Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 718
Filter
1.
Pharmacoepidemiol Drug Saf ; 33(6): e5793, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38783553

ABSTRACT

PURPOSE: To evaluate the impact of rescheduling hydrocodone combination products (HCPs) from schedule III of the Controlled Substances Act to the more restrictive schedule II on unintentional pediatric exposures (≤5 years old). METHODS: Using U.S. data on outpatient retail pharmacy dispensing, emergency department (ED) visits, and poison center (PC) exposure cases, we assessed trends in prescriptions dispensed and unintentional pediatric exposure cases involving hydrocodone (rescheduled from III to II) compared to oxycodone (schedule II) and codeine (schedule III for combination products) using descriptive and interrupted time-series (ITS) analyses during the 16 quarters before and after the October 2014 rescheduling of HCPs. RESULTS: Dispensing of hydrocodone products was declining before rescheduling but declined more steeply post-rescheduling. In ITS analyses, both hydrocodone and oxycodone had significant slope decreases in PC case rates in the post versus pre-period that was larger for hydrocodone, while codeine had a small but significant slope increase in PC case rates. An estimated 4202 ED visits for pediatric hydrocodone exposures occurred in the pre-period and 2090 visits occurred in the post-period, a significant decrease of 50.3%. Oxycodone exposures showed no significant decrease. CONCLUSIONS: Pediatric hydrocodone unintentional exposure ED visits and PC cases decreased after HCP rescheduling more than would be expected had the pre-rescheduling trend continued; the acceleration in the decrease in hydrocodone PC cases was partially offset by a slowing in the decrease in codeine-involved cases. The trend changes were likely due to multiple factors, including changes in dispensing that followed the rescheduling. Unintentional pediatric medication exposures and poisonings remain a public health concern requiring ongoing, multifaceted mitigation efforts.


Subject(s)
Analgesics, Opioid , Codeine , Drug and Narcotic Control , Emergency Service, Hospital , Hydrocodone , Oxycodone , Poison Control Centers , Humans , Analgesics, Opioid/adverse effects , Child, Preschool , Oxycodone/adverse effects , Poison Control Centers/statistics & numerical data , United States/epidemiology , Emergency Service, Hospital/statistics & numerical data , Drug and Narcotic Control/legislation & jurisprudence , Infant , Interrupted Time Series Analysis , Child , Drug Combinations
2.
BMC Geriatr ; 24(1): 319, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38580920

ABSTRACT

BACKGROUND: Tramadol is increasingly used to treat acute postoperative pain among older adults following total hip and knee arthroplasty (THA/TKA). However, tramadol has a complex pharmacology and may be no safer than full opioid agonists. We compared the safety of tramadol, oxycodone, and hydrocodone among opioid-naïve older adults following elective THA/TKA. METHODS: This retrospective cohort included Medicare Fee-for-Service beneficiaries ≥ 65 years with elective THA/TKA between January 1, 2010 and September 30, 2015, 12 months of continuous Parts A and B enrollment, 6 months of continuous Part D enrollment, and no opioid use in the 6 months prior to THA/TKA. Participants initiated single-opioid therapy with tramadol, oxycodone, or hydrocodone within 7 days of discharge from THA/TKA hospitalization, regardless of concurrently administered nonopioid analgesics. Outcomes of interest included all-cause hospitalizations or emergency department visits (serious adverse events (SAEs)) and a composite of 10 surgical- and opioid-related SAEs within 90-days of THA/TKA. The intention-to-treat (ITT) and per-protocol (PP) hazard ratios (HRs) for tramadol versus other opioids were estimated using inverse-probability-of-treatment-weighted pooled logistic regression models. RESULTS: The study population included 2,697 tramadol, 11,407 oxycodone, and 14,665 hydrocodone initiators. Compared to oxycodone, tramadol increased the rate of all-cause SAEs in ITT analyses only (ITT HR 1.19, 95%CLs, 1.02, 1.41; PP HR 1.05, 95%CLs, 0.86, 1.29). Rates of composite SAEs were not significant across comparisons. Compared to hydrocodone, tramadol increased the rate of all-cause SAEs in the ITT and PP analyses (ITT HR 1.40, 95%CLs, 1.10, 1.76; PP HR 1.34, 95%CLs, 1.03, 1.75), but rates of composite SAEs were not significant across comparisons. CONCLUSIONS: Postoperative tramadol was associated with increased rates of all-cause SAEs, but not composite SAEs, compared to oxycodone and hydrocodone. Tramadol does not appear to have a superior safety profile and should not be preferentially prescribed to opioid-naïve older adults following THA/TKA.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Tramadol , Humans , Aged , United States/epidemiology , Analgesics, Opioid/adverse effects , Tramadol/adverse effects , Oxycodone/adverse effects , Arthroplasty, Replacement, Knee/adverse effects , Hydrocodone , Retrospective Studies , Arthroplasty, Replacement, Hip/adverse effects , Medicare
3.
J Anal Toxicol ; 48(4): 242-251, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38676414

