Medication errors and associated serious outcomes in COVID-19 antivirals: a real-world study based on FDA Adverse Event Reporting System database

Abstract

Background:

The Food and Drug Administration (FDA) authorized three COVID-19 antivirals, including remdesivir, nirmatrelvir/ritonavir, and molnupiravir. Although medication errors involving these treatments have been reported, national-level evidence on their frequency and clinical impact remains limited.

Objectives:

This study aimed to evaluate medication errors and associated serious clinical outcomes linked to FDA-approved COVID-19 antivirals using national postmarketing safety data.

Design:

A retrospective pharmacovigilance study using postmarketing adverse event reports.

Methods:

We analyzed data from the FDA Adverse Event Reporting System (FAERS) from January 2020 to December 2024. COVID-19 antivirals were identified using both their generic and brand names. Medication errors were identified using MedDRA preferred terms categorized under “medication errors and other product use errors.” Serious outcomes included death, hospitalization, life-threatening conditions, disability, required medical intervention to prevent permanent harm, and other clinically significant events. Descriptive analyses summarized the report characteristics. Disproportionality analysis was performed using reporting odds ratios (RORs) with 95% confidence intervals (CIs) to evaluate associations between antivirals and medication errors, as well as between medication errors and serious outcomes.

Results:

Among 10,768 medication error reports involving COVID-19 antivirals, nirmatrelvir/ritonavir accounted for the highest number of reports, while molnupiravir had the highest proportion of medication errors relative to total reports. Remdesivir (ROR = 0.50, 95% CI: 0.48–0.53) and nirmatrelvir/ritonavir (ROR = 0.86, 95% CI: 0.84–0.88) were associated with lower odds of medication errors, whereas molnupiravir showed significantly increased odds (ROR = 3.98, 95% CI: 3.77–4.21). Medication errors were significantly associated with serious outcomes, including death (ROR = 1.31, 95% CI: 1.19–1.46), life-threatening events (ROR = 1.38, 95% CI: 1.21–1.57), and required interventions to prevent permanent harm (ROR = 3.84, 95% CI: 2.58–5.72).

Conclusion:

Medication errors involving COVID-19 antivirals remain a safety concern, particularly with molnupiravir. Errors were associated with serious outcomes, highlighting the need for targeted safety interventions in prescribing and dispensing practices to reduce preventable harm.

Plain language summary

Medication errors in COVID-19 antivirals

This study analyzed medication errors related to three COVID-19 antivirals, including remdesivir, molnupiravir, and nirmatrelvir/ritonavir (commonly known as Paxlovid). Using a large national database maintained by the United States Food and Drug Administration, we analyzed data from 2020 to 2024 to understand how often these drugs were involved in medication errors and what the consequences were. We found that errors increased in early 2022 after oral COVID-19 antivirals became widely available. Molnupiravir had the highest proportion of reported errors, while remdesivir and nirmatrelvir/ritonavir had fewer. Although errors were not especially common, they sometimes led to serious outcomes. In particular, medication errors involving remdesivir were more likely to result in severe consequences, such as death or hospitalization. Errors with the oral antivirals were less often linked to serious outcomes. These findings show the importance of continued monitoring and improved systems for prescribing and dispensing new medications, especially when treatments are introduced quickly during a public health emergency.

Keywords

COVID-19 FAERS medication errors molnupiravir nirmatrelvir/ritonavir remdesivir

Introduction

The SARS-CoV-2 virus, a novel coronavirus responsible for causing Coronavirus Disease 2019 (COVID-19), emerged in December 2019 and rapidly developed into a global pandemic.^1,2 As of April 2025, the World Health Organization (WHO) has reported nearly 800 million confirmed COVID-19 cases and more than 7 million deaths worldwide.³ In response to this unprecedented public health emergency, healthcare systems around the world mobilized rapidly to develop effective treatments.⁴ In the United States, the Food and Drug Administration (FDA) utilized expedited regulatory pathways to authorize several COVID-19 antivirals for emergency use.^5–7 Specifically, Emergency Use Authorizations (EUAs) were granted for remdesivir in May 2020, and for both nirmatrelvir/ritonavir and molnupiravir in December 2021 (Table 1).^5–7

Table 1.

