Food And Drug Administration Warning Research Articles

Readability, Content, and Quality of Online Patient Education Materials on Anesthesia and Neurotoxicity in the Pediatric Population.

Internet-based patient education materials (PEMs) are often above the recommended sixth grade reading level recommended by the U.S. Department of Health and Human Services. In 2016 the U.S. Food and Drug Administration (FDA) released a warning statement against use of general anesthetic drugs in children and pregnant women due to concerns about neurotoxicity. The aim of this study is to evaluate readability, content, and quality of Internet-based PEMs on anesthesia in the pediatric population and neurotoxicity. The websites of U.S. medical centers with pediatric anesthesiology fellowship programs were searched for PEMs pertaining to pediatric anesthesia and neurotoxicity. Readability was assessed. PEM content was evaluated using matrices specific to pediatric anesthesia and neurotoxicity. PEM quality was assessed with the Patient Education Material Assessment Tool for Print. A one-sample t-test was used to compare the readability of the PEMs to the recommended sixth grade reading level. We identified 27 PEMs pertaining to pediatric anesthesia and eight to neurotoxicity. Mean readability of all PEMs was greater than a sixth grade reading (p <0.001). While only 13% of PEMs on anesthesia for pediatric patient mentioned the FDA warning, 100% of the neurotoxicity materials did. PEMs had good understandability (83%) and poor actionability (60%). The readability, content, and quality of PEMs are poor and should be improved to help parents and guardians make informed decisions about their children's health care. · The FDA issued a warning statement against the use of general anesthetic drugs in children and pregnant women.. · Readability, content, and quality of Internet-based patient education materials on the topic of neurotoxicity are poor.. · Improving the readability, content, and quality of PEMs could aid parents in making important health care decisions..

Institutional Variability in Anesthesia Time for Mehta Casting in Early-Onset Scoliosis (EOS).

Mehta casting is a potentially curative intervention for early-onset scoliosis (EOS) that typically requires multiple anesthetics. The Food and Drug Administration (FDA) reported that >3 hours of anesthesia under the age of 3 years old may alter brain development; however, no standard exists for the duration of anesthesia during casting. The purpose of this study is to quantify the variability in anesthesia during Mehta casting. We hypothesize that significant institutional variability exists and may be attributed to modifiable factors. An EOS registry was used to identify patients who underwent at least one Mehta casting procedure. Anesthesia exposure was quantified, and site variability was assessed by patient characteristics, cast placement, procedure type, and equipment used. Our cohort consisted of 208 patients from 5 institutions (age 2.6±1.4y). There were 1097 Mehta casting procedures, with 5.4±3.6 castings per patient. Of these patients, 106 (51%) were female, with an average age of 2.11±1.29 years old at the time casting was initiated. Patient etiologies included 154 idiopathic (74.0%), 22 syndromic (10.6%), 18 congenital (8.7%), 11 neuromuscular (5.3%), and 3 unknown (1.4%). Anesthesia time was 69±31 minutes and varied significantly between sites (59±14 to 117±46min; P <0.001). Cumulative anesthesia time for patients under 3 years was 320±197 minutes with 120/161 (74.5%) patients exceeding 3 hours. Anesthesia time was lower after the FDA warning in 2016 compared with pre-2016 (71±30 vs. 66±32, P =0.008). Patients undergoing Mehta casting are at significant risk of exceeding 3 hours of anesthesia, which the FDA has stated may be harmful for children <3 years. Significant site variability indicates that standardization protocols should be developed to encourage best practices and minimize anesthetic times. Prognostic Level II.

Managing a policy paradox? Responses to textual warning labels on E-cigarette advertisements among U.S. national samples of youth overall and adults who smoke or vape

