Comparative safety of tramadol and other opioids following total hip and knee arthroplasty.

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.

Opioid-induced respiratory depression suspected of drug interaction in a prostate cancer patient: a case report.

BACKGROUND: Many of the drugs used for the treatment and alleviation of symptoms in cancer patients are known to inhibit or induce cytochrome P450 (CYP). Therefore, it is important to pay attention to the drug interactions of opioid analgesics that are metabolized by CYPs, because for example when using oxycodone metabolized by CYP3A4, it is possible that the effect will be attenuated or enhanced by the concomitant use of drugs that induce or inhibit CYP3A4. Aprepitant, an antiemetic drug used in many patients receiving anticancer drugs, is known as a moderate competitive inhibitor of CYP3A4. We experienced a case of respiratory depression caused by opioids, which was suspected to be caused by a drug interaction with antiemetics especially aprepitant. CASE DESCRIPTION: The patient was a 72-year-old man. He had been treated with continuous oxycodone infusion for perianal pain associated with the rectal invasion of prostate cancer. No comorbidities other than renal dysfunction were observed. Oxycodone treatment was started at 48 mg/day, and was increased to 108 mg/day, and then the pain decreased. Once the pain was controlled, chemotherapy was planned. Antiemetics (dexamethasone, palonosetron, and aprepitant) were administered before anticancer drug administration. Approximately 3 hours after antiemetics administration and before the administration of the anticancer drugs, a ward nurse noticed that oversedation and respiratory depression had occurred. When the patient was called, he immediately woke up and was able to talk normally, so the anticancer drugs were administered as scheduled. About 2 hours after the nurse noticed oversedation, the attending physician reduced the dose of oxycodone infusion to 48 mg/day. After that, his drowsiness persisted, but his respiratory condition improved. Despite reducing the dose of oxycodone to less than half, the pain remained stable at numeric rating scale (NRS) 0-1, without the use of a rescue dose. The patient was discharged from the hospital 36 days after the administration of anticancer drugs, without any problems. CONCLUSIONS: The cause of respiratory depression in this case was thought to be a combination of factors, including drug interactions between oxycodone and antiemetics, and oxycodone accumulation due to renal dysfunction.

Refractory Hypoglycemia Due to Sulfonylurea Contamination of Illicit Opioid Medications.

Illicit drug supply adulteration can heighten the risk for adverse health outcomes. Sulfonylurea medications are widely used in the treatment of diabetes mellitus (DM). Unintentional or intentional overdose of sulfonylureas can cause refractory hypoglycemia. This case report describes a 62-year-old male patient who presented to the emergency department (ED) after being found on the ground with signs of mild trauma. He was noted to be persistently hypoglycemic despite boluses of intravenous dextrose, a dextrose infusion, and oral nutrition. The patient did report purchase and oral ingestion of pills sold as oxycodone and that the pill shape and color were different from his usual supply. The patient was empirically treated with octreotide resulting in normalization of his serum glucose. Testing demonstrated a serum glipizide concentration six times the reporting range. This case represents unintentional sulfonylurea exposure in the setting of non-prescribed oxycodone use, resulting in hypoglycemia refractory to intravenous dextrose and oral nutrition. Octreotide is an additional potential treatment for this condition. As in this case, ingestion of street drugs may present a potential source of sulfonylurea exposure. Opioid contamination with sulfonylureas has not been widely reported in the literature and knowledge about this potential exposure is important for the prompt recognition and treatment of these patients by emergency physicians.

Chronic Pain Management in a CYP2D6 Poor Metabolizer: A Case Report for Oxycodone.