ABSTRACT

The NC Office of the Chief Medical Examiner regularly assumes jurisdiction over deaths that are suspicious, unusual or unattended by a medical professional. In recent years, the presence of counterfeit pills is occasionally suggested by investigatory notes and/or scene findings that document reported consumption of prescription drugs, or prescription drugs on scene, which are not reflected in the final autopsy findings after toxicological analysis of the decedent's blood samples. Counterfeit pill consumption is a major public health hazard worthy of attention from the forensic toxicology community. Seventy-five cases from January 2020 to December 2022 serve as a convenience sample of cases where prescription pills including formulations of alprazolam, oxycodone and hydrocodone were specifically referenced during the death scene investigation as recently consumed, yet an unexpected substance was found during toxicological analysis rather than the expected pharmaceutical drug. Of note, novel benzodiazepines detected included flualprazolam, etizolam, clonazolam metabolite (8-aminoclonazolam), bromazolam, flubromazolam and desalkylflurazepam. Decedents' ages ranged from 16 to 69, across 33 different NC counties. Case notes indicated that eight of the decedents obtained pills through direct personal relationships, six decedents obtained them from "the street" and one decedent likely purchased pills online. Pills were largely consumed orally or through insufflation. Seven case reports contained indication that decedents knew or suspected the counterfeit nature of their pills. This study describes the context and characteristics of 2020-2022 suspected counterfeit pill-involved deaths in NC to further the understanding of the forensic science community, law enforcement partners, public health stakeholders and those potentially at risk through the consumption of counterfeit pills.


Subject(s)
Counterfeit Drugs , Forensic Toxicology , Humans , Adult , Male , Middle Aged , Female , Young Adult , Aged , Benzodiazepines/analysis , Adolescent , Oxycodone/analysis , Prescription Drugs , Substance Abuse Detection/methods , Alprazolam/analysis , Hydrocodone
4.
Pain Med ; 25(3): 173-186, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38243702

ABSTRACT

OBJECTIVE: This study compared opioid utilization trajectories of persons initiating tramadol, short-acting hydrocodone, or short-acting oxycodone, and it characterized opioid dose trajectories and type of opioid in persistent opioid therapy subsamples. METHODS: A retrospective cohort study of adults with chronic non-cancer pain who were initiating opioid therapy was conducted with the IQVIA PharMetrics® Plus for Academics data (2008-2018). Continuous enrollment was required for 6 months before ("baseline") and 12 months after ("follow-up") the first opioid prescription ("index date"). Opioid therapy measures were assessed every 7 days over follow-up. Group-based trajectory modeling (GBTM) was used to identify trajectories for any opioid and total morphine milligram equivalent measures, and longitudinal latent class analysis was used for opioid therapy type. RESULTS: A total of 40 276 tramadol, 141 023 hydrocodone, and 45 221 oxycodone initiators were included. GBTM on any opioid therapy identified 3 latent trajectories: early discontinuers (tramadol 39.0%, hydrocodone 54.1%, oxycodone 61.4%), late discontinuers (tramadol 37.9%, hydrocodone 39.4%, oxycodone 33.3%), and persistent therapy (tramadol 6.7%, hydrocodone 6.5%, oxycodone 5.3%). An additional fourth trajectory, intermittent therapy (tramadol 16.4%), was identified for tramadol initiators. Of those on persistent therapy, 2687 individuals were on persistent therapy with tramadol, 9169 with hydrocodone, and 2377 with oxycodone. GBTM on opioid dose resulted in 6 similar trajectory groups in each persistent therapy group. Longitudinal latent class analysis on opioid therapy type identified 6 latent classes for tramadol and oxycodone and 7 classes for hydrocodone. CONCLUSION: Opioid therapy patterns meaningfully differed by the initial opioid prescribed, notably the presence of intermittent therapy among tramadol initiators and higher morphine milligram equivalents and prescribing of long-acting opioids among oxycodone initiators.