ContextCurrent use and potential future uptake of e-cigarettes among youth remain public health concerns in the U.S., even as people who smoke combustible cigarettes could benefit from switching completely to e-cigarettes. The U.S. Food and Drug Administration (FDA) is considering alternative warning messages, but warnings that discourage youth from use may also deter people who smoke from switching. This study tests ten pre-registered hypotheses on effects of warning messages with national samples of youth overall and adults who smoke and/or vape. MethodsNORC recruited 1639 adults (ages 18+) who smoke, vape, or use both products, from their probability-sampled AmeriSpeak Panel and augmented their AmeriSpeak Teen Panel with Lucid's nonprobability opt-in panel to recruit 1217 youth (ages 14–17) to participate in a web-based survey experiment. We randomly assigned respondents to view one of five warning label conditions and respond to measures of their e-cigarette risk beliefs, willingness to use e-cigarettes, and (among people who smoke or vape) considerations to quit these products. FindingsRelative to the current FDA warning about nicotine, warning messages about the harms of e-cigarette use for youth brain development did not influence risk beliefs or reduce willingness to use these products among youth. Brain development warning messages did increase beliefs about these harms among adults but did not increase quit considerations among people who vape, relative to the FDA warning. Warning messages with information about chemical constituents of vaping products and the harm of these chemicals produced higher e-cigarette quit considerations than did the FDA warning among adults who vape. ConclusionPotential alternative warning label messages were largely ineffective relative to the current FDA warning about nicotine, though limited evidence suggests some potential for chemical + harm messaging to encourage people who use both e-cigarettes and cigarettes to consider quitting both.

Identification and Characterization of Synthetic Nicotine Product Promotion and Sales on Instagram Using Natural Language Processing.

There has been a rapid proliferation of synthetic nicotine products in recent years, despite newly established regulatory authority and limited research into its health risks. Previous research has implicated social media platforms as an avenue for nicotine product unregulated sales. Yet, little is known about synthetic nicotine product content on social media. We utilized natural language processing to characterize the sales of synthetic nicotine products on Instagram. We collected Instagram posts by querying Instagram hashtags (eg, "#tobaccofreenicotine) related to synthetic nicotine. Using Bidirectional Encoder Representations from Transformers, collected posts were categorized into thematically related topic clusters. Posts within topic clusters relevant to study aims were then manually annotated for variables related to promotion and selling (eg, cost discussion, contact information for offline sales). A total of 7425 unique posts were collected with 2219 posts identified as related to promotion and selling of synthetic nicotine products. Nicotine pouches (52.9%, n = 1174), electronic nicotine delivery systems (30.6%, n = 679), and flavored e-liquids (14.1%, n = 313) were most commonly promoted. About 16.1% (n = 345) of posts contained embedded hyperlinks and 5.8% (n = 129) provided contact information for purported offline transactions. Only 17.6% (n = 391) of posts contained synthetic nicotine-specific health warnings. In the United States, synthetic nicotine products can only be legally marketed if they have received premarket authorization from the Food and Drug Administration (FDA). Despite these prohibitions, Instagram appears to be a hub for potentially unregulated sales of synthetic and "tobacco-free" products. Efforts are needed by platforms and regulators to enhance content moderation and prevent unregulated online sales of existing and emerging synthetic nicotine products. There is limited clinical understanding of synthetic nicotine's unique health risks and how these novel products are changing over time due to regulatory oversight. Despite synthetic nicotine-specific regulatory measures, such as the requirement for premarket authorization and FDA warning letters issued to unauthorized sellers, access to and promotion of synthetic nicotine is widely occurring on Instagram, a platform with over 2 billion users and one that is popular among youth and young adults. Activities include direct-to-consumer sales from questionable sources, inadequate health warning disclosure, and exposure with limited age restrictions, all conditions necessary for the sale of various tobacco products. Notably, the number of these Instagram posts increased in response to the announcement of new FDA regulations. In response, more robust online monitoring, content moderation, and proactive enforcement are needed from platforms who should work collaboratively with regulators to identify, report, and remove content in clear violation of platform policies and federal laws. Regulatory implementation and enforcement should prioritize digital platforms as conduits for unregulated access to synthetic nicotine products and other future novel and emerging tobacco products.

Lamotrigine use and potential for adverse cardiac effects: A retrospective evaluation in a Veteran population