U.S. FDA authorization of COVID-19 antivirals.

Generic name	Brand name	Administration route	FDA EUA date	Full FDA approval date	Indication
Remdesivir	Veklury^®	Intravenous	May 1, 2020	October 22, 2020	COVID-19 in hospitalized and nonhospitalized patients
Nirmatrelvir/Ritonavir	Paxlovid™	Oral	December 22, 2021	May 25, 2023	Mild-to-moderate COVID-19 in high-risk outpatients
Molnupiravir	Lagevrio^®	Oral	December 23, 2021	Not fully approved	Mild-to-moderate COVID-19 in high-risk outpatients

EUA, Emergency Use Authorization; FDA, Food and Drug Administration.

Fast-track approval of COVID-19 antivirals was essential for saving lives and curbing the spread of the virus.^8,9 However, the rapid deployment may have limited the time available to establish robust administrative systems capable of managing the complexities of prescribing, dispensing, and monitoring these treatments.¹⁰ Between December 2021 and May 2022, over one million COVID-19 antiviral prescriptions were dispensed in the United States.¹¹ Moreover, from December 2021 through August 2023, a single national pharmacy chain dispensed more than 3.5 million nirmatrelvir/ritonavir prescriptions to nearly three million individuals.¹²

This high volume of antiviral prescriptions has amplified concerns about medication safety, particularly regarding administration complexity and the risk of medication errors.^13,14 Medication errors are a long-standing issue in healthcare, especially in high-pressure or emergent settings.¹⁵ A systematic review of 24 studies found that medication errors occurred in emergency departments at an average rate of 22.6%.¹⁶ Also, a review of 91 studies in hospital and long-term care settings reported a median error rate ranging from 8% to 25%.¹⁷ Regarding COVID-19 antivirals, early in the pandemic, the Institute for Safe Medication Practices (ISMP) reported medication errors related to remdesivir due to labeling confusion under EUA conditions.¹⁴ In addition, a study conducted at an independent community pharmacy in Pennsylvania in April 2022 found that 78% of nirmatrelvir/ritonavir prescriptions involved medication-related problems, including dosing errors and drug–drug interactions.¹⁸ These findings highlight the challenges associated with safely prescribing newly authorized treatments under expedited timelines.

Moreover, medication errors can lead to serious clinical outcomes. The WHO identifies medication errors as a leading cause of preventable harm worldwide, often resulting in prolonged hospitalizations, permanent injury, or death.^19,20 These errors can occur at any stage of the medication-use process, including prescribing, dispensing, and administration.^19,20 In the United States, the Institute of Medicine’s landmark report estimates that medication errors cause over 7000 deaths annually.²¹ Additionally, a study found that among emergency department visits involving medication errors, approximately 24.3% result in hospitalization.²²

Despite the concerns, national-level evidence on medication errors and associated adverse outcomes related to COVID-19 antivirals remains limited. Therefore, this study aims to address this gap by utilizing the data from the U.S. FDA’s Adverse Event Reporting System (FAERS) to evaluate the safety profiles of remdesivir, molnupiravir, and nirmatrelvir/ritonavir, with a specific focus on medication errors and their associated serious clinical outcomes.

Methods

Study design and data source

This cross-sectional study analyzed adverse event reports submitted to FAERS, which supports postmarketing safety surveillance of drugs and therapeutic biological products in the United States.²³ Specifically, Quarterly Data Extract files containing reports submitted between January 1, 2020, and December 31, 2024, were used.²⁴

FAERS is a spontaneous reporting system maintained by the U.S. FDA to collect adverse event and medication error reports from healthcare professionals, consumers, and manufacturers.²⁵ Reporting is mandatory for manufacturers but voluntary for healthcare professionals and consumers.²⁵ Specifically, the FAERS database contains multiple datasets, including patient demographics (DEMO), drug and biologic information for all reported medications (DRUG), adverse events coded using MedDRA (REAC), patient outcomes (OUTC), report sources (RPSR), therapy start and end dates (THER), and indications for drug use (INDI).²⁵ These datasets are linked using the unique Individual Safety Report number.²⁵