Subject(s)
Chronic Pain , Tramadol , Adult , Humans , Analgesics, Opioid/therapeutic use , Tramadol/therapeutic use , Oxycodone/therapeutic use , Hydrocodone/therapeutic use , Follow-Up Studies , Retrospective Studies , Chronic Pain/drug therapy
5.
J Emerg Med ; 66(3): e313-e322, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38290881

ABSTRACT

BACKGROUND: Emergency physicians play a critical role in mitigating the opioid epidemic in public health. OBJECTIVES: To analyze the prescribing of emergency physicians for opioids among Medicare beneficiaries enrolled in the Part D program from 2013 to 2019. METHODS: We conducted a retrospective, cross-sectional, descriptive analysis of Medicare Part D prescriber data, focusing on opioid claims between 2013 and 2019. The primary outcome variables evaluated included proportion of opioid claims, trends of the most prescribed opioids, cost of opioid claims, and days' supply per claim. RESULTS: A total of 63,586 emergency physicians were identified over the study period. Opioid prescription by emergency physicians decreased from 14.45% to 11.55%, and the cost spent on opioid drugs declined by 50%. The use of drugs such as hydrocodone-acetaminophen and oxycodone-acetaminophen declined substantially, whereas tramadol and acetaminophen-codeine prescription increased. The opioid prescribing rate and days' supply also decreased. CONCLUSIONS: The decline in traditional opioid agents such as hydrocodone-acetaminophen was partly offset by an increase in opioids like tramadol, which carry additional potential adverse events. Opioid prescribing rate, average days' supply, and cost of opioid drugs significantly decreased from 2015 to 2019, after a spike in 2015. All regions observed a decrease in emergency physicians, but opioid prescribing rates varied across regions. These trends highlight successful opioid stewardship practices in some areas and the need for further development in others. This information can aid in designing tailored guidelines and policies for emergency physicians to promote effective opioid stewardship practices.


Subject(s)
Medicare Part D , Physicians , Tramadol , Aged , Humans , United States , Analgesics, Opioid/therapeutic use , Acetaminophen/pharmacology , Acetaminophen/therapeutic use , Hydrocodone/therapeutic use , Retrospective Studies , Cross-Sectional Studies , Practice Patterns, Physicians' , Drug Prescriptions
6.
Subst Abuse Treat Prev Policy ; 19(1): 4, 2024 01 04.
Article in English | MEDLINE | ID: mdl-38178238

ABSTRACT

INTRODUCTION: The 2010 release of an abuse deterrent formulation (ADF) of OxyContin, a brand name prescription opioid, has been cited as a major driver for the reduction in prescription drug misuse and the associated increasing illicit opioid use and overdose rates. However, studies of this topic often do not account for changes in supplies of other prescription opioids that were widely prescribed before and after the ADF OxyContin release, including generic oxycodone formulations and hydrocodone. We therefore sought to compare the impact of the ADF OxyContin release to that of decreasing prescription opioid supplies in West Virginia (WV). METHODS: Opioid tablet shipment and overdose data were extracted from The Washington Post ARCOS (2006-2014) and the WV Forensic Drug Database (2005-2020), respectively. Locally estimated scatterplot smoothing (LOESS) was used to estimate the point when shipments of prescription opioids to WV began decreasing, measured via dosage units and morphine milligram equivalents (MMEs). Interrupted time series analysis (ITSA) was used to compare the impact LOESS-identified prescription supply changes and the ADF OxyContin release had on prescription (oxycodone and hydrocodone) and illicit (heroin, fentanyl, and fentanyl analogues) opioid overdose deaths in WV. Model fit was compared using Akaike Information Criteria (AIC). RESULTS: The majority of opioid tablets shipped to WV from 2006 to 2014 were generic oxycodone or hydrocodone, not OxyContin. After accounting for a 6-month lag from ITSA models using the LOESS-identified change in prescription opioid shipments measured via dosage units (2011 Q3) resulted in the lowest AIC for both prescription (AIC = -188.6) and illicit opioid-involved overdoses (AIC = -189.4), indicating this intervention start date resulted in the preferred model. The second lowest AIC was for models using the ADF OxyContin release as an intervention start date. DISCUSSION: We found that illicit opioid overdoses in WV began increasing closer to when prescription opioid shipments to the state began decreasing, not when the ADF OxyContin release occurred. Similarly, the majority of opioid tablets shipped to the state for 2006-2014 were generic oxycodone or hydrocodone. This may indicate that diminishing prescription supplies had a larger impact on opioid overdose patterns than the ADF OxyContin release in WV.