ObjectiveTo identify the impact of lamotrigine (LTG) on cardiac rhythm and conduction abnormalities for Veterans, an especially vulnerable population. BackgroundIn October 2020 the US Food and Drug Administration (FDA) added a new warning to the label of lamotrigine (Lamictal™) regarding its potential to cause cardiac rhythm and conduction abnormalities [1]. This warning came following in vitro data which suggested Class IB antiarrhythmic effects occurring at clinically achievable concentrations of lamotrigine [2]. However, it is unclear whether the in vitro findings will result in adverse clinical outcomes. Our objective was to assess for evidence for adverse clinical outcomes in a vulnerable population and examine for subtler signs of an association between lamotrigine and cardiac rhythm disturbances. MethodsA retrospective chart review was conducted using records between 10-01-2017 and 07-06-2021, identifying patients at the William S. Middleton Memorial Veterans Hospital who were prescribed lamotrigine. Data collected included: dates of lamotrigine initiation or discontinuation, lamotrigine dosing over the time of the prescription and maximum lamotrigine dose, any cardiac-related ICD-10-CM codes or a history of a cardiology appointment, EKGs with any abnormalities or changes, any concomitantly prescribed medications with known potential to cause cardiac abnormalities, any cardiac deaths. This retrospective chart review was approved by the University of Wisconsin-Madison Institutional Review Board. ResultsTwo hundred and thirty-three (189 male) patients with a lamotrigine prescription and 41.2 % (n = 96) of these patients had an EKG performed while prescribed lamotrigine. The average age of patients was 64.3 ± 13.0 (range 29 to 90) years and mean maximum lamotrigine daily dose was 250.8 ± 148.2 mg (range 25 to 800 mg). Nearly half (47.9 %, 46/96) of the patients were prescribed a concomitant sodium channel blocking medication in addition to lamotrigine. Eighty-four of the patients (87.5 %, 84/96) had a cardiac diagnosis, while 12 (12.5 %, 12/96) did not. A total of 12 deaths occurred within the review period, with two cardiac deaths from congestive heart failure. Four cases did not have information on cause of death. No LTG-associated cardiac adverse effects were noted as part of clinical care, though rash was noted in 5 cases. A total of 7 (7.3 %, 7/96) patients were found to have EKG abnormalities potentially related to lamotrigine, including 7.1 % (6/84) of those with a cardiac diagnosis and 8.3 % (1/12) of those without a cardiac diagnosis. ConclusionsWhile recent FDA warnings have suggested caution regarding cardiac complications associated with lamotrigine based on in vitro studies, the clinical implications are uncertain. Despite selecting a particularly vulnerable population, this retrospective chart review did not identify any deaths due to cardiac rhythm or conduction causes, nor demonstrate unambiguous cardiac complications related to lamotrigine. Even using permissive criteria (including any prolonged PR or QTc) to examine for subtle effects, only a low incidence (<10 %) of potential complications was found. Broader implications of this study are limited by the number of patients included and the retrospective nature of the study. Therefore, further studies are warranted to evaluate a link between cardiac complications and the use of lamotrigine, including the role of concomitant medications such as other sodium channel blocking agents and psychotropic medications.

Including the term ‘tobacco-free nicotine’ in the nicotine addiction warning label mandated by the US Food and Drug Administration alters risk perceptions and use intentions

BackgroundThe US Food and Drug Administration (FDA) requires a warning label on nicotine e-cigarettes and pouches: ‘This product contains nicotine. Nicotine is an addictive chemical’. Some brands marketing synthetic nicotine...

Opioid and Benzodiazepine Co-Prescribing Trends from the Emergency Department from 2012 to 2019: A National Analysis

BackgroundIn 2016, the U.S. Food and Drug Administration (FDA) issued its strongest safety warning (“Black Box Warning”) for concomitant use of prescription opioids and benzodiazepines due to overdose deaths. ObjectiveOur objective was to look at trends of opioid and benzodiazepine co-prescribing in the emergency department (ED) using national data, because recent data are sparse. MethodsThis is a retrospective review of data collected by the National Hospital Ambulatory Medical Care Survey between 2012 and 2019. Our primary outcome was to determine whether there was a trend in ED visits when opioids and benzodiazepines were co-prescribed at discharge. We also compared the rate of visits when co-prescribing occurred before (2012–2015) and after (2017–2019) the 2016 FDA warning. We identified commonly co-prescribed benzodiazepines and opioids, and the rate of naloxone co-prescribing. We used descriptive statistics and bivariate tests to describe data. ResultsBetween 2012 and 2019, there were 4,489,613 ED visits (0.41% of ED visits) when benzodiazepines and opioids were co-prescribed. There was no trend in the rate of co-prescribing overall, but a decrease in visits after the 2016 FDA Black Box Warning (2012–2015: mean 0.49%; 2017–2019: mean 0.29%; p < 0.0001). There were 7980 ED visits (0.18%) when naloxone was co-prescribed for these visits within this time frame and an increase over time (p < 0.001). ConclusionsOur study found that between 2012 and 2019, there was no overall reduction in co-prescribing of opioids and benzodiazepines across EDs nationwide, but a decrease after the 2016 Black Box Warning.