The study followed the STROBE reporting guideline for cross-sectional studies, ensuring transparent reporting of data source, study population, measurement of variables, statistical methods, and study limitations (Supplemental Material).²⁶

Data extraction and cleaning were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). To minimize data handling bias, standardized FDA FAERS documentation was followed, and all data extraction and variable mapping procedures were independently verified by two investigators (X.X. and Z.C.). Adverse event terms were further grouped using MedDRA version 27.1 (International Council for Harmonisation, Geneva, Switzerland) into hierarchical categories, including preferred terms (PTs), high-level terms, high-level group terms (HLGTs), and system organ classes, to improve consistency and interpretability across reports.²⁷

Measurements

FDA-approved COVID-19 antivirals were identified in the FAERS database based on both their generic and brand names. Specifically, records for remdesivir and Veklury, nirmatrelvir/ritonavir and Paxlovid, and molnupiravir and Lagevrio were included to capture all relevant reports for each drug (Table 1).

Medication errors were the primary adverse event of interest and were identified based on PTs categorized under the HLGT “Medication errors and other product use errors and issues” in MedDRA.

The primary outcomes in this study were serious clinical outcomes as defined by the FDA, including death, life-threatening conditions, hospitalization, disability, congenital anomalies, medical interventions required to prevent permanent impairment or damage, and others.²⁸ These outcomes are key indicators of the clinical severity of medication errors and are routinely monitored by regulatory authorities, pharmaceutical manufacturers, and healthcare providers as part of postmarketing safety surveillance.²⁹

Statistical analysis

Descriptive analysis was used to summarize patient characteristics associated with adverse event reports for remdesivir, nirmatrelvir/ritonavir, and molnupiravir in the FAERS database. Frequencies and percentages were calculated for each characteristic by antiviral agent. We also analyzed quarterly trends in the number and percentage of medication error reports. Descriptive statistics were used to calculate the total number of medication error reports per drug in each quarter, as well as the percentage of medication error reports among all FAERS reports for each drug.

Disproportionality analysis was conducted to evaluate the association between COVID-19 antivirals and medication errors using reporting odds ratios (RORs) with 95% confidence intervals (CIs). An overall analysis was performed across all COVID-19 antivirals, followed by subgroup analyses for remdesivir, nirmatrelvir/ritonavir, and molnupiravir individually. The comparator group included all other medications in the FAERS database. An ROR greater than 1, with the lower bound of the 95% CI exceeding 1, was considered a potential signal of disproportionate reporting.

Similarly, disproportionality analysis was used to examine the relationship between medication errors and serious outcomes as defined by the FDA. Each outcome associated with a medication error report served as the event of interest, and the comparator group consisted of all other FAERS reports that included medication errors. Subgroup analyses were further conducted for each COVID-19 antiviral.

All analyses were conducted using SAS version 9.4. A two-sided p-value of <0.05 was considered statistically significant.

Results

A total of 1,347,577 medication error reports were identified from the FAERS database between Q1 2020 and Q4 2024. Among these, 10,768 reports were related to COVID-19 antivirals, including remdesivir (N = 1203), nirmatrelvir/ritonavir (N = 7491), and molnupiravir (N = 2157). The remaining 1,336,809 reports were associated with medications other than the three COVID-19 antivirals. The flow of report selection is illustrated in Figure 1.

Figure 1.

Flow diagram of the selection of medication error reports related to COVID-19 antivirals.

Report characteristics

Table 2 summarizes the characteristics of medication error reports related to the COVID-19 antivirals in FAERS. Across all three antivirals, most reports came from older adults, particularly those aged 65 and above. Molnupiravir had the highest proportion in this age group (56.7%), followed by remdesivir (36.7%) and nirmatrelvir/ritonavir (39.9%). Females were more common among remdesivir reports (53.0%), while males made up the majority for nirmatrelvir/ritonavir (50.6%) and molnupiravir (52.7%). A substantial portion of the weight data was missing for all three drugs. Most reports for remdesivir (65.0%) and nirmatrelvir/ritonavir (63.8%) originated from the United States, whereas molnupiravir (91.6%) was predominantly reported from non-US countries.

