Investigating the Amoxicillin Shortage in Pennsylvania in the Era of Supply Chain Challenges: A Cross-Sectional Study

All hospital affiliated pharmacies (3/3, 100%) and most of the commercial pharmacies (3/4, 75.0%) experienced an ongoing amoxicillin shortage beginning between August 2022 and October 2022. At the time of manuscript writing, the shortage was ongoing according to the FDA’s Drug Shortages list. USAntibiotics, the sole manufacturer of amoxicillin in the US, reported an amoxicillin shortage, which was similarly ascribed to demand increase in response to infections. Teva Pharmaceuticals, the only distributor of amoxicillin that answered the survey, did not experience a shortage of amoxicillin. The amoxicillin shortage primarily impacted the suspension formulas. All respondents who had experienced amoxicillin shortages also experienced deficiencies of amoxicillin capsule/chew tab/tablet and other antibiotics, presenting three to four weeks after the onset of the suspension formula shortage.

When asked to report on possible cause of the scarcity, 83.3% (5/6) of pharmacies with amoxicillin shortage attributed the crisis to rise in demand due to increase in infection rate, and 16.7% (1/6) to insufficient manufacturing capability. No significant shortage was experienced from Teva Pharmaceutical’s perspective, the only amoxicillin distributor company that could be reached for comment. Questions regarding USAntibiotics’ current manufacturing status and ability to produce at the maximal capacity they are licensed for were not answered. No medication recalls regarding amoxicillin were announced from August 2022 to December 2022. Lastly, in an analysis conducted by the American Society of Health-System Pharmacists (ASHP), amongst the top reasons for drug shortages in 2022, 56% were unknown/ undisclosed, followed by 19% supply and demand imbalance and 18% manufacturing difficulty, indicating much of the true cause remains unknown.6 In recent years, the frequency of drug shortages have steadily increased, from 113.8 medication deficiencies/ year (2001-2010) to 171.9 medication deficiencies/year (2011-2020).6

Antibiotics are the second most common drug class facing shortages, with 38 different antibiotics lacking in supply as of 12/31/2022. An October 2022 survey performed by the National Community Pharmacists Association revealed 98% of respondents experience drug shortages with 66% facing amoxicillin backorders. 7 Similarly, 85.7% responding pharmacies in eastern Pennsylvania contacted in this investigation reported deficiencies in amoxicillin supply.

Several reasonable deductions may be drawn from our findings regarding the cause of amoxicillin shortage. The diminished amoxicillin supply coincided with the seasonal resurgence of influenza and RSV, which is exacerbated by new COVID-19 infections.8 Not only are antibiotics commonly prescribed for patients presenting with viral illnesses, but amoxicillin is also the first line therapy for secondary bacterial diseases that can follow viral infection.9 With 83.3% of responding pharmacies reporting increases in amoxicillin prescriptions, it is reasonable to attribute the shortage to an increase in demand. The shortage appears to have mainly impacted amoxicillin suspension. Shortage of this formulation, coupled with the disproportionate effects of seasonal viral epidemics on children, disproportionately impacts pediatric patients and the timing of viral infection surges were disrupted by pandemic-related decreased infection for two years. Although only 1/6 (16.7%) of the pharmacies we surveyed attributed the low amoxicillin inventory to manufacturing deficiency, the COVID-19 pandemic likely contributed to the shortage directly or indirectly. COVID-19 contributed to shortages of many essential medications.10 Early on, measures to prevent COVID-19 spread led to closure of many pharmaceutical factories.11 With prolonged lockdown policies in China, several major sources of raw and active ingredients for amoxicillin were limited in quantity, further diminishing the pharmaceutical output in the US.11,12

Shortages were also observed for amoxicillin in capsule/chew tab/tablet, amoxicillin-clavulanic acid, and other antibiotic classes; however, these shortages were found weeks after depletion of amoxicillin suspension formulas. Due to the unique temporal relationship, most respondents attributed the other amoxicillin formation shortages to trickle-down demand for substitutes.

These abruptly occurring scarcities of essential medications lead to practice changes that can lead to multiple adverse events, including inadequate or improper treatment of medical conditions, delay in definitive treatment, and adverse drug reactions or interactions. Time spent visiting multiple pharmacies in search of a supply-limited medication may also negatively impact quality of life.13,14 Additionally, the amoxicillin shortage exposes patients to second-line therapies at increased price points.15,16

Different strategies were employed by the private and public sectors in response to the worsening drug shortages. Multiple pharmacies participating in this study increased usage of networkwide real-time monitoring of inventories to supplement and adjust stockpile as necessary to maximize prescription fulfillment without compromising optimal choices. Additionally, recent shortages sparked public interest in legislation to address the growing scarcity. In 2021, the PASTEUR Act was introduced to the US Congress to stimulate the development of new antibiotics with government backing.17 In reality, the drug shortage problem is multifactorial and likely requires a comprehensive action plan to anticipate and adapt to future drug supply deficiencies.

The amoxicillin shortage at the end of 2022 coincided with increased viral infections in the fall, a time characterized by heightened demand for antibiotic prescriptions. Suspension formulas were primarily impacted by the scarcity, with trickle-down shortages impacting other formulations and antibiotic classes weeks later. Concerted efforts from individual entities, supply chain, and legislature may be necessary to combat the complex causes behind increasingly frequent medication shortages.

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