Hypnotic prescriptions in Japan may be shifting from benzodiazepine receptor agonists to other types of hypnotics, melatonin receptor agonists, and orexin receptor antagonists

Hypnotic prescriptions in Japan may be shifting from benzodiazepine receptor agonists to other types of hypnotics, melatonin receptor agonists, and orexin receptor antagonists

396 Quantitative Analysis of FDA Warning Letters Related to the Use of Social Media Sites in Product Misbranding for the Treatment, Prevention, or Diagnosis of COVID-19

OBJECTIVES/GOALS: Food and Drug Administration (FDA) warning letters regarding misbranding of products intended to treat, prevent, or diagnose COVID-19 were used as a proxy for assessing misinformation on social media. The FDA database of Warning Letters was used to identify the largest misinformation contributor. METHODS/STUDY POPULATION: On November 9, 2022, the full dataset of warning letters dating back to January 1, 2018 was extracted from the FDA website. Separate datasets were also extracted using the search terms: Facebook’, Twitter’, YouTube’, and Instagram’. The data entries were organized by issuing office and subject. The subjects were then filtered to only include letters related to misbranding of products for COVID-19. Letters regarding medical devices, manufacturing practices, and adulterated products were excluded from the analysis. Cumulative totals were collected for the number of letters issued for each search term. These totals were stratified by year and scaled by platform size for relative comparison. RESULTS/ANTICIPATED RESULTS: The FDA’s Center for Drug Evaluation and Research issued the most letters related to misbranding of COVID-19 products, 153 out of the 2798 entries in the complete dataset. Analysis of the datasets by search term show: 53, 18, 24, and 17 letters were related to Facebook, Twitter, YouTube, and Instagram respectively. Forty-one letters were related to other non-social media sources. Facebook had the most letters issued, however when scaled to account for the size of each respective platform’s approximate user base, Twitter had the largest proportional amount of misinformation regarding agents for the management of COVID-19, followed by Facebook, then Instagram. Most letters were issued in 2020. DISCUSSION/SIGNIFICANCE: In light of COVID-19, many social media sites adopted policies to limit inaccurate information. The success of these efforts have been variable. Although Facebook is the largest absolute contributor assessed, greater attention should be given to the policies of other platforms utilized by the industry.

Change in Pediatric Adenotonsillectomy Postoperative Visit Patterns After Opioid Food and Drug Administration Warning.

This study aimed to determine the association between opioid prescriptions given after tonsillectomy with adenoidectomy (T + A) and pain-related return visit rates in pediatric patients. Determine association between Food and Drug Administration (FDA) black box warning against opioid use in this population and pain-related return visit rates. This was a single-institution retrospective cohort study of pediatric patients who underwent T + A between April 2012 and December 2015 and had return visits to the emergency department or urgent care center. Data were obtained from the hospital electronic warehouse using International Classification of Diseases-9/10 procedure codes. Odds ratios (ORs) with 95% confidence intervals (CIs) for return visits were calculated. Multivariate logistic regression analysis was used to measure association between opioid prescriptions and return visit rates as well as FDA warning and return visit rates adjusting for confounders. There were 4778 patients who underwent T + A, median age, 5 years. Of these, 752 (15.7%) had return visits. Pain-related return visits were higher in patients who received opioid prescriptions (adjusted OR, 1.31; 95% CI, 1.09-1.57). After FDA warning, opioids were prescribed at a lower rate (47.9%) compared with previous (98.6%) (OR, 0.01; 95% CI, 0.008-0.02). Pain-related return visits were lower after FDA warning (OR, 0.73; 95% CI, 0.61-0.87). Steroid prescription rate increased after FDA warning (OR, 415; 95% CI, 197-874). Opioid prescriptions were associated with higher pain-related return visits after T + A, whereas issuance of FDA black box warning against codeine use was associated with lower pain-related return visits. Our data suggest that the black box warning potentially had unintended benefits in pain management and health care usage.

Implementation of CYP2D6-guided opioid therapy at Cincinnati Children's Hospital Medical Center.

