Conflicting information regarding the benefits of hydroxychloroquine/chloroquine and azithromycin in coronavirus disease 2019 (COVID-19) treatment and hypothetical concerns for drugs, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), have challenged care during the pandemic.1 However, limited data are available about how prescription of these therapies has changed. The objective of this exploratory analysis was to evaluate prescription patterns of these therapies, along with other commonly used drugs for reference, in the United States during the COVID-19 pandemic. We hypothesized that the prescription of hydroxychloroquine/chloroquine and azithromycin would exceed historical estimates while ACE inhibitor/ARB use would be reduced.
Trends in mean weekly prescriptions dispensed between February 16 and April 25, 2020, of hydroxychloroquine/chloroquine, azithromycin, and the top 10 drugs based on total claims in 2019, which included the most common ACE inhibitor (lisinopril) and ARB (losartan), were compared with mean weekly prescriptions dispensed from February 17 to April 27, 2019 (Table). We used all-payer US pharmacy data from 58 332 chain, independent, and mail-order pharmacies across 14 421 zip codes in 50 states, reflecting approximately 17 million deidentified claims.2 Prescriptions of hydroxychloroquine/chloroquine were also examined based on fill quantity (<28 tablets, 28-60 tablets, or >60 tablets). Pharmacy claims were assigned weights to match prescription data from the Medical Expenditures Panel Survey 2015-2017 to generate national estimates.2 Estimates were scaled to total retail prescription drug fills in the United States in 2019 to obtain weekly fill estimates at the drug level. Confidence intervals were obtained using bootstrapping methods, resampling pharmacies with replacement, with 1000 replications. Analyses were performed using R software version 3.6.1 (R Foundation).
Fills for all drugs except amoxicillin and hydrocodone-acetaminophen peaked during the week of March 15 to March 21, 2020, followed by subsequent declines (Figure, A). During this week, hydroxychloroquine/chloroquine fills increased from 2208 in 2019 to 45 858 prescriptions for fewer than 28 tablet fills (+1977.0% increase), 70 472 to 196 606 prescriptions for 28 to 60 tablet fills (+179.0%), and 44 245 to 124 833 prescriptions for more than 60 tablet fills (+182.1%) (Figure, B). At study end, these increases remained sustained for fewer than 28 tablet fills (+848.4%) and 28 to 60 tablet fills (+53.3%), while more than 60 tablet fills of hydroxychloroquine/chloroquine were below 2019 estimates (−64.0% decrease). Overall, there were 483 425 excess fills of hydroxychloroquine/chloroquine during the 10-week period in 2020 compared with 2019. The sharpest declines at study end were noted for amoxicillin (−64.4%), azithromycin (−62.7%), and hydrocodone-acetaminophen (−21.8%); however, cardiometabolic therapies remained stable or declined slightly (amlodipine [−9.2%], atorvastatin [−9.1%], lisinopril [−15.3%], and losartan [+1.7%]) compared with 2019 estimates.
These data demonstrated a surge in hydroxychloroquine/chloroquine prescription fills, likely due to off-label prescriptions for COVID-19. The growth observed in the week of March 15 to March 21 followed the World Health Organization declaring a global pandemic on March 11, the United States declaring a national emergency on March 13, a single-group nonrandomized study3 published on March 17, and President Trump’s support of the drug on March 19. This surge in prescriptions corresponds to a previously reported spike in internet searches for purchasing hydroxychloroquine/chloroquine.4 There was subsequent reduction in longer-term prescription fills, which could indicate decreased availability for patients with systemic lupus erythematosus and rheumatoid arthritis. These observed patterns appear to be in keeping with drug shortages of hydroxychloroquine reported to the US Food and Drug Administration starting March 31.5
Theoretical concerns have been raised that ACE inhibitors/ARBs may increase susceptibility to COVID-19 illness. However, in this analysis, prescriptions of the most frequently used ACE inhibitor (lisinopril) and ARB (losartan) did not appear to substantially decline compared with other commonly prescribed medications for chronic conditions.1 The modest decline for most common long-term therapies after peak could represent reduced contact with prescribing clinicians, restricted access to pharmacies, pharmacist rationing, loss of insurance from unemployment, or replete supplies from early stockpiling. Steep declines for amoxicillin and azithromycin appeared out of proportion to expected seasonal declines and could represent fewer outpatient prescriptions for upper respiratory tract infection symptoms.
The limitations of the study included that prescription indications, patient or prescriber information, new or refill prescription status, or barriers to access could not be accounted for. Mechanisms to safeguard patients against both overprescription and drug shortages during public health crises should be explored.
Corresponding Author: Haider J. Warraich, MD, VA Boston Healthcare System, 1400 VFW Pkwy, 4B-132, Boston, MA 02132 (email@example.com).
Accepted for Publication: May 13, 2020.
Published Online: May 28, 2020. doi:10.1001/jama.2020.9184
Author Contributions: Drs Vaduganathan and Warraich had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Vaduganathan, van Meijgaard, Warraich.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Vaduganathan, Mehra, Warraich.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Vaduganathan, van Meijgaard, Warraich.
Administrative, technical, or material support: van Meijgaard, Warraich.
Supervision: van Meijgaard, Warraich.
Conflict of Interest Disclosures: Dr Vaduganathan reported being supported by the KL2/Catalyst Medical Research Investigator Training award (National Institutes of Health/National Center for Advancing Translational Sciences Award UL 1TR002541); serving on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa; and participating on clinical end point committees for studies sponsored by Novartis and the National Institutes of Health. Dr van Meijgaard is an employee of GoodRx. Dr Mehra reported receiving travel support and consulting fees, paid to Brigham and Women’s Hospital, from Abbott; fees for serving on a steering committee from Medtronic and Janssen (Johnson & Johnson); fees for serving on a data and safety monitoring board from Mesoblast; consulting fees from Portola, Bayer, and Triple Gene; and fees for serving as a scientific board member from NuPulseCV, Leviticus, and FineHeart. Dr Mehra also reported receiving personal fees from Baim Institute for Clinical Research and Roivant. Dr Joseph reported receiving grants from Novartis, Amgen, Otsuka, and Kowa and is a consultant for Novartis. No other disclosures were reported.
Additional Contributions: We acknowledge Diane Li, BA, and Amanda Nguyen, PhD, employees of GoodRx, who assisted with curation and analysis of the data. They did not receive additional financial compensation for these contributions.
Disclaimer: These analyses are based on a representative sample of US pharmacy claims and not based on GoodRx transactions.
et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents
. Published online March 20, 2020. doi:10.1016/j.ijantimicag.2020.105949PubMedGoogle Scholar