Table 2.

Characteristics of medication error reports associated with COVID-19 antivirals.

Characteristics	Remdesivir, total N = 1203		Nirmatrelvir\ritonavir, total N = 7491		Molnupiravir, total N = 2157
Characteristics	n	%	n	%	n	%
Age (years)
<18	42	3.5	47	0.6	62	2.9
18–35	86	7.1	240	3.2	61	2.8
35–50	134	11.1	558	7.4	114	5.3
50–65	251	20.9	1164	15.5	265	12.3
⩾65	442	36.7	2989	39.9	1222	56.7
Missing	248	20.6	2493	33.3	433	20.1
Sex
Male	384	31.9	3791	50.6	1136	52.7
Female	637	53.0	2487	33.2	838	38.9
Missing	182	15.1	1213	16.2	183	8.5
Weight
<50 kg	41	3.4	151	2.0	67	3.1
50–75 kg	72	6.0	1002	13.4	144	6.7
75–100 kg	105	8.7	646	8.6	48	2.2
⩾100 kg	65	5.4	220	2.9	12	0.6
Missing	920	76.5	5472	73.0	1886	87.4
Occurrence country
US	782	65.0	4782	63.8	165	7.6
Non-US	397	33.0	2447	32.7	1975	91.6
Missing	24	2.0	262	3.5	17	0.8

kg, kilogram; N, number; US, United States; %, percentage.

Medication error trend

Figure 2 shows quarterly trends in medication error reports related to COVID-19 antivirals submitted to the FAERS from 2020 to 2024. Figure 2(a) shows the number of reported medication errors, which rose sharply in 2022 following the EUAs of nirmatrelvir/ritonavir and molnupiravir in late 2021. Nirmatrelvir/ritonavir exhibited the highest volume of reports, peaking in 2022 Q3 with over 1600 cases. Figure 2(b) presents the percentage of medication error reports among all FAERS reports. Molnupiravir consistently had the highest relative proportion, exceeding 40% in most quarters, while remdesivir and nirmatrelvir/ritonavir had a medication error rate between 10% and 20%. In addition, while the number of medication error reports declined after 2022, the percentage of errors remained consistent through the end of 2024.

Figure 2.

Trends in medication error reports for COVID-19 antivirals submitted to FAERS from 2020 to 2024. (a) Quarterly number of medication error reports; (b) Quarterly percentage of medication error reports among all FAERS reports.

Medication errors and associated outcomes

Table 3 presents the RORs for medication errors associated with each antiviral. The overall ROR of all three COVID-19 antivirals was 0.93 (95% CI: 0.91–0.95), indicating a disproportionately lower number of medication error reports relative to other adverse events. Specifically, remdesivir had a significantly lower ROR of 0.50 (95% CI: 0.48–0.53), and nirmatrelvir/ritonavir also showed significantly reduced odds of medication errors (ROR = 0.86, 95% CI: 0.84–0.88). However, molnupiravir was associated with significantly higher odds (ROR = 3.98, 95% CI: 3.77–4.21).

Table 3.

ROR of medication errors.

Medications	Case report	ROR	LL	UL
All^a	10,768	0.93	0.91	0.95
Remdesivir	1203	0.50	0.48	0.53
Nirmatrelvir/ritonavir	7491	0.86	0.84	0.88
Molnupiravir	2157	3.98	3.77	4.21

The total case reports for “All” medications are not equal to the sum of individual medications because some reports include multiple medications.

LL, lower limit; ROR, reporting odds ratio; UL, upper limit.