We describe the implementation of CYP2D6-focused pharmacogenetic testing to guide opioid prescribing in a quaternary care, nonprofit pediatric academic medical center. Children are often prescribed oral opioids after surgeries, for cancer pain, and occasionally for chronic pain. In 2004, Cincinnati Children's Hospital Medical Center implemented pharmacogenetic testing for CYP2D6 metabolism phenotype to inform codeine prescribing. The test and reports were updated to align with changes over time in the testing platform, the interpretation of genotype to phenotype, the electronic health record, and Food and Drug Administration (FDA) guidance. The use of the test increased when a research project required testing and decreased as prescribing of oxycodone increased due to FDA warnings about codeine. Education about the opioid-focused pharmacogenetic test was provided to prescribers (eg, the pain and sickle cell teams) as well as patients and families. Education and electronic health record capability increased provider compliance with genotype-guided postsurgical prescribing of oxycodone, although there was a perceived lack of utility for oxycodone prescribing. The implementation of pharmacogenetic testing to inform opioid prescribing for children has evolved with accumulating evidence and guidelines, requiring changes in reporting of results and recommendations.

Global online interest in finasteride sexual side effects.

Prior literature has suggested that finasteride may negatively impact men's sexual health. In 2011, the Food and Drug Administration(FDA) provided a warning on finasteride drug labels to incorporate sexual side effects such as reduced libido and erectile dysfunction. We aimed to evaluate global online interest in finasteride sexual side effects, their penetrance and variation, and how they compared overtime. We also aimed to evaluate the influence of the FDA label warnings on web-based searches for finasteride side effects. We utilized Google search engine from January 2004 to December 2020 to include separate trends from web searches of "Propecia," "Propecia side effects," "finasteride", "finasteride side effects", and "post-finasteride syndrome" compared amongst the United States, United Kingdom, and Australia. We performed join-point regression analysis. We compared the annual relative search volume (ARSV) and annual percentage change (APC) to evaluate for loss or gain of interest in the respective key terms. We determined thatthe average ARSV for "finasteride" was 14.8% in 2004 and increased significantly to 57.3% in 2020 (APC: +9.25%, 95% CI 8 to 10.5, p < 0.001). Likewise, there was significant increased interest in "finasteride side effects" (APC: +20.7, p < 0.001) and "post-finasteride syndrome" (APC: +29.2; p < 0.001) in the United States overtime. Finally, when we compared trends before and after the FDA warnings, the average ASRV of "finasteride", "finasteride side effects", and "post-finasteride syndrome" all increased significantly (p = 0.001, p = 0.014, p < 0.001), respectively. Thus, it is evident that there is a global web-based interest in finasteride and its sexual health side effects, particularly after the FDA warning in 2011. There is boosted public awareness, and thus providers should have more detailed and careful conversations with patients prior to starting a 5α-reductase inhibitor such as finasteride.

Assessment of Knowledge Regarding Safety Profile, Use, and Boxed Warnings of Fluoroquinolones Among Healthcare Professionals in Saudi Arabia: A Potential Implication for Drug Regulatory Authorities.

BackgroundDespite a series of “boxed warnings” (BWs) issued by the US Food and Drug Administration (FDA), fluoroquinolones (FQs) are among the most prescribed antibiotics across the world. Moreover, few studies demonstrated that BW of FQs had less or no impact on prescribing patterns among healthcare professionals (HCPs), which might be attributed to the lack of knowledge toward such warnings. Since FQs contribute to a major proportion of antimicrobial prescriptions in the Kingdom of Saudi Arabia (KSA), this study aimed to ascertain the extent of knowledge toward safety profile, use, and BW of FQs among HCPs working in the KSA.MethodsThis cross-sectional study (May–August 2021) was conducted among HCPs working in KSA through a validated questionnaire. The HCPs were requested to identify the indications, adverse effects (AEs), and BW of FQs. The knowledge score (out of 40) was estimated among participants, and its association with demographics was ascertained through the chi-square test, Student's t-test, or Mann-Whitney U-test and one-way ANOVA, or Kruskal-Wallis test, where appropriate.ResultsOf the 573 participants (age: 36.1 ± 10.6 years, men: 59.7%), 262 (45.8%) were prescribers reporting frequent use of ciprofloxacin, levofloxacin, and ofloxacin. One-fourth (25.6%) of the prescribers did not recognize nalidixic acid as an agent from FQs class. About 60% of participants correctly identified the mechanism of action of FQs. The average knowledge score was 14.8 ± 6.4, where only 21.5% of respondents scored ≥50%. The average knowledge score for indications, AEs, and BW domains was 5.29 ± 3.05, 6.17 ± 4.05, and 2.3 ± 1.5, respectively. Only 75 (13.1%) participants recognized half of the BW, and 38.6% of participants identified at least one warning. The HCPs aged >40 years (p = 0.043), having non-Saudi's nationality (p < 0.001), working in Riyadh and Eastern regions (p < 0.001), having pharmacy and medicine disciplines (p < 0.001), practicing in public sectors (p = 0.004), and having more than 10 years of experience (p < 0.001) were significantly associated with high knowledge score.ConclusionThis study demonstrates the unsatisfactory knowledge toward safety profile, use, and BW of FQs among HCPs which may put patients at increased risks of AEs. The knowledge score differed among various socio-demographic groups. There is a dire need to initiate the antimicrobial-focused educational campaigns among HCPs regardless of their specialties and methods to improve education and disseminate FDA warnings in practice.

