-
Journal of Opioid Management 2018To evaluate frequency and risk factors for dextropropoxypheneinduced QT-interval prolongation in the clinical setting. (Observational Study)
Observational Study
OBJECTIVE
To evaluate frequency and risk factors for dextropropoxypheneinduced QT-interval prolongation in the clinical setting.
DESIGN
Prospective, noninterventional, observational, longitudinal cohort approach. Electrocardiograms were blindly evaluated by independent professionals.
SETTING
General ward of a public hospital of metropolitan Buenos Aires.
PATIENTS, PARTICIPANTS
Ninety-two patients with indication of receiving dextropropoxyphene for analgesic purposes were included consecutively. All patients finished the study.
INTERVENTIONS
All patients were monitored with electrocardiographic controls (previous to drug administration and during steady state) to diagnose and quantify changes in the duration of the QTc interval.
MAIN OUTCOME MEASURE
Frequency of drug-induced QTc interval prolongation, QTc interval correlation with plasma drug, and metabolite levels.
RESULTS
Ninety-two patients were studied (50 percent males). All patients received a (mean ± SD [range]) dextropropoxyphene dose of 125 ± 25[100-150] mg/d. Dextropropoxyphene and norpropoxyphene concentrations were 112 ± 38[45-199] and 65 ± 33[13-129] ng/mL, respectively. The intra-treatment QTc interval was >450 ms in only one patient (only with the Hodge correction). There were no cases of QTc > 500 ms, and there were no significant differences in the results considering different correction formulas (Bazzet, Fridericia, Framingham, Hodges). Dextropropoxyphene concentrations correlated with QTc (R > 0.45) interval and ΔQTc (R 0.52-0.87), whereas norpropoxyphene correlation was even greater for QTc (R > 0.40-0.64) and ΔQTc (R > 0.47-0.92). Depending on the QTc correction formula, eight patients presented ΔQTc > 30 ms and one patient with ΔQTc > 60 ms. No patient presented arrhythmia during the study.
CONCLUSIONS
The authors did not observe a relationship between dextropropoxyphene and QTc interval prolongation at the therapeutic doses used in Argentina.
Topics: Action Potentials; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Argentina; Arrhythmias, Cardiac; Dextropropoxyphene; Drug Monitoring; Electrocardiography; Female; Heart Conduction System; Heart Rate; Humans; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Risk Factors
PubMed: 30387857
DOI: 10.5055/jom.2018.0466 -
Methods in Molecular Biology (Clifton,... 2019The use and adherence monitoring of opioids in pain management is recommended by numerous clinical practice guidelines. Many physicians use urine immunoassay screening...
The use and adherence monitoring of opioids in pain management is recommended by numerous clinical practice guidelines. Many physicians use urine immunoassay screening tests, which suffer from a lack of sensitivity and specificity, to verify compliance to pain medications. However, several immunoassay tests are required to comprehensively detect the synthetic, semisynthetic, and natural opioids due to the limited cross-reactivity of each assay. Superior testing strategies are required to specifically identify low concentrations of opioids found in adherent pain management patients. Therefore we present a method for the qualitative identification of 33 opioids and metabolites (codeine, codeine-6-β-glucuronide, morphine, morphine-6-β-glucuronide, 6-acetylmorphine, hydrocodone, norhydrocodone, dihydrocodeine, hydromorphone, hydromorphone-3-β-glucuronide, oxycodone, noroxycodone, oxymorphone, oxymorphone-3-β-glucuronide, noroxymorphone, meperidine, normeperidine, methadone, EDDP, propoxyphene, norpropoxyphene, tramadol, O-desmethyltramadol, tapentadol, tapentadol-β-glucuronide, N-desmethyltapentadol, buprenorphine, norbuprenorphine, norbuprenorphine glucuronide, naloxone, naloxone glucuronide, fentanyl, and norfentanyl) in unhydrolyzed urine using a liquid chromatography tandem mass spectrometry (LC-MS/MS) with high-resolution, accurate-mass Orbitrap detection.
Topics: Analgesics, Opioid; Chromatography, Liquid; Humans; Pain Management; Substance Abuse Detection; Tandem Mass Spectrometry
PubMed: 30350277
DOI: 10.1007/978-1-4939-8823-5_4 -
Clinical Gastroenterology and... Jun 2019Many patients with gastroparesis are prescribed opioids for pain control, but indications for opioid prescriptions and the relationship of opioid use to gastroparesis...
BACKGROUND & AIMS
Many patients with gastroparesis are prescribed