Subject(s)
Drug Overdose , Opiate Overdose , Humans , Analgesics, Opioid/therapeutic use , Oxycodone , Interrupted Time Series Analysis , Hydrocodone , West Virginia , Drug Overdose/prevention & control , Drug Overdose/drug therapy , Prescriptions , Fentanyl
7.
JDR Clin Trans Res ; 9(1): 72-84, 2024 Jan.
Article in English | MEDLINE | ID: mdl-36680313

ABSTRACT

BACKGROUND: With addiction rates and opioid deaths increasing, health care providers are obligated to help stem the opioid crisis. As limited studies examine the comparative effectiveness of fixed-dose combination nonopioid analgesia to opioid-containing analgesia, a comparative effectiveness study was planned and refined by conducting a pilot study. METHODS: The Opioid Analgesic Reduction Study (OARS) pilot, a stratified, randomized, multisite, double-blind clinical trial, was designed to test technology and procedures to be used in the full OARS trial. Participants engaged in the full protocol, enabling the collection of OARS outcome data. Eligible participants reporting to 1 of 5 sites for partial or full bony impacted mandibular third molar extraction were stratified by biologic sex and randomized to 1 of 2 treatment groups, OPIOID or NONOPIOID. OPIOID participants were provided 20 doses of hydrocodone 5 mg/acetaminophen 300 mg. NONOPIOID participants were provided 20 doses of ibuprofen 400 mg/acetaminophen 500 mg. OARS outcomes data, including pain experience, adverse effects, sleep quality, pain interference, overall satisfaction, and remaining opioid tablets available for diversion, were collected via surveys, electronic medication bottles, eDiary, and activity/sleep monitor. RESULTS: Fifty-three participants were randomized with 50 completing the OARS pilot protocol. Across all outcome pain domains, in all but 1 time period, NONOPIOID was better in managing pain than OPIOID (P < 0.05 level). Other outcomes suggest less pain interference, less adverse events, better sleep quality, better overall satisfaction, and fewer opioid-containing tablets available for diversion. DISCUSSION: Results suggest patients requiring impacted mandibular third molar extraction would benefit from fixed-dose combination nonopioid analgesia. KNOWLEDGE TRANSFER STATEMENT: Study results suggest fixed-dose nonopioid combination ibuprofen 400 mg/acetaminophen 500 mg is superior to opioid-containing analgesic (hydrocodone 5 mg/acetaminophen 500 mg). This knowledge should inform surgeons and patients in the selection of postsurgical analgesia.


Subject(s)
Analgesics, Non-Narcotic , Analgesics, Opioid , Humans , Analgesics, Opioid/therapeutic use , Analgesics, Opioid/adverse effects , Acetaminophen/therapeutic use , Acetaminophen/adverse effects , Ibuprofen/therapeutic use , Ibuprofen/adverse effects , Hydrocodone/adverse effects , Pilot Projects , Drug Combinations , Analgesics, Non-Narcotic/therapeutic use , Analgesics, Non-Narcotic/adverse effects , Pain/chemically induced , Pain/drug therapy , Double-Blind Method
8.
Exp Biol Med (Maywood) ; 248(21): 1944-1951, 2023 11.
Article in English | MEDLINE | ID: mdl-38158803

ABSTRACT

The opioid epidemic has become a serious national crisis in the United States. An indepth systematic analysis of opioid-related adverse events (AEs) can clarify the risks presented by opioid exposure, as well as the individual risk profiles of specific opioid drugs and the potential relationships among the opioids. In this study, 92 opioids were identified from the list of all Food and Drug Administration (FDA)-approved drugs, annotated by RxNorm and were classified into 13 opioid groups: buprenorphine, codeine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, tapentadol, and tramadol. A total of 14,970,399 AE reports were retrieved and downloaded from the FDA Adverse Events Reporting System (FAERS) from 2004, Quarter 1 to 2020, Quarter 3. After data processing, Empirical Bayes Geometric Mean (EBGM) was then applied which identified 3317 pairs of potential risk signals within the 13 opioid groups. Based on these potential safety signals, a comparative analysis was pursued to provide a global overview of opioid-related AEs for all 13 groups of FDA-approved prescription opioids. The top 10 most reported AEs for each opioid class were then presented. Both network analysis and hierarchical clustering analysis were conducted to further explore the relationship between opioids. Results from the network analysis revealed a close association among fentanyl, oxycodone, hydrocodone, and hydromorphone, which shared more than 22 AEs. In addition, much less commonly reported AEs were shared among dihydrocodeine, meperidine, oxymorphone, and tapentadol. On the contrary, the hierarchical clustering analysis further categorized the 13 opioid classes into two groups by comparing the full profiles of presence/absence of AEs. The results of network analysis and hierarchical clustering analysis were not only consistent and cross-validated each other but also provided a better and deeper understanding of the associations and relationships between the 13 opioid groups with respect to their adverse effect profiles.


