Impact of the 2017 FDA Drug Safety Communication on Codeine and Tramadol Dispensing to Children.
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SUBMITTER: Renny MH
PROVIDER: S-EPMC9647590 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
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Impact of the 2017 FDA Drug Safety Communication on Codeine and Tramadol Dispensing to Children.
Renny Madeline H MH Jent Victoria V Townsend Tarlise T Cerdá Magdalena M
Pediatrics 20221101 5
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Project description:Background: Tramadol and codeine are metabolized by CYP2D6 and are subject to drug-gene and drug-drug interactions. Methods: This interim analysis examined prescribing behavior and efficacy in 102 individuals prescribed tramadol or codeine while receiving pharmaco-genotyping as part of the INGENIOUS trial (NCT02297126). Results: Within 60 days of receiving tramadol or codeine, clinicians more frequently prescribed an alternative opioid in ultrarapid and poor metabolizers (odds ratio: 19.0; 95% CI: 2.8-160.4) as compared with normal or indeterminate metabolizers (p = 0.01). After adjusting the CYP2D6 activity score for drug-drug interactions, uncontrolled pain was reported more frequently in individuals with reduced CYP2D6 activity (odds ratio: 0.50; 95% CI: 0.25-0.94). Conclusion: Phenoconversion for drug-drug and drug-gene interactions is an important consideration in pharmacogenomic implementation; drug-drug interactions may obscure the potential benefits of genotyping.
| S-EPMC6562829 | biostudies-literature
Project description:ObjectiveTo assess the potential impact of Pharmacogenomic (PGx) variation in cytochrome P450 2D6 (CYP2D6) enzyme function, using loss in quality-adjusted life years (QALYs) associated with treatment problems, and the willingness to pay to avoid treatment problems from patients' and payers' perspectives.Patients and methodsThe study included patients prescribed tramadol or codeine, or both, between January 1, 2005, and December 31, 2017. Demographic information and adverse drug events, including adverse drug events and poor pain control, were collected from the electronic health records using natural language processing techniques and review by trained abstractors. Patients' willingness to pay and QALY estimates were based on comprehensive literature review. The CYP2D6 phenotypes were divided into 4 groups: ultra-rapid metabolizers, normal metabolizers, intermediate metabolizers, and poor metabolizers.ResultsAmong the 2860 identified patients, 63 (2%) were ultrarapid metabolizers, 1449 (50%) were normal metabolizers, 1155 (40%) were intermediate metabolizers, and 193 (7%) were poor metabolizers. The patients' average estimated willingness-to-pay value to avoid treatment problems was $23 per month; poor metabolizers developed problems with the highest estimated willingness-to-pay value ($32 per month). The mean QALY loss among all patients was 0.024 QALYs (8.8 healthy days); poor metabolizers had the highest loss (0.027 QALYs, 9.9 healthy days).ConclusionPatients with various phenotypes developed different treatment problem profiles. Poor CYP2D6 metabolizers developed problems with highest willingness to pay, and they might potentially benefit most from PGx-guided treatment and problem prevention.
| S-EPMC7930862 | biostudies-literature
Project description: Not available
| S-EPMC8222773 | biostudies-literature
Project description:The current Dutch Pharmacogenetics Working Group (DPWG) guideline, describes the gene-drug interaction between CYP2D6 and the opioids codeine, tramadol and oxycodone. CYP2D6 genotype is translated into normal metaboliser (NM), intermediate metaboliser (IM), poor metaboliser (PM) or ultra-rapid metaboliser (UM). Codeine is contraindicated in UM adults if doses >20 mg every 6 h (q6h), in children ≥12 years if doses >10 mg q6h, or with additional risk factors. In PMs, an alternative analgesic should be given which is not or to a lesser extent metabolised by CYP2D6 (not tramadol). In IMs with insufficient analgesia, a higher dose or alternative analgesic should be given. For tramadol, the recommendations for IMs and PMs are the same as the recommendation for codeine and IMs. UMs should receive an alternative drug not or to a lesser extent metabolised by CYP2D6 or the dose should be decreased to 40% of the commonly prescribed dose. Due to the absence of effect on clinical outcomes of oxycodone in PMs, IMs and UMs no action is required. DPWG classifies CYP2D6 genotyping for codeine "beneficial" and recommends testing prior to, or shortly after initiation of treatment in case of higher doses or additional risk factors. CYP2D6 genotyping is classified as "potentially beneficial" for tramadol and can be considered on an individual patient basis.