The objective of this case report is to illustrate pharmacogenomics (PGx)-guided oxycodone treatment, given the conflicting data on the analgesic response from oxycodone in Cytochrome P450 (CYP)2D6 poor metabolizers (PMs). PGx-guided therapy can help improve treatment outcomes. This case report describes a 58-year-old patient who was prescribed oxycodone for chronic pain management. The patient presented with a history of inadequate pain control despite analgesic treatment with oxycodone (morphine milliequivalent [MME] = 22.5). Pharmacogenetic testing revealed that the patient was a CYP2D6 Poor Metabolizer (PM), which may shed light on the observed lack of analgesic response to oxycodone. The clinical pharmacist recommended switching to an alternative opioid not metabolized via the CYP2D6 pathway. The patient was subsequently switched to hydromorphone (MME = 16), resulting in improved pain control and fewer side effects. The newer hydromorphone dose accounted for a 30% MME dose reduction. The patient's initial average and worst pain score were 7 and 9 out of 10, respectively, per the numeric rating scale (NRS). Upon follow-up with the patient in two weeks, her average and worst pain scores improved to 3 and 3.5 out of 10, respectively, per the NRS. Further PGx testing results led to an overall positive outcome, such as her willingness to participate in physical therapy as a result of improved pain scores. This case highlights the importance of considering individual variability in drug metabolism when prescribing medications, particularly opioids such as oxycodone, to ensure optimal therapeutic outcomes and minimize the risk of adverse events in CYP2D6 PMs.

Pharmacological prevention and treatment of opioid-induced constipation in cancer patients: A systematic review and meta-analysis.

BACKGROUND: Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients. METHODS: A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed. RESULTS: Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I2 = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I2 = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I2 = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I2 = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates. CONCLUSIONS: Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.

Breast milk oxycodone concentrations in mothers given oxycodone for post-Caesarean delivery pain management.

AIMS: Both effective analgesia and early breastfeeding play an important role in maternal and neonatal well-being after Caesarean delivery. We studied controlled-release oxycodone tablet treatment for postoperative pain management and determined the excretion of oxycodone into breast milk. METHODS: Controlled-release oxycodone/naloxone 10/5-mg tablets (n = 21) or controlled-release oxycodone 10-mg tablets (n = 22) were administered to mothers twice a day for the first 3 days after elective Caesarean delivery as a part of multimodal analgesia. Maternal plasma and breast milk samples were collected daily. Oxycodone, noroxycodone, oxymorphone and noroxymorphone concentrations were analysed with ultra-performance liquid chromatography-mass spectrometry. Maternal pain intensity was recorded with an 11-point Numeric Rating Scale (0-10). Neonatal oxycodone exposure was estimated by simulating five different exposure scenarios, including the highest possible exposure through breast milk. RESULTS: The mean oxycodone and noroxycodone milk-to-maternal plasma ratios were 3.2 and 3.0, respectively. A strong correlation was found between plasma and breast milk oxycodone (R2 = 0.87) and noroxycodone concentrations (R2 = 0.91). In the simulated highest neonatal exposure scenario, the neonate's maximum plasma concentration was estimated to be 5.4 ng/mL and the estimated weight-adjusted infant oxycodone dose was less than 10% of the maternal dose. Pain intensities were similarly low between the two treatment groups. CONCLUSIONS: The oxycodone dose received from colostrum and breast milk during the first three postoperative days after Caesarean delivery is assumed safe for healthy, term neonates, but in extreme cases it is possible for the neonate to receive a dose through breast milk that may elicit opioid effects.

Prescription opioids induced microbial dysbiosis worsens severity of chronic pancreatitis and drives pain hypersensitivity.

Opioids, such as morphine and oxycodone, are widely used for pain management associated with chronic pancreatitis (CP); however, their impact on the progression and pain sensitivity of CP has never been evaluated. This report investigates the impact of opioid use on the severity of CP, pain sensitivity, and the gut microbiome. C57BL/6 mice were divided into control, CP, CP with morphine/oxycodone, and either morphine or oxycodone alone groups. CP was induced by administration of caerulein (50ug/kg/h, i.p. hourly x7, twice a week for 10 weeks). The mouse-to-pancreas weight ratio, histology, and Sirius red staining were performed to measure CP severity. Tail flick and paw pressure assays were used to measure thermal and mechanical pain. DNA was extracted from the fecal samples and subjected to whole-genome shotgun sequencing. Germ-free mice were used to validate the role of gut microbiome in sensitizing acute pancreatic inflammation. Opioid treatment exacerbates CP by increasing pancreatic necrosis, fibrosis, and immune-cell infiltration. Opioid-treated CP mice exhibited enhanced pain hypersensitivity and showed distinct clustering of the gut microbiome compared to untreated CP mice, with severely compromised gut barrier integrity. Fecal microbiota transplantation (FMT) from opioid-treated CP mice into germ-free mice resulted in pancreatic inflammation in response to a suboptimal caerulein dose. Together, these analyses revealed that opioids worsen the severity of CP and induce significant alterations in pain sensitivity and the gut microbiome in a caerulein CP mouse model. Microbial dysbiosis plays an important role in sensitizing the host to pancreatic inflammation.

