the landscape and Implications for Antidotal Therapies,” serves to highlight an ongoing problem that impacts all healthcare providers regardless of their role in patient care [3]. Several past studies show a need for a multidisciplinary team approach to find alternative treatment plans when dealing with drug shortages at the bedside [4,5,6].

An enormous amount of labor and resources are required to address shortages. Often, lack of drug availability results in purchasing more-expensive substitute products [1, 7, 8]. Labor costs for direct patient care are incurred through personnel costs for the management of the multiple medication dispensing automation systems, smart pumps, and electronic medical record changes that must be made. In addition, there is a cost associated with educating healthcare staff in all positions of direct and indirect patient care to ensure medication safety when using an alternative agent. An estimated $216 million dollars in extra labor costs are absorbed by healthcare institutions due to more expensive alternatives [1, 8]. Troger and Burns describe multiple strategies that healthcare institutions and healthcare providers employ to mitigate the financial burden of drug shortages on the healthcare system. These include negotiating bulk prices, preferential reimbursement arrangements, outsourcing to third parties that negotiate lower drug prices, and limiting medication orders to a formulary or specific manufacturer with an established reduced cost purchasing agreement with the pharmacy. While all of these are good strategies to ease the burden of drug shortage costs, more collaborative research is needed to assess the consequences of drug shortages at the level of bedside care [3].

Studies examining bedside costs are limited but extremely important to consider. Alternative products commonly have different concentrations, strengths, dosage forms, or potential adverse drug reactions. Providers must be educated on these differences to avoid medication mistakes. Providers consult poison centers for recommendations to care for the poisoned patient, and sometimes, these centers can assist in locating necessary antidotes. Poison information specialists must be apprised of alternatives, educated on when they are appropriate for consideration, and notified who has access to what products in the region they serve. Shortages create high levels of stress, frustration, and burnout for everyone involved, including purchasing agents, pharmacists, pharmacy technicians, nurses, physicians, and patients leading to poor morale and increased risk for error.

Many of these bedside issues were revealed in 2018 during an outbreak of brodifacoum-contaminated synthetic cannabinoids that affected patients in multiple states [6]. Because brodifacoum, a product with a significantly long half-life, inhibited vitamin K–dependent clotting factors, patients were initially treated with intravenous vitamin K1 until they were able to tolerate an oral regimen. The recommended oral regimen may require 30 tablets a day for each patient for several weeks. At the time of this outbreak, production of vitamin K tablets was limited to a single manufacturer whose supply was quickly depleted. Fortunately, emergency medicine pharmacists in one region developed an alternative treatment plan by using intravenous vitamin K1 orally. This strategy proved to be successful in treating coagulopathy in a large number of patients, prevented depletion of their institution’s oral vitamin K1 supplies, and reduced overall inpatient costs since IV vitamin K1 was less expensive than oral vitamin K1. This strategy provided an added benefit of increased patient compliance with their treatment plan because of the decrease in pill burden. During that large brodifacoum outbreak, EM clinical pharmacists at the bedside worked with several members of the healthcare team to ensure that poisoned patients received the necessary antidote for their survival despite a critical drug shortage. Through the collaboration that exists with poison centers, these EM clinical pharmacists were able to share their successful strategy with recommendations to smaller, rural hospitals to provide the necessary antidotal treatment without the need for a patient transfer. A tremendous amount of labor and educational resources for providers and patients went into developing this alternative treatment regimen in order to prevent any medication errors and to reduce treatment failure.

In some cases, compounding by hospital and specialty pharmacies can help to alleviate access to necessary treatment, but laws surrounding compounding are stringent and vary from state to state. Compounding in bulk is generally limited when a proprietary product already exists. For several years, medications used to chelate heavy metals, often used to reduce the lead burden in young children with significantly elevated lead levels, have been inaccessible in the USA. Importing these or a similar product from other countries is a complicated process involving approval at the level of the FDA. Importation is severely restricted. In the community, poison centers in conjunction with public health departments can work with specialty pharmacies who can compound alternatives. Unfortunately, these pharmacies often exist outside of hospital system pharmacies posing a challenge to their use inside the hospital setting. Furthermore, compounding is not an option in every shortage and more expensive bedside alternatives do not always translate to a more beneficial therapeutic option. This burden trickles down to bedside patient care where many healthcare providers will not be able to provide necessary drug treatment. This situation was illustrated in 2011 when the USA experienced a shortage of norepinephrine, the most administered vasopressor for critically ill patients [9]. Ultimately, phenylephrine was used as an alternative vasopressor and a retrospective review found that patients admitted to hospitals in septic shock during the shortage had a higher in-hospital mortality rate [9].

We commend Troger and Burns for their thoughtful review about such a difficult situation with very complex solutions, when they exist. Collaboration among all positions in healthcare, inside and outside the hospital setting, needs to continue. Work must be done alongside policymakers both at the local and national levels to find sustainable bedside solutions to provide necessary medication treatments. Drug shortages have left many providers to practice under crisis standards of care and the health of the nation is at stake .