| S-EPMC9553935 | biostudies-literature
Project description:IntroductionHip fractures among older people are a major public health issue, which can impact quality of life and increase mortality within the year after they occur. A recent observational study found an increased risk of hip fracture in subjects who were new users of tramadol compared with codeine. These drugs have somewhat different indications. Tramadol is indicated for moderate to severe pain and can be used for an extended period; codeine is indicated for mild to moderate pain and cough suppression.ObjectiveIn this observational study, we compared the risk of hip fracture in new users of tramadol or codeine, using multiple databases and analytical methods.MethodsUsing data from the Clinical Practice Research Datalink and three US claims databases, we compared the risk of hip fracture after exposure to tramadol or codeine in subjects aged 50-89 years. To ensure comparability, large-scale propensity scores were used to adjust for confounding.ResultsWe observed a calibrated hazard ratio of 1.10 (95% calibrated confidence interval 0.99-1.21) in the Clinical Practice Research Datalink database, and a pooled estimate across the US databases yielded a calibrated hazard ratio of 1.06 (95% calibrated confidence interval 0.97-1.16).ConclusionsOur results did not demonstrate a statistically significant difference between subjects treated for pain with tramadol compared with codeine for the outcome of hip fracture risk.
| S-EPMC9296392 | biostudies-literature
Project description:Relatively few neonatal drug development studies have been conducted, but an increase is expected with the enactment of the Food and Drug Administration Safety and Innovation Act (FDASIA). Understanding the safety of drugs studied in neonates is complicated by the unique nature of the population and the level of illness. The objective of this study was to examine neonatal safety data submitted to the FDA in studies pursuant to the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) between 1998 and 2015.FDA databases were searched for BPCA and/or PREA studies that enrolled neonates. Studies that enrolled a minimum of 3 neonates were analyzed for the presence and content of neonatal safety data.The analysis identified 40 drugs that were studied in 3 or more neonates. Of the 40 drugs, 36 drugs received a pediatric labeling change as a result of studies between 1998 and 2015, that included information from studies including neonates. Fourteen drugs were approved for use in neonates. Clinical trials for 20 of the drugs reported serious adverse events (SAEs) in neonates. The SAEs primarily involved cardiovascular events such as bradycardia and/or hypotension or laboratory abnormalities such as anemia, neutropenia, and electrolyte disturbances. Deaths were reported during studies of 9 drugs.Our analysis revealed that SAEs were reported in studies involving 20 of the 40 drugs evaluated in neonates, with deaths identified in 9 of those studies. Patients enrolled in studies were often critically ill, which complicated determination of whether an adverse event was drug-related. We conclude that the traditional means for collecting safety information in drug development trials needs to be adjusted for neonates and will require the collaboration of regulators, industry, and the clinical and research communities to establish appropriate definitions and reporting strategies for the neonatal population.
| S-EPMC5549935 | biostudies-other
Project description:ImportanceAlthough tramadol is increasingly used to manage chronic noncancer pain, few safety studies have compared it with other opioids.ObjectiveTo assess the associations of tramadol, compared with codeine, with mortality and other adverse clinical outcomes as used in outpatient settings.Design, setting, and participantsRetrospective, population-based, propensity score-matched cohort study using a primary care database with routinely collected medical records and pharmacy dispensations covering more than 80% of the population of Catalonia, Spain (≈6 million people). Patients 18 years or older with 1 or more year of available data and dispensation of tramadol or codeine (2007-2017) were included and followed up to December 31, 2017.ExposuresNew prescription dispensation of tramadol or codeine (no dispensation in the previous year).Main outcomes and measuresOutcomes studied were all-cause mortality, cardiovascular events, fractures, constipation, delirium, falls, opioid abuse/dependence, and sleep disorders within 1 year after the first dispensation. Absolute rate differences (ARDs) and hazard ratios (HRs) with 95% confidence intervals were calculated using cause-specific Cox models.ResultsOf the 1 093 064 patients with a tramadol or codeine dispensation during the study period (326 921 for tramadol, 762 492 for codeine, 3651 for both drugs concomitantly), a total of 368 960 patients (184 480 propensity score-matched pairs) were included after study exclusions and propensity score matching (mean age, 53.1 [SD, 16.1] years; 57.3% women). Compared with codeine, tramadol dispensation was significantly associated with a higher risk of all-cause mortality (incidence, 13.00 vs 5.61 per 1000 person-years; HR, 2.31 [95% CI, 2.08-2.56]; ARD, 7.37 [95% CI, 6.09-8.78] per 1000 person-years), cardiovascular events (incidence, 10.03 vs 8.67 per 1000 person-years; HR, 1.15 [95% CI, 1.05-1.27]; ARD, 1.36 [95% CI, 0.45-2.36] per 1000 person-years), and fractures (incidence, 12.26 vs 8.13 per 1000 person-years; HR, 1.50 [95% CI, 1.37-1.65]; ARD, 4.10 [95% CI, 3.02-5.29] per 1000 person-years). No significant difference was observed for the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders.Conclusions and relevanceIn this population-based cohort study, a new prescription dispensation of tramadol, compared with codeine, was significantly associated with a higher risk of subsequent all-cause mortality, cardiovascular events, and fractures, but there was no significant difference in the risk of constipation, delirium, falls, opioid abuse/dependence, or sleep disorders. The findings should be interpreted cautiously, given the potential for residual confounding.