Table 4 shows the RORs for serious outcomes associated with medication errors across all three COVID-19 antivirals. Events classified as death (ROR = 1.31, 95% CI: 1.19–1.46), life threatening (ROR = 1.38, 95% CI: 1.21–1.57), and requiring intervention to prevent permanent impairment or damage (ROR = 3.84, 95% CI: 2.58–5.72) were significantly more likely to be associated with medication errors in COVID-19 antivirals compared to other medications. In contrast, the odds of hospitalization (ROR = 0.68, 95% CI: 0.64–0.73), disability (ROR = 0.38, 95% CI: 0.29–0.49), and other outcomes (ROR = 0.36, 95% CI: 0.34–0.39) were significantly lower. No cases of congenital anomalies were reported.

Table 4.

ROR of outcomes following medication errors.

Outcomes	Case report	ROR	LL	UL
Death	380	1.31	1.19	1.46
Life-threatening	241	1.38	1.21	1.57
Hospitalization	1045	0.68	0.64	0.73
Disability	55	0.38	0.29	0.49
Congenital anomaly	0	—	—	—
Required intervention to prevent permanent impairment/damage	25	3.84	2.58	5.72
Others	1354	0.36	0.34	0.39

LL, lower limit; ROR, reporting odds ratio; UL, upper limit.

Subgroup analysis revealed distinct outcome patterns by medication (Figure 3). For remdesivir, medication errors were associated with higher occurrence of death (ROR = 10.60, 95% CI: 9.25–12.13), life-threatening events (ROR = 9.40, 95% CI: 7.96–11.10), hospitalization (ROR = 4.84, 95% CI: 4.32–5.43), required interventions to prevent damage (ROR = 6.77, 95% CI: 2.80–16.33), and the others (ROR = 1.45, 95% CI: 1.29–1.63). On the other hand, the ROR for disability was significantly reduced (ROR = 0.31, 95% CI: 0.13–0.74).

Figure 3.

Subgroup analysis of serious outcomes associated with medication errors by COVID-19 antiviral: (a) remdesivir, (b) nirmatrelvir/ritonavir, and (c) molnupiravir.

For nirmatrelvir/ritonavir, medication errors were significantly associated with lower odds of serious outcomes, including death (ROR = 0.34, 95% CI: 0.27–0.43), life-threatening events (ROR = 0.54, 95% CI: 0.42–0.69), hospitalization (ROR = 0.39, 95% CI: 0.35–0.43), disability (ROR = 0.47, 95% CI: 0.35–0.62), and other adverse outcomes (ROR = 0.30, 95% CI: 0.28–0.33). However, required interventions to prevent damage were significantly elevated (ROR = 4.17, 95% CI: 2.65–6.58).

Similar to nirmatrelvir/ritonavir, for molnupiravir, medication errors were associated with lower reporting frequencies across multiple serious outcomes, including death (ROR = 0.68, 95% CI: 0.50–0.93), life-threatening events (ROR = 0.39, 95% CI: 0.23–0.66), hospitalization (ROR = 0.37, 95% CI: 0.30–0.44), disability (ROR = 0.10, 95% CI: 0.03–0.32), and other adverse outcomes (ROR = 0.18, 95% CI: 0.15–0.21). No significant associations were observed for required interventions to prevent damage (ROR = 0.75, 95% CI: 0.11–5.32).

Discussion

Using FAERS data from 2020 to 2024, this study investigated medication errors and their associated serious outcomes in three COVID-19 antivirals. While the overall medication errors were not disproportionately high in all three COVID-19 antivirals, differences were observed across individual drugs. Molnupiravir showed a significantly higher ROR for medication errors, whereas remdesivir and nirmatrelvir/ritonavir had significantly lower ROR. These differences likely reflect variations in clinical use. Remdesivir is administered in inpatient settings under professional supervision, which might help reduce the error rate.^30,31 Molnupiravir, though simple to administer orally, is typically prescribed in outpatient settings with limited oversight, which could increase the risk of misuse.^32,33 Provider familiarity and safety guidance might also play roles. Although both are administered orally, nirmatrelvir/ritonavir has prompted extensive safety alerts and prescribing guidelines, particularly regarding renal dosing and drug–drug interactions, which might enhance provider vigilance.^13,34,35 In contrast, molnupiravir, being newer and less commonly prescribed, might be less familiar to clinicians, which could further contribute to a higher risk of medication errors in real-world outpatient settings.³³