Subject(s)
Analgesics, Opioid , Oxycodone , Analgesics, Opioid/adverse effects , Bayes Theorem , Data Mining , Fentanyl , Hydrocodone , Hydromorphone , Meperidine , Oxymorphone , Tapentadol , United States/epidemiology
9.
Harm Reduct J ; 20(1): 142, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37779203

ABSTRACT

INTRODUCTION: Due to concerns over potential interactions between some hepatitis C direct-acting antivirals (DAAs) and opioids, we describe adverse event (AE) reports of concomitant use of opioids and DAAs. METHODS: AEs reported (July 28, 2017-December 31, 2021) with the administration of the DAAs glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir/voxilaprevir, and elbasvir/grazoprevir as suspect products were downloaded from the US Food and Drug Administration AE Reporting System Public Dashboard. The number of AE reports containing opioids (fentanyl, hydrocodone, oxycodone) as co-suspect products/concomitant products were counted and summarized by severity, reporting country and whether an outcome of death was reported. Overdose AEs were counted irrespective of opioid use, and changes over time were assessed. RESULTS: In total, 40 AEs were reported for DAAs and concomitant fentanyl use, 25 (62.5%) were in the USA, 35 (87.5%) were considered serious, and 14 (35.0%) resulted in death; and 626 were reported with concomitant oxycodone/hydrocodone use, 596 (95.2%) were in the USA, 296 (47.3%) were considered serious, and 28 (4.5%) resulted in death. There were 196 overdose AEs (32 [16%] deaths) declining from 2018 (N = 56) to 2021 (N = 29). CONCLUSIONS: Treating people with hepatitis C virus (HCV) infection who use drugs is key to achieving HCV elimination. Low numbers of DAA AE reports with opioids may provide reassurance to prioritize HCV treatment in this population. These data contribute to evidence supporting the continued scale-up of DAA treatment among people who use drugs to achieve HCV elimination goals.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Humans , Sofosbuvir/adverse effects , Antiviral Agents/adverse effects , Hepacivirus , Analgesics, Opioid/adverse effects , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Oxycodone/therapeutic use , Hydrocodone/therapeutic use , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Fentanyl/adverse effects
10.
JAMA ; 330(20): 2016-2017, 2023 11 28.
Article in English | MEDLINE | ID: mdl-37902730

ABSTRACT

On day 7 after hospital admission, a patient with end-stage kidney disease prescribed sevelamer, hydrocodone-acetaminophen, hydromorphone, and chewable lanthanum tablets developed intermittent apneic episodes, bilateral rhonchi, and responsiveness to verbal commands only with deep painful stimulus; a chest radiograph showed 4 radio-opaque coin-shaped opacities in the stomach. What is the diagnosis and what would you do next?


Subject(s)
Foreign Bodies , Stomach , Tablets , Humans , Analgesics, Opioid , Hydrocodone , Kidney Failure, Chronic , Stomach/diagnostic imaging , Lanthanum , Foreign Bodies/diagnostic imaging
11.
J Pharmacol Exp Ther ; 387(2): 150-169, 2023 11.
Article in English | MEDLINE | ID: mdl-37679047

ABSTRACT

Awareness of drug interactions involving opioids is critical for patient treatment as they are common therapeutics used in numerous care settings, including both chronic and disease-related pain. Not only do opioids have narrow therapeutic indexes and are extensively used, but they have the potential to cause severe toxicity. Opioids are the classical pain treatment for patients who suffer from moderate to severe pain. More importantly, opioids are often prescribed in combination with multiple other drugs, especially in patient populations who typically are prescribed a large drug regimen. This review focuses on the current knowledge of common opioid drug-drug interactions (DDIs), focusing specifically on hydrocodone, oxycodone, and morphine DDIs. The DDIs covered in this review include pharmacokinetic DDI arising from enzyme inhibition or induction, primarily due to inhibition of cytochrome p450 enzymes (CYPs). However, opioids such as morphine are metabolized by uridine-5'-diphosphoglucuronosyltransferases (UGTs), principally UGT2B7, and glucuronidation is another important pathway for opioid-drug interactions. This review also covers several pharmacodynamic DDI studies as well as the basics of CYP and UGT metabolism, including detailed opioid metabolism and the potential involvement of metabolizing enzyme gene variation in DDI. Based upon the current literature, further studies are needed to fully investigate and describe the DDI potential with opioids in pain and related disease settings to improve clinical outcomes for patients. SIGNIFICANCE STATEMENT: A review of the literature focusing on drug-drug interactions involving opioids is important because they can be toxic and potentially lethal, occurring through pharmacodynamic interactions as well as pharmacokinetic interactions occurring through inhibition or induction of drug metabolism.