Opioids in geriatric units in 14 Belgian hospitals: prevalence, dosage and associated factors.

Introduction: Adverse effects of opioids are common among older individuals, and undertreatment as well as overuse can be an issue. Epidemiological data on opioid use in older individuals are available, but scarce in hospitalized patients.Aims: The aim of this study is to examine the one-day prevalence of opioid use among older inpatients and identify the factors associated with both opioid use and dosage.Materials and methods: One-day cross-sectional study with data collected from geriatric units across 14 Belgian hospitals. The primary focus of the study is to assess the prevalence of opioid use and dosage, along with identifying associated factors. To achieve this, a multiple binary logistic regression model was fitted for opioid use, and a multiple linear regression model for opioid dose.Results: Opioids were used in 24.4% of 784 patients, of which 57.9% was treated with tramadol, 13.2% with oxycodone or morphine and 28.9% with transdermal buprenorphine or fentanyl. The odds for opioid use were 4.2 times higher in patients in orthogeriatric units compared to other patients (OR=4.2, 95% CI=2.50-7.05). The prevalence of opioid use was 34% higher in patients without dementia compared to patients with dementia (OR=0.66, 95% CI=0.46-0.95). The overall mean daily dosage was 14.07mg subcutaneous morphine equivalent. After adjustment for age, gender and dementia, dosage was only associated with type of opioid: the estimated mean opioid dose was 70% lower with tramadol (mean ratio=0,30,95% CI=0,23-0,39) and 67% lower with oxycodone and morphine (mean ratio=0,33, 95% CI=0,22-0,48) compared to transdermal buprenorphine and transdermal fentanyl.Conclusions: One in four patients received opioid treatment. It is not clear whether this reflects under- or overtreatment, but these results can serve as a benchmark for geriatric units to guide future pain management practices. The utilization of transdermal fentanyl and buprenorphine, resulting in higher doses of morphine equivalent, poses significant risks for side effects.

Drug-drug interaction perpetrators of oxycodone in patients with cancer: frequency and clinical relevance.

AIM: Oxycodone is known to have numerous drug-drug interactions (DDIs) that can potentially decrease efficacy or lead to adverse drug reactions (ADRs). However, there is limited research on the frequency of DDIs associated with oxycodone, which is important in optimising pharmacovigilance and the need for additional research on certain DDIs. In this study, the frequency of pharmacologically and clinically relevant DDI perpetrators was studied in patients with cancer. METHODS: This was a cross-sectional study using hospital pharmacy records of patients with cancer who were prescribed oxycodone between September 2021 and September 2022. Medication records of patients prescribed oxycodone during a period of ≥ 5 consecutive days (= oxycodone treatment episodes) were reviewed to identify the concomitant use of pharmacologically relevant perpetrators, based on reference sources (Lexicomp®, Micromedex®, the Dutch Kennisbank and the Dutch Commentaren Medicatiebewaking). The clinical relevance was examined by a clinical pharmacologist and a medical oncologist. Additionally, the frequency of double interactions-concomitant oxycodone use with two CYP3A4 and / or CYP2D6 perpetrators-was studied. RESULTS: Overall, 254 oxycodone treatment episodes were included, of which 227 (89.4%) were found to contain at least one pharmacologically relevant DDI perpetrator. Of these, 210 (82.7%) were considered to be clinically relevant. A total of 80 different pharmacologically relevant perpetrators were identified, with 65 (81.3%) being considered clinically relevant. Double interactions were observed in 21 (8.3%) oxycodone treatment episodes. CONCLUSION: A high frequency of pharmacologically and clinically relevant perpetrators of oxycodone was observed in our cohort. Moreover, a high number of double interactions involving oxycodone was registered. More intense monitoring of DDIs may be needed to improve medication safety of patients with cancer taking oxycodone.