In addition, we have analyzed trends in COVID-19 medication error events by examining both the number and the percentage of errors. Centers for Disease Control and Prevention reported 1,076,762 oral COVID-19 antiviral prescriptions dispensed in the United States between December 23, 2021, and May 21, 2022, including 827,924 for nirmatrelvir/ritonavir and 248,838 for molnupiravir.¹¹ In addition, according to the US Department of Health and Human Services (HHS) and its Administration for Strategic Preparedness and Response, nearly 30 million COVID-19 therapeutic courses in total were distributed through the federal program between November 2020 and December 2023.³⁶ In our FAERS analysis, 10,768 medication error reports were identified. When compared with national dispensing volume, the proportion of reported errors was low, suggesting that these events were uncommon relative to overall exposure. In addition, nationally, nirmatrelvir/ritonavir accounted for roughly 75%–85% and molnupiravir for 15%–25% of oral antiviral use. Similarly, in FAERS, medication error reports were distributed at about 70% for nirmatrelvir/ritonavir, 20% for molnupiravir, and 10% for remdesivir, consistent with national utilization trends and reflecting broader prescribing patterns during the study period.

These trends were also consistent with our disproportionality analysis and provided additional context regarding the relative safety profiles of each antiviral. Molnupiravir consistently had the highest proportion of medication errors relative to its total FAERS reports, exceeding 40%. Nirmatrelvir/ritonavir, while associated with a high number of medication error reports, had a lower relative percentage, generally ranging from 10% to 20%. Remdesivir had both the lowest number and the lowest percentage of medication error reports among the three antivirals. Notably, medication error reports increased sharply in early 2022, following the EUA of nirmatrelvir/ritonavir and molnupiravir.^6,7 This increase was linked to the growing demand for anti-COVID-19 medications.^11,37 Following this, an increase in incorrect dosing events was reported to the FDA and the ISMP.³⁸ In response to the rise in adverse events, ISMP immediately released a recommendation letter to address the issue of how to prevent nirmatrelvir/ritonavir issues.³⁸ Additionally, although the absolute number of error reports declined after 2022, the proportion of medication errors among all FAERS reports for each agent remained relatively stable. These findings suggest that despite decreasing COVID-19 incidence and antiviral use, medication errors persist, which highlights the need for continued efforts to improve prescribing and dispensing practices.^18,39

When it comes to the serious outcomes associated with the medication errors in the COVID-19 antivirals, despite lower overall odds of medication errors, remdesivir errors were significantly associated with serious outcomes, including death, hospitalization, and life-threatening events. This finding may be explained by the clinical severity of patients receiving remdesivir, who are often hospitalized and more acutely ill, which may contribute to the higher occurrence of reported serious outcomes related to medication errors.⁴⁰ On the other hand, nirmatrelvir/ritonavir and molnupiravir had lower odds of most serious outcomes, which may reflect both lower baseline occurrence and improved familiarity over time. However, both drugs showed increased RORs for required interventions to prevent permanent harm, which could indicate reporting signals related to misuse, drug–drug interactions, or delayed recognition of adverse effects in outpatient use.

Medication errors remain a persistent global challenge involving multiple stakeholders across the medication-use process. These errors cannot be solely attributed to patients, as systemic factors also play a critical role. For instance, dispensing practices have been associated with error rates as high as 55%, while administration errors occur in 8%–25% of clinical encounters and in 2%–33% of home-based settings.^17,41,42 In response to these concerns, numerous initiatives have been implemented to enhance medication safety through regulatory and technological interventions. The Medical Error Reduction Act of 2000 proposed the development of state-level reporting systems and a centralized national error database to facilitate monitoring and prevention efforts.⁴³ Although the bill was not enacted, it catalyzed a series of safety-focused reforms. It informed subsequent efforts by the Agency for Healthcare Research and Quality and helped lay the foundation for the Patient Safety and Quality Improvement Act of 2005, which formally established a national voluntary reporting system through Patient Safety Organizations.⁴⁴ In addition, technological advances such as bar-coded medication administration have reduced administration errors by 54%–87%, and computerized provider order entry systems have decreased overall medication errors by up to 80% and serious errors by 55%.^45,46 More recently, regulatory frameworks such as the Ohio Administrative Code Rule have mandated that pharmacists report medication errors involving patient harm or professional misconduct.⁴⁷