Subject(s)
Analgesics, Opioid , Oxycodone , Humans , Analgesics, Opioid/adverse effects , Analgesics, Opioid/pharmacokinetics , Oxycodone/adverse effects , Hydrocodone/therapeutic use , Pain/drug therapy , Drug Interactions , Morphine/adverse effects , Cytochrome P-450 Enzyme System/metabolism
12.
Ann Clin Lab Sci ; 53(4): 671-672, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37625839

ABSTRACT

OBJECTIVE: Determining deception in urine drug testing. Some of the patients undergoing urine drug tests have not taken the prescribed drug and attempt to deceive the laboratory test by placing the parent drug in the collection cup. METHODS: One of the ways to determine if this is occurring is to monitor the major metabolite of the drug. By using the metabolite/parent drug ratio this attempt at deception can be uncovered. RESULTS: Of the five drugs we examined, oxycodone, hydrocodone, buprenorphine, methadone, and fentanyl, we found buprenorphine to be the most prevalent drug to this type of deception. CONCLUSION: Deception can be identified using the metabolite/parent drug ratio.


Subject(s)
Buprenorphine , Substance Abuse Detection , Humans , Fentanyl , Hydrocodone , Deception
14.
N Engl J Med ; 389(5): 393-405, 2023 Aug 03.
Article in English | MEDLINE | ID: mdl-37530822

ABSTRACT

BACKGROUND: The NaV1.8 voltage-gated sodium channel, expressed in peripheral nociceptive neurons, plays a role in transmitting nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied. METHODS: After establishing the selectivity of VX-548 for NaV1.8 inhibition in vitro, we conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy. In the abdominoplasty trial, participants were randomly assigned in a 1:1:1:1 ratio to receive one of the following over a 48-hour period: a 100-mg oral loading dose of VX-548, followed by a 50-mg maintenance dose every 12 hours (the high-dose group); a 60-mg loading dose of VX-548, followed by a 30-mg maintenance dose every 12 hours (the middle-dose group); hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. In the bunionectomy trial, participants were randomly assigned in a 2:2:1:2:2 ratio to receive one of the following over a 48-hour treatment period: oral high-dose VX-548; middle-dose VX-548; low-dose VX-548 (a 20-mg loading dose, followed by a 10-mg maintenance dose every 12 hours); oral hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. The primary end point was the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour period (SPID48), a measure derived from the score on the Numeric Pain Rating Scale (range, 0 to 10; higher scores indicate greater pain) at 19 time points after the first dose of VX-548 or placebo. The main analysis compared each dose of VX-548 with placebo. RESULTS: A total of 303 participants were enrolled in the abdominoplasty trial and 274 in the bunionectomy trial. The least-squares mean difference between the high-dose VX-548 and placebo groups in the time-weighted SPID48 was 37.8 (95% confidence interval [CI], 9.2 to 66.4) after abdominoplasty and 36.8 (95% CI, 4.6 to 69.0) after bunionectomy. In both trials, participants who received lower doses of VX-548 had results similar to those with placebo. Headache and constipation were common adverse events with VX-548. CONCLUSIONS: As compared with placebo, VX-548 at the highest dose, but not at lower doses, reduced acute pain over a period of 48 hours after abdominoplasty or bunionectomy. VX-548 was associated with adverse events that were mild to moderate in severity. (Funded by Vertex Pharmaceuticals; VX21-548-101 and VX21-548-102 ClinicalTrials.gov numbers, NCT04977336 and NCT05034952.).


Subject(s)
Acetaminophen , Acute Pain , Humans , Acetaminophen/therapeutic use , Hydrocodone/adverse effects , Acute Pain/drug therapy , Analgesics, Opioid/therapeutic use , Pain, Postoperative/drug therapy , Analgesics/therapeutic use , Double-Blind Method
15.
Ann Clin Lab Sci ; 53(3): 460-468, 2023 May.
Article in English | MEDLINE | ID: mdl-37437938

ABSTRACT

We propose that quantitative urine drug concentrations from LC-MS/MS measurements can be used to estimate zero and first order pharmacokinetics of the drugs oxycodone, hydrocodone, buprenorphine, methadone, and fentanyl. We observed the ratio of metabolite to parent drug could be used for this estimate. As the amount of observed parent drug increased, the metabolic ratio decreased, indicating a shift from first order to zero order metabolism. After making assumptions of bioavailability, percent of drug excreted into urine, we developed estimates of the saturating dosages for these drugs.