Risk for Postmarket Black Box Warnings in FDA-Approved Monoclonal Antibodies.

ObjectiveTo estimate the potential risk for a future postmarket black box warning (BBW) of US Food and Drug Administration (FDA)-approved monoclonal antibodies (mAbs) because of the importance for medical clinicians to understand mAb risks and benefits, including unknown future risks, especially for recently approved mAbs.MethodsThe complete dates of the study were March 16, 2020, through May 12, 2021. We searched the FDALabel database online and reviewed the scientific literature to determine current and previous FDA-approved mAbs as of March 2020. The BBWs and initial FDA-issued safety warnings were identified. The BBWs were categorized as premarket or postmarket. For mAbs with specific postmarket BBWs, previous FDA labels were evaluated to identify the presence or absence of an initial corresponding specific FDA warning.ResultsIn March 2020, a total of 83 mAbs had FDA approval; 33 had BBWs (27 premarket and 13 postmarket BBWs). Of these 33 mAbs, 55 individual specific BBWs existed (36 premarket and 19 postmarket specific warnings). On average, the specific BBWs occurred in the postmarket period at a rate of 3.4% (19/562) per year. Most (73.7%; 14/19) specific postmarket BBWs were preceded by an FDA warning in a median time of 3.61 (interquartile range, 1.36-5.78) years. Specific postmarket BBWs not preceded by a specific FDA product label warning occurred at an average rate of 0.9% (5/562) per year.ConclusionSpecific postmarket BBWs occurred in FDA-approved mAbs at a rate of 3.4% per year. Specific postmarket BBWs not preceded by a specific FDA product label warning had a rate of 0.9% per year.

Trends in Incident Varenicline Prescribing Among Veterans Following the US Food and Drug Administration Drug Safety Warnings.

Objective: To evaluate national trends in incident varenicline and nicotine replacement therapy (NRT) prescribing among Department of Veterans Affairs (VA) beneficiaries before and after US Food and Drug Administration (FDA) warnings regarding neuropsychiatric side effects with varenicline use. Methods: All adult VA patients identified as smokers from 2007 to 2019 (N = 3,600,947) were determined and monthly counts of new varenicline and NRT users were calculated. An interrupted time-series analysis estimated the effect of the FDA warnings on varenicline and NRT prescribing overall and among Veterans with and without mental health disorders. Results: The incident use rate of varenicline decreased from a peak of 6.2 per 1,000 veteran smokers in October 2007 to 1.0 by July 2009 following the first FDA warning (pre-warning monthly slope = −0.27; P = .03). New NRT use increased from 10.7 per 1,000 veteran smokers in October 2007 to a peak of 12.6 per 1,000 in July 2009 (slope change = 0.71; P = .01), suggesting potential substitution. Following removal of the FDA boxed warning in December 2016, varenicline prescribing increased but did not return to pre-warning levels by December 2019. Among veterans with and without mental health disorders, varenicline use decreased 90% and 88%, respectively, following the first FDA warning, and both groups had comparable rates of new NRT use. Conclusions: Following the first FDA warning, incident use of varenicline declined significantly among veterans both with and without mental health disorders. Despite removal of the FDA boxed warning in December 2016, new use of varenicline had not returned to pre-warning levels 3 years following the removal.

Effect of the FDA Black Box Suicidality Warnings for Antidepressants on Suicide Rates in the USA.