A Multicenter Retrospective Observational Study Analyzing the Effect of Polypharmacy on Oxycodone Tolerability.

Polypharmacy is becoming increasingly troublesome in the treatment of cancer. The aim of this study was to explore the effects of concomitant polypharmacy comprising drugs that inhibit CYP3A4 and/or CYP2D6 on the oxycodone tolerability in patients with cancer. We conducted a multicenter retrospective study encompassing 20 hospitals. The data used for the study were obtained during the first 2 wk of oxycodone administration. The incidence of oxycodone discontinuation or dose reductions due to side effects and oxycodone-induced nausea and vomiting (OINV) were compared between patients not treated with either inhibitor and those treated with concomitant CYP3A4 or CYP2D6 inhibitors. The incidence of oxycodone discontinuation or dose reductions in patients treated with ≥3 concomitant CYP2D6 inhibitors (18.2%) tended to be higher than that in patients without this treatment (8.2%; p = 0.09). Moreover, the incidence of OINV in patients treated with 2 concomitant CYP3A4 inhibitors (29.8%) was significantly higher than that in patients without this treatment (15.5%; p = 0.049). Multivariate analysis showed that more than two concomitant CYP3A4 inhibitors and no concomitant use of naldemedine were independent risk factors for OINV. Concomitant polypharmacy involving CYP3A4 inhibitors increases the risk of OINV. Therefore, medications concomitantly used with oxycodone should be optimized.

Comparison of different sustained-release opioids and acute respiratory conditions in patients with cancer and chronic kidney disease.

STUDY OBJECTIVE: Few data are available on the association between the use of oxycodone in patients with chronic kidney disease (CKD) and acute respiratory conditions. The aim of this study was to investigate whether oxycodone is associated with an increased risk of acute respiratory conditions in patients with cancer and CKD compared with other opioids. DESIGN AND SETTING: The data were obtained from a claims database in Japan. Patients with cancer and CKD who had received sustained-release opioids, including oral oxycodone, oral morphine, or transdermal fentanyl, between April 2014 and May 2021 were selected. The primary outcome was defined as an acute respiratory condition. Data for age and sex, morphine equivalent daily dose, concomitant use of specified medications, comorbidities defined based on the modified Charlson comorbidity index, substance use disorder, and lung cancer or metastatic lung cancer were investigated as covariates. Distribution of acute respiratory conditions was compared among the three sustained-release opioid groups using the log-rank test. Estimates of the incidence of acute respiratory conditions were compared among the groups using a Cox proportional hazards model with time-varying variables. MAIN RESULTS: A significant difference in the distribution of acute respiratory conditions was found among the three groups (p < 0.01). Cox regression analysis showed a significantly higher risk of acute respiratory conditions with morphine (hazard ratio [HR]: 3.04, 95% confidence interval [CI]: 1.07-8.65, p = 0.04) compared with oxycodone but no significant difference in risk with oxycodone (HR 0.67, 95% CI: 0.32-1.38, p = 0.27) compared with fentanyl. CONCLUSIONS: The findings suggest that the risk of acute respiratory conditions may be lower in patients with CKD who use oxycodone for cancer pain than in those who use morphine. Additionally, no difference in the risk of acute respiratory conditions was found between oxycodone and fentanyl use.

Tapentadol Versus Oxycodone for Opioid-Related Adverse Drug Events and Clinical Outcomes After Inpatient Surgery.