Subject(s)
Drug Elimination Routes , Tandem Mass Spectrometry , Humans , Chromatography, Liquid , Fentanyl , Hydrocodone
16.
Pain Manag ; 13(6): 329-334, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37458236

ABSTRACT

Aim: Serotonin syndrome (SS) is a life-threatening syndrome that occurs with the use of serotonergic drugs, most commonly due to two or more agents. Cerebral palsy is associated with mood disorders, and more commonly pain, with a prevalence of up to 50-80%. Case presentation: A 58-year-old female with cerebral palsy, metastatic malignancy and mood disorder who presented to the emergency department with acute-on-chronic pain, and signs of SS. She was initiated on iv. dilaudid, titrated off oral medications and scheduled for a left-sided sacroiliac joint injection. Results: It was suspected that due to additional doses of hydrocodone and cyclobenzaprine, she developed moderate-SS. Conclusion: Physicians need to be cognizant of comorbidities and uncommon pain medications that can predispose patients to SS.


Subject(s)
Cerebral Palsy , Serotonin Syndrome , Female , Humans , Middle Aged , Hydrocodone/adverse effects , Serotonin Syndrome/chemically induced , Serotonin Syndrome/complications , Serotonin Syndrome/drug therapy , Cerebral Palsy/complications , Cerebral Palsy/drug therapy , Pain/drug therapy
17.
J Opioid Manag ; 19(2): 149-156, 2023.
Article in English | MEDLINE | ID: mdl-37270422

ABSTRACT

OBJECTIVE: To explore the impact on opioid prescribing patterns and trends after implementing a prescription drug monitoring program (PDMP) in Pennsylvania from 2016 to 2020. DESIGN: A cross-sectional data analysis using deidentified data from Pennsylvania's PDMP delivered by the Pennsylvania Department of Health was undertaken. SETTING: Data were collected from the entire state of Pennsylvania, and statistics were run at Rothman Orthopedic Institute Foundation for Opioid Research & Education. INTERVENTIONS: Evaluating the effect on opioid prescriptions after introduction of the PDMP. MAIN OUTCOME MEASURE: In 2016, nearly 2 million opioid prescriptions were given to patients across the state. However, by the end of the study period in 2020, there was a 38 percent decrease in opioid prescriptions written. RESULTS: Beginning with Q3 2016, each subsequent quarter saw fewer opioids prescribed, decreasing on average by 3.4 ± 1.7 percent through Q1 2020. Specifically, over 700,000 fewer prescriptions were in the first quarter of 2020 compared to the third quarter in 2016. The opioids that were most frequently prescribed were oxycodone, hydrocodone, and morphine. CONCLUSION: While fewer prescriptions were being prescribed overall, the breakdown of drug type being prescribed remained similar in 2020 compared to 2016. Fentanyl and hydrocodone saw the largest decrease between 2016 and 2020.


Subject(s)
Analgesics, Opioid , Hydrocodone , Humans , Analgesics, Opioid/adverse effects , Hydrocodone/adverse effects , Pennsylvania , Cross-Sectional Studies , Practice Patterns, Physicians' , Drug Prescriptions
18.
Aesthet Surg J ; 43(9): 978-985, 2023 08 17.
Article in English | MEDLINE | ID: mdl-37185594

ABSTRACT

BACKGROUND: The United States is experiencing the highest opioid overdose death rate in our nation's history. Misuse and addiction to opioids, including prescription pain relievers, is a serious national crisis that affects public health as well as social and economic welfare. OBJECTIVES: The aim of the study was to critically evaluate postoperative opioid-prescribing patterns. METHODS: The PearlDiver database (Colorado Springs, CO) was queried for body contouring patients from 2010 to 2020. We identified patients that underwent panniculectomy, abdominoplasty, brachioplasty, thighplasty, mastopexy, breast augmentation, breast reduction, and liposuction for analysis. We subsequently analyzed the opioid use, with a focus on comorbid conditions and complications that are associated with increased use of opioids. RESULTS: A total of 56,773 patients underwent body contouring surgery. The most common opioid prescribed was hydrocodone with acetaminophen (37,017 patients). Average days of therapy was 17.92 days. Comorbid conditions and postoperative complications were examined for risk of increased opioid prescriptions. Patients with peripheral vascular disease and smoking were prescribed significantly more morphine milliequivalents (MME) of opioids than patients without peripheral vascular disease (871.97 vs 535.41; P < .001) and smoking (1069.57 vs 440.84; P < .001). Patients who developed surgical site infection, disruption of wound, and venous thromboembolism were prescribed a significantly higher MME of opioids (1213.63 vs 561.59; P < .001). CONCLUSIONS: Our data provide information on opioid prescription patterns in the body contouring population, with focused review of comorbid conditions and complications in relation to opioid-prescribing patterns. We hope that the data will improve opioid prescription habits among plastic surgeons in the setting of a global opioid crisis.