Background: Some authors claimed that the US Food and Drug Administration (FDA) black box warning on treatment-emergent suicidality with antidepressants in adolescents (issued 2004) and young adults (issued 2006) led to an increase of suicides, based on the analyses of ecological data with debatable assumptions about putative changes in suicide rates. Aims: To explore if putative changes in suicide rates in adolescents and young adults at the time of the FDA warnings is a detectable signal in the data or compatible with random fluctuations. Method: We applied different changepoint analyses for adolescent and young adult suicide rates from 1981 to 2019 in the USA. Results: Changepoint analysis did not support a detrimental effect of the FDA black box warnings. The downward trend of suicides reversed several years after the warning in adolescents (2007-2009) and many years before in young adults (1999-2001). Limitations: Our analyses cannot rule out detrimental effects of the FDA warnings. However, even if there was such an effect, it was likely small and indistinguishable from random fluctuations in the available suicide data. Conclusion: There is no detectable change of trend in adolescent or young adult suicide rates in line with a detrimental effect of the FDA black box warnings on treatment-emergent suicidality.

Association of Fluoroquinolone Prescribing Rates With Black Box Warnings from the US Food and Drug Administration

In 2013 and 2016, the US Food and Drug Administration (FDA) issued warnings and recommended limited use of fluoroquinolones for patients with certain acute conditions. It is not clear how prescribers have responded to these warnings. To analyze changes in prescribing of fluoroquinolones after the 2013 and 2016 FDA warnings and to examine the physician characteristics associated with these changes. This cross-sectional study used Medicare administrative claims data on Medicare fee-for-service beneficiaries and OneKey data on physicians and their organizations from January 1, 2011, to December 31, 2017. The sample was restricted to outpatient visits for sinusitis, bronchitis, and uncomplicated urinary tract infections. An interrupted time series approach was used to analyze the changes in the prescription rate after each FDA warning. Data analysis was performed between January 1, 2011, and December 31, 2017. Two FDA black box warnings released in August 2013 and July 2016. The main outcome was an indicator for fluoroquinolone prescriptions in 3 periods: before the 2013 warning (baseline period), after the 2013 warning but before the 2016 warning (postwarning period 1), and after the 2016 warning (postwarning period 2). The sample comprised 1 238 397 unique patients with a total of 2 720 071 outpatient acute care visits. Of this sample, 848 360 were women (68.5%), and the mean (SD) age was 69.7 (12.6) years. The immediate prescribing levels of fluoroquinolones in postwarning period 1 increased by 3.42 percentage points (95% CI, 3.23-3.62; P < .001) and declined by -0.77 percentage points (95% CI, -1.00 to -0.54; P < .001) in postwarning period 2. The prescribing trend increased by 0.08 percentage points per month (95% CI, 0.08-0.10; P < .001) in postwarning period 1 and 0.06 percentage points per month (95% CI, 0.04-0.08; P < .001) in postwarning period 2. In postwarning period 1, the prescribing levels for physicians who were affiliated with hospitals with a top 10th percentile case mix index vs those without such affiliation decreased by -1.13 percentage points (95% CI, -1.92 to -0.34; P = .005), whereas the levels for primary care physicians declined by -1.34 percentage points (95% CI, -1.78 to -0.88; P < .001) compared with non-primary care physicians in postwarning period 2. Physicians at teaching hospitals were the only ones who showed a decline in prescribing trend in postwarning period 1. This cross-sectional study found an overall decline in prescribing of fluoroquinolones after the release of FDA warnings. Understanding the association of physician and organizational characteristics with fluoroquinolone prescribing behavior may ultimately help to identify mechanisms to improve de-adoption.