Oxycodone is a commonly prescribed opioid for postoperative pain. However, there has been a marked increase in the use of tapentadol over the previous decade due to a perceived superior safety profile of tapentadol compared to oxycodone. There is limited real-world evidence on the safety of tapentadol compared to oxycodone after surgery. The primary objective was to examine the impact of tapentadol compared to oxycodone use on the incidence of opioid-related adverse drug events after surgery. Data for adult surgical patients receiving tapentadol or oxycodone during hospitalization between January 1, 2018, and December 31, 2021, were collected from electronic medical records of 3 tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events. Patients receiving tapentadol or oxycodone were matched using nearest-neighbour propensity score matching. In the matched cohorts (n = 1,530 vs n = 2,775; mean [standard deviation] age 62.3 [17.0] years vs 61.9 [standard deviation 17.9] years; 43% vs 45% male for the tapentadol vs oxycodone groups, respectively), patients given tapentadol experienced a similar incidence of adverse events overall (14.4%, 220/1,530 vs 12.6%, 349/2,775; P = .100; 95% CI -.35% to 3.95%). Secondary outcomes included an increased risk of delirium (2.7%, 41/1,530 vs 1.3%, 37/2,775), arrhythmias (3.4%, 52/1,530 vs 2.2%, 62/2,775), and length of hospital stay (5 [range 1-201] vs 4 [range 1-226] days) compared with oxycodone use. Further real-world studies are warranted to determine the impact of tapentadol use on a broad range of patient outcomes. PERSPECTIVE: This study provides an early signal that tapentadol use may be associated with an increased risk of some adverse events and a longer length of stay. Further research is needed to examine the impact of tapentadol use on a broad range of patient outcomes in clinical practice settings.

A Retrospective Observational Study of Factors Affecting the Efficacy of Concurrent Prescription of Naldemedine for Opioid-Induced Constipation Caused by Oxycodone Tablets.

Naldemedine is indicated for the treatment of opioid-induced constipation (OIC), but reports on its efficacy in preventing OIC are few. Therefore, we retrospectively investigated factors affecting the efficacy of concurrent prescription of naldemedine on OIC. Outpatients with cancer who were started on oxycodone 10 mg/d were included in the study. The eligible patients were classified by their physicians into the following three groups: Group A used regular laxatives before the introduction of oxycodone and initiated naldemedine treatment simultaneously with oxycodone administration, Group B did not take laxatives before the introduction of oxycodone and started naldemedine simultaneously with oxycodone administration, and Group C had been administering regular laxatives before the introduction of oxycodone and were not prescribed naldemedine simultaneously with oxycodone treatment. The Support Team Assessment Schedule Japanese edition score for constipation, frequency of defecation, Bristol Stool Form Scale, sense of incomplete rectal evacuation, and development or worsening of straining to pass bowel movements were compared among the three groups before and after oxycodone administration. In Group B, there was significant worsening of the four parameters except for the sense of incomplete rectal evacuation, whereas Groups A and C did not present any changes. In logistic regression analysis, body weight ≥51.8 kg was a factor significantly decreasing the preventive effect of naldemedine on OIC, and regular use of laxatives was a factor significantly increasing the preventive effect of naldemedine on OIC. Thus, the initiation of naldemedine should be considered depending on the body weight and regular laxative use.

The Role of Non-Pharmaceutical Fentanyl-Contaminated Counterfeit Oxycodone in Increasing Opioid Overdoses: A Commentary Review.

Importance: Opioid misuse/abuse is a pervasive problem in the United States, and the growing use of fentanyl-contaminated products is adding fuel to the opioid crisis.Objective: To review the rising prevalence of nonprescription fentanyl in counterfeit oxycodone, paying specific attention to oxycodone for cost analysis.Evidence Review: A literature search was performed using 3 databases (Google Scholar, PubMed, and Clinical Key) to identify English-language articles published from January 2010 to October 2022. Search terms were street oxycodone and prescription oxycodone, street oxycodone. An additional search of fentanyl was performed to gather more information about the pharmacology behind fentanyl overdoses. Studies and articles were selected based on information related to the presence of non-prescription fentanyl in illicit supplies of oxycodone. Additional articles were included to demonstrate the cost, manufacturing, and overdose rates of fentanyl-laced counterfeit opioids. A total of 13 articles were included in the final review.Findings: The demand for illicit oxycodone provides an opportunity in which counterfeiters can thrive, using dangerous adulterating agents such as fentanyl to maximize their profits. Those purchasing oxycodone illicitly may or may not be aware of the presence of fentanyl in their tablets, which has clearly resulted in rising overdose numbers.Conclusion: Clinicians should counsel patients at risk for opioid misuse on the risks of counterfeit oxycodone.Prim Care Companion CNS Disord 2023;25(6):22nr03433. Author affiliations are listed at the end of this article.