| S-EPMC8527363 | biostudies-literature
Project description:PurposeIn June 2013, following recommendations from the World Health Organization (WHO) and Food and Drug Administration (FDA), the European Medicines Agency agreed updates to the codeine product information regarding use for pain in children younger than 12 years and children undergoing tonsillectomy or adenoidectomy (TA) for obstructive sleep apnoea. This study was conducted to (a) assess effectiveness of these measures on codeine prescribing in the "real-world" setting and (b) test feasibility of a study using a common protocol by regulators with access to databases.MethodsThe study was performed using BIFAP (Spain), CPRD (UK), and IMS® Disease Analyzer (France and Germany) databases. Prescribers included general practitioners (GPs) (France and UK), GPs and paediatricians together (Spain), and GPs, paediatricians, and ear, nose, and throat (ENT) specialists separately (Germany). Between January 2010 and June 2015, prevalence of codeine prescribing was obtained every 6 months, and a time series analysis (joinpoint) was performed. Codeine prescribing within ±30 days of TA was also identified. Furthermore, doses, durations, and prior prescribing of other analgesics were investigated.ResultsOver the 5-year period, codeine prescribing decreased in children younger than 12 years (by 84% in France and Spain, 44% in GP practices in Germany, and 33% in the United Kingdom). The temporal pattern was compatible with the regulatory intervention in France and the United Kingdom, whereas a decrease throughout the study period was seen in Germany and Spain. Decreased prescribing associated with TA was suggested in ENT practices in Germany.ConclusionsCodeine prescribing for children decreased in line with introduced regulatory measures. Multidatabase studies assessing impact of measures by EU regulators are feasible.
| S-EPMC6771637 | biostudies-literature
Project description:Objective. Our objective was to examine the impact of the U.S. FDA's 2013 black box warning against codeine on codeine and other opioid prescription filling after pediatric tonsillectomy and/or adenoidectomy (T/A) overall and by child race and provider urbanity/rurality. Methods. Patients ≤ 18 who underwent T/A in 8/2011 to 8/2016 were identified in Ohio Medicaid claims. Interrupted time series analyses were used to evaluate the impact of the FDA warning on codeine or other opioid prescription filling post-T/A. Results. In August 2011, codeine prescription filling was lower among black than white children (P < .001) and among children treated at institutions in metropolitan counties than less populous counties (P < .001). The FDA warning was associated with a 24.0% drop in codeine prescription filling (P < .001) and 5.5% increase in alternative opioid prescription filling (P = .046). At conclusion, there remained geographic but no longer racial disparities in codeine prescribing. Conclusion. Codeine prescribing after pediatric T/A decreased after the FDA's black box warning. However, geographic disparities in codeine prescribing remain.
| S-EPMC7812397 | biostudies-literature
Project description:BackgroundThe Food and Drug Administration (FDA) issues drug safety communications (DSCs) to health care professionals, patients, and the public when safety issues emerge related to FDA-approved drug products. These safety messages are disseminated through social media to ensure broad uptake.ObjectiveThe objective of this study was to assess the social media dissemination of 2 DSCs released in 2013 for the sleep aid zolpidem.MethodsWe used the MedWatcher Social program and the DataSift historic query tool to aggregate Twitter and Facebook posts from October 1, 2012 through August 31, 2013, a period beginning approximately 3 months before the first DSC and ending 3 months after the second. Posts were categorized as (1) junk, (2) mention, and (3) adverse event (AE) based on a score between -0.2 (completely unrelated) to 1 (perfectly related). We also looked at Google Trends data and Wikipedia edits for the same time period. Google Trends search volume is scaled on a range of 0 to 100 and includes "Related queries" during the relevant time periods. An interrupted time series (ITS) analysis assessed the impact of DSCs on the counts of posts with specific mention of zolpidem-containing products. Chow tests for known structural breaks were conducted on data from Twitter, Facebook, and Google Trends. Finally, Wikipedia edits were pulled from the website's editorial history, which lists all revisions to a given page and the editor's identity.ResultsIn total, 174,286 Twitter posts and 59,641 Facebook posts met entry criteria. Of those, 16.63% (28,989/174,286) of Twitter posts and 25.91% (15,453/59,641) of Facebook posts were labeled as junk and excluded. AEs and mentions represented 9.21% (16,051/174,286) and 74.16% (129,246/174,286) of Twitter posts and 5.11% (3,050/59,641) and 68.98% (41,138/59,641) of Facebook posts, respectively. Total daily counts of posts about zolpidem-containing products increased on Twitter and Facebook on the day of the first DSC; Google searches increased on the week of the first DSC. ITS analyses demonstrated variability but pointed to an increase in interest around the first DSC. Chow tests were significant (P<.0001) for both DSCs on Facebook and Twitter, but only the first DSC on Google Trends. Wikipedia edits occurred soon after each DSC release, citing news articles rather than the DSC itself and presenting content that needed subsequent revisions for accuracy.ConclusionsSocial media offers challenges and opportunities for dissemination of the DSC messages. The FDA could consider strategies for more actively disseminating DSC safety information through social media platforms, particularly when announcements require updating. The FDA may also benefit from directly contributing content to websites like Wikipedia that are frequently accessed for drug-related information.
| S-EPMC5775485 | biostudies-literature