Our findings underscore the importance of robust safety monitoring even after emergency authorizations. While expedited access to treatment was necessary during the pandemic, long-term safety management systems must be equipped to detect and mitigate evolving risks, especially in outpatient and pharmacy settings. The elevated error rates and potential for serious outcomes with newer antivirals such as molnupiravir also highlight the need for clearer labeling, standardized dosing instructions, and targeted education for both prescribers and patients.

Limitations

However, several limitations in our study should be noted. First, FAERS data rely on voluntary reporting, which may lead to underreporting, reporting bias, and incomplete information, limiting the generalizability of findings.⁴⁸ In particular, a notable portion of FAERS reports lacked demographic or clinical details such as age, sex, and weight. Missingness ranged from about 15%–33% for sex and age, and over 70% for weight across drugs. This incomplete reporting, common in spontaneous systems and intensified during the COVID-19 pandemic, may bias the interpretation of patient characteristics and limit subgroup analyses.^49,50 Therefore, findings should be viewed as signal-generating rather than confirmatory. Second, the use of RORs allows signal detection but does not establish causality and may be influenced by heightened media or clinical attention.⁵¹ Although FAERS includes several date fields, these mainly reflect administrative reporting timestamps rather than the true timing of drug administration or event onset.^24,52 Therapy start and end dates are inconsistently reported, and outcome dates such as death are unavailable in the public dataset, preventing reliable assessment of temporal relationships.^52,53 Moreover, because antivirals are prescribed to patients with confirmed COVID-19 of varying severity, some serious outcomes may reflect disease progression rather than drug-related toxicity or errors.⁵⁴ This confounding by indication limits causal inference, underscoring the need for linked EHR or claims data to evaluate outcome timing more accurately. Third, FAERS lacks detailed clinical data, including patients’ preexisting conditions and comorbidities, which limit the ability to fully assess risk factors and severity.⁴⁸ These limitations underscore the need for ongoing research, particularly on drug–drug interactions and potential long-term outcomes of COVID-19 antiviral treatments.^51,55 Strengthening postmarketing surveillance and integrating pharmacovigilance into routine care remain essential for improving medication safety and informing regulatory decisions.

Conclusion

Medication errors related to COVID-19 antivirals were relatively uncommon but varied substantially in frequency and severity across drugs. While nirmatrelvir/ritonavir accounted for the highest number of error reports, remdesivir was associated with significantly greater odds of serious outcomes, including death and life-threatening events. Molnupiravir exhibited the highest proportion of errors among its total adverse event reports but showed lower severity overall. These findings highlight the need for drug-specific safety strategies, especially for agents administered in complex inpatient settings like remdesivir. Ongoing pharmacovigilance, clearer prescribing guidance, and targeted provider education are critical to reducing preventable harm and improving medication safety during and beyond the pandemic.

Supplemental Material

sj-docx-1-taw-10.1177_20420986251396038 – Supplemental material for Medication errors and associated serious outcomes in COVID-19 antivirals: a real-world study based on FDA Adverse Event Reporting System database

Supplemental material, sj-docx-1-taw-10.1177_20420986251396038 for Medication errors and associated serious outcomes in COVID-19 antivirals: a real-world study based on FDA Adverse Event Reporting System database by Xiaomo Xiong, Zhanghe Chen and Bingfang Yan in Therapeutic Advances in Drug Safety

Footnotes

Acknowledgements

The authors acknowledge the support of the National Institutes of Health (R01AI172959).

Declarations

ORCID iD

Xiaomo Xiong

Supplemental material

Supplemental material for this article is available online.

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