Growth in Suicide Rates Among Children During the Illicit Opioid Crisis.

This article documents child suicide rates from 1980 to 2020 in the United States using the National Vital Statistics System Multiple Cause of Death database. After generally declining for decades, suicide rates among children aged 10-17 accelerated from 2011 to 2018 in an unprecedented rise in both duration and magnitude. I consider the role of the illicit opioid crisis in driving this mental health crisis. In August 2010, an abuse-deterrent version of OxyContin was introduced and the original formulation was removed from the market, leading to a shift to illicit opioids and stimulating growth in illicit opioid markets. Areas more exposed to reformulation-as measured by pre-reformulation rates of OxyContin misuse in the National Survey on Drug Use and Health-were more affected by the transition to illicit opioids and experienced sharper growth in child suicide rates. The evidence suggests that children's illicit opioid use did not increase, implying that the illicit opioid crisis engendered higher suicide propensities by increasing suicidal risk factors for children, such as increasing rates of child neglect and altering household living arrangements. In complementary analyses, I document how living conditions declined for children during this time period.

Study on the association between adverse drug reactions to opioids and gene polymorphisms: a case-case-control study.

OBJECTIVE: Adverse drug reactions (ADRs) caused by opioid drugs show individual differences. Our objective was to explore the association between gene polymorphism and ADRs induced by opioid drugs. METHODS: Evidence-based medical data analysis was conducted for genes related to ADRs induced by opioid drugs to select target genes. Sixty patients with cancer pain who had ADRs after taking opioid drugs (morphine, codeine, oxycodone) and 60 patients without ADRs after taking opioid drugs were used as the experimental group and control group, respectively. Then, we used polymerase chain reaction (PCR) or in situ hybridization to detect target genes. By combining with clinical data such as age, sex, dosage and duration of medication, the effect of gene polymorphism on the ADR of patients after taking opioid drugs was statistically analysed. RESULTS: Based on a database search and evidence-based medical data, we identified CYP2D6*10, CYP3A5*3, ABCB1, and OPRM1 as target genes for detection. The results of statistical analysis showed no significant difference in genotype distribution between the experimental group and the control group (p > 0.05). However, if 32 patients with ADRs after taking oxycodone and 32 controls were selected for comparison, the SPSS22.0 and SNPStats genetic models showed that the ABCB1 (062rs1045642) CT and TT genotypes correlated with the occurrence of ADRs (p < 0.05): the total number of CT + TT genotypes in the experimental group was 29 (90.62%), with 11 (34.37%) CT + TT genotypes types in the control group. CONCLUSION: Polymorphism of ABCB1 (062rs1045642) is related to ADRs caused by oxycodone, and the incidence of ADRs is higher with the allele T. Polymorphism of ABCB1 is expected to become a clinical predictor of ADRs to oxycodone, and attention should be given to the occurrence of serious ADRs in patients with ABCB1 (062rs1045642) CT and TT genotypes.

Differences in severity of poison centers exposures involving XTAMPZA® ER versus other opioid analgesics.

Aims: Xtampza® ER (Collegium Pharmaceutical, MA, USA) is an abuse-deterrent formulation (ADF) of oxycodone intended to deter tampering for use by unintended routes of administration. We assessed whether Xtampza ER exposures were less likely to result in severe medical outcomes relative to other opioid analgesic exposures. Materials & methods: Exposures reported to participating poison centers between 2016 and 2021 inclusive that were followed to a known medical outcome were analyzed. Xtampza ER was compared with other ADF opioids, non-ADF extended-release opioids, single-entity oxycodone immediate-release, unspecified oxycodone and unspecified morphine. Results & conclusion: No Xtampza ER exposures involved unintended routes of administration. Xtampza ER exposures were less likely to be abuse, misuse or suspected suicidal, and medical outcomes were less severe than comparators.