Quantity of phenibut in dietary supplements before and after FDA warnings

Introduction Phenibut is used to treat anxiety, insomnia, alcohol withdrawal and other conditions in Russia. The drug, however, has abuse potential and may cause lethargy, delirium, psychosis and coma. In the United States (US), the US Food and Drug Administration (FDA) has never approved the use of phenibut as a prescription medication, but the drug is available over-the-counter in dietary supplements. More than 80 cases of coma and death have been associated with phenibut consumption and withdrawal, and the FDA recently warned that the drug is not permitted in over-the-counter supplements. We designed our study to determine the presence and quantity of phenibut in over-the-counter supplements before and after the FDA warnings. Methods Phenibut products were included if they (a) listed phenibut or a synonym as an ingredient on the label, (b) were labeled as a dietary supplement, and (c) were available for sale both before and after the FDA warning. Supplements were analyzed by liquid chromatography time-of-flight mass spectrometry; quantification was performed by isotope dilution method. Results Four brands of dietary supplements labeled as containing phenibut met the inclusion criteria. Prior to the FDA warnings, two of the four brands contained phenibut, at dosages of 484 mg and 487 mg per serving. After the FDA warning, all four products contained phenibut, ranging in dosages from 21 mg to 1,164 mg per serving. Phenibut was first detected only after the FDA warnings in two brands, and the quantity of phenibut increased in three of four products after the FDA warnings. Quantities detected per dose were as much as 450% greater than a typical 250 mg pharmaceutical tablet manufactured in Russia. Conclusion Following FDA issuing an advisory that phenibut is not permitted in dietary supplements, the quantity of phenibut increased in 3 of 4 brands of over-the-counter phenibut supplements.

Adverse Events Associated With Synthetic Male Slings: An Analysis of the Food and Drug Administration Manufacturer and User Facility Device Experience Database.

PurposeWe sought to describe and analyze the adverse events associated with synthetic male slings reported to the U.S. Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database.MethodsWe queried the MAUDE database for all entries including the terms “Male Sling,” “InVance,” “Virtue,” or “Advance” from January 1st, 2009 to December 31st, 2018. We collected and analyzed information about the event type, date received, report source, source type, and manufacturer. We reviewed and categorized the event description text for each medical device report (MDR).ResultsA total of 497 adverse events related to the male sling were identified. The adverse events were classified as injury (95.4%), malfunction (4.2%), and other (0.4%). There were no deaths described. The slings involved were the Advance or Advance XP sling (69.8%), InVance (15.5%), Virtue Quadratic (12.3%), or unknown (2.4%). The 4 most common adverse events described were urinary incontinence (46.7%), sling erosion (9.1%), mechanical malfunction (8.2%), and pain/numbness (8.2%). There was no increase in the number of reports in the years following the FDA warnings for urogynecologic mesh.ConclusionsThere was an overall modest number of MDRs related to male slings and the majority of them were reported by the manufacturer. The reporting of adverse events for male slings does not seem to be affected by the controversy and scrutiny towards transvaginal mesh and midurethral slings. Further clinical studies and more objective and detailed databases are needed to investigate the safety of these synthetic slings.

Outpatient Fluoroquinolone Prescription Fills in the United States, 2014 to 2020: Assessing the Impact of Food and Drug Administration Safety Warnings.

The impact of United States Food and Drug Administration (FDA) safety warnings on outpatient fluoroquinolone use is unclear. Annual changes in outpatient ciprofloxacin, levofloxacin, and moxifloxacin prescription fills (IQVIA National Prescription Audit databases) were assessed using a regression model. Monthly fills during baseline (August 2014 to April 2016) and first (May 2016 to June 2018) and second FDA warning periods (July 2018 to February 2020) were compared by interrupted time series analysis. From 2015 through 2019, total fluoroquinolone fills decreased from 35,616,786 (111.1/1,000 persons) to 21,100,050 (64.3/1,000 persons) annually (10.8% annually [P = 0.001]). Ciprofloxacin, levofloxacin, and moxifloxacin fills decreased annually by 10.4% (P = 0.001), 11.2% (P < 0.001), and 17.7% (P = 0.008), respectively. During the baseline period, there was no significant change in monthly fluoroquinolone fills. In May 2016 and during the first warning period, monthly fluoroquinolone fills decreased significantly (P < 0.001); the trend of decreased fills was significantly greater than that of the baseline period (P = 0.02). There was no change in fluoroquinolone fills in July 2018. Monthly fills decreased significantly throughout the second warning period (P < 0.001), but the trend did not differ from that of the first warning period. Trends for ciprofloxacin, the most commonly prescribed fluoroquinolone, were similar to those for the class. Fills of prescriptions by infectious diseases specialists (P < 0.005) and nurse practitioners (P = 0.04) significantly increased during the study. U.S. outpatient fluoroquinolone prescription fills significantly decreased from August 2014 to February 2020, most strongly in association with May 2016 FDA warnings. FDA safety warnings are useful tools for leveraging outpatient antimicrobial stewardship.