Subject(s)
Body Contouring , Opioid-Related Disorders , Humans , United States/epidemiology , Analgesics, Opioid/adverse effects , Body Contouring/adverse effects , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/etiology , Opioid-Related Disorders/drug therapy , Hydrocodone , Practice Patterns, Physicians' , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology
19.
BMC Health Serv Res ; 23(1): 364, 2023 Apr 13.
Article in English | MEDLINE | ID: mdl-37046254

ABSTRACT

BACKGROUND: Prescription opioids remain an important contributor to the United States opioid crisis and to the development of opioid use disorder for opioid-naïve individuals. Recent legislative actions, such as the implementation of state prescription drug monitoring programs (PDMPs), aim to reduce opioid morbidity and mortality through enhanced tracking and reporting of prescription data. The primary objective of our study was to describe the opioid prescribing trends in the state of Pennsylvania (PA) as recorded by the PA PDMP following legislative changes in reporting guidelines, and discuss the PDMP's role in a multifactorial approach to opioid harm reduction. METHODS: State-level opioid prescription data summaries recorded by the PA PDMP for each calendar quarter from August 2016 through March 2020 were collected from the PA Department of Health. Data for oxycodone, hydrocodone, and morphine were analyzed by quarter for total prescription numbers and refills. Prescription lengths, pill quantities, and average morphine milliequivalents (MMEs) were analyzed by quarter for all 14 opioid prescription variants recorded by the PA PDMP. Linear regression was conducted for each group of variables to identify significant differences in prescribing trends. RESULTS: For total prescriptions dispensed, the number of oxycodone, hydrocodone, and morphine prescriptions decreased by 34.4, 44.6, and 22.3% respectively (p < 0.0001). Refills fluctuated less consistently with general peaks in Q3 of 2017 and Q3 of 2018 (p = 0.2878). The rate of prescribing for all opioid prescription lengths decreased, ranging in frequency from 22 to 30 days (47.5% of prescriptions) to 31+ days of opioids (0.8% of prescriptions) (p < 0.0001). Similarly, decreased prescribing was observed for all prescription amounts, ranging in frequency from 22 to 60 pills (36.6% of prescriptions) to 60-90 pills (14.2% of prescriptions) (p < 0.0001). Overall, the average MME per opioid prescription decreased by 18.9%. CONCLUSIONS: Per the PA PDMP database, opioid prescribing has decreased significantly in PA from 2016 to 2020. The PDMP database is an important tool for tracking opioid prescribing trends in PA, and PDMPs structured similarly in other states may enhance our ability to understand and influence the trajectory of the U.S. opioid crisis. Further research is needed to determine optimal PDMP policies and practices nationwide.


Subject(s)
Prescription Drug Monitoring Programs , Humans , United States , Analgesics, Opioid/therapeutic use , Pennsylvania/epidemiology , Hydrocodone/therapeutic use , Oxycodone/therapeutic use , Opioid Epidemic , Practice Patterns, Physicians'
20.
Hepatol Commun ; 7(4)2023 04 01.
Article in English | MEDLINE | ID: mdl-36972394

ABSTRACT

BACKGROUND: During the opioid epidemic, misuse of acetaminophen-opioid products resulted in supratherapeutic acetaminophen ingestions and cases of hepatotoxicity. In 2014, the US Food and Drug Administration (FDA) limited the amount of acetaminophen in combination products to 325 mg, and the US Drug Enforcement Administration (DEA) changed hydrocodone/acetaminophen from schedule III to schedule II. This study assessed whether these federal mandates were associated with changes in acetaminophen-opioid supratherapeutic ingestions. METHODS: We identified emergency department encounters at our institution of patients with a detectable acetaminophen concentration and manually reviewed these charts. RESULTS: We found a decline in acetaminophen-opioid supratherapeutic ingestions after 2014. A downtrend in hydrocodone/acetaminophen ingestions accompanied a relative increase in codeine/acetaminophen ingestions from 2015 onwards. CONCLUSION: This experience at one large safety net hospital suggests a beneficial impact of the FDA ruling in reducing likely unintentional acetaminophen supratherapeutic ingestions, carrying a risk of hepatotoxicity, in the setting of intentional opioid ingestions.


Subject(s)
Acetaminophen , Chemical and Drug Induced Liver Injury , Humans , Analgesics, Opioid/therapeutic use , Hydrocodone/therapeutic use , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/drug therapy
SELECTION OF CITATIONS
SEARCH DETAIL
...