Comparison of Analgesic Efficacy and Safety of Low-Dose Transdermal Fentanyl and Oral Oxycodone in Opioid-Naïve Patients with Cancer Pain.

In Japan, a low-dose transdermal fentanyl (TDF; 0.5 mg) has been approved to address pain in opioid-naïve patients with cancer; however, efficacy and safety data are lacking. To determine the efficacy and safety of TDF, patients with opioid-naïve cancer pain prescribed TDF (0.5 mg/d) and oral oxycodone sustained-release formulation (OXY) 10 mg/d were extracted from electronic medical and nursing records. Overall, 40 and 101 subjects were analyzed in the TDF and OXY groups, respectively. Compared with baseline (median [minimum, maximum]) values, changes in the Numerical Rating Scale (NRS) score on days 1, 3, and 7 post-administration were as follows: TDF (0 [-5, 4]) and OXY (-1.0 [-8, 3]); TDF (-1.5 [-6, 3]) and OXY (-2.0 [-8, 4]); and TDF (-2.0[-6, 3]) and OXY (-3.0[-8, 5]), respectively. No significant difference was observed between the groups on days 1 and 3; however, the change in the NRS on day 7 was significantly higher in the OXY group than that in the TDF group. Regarding adverse events, nausea occurred in 12.5 and 13.9% of patients in the TDF and OXY groups, respectively, while 12.5% of TDF- and 10.9% of OXY-treated patients experienced somnolence, revealing similar occurrence in both groups. However, constipation was more common in the OXY group (TDF: 50.0%, OXY: 71.3%). No serious adverse events (e.g., respiratory depression) were observed in either group. Low-dose TDF (0.5 mg), available only in Japan, showed comparable efficacy and safety to OXY (10 mg/d) and can be a first choice for opioid-naïve patients with cancer pain.

Opioid prescribing, pain, and hospital stay of general surgery patients with oxycodone allergies in South Australia.

BACKGROUND: The frequency of oxycodone adverse reactions, subsequent opioid prescription, effect on pain and patient care in general surgery patients are not well known. This study aimed to determine prevalence of documented oxycodone allergy and intolerances (independent variables) in a general surgical cohort, and association with prescribing other analgesics (particularly opioids), subjective pain scores, and length of hospital stay (dependent variables). METHODS: This retrospective cohort study included general surgery patients from two South Australian hospitals between April 2020 and March 2022. Multivariable logistic regression evaluated associations between previous oxycodone allergies and intolerances, prescription records, subjective pain scores, and length of hospital stay. RESULTS: Of 12 846 patients, 216 (1.7%) had oxycodone allergies, and 84 (0.7%) oxycodone intolerances. The 216 oxycodone allergy patients had lower odds of receiving oxycodone (OR 0.17, P < 0.001), higher odds of tramadol (OR 3.01, P < 0.001) and tapentadol (OR 2.87, P = 0.001), but 91 (42.3%) still received oxycodone and 19 (8.8%) morphine. The 84 with oxycodone intolerance patients had lower odds of receiving oxycodone (OR 0.23, P < 0.001), higher odds of fentanyl (OR 3.6, P < 0.001) and tramadol (OR 3.35, P < 0.001), but 42 (50%) still received oxycodone. Patients with oxycodone allergies and intolerances had higher odds of elevated subjective pain (OR 1.60, P = 0.013; OR 2.36, P = 0.002, respectively) and longer length of stay (OR 1.36, P = 0.038; OR 2.24, P = 0.002, respectively) than patients without these. CONCLUSIONS: General surgery patients with oxycodone allergies and intolerances are at greater risk of worse postoperative pain and longer length of stay, compared to patients without. Many still receive oxycodone, and other opioids that could cause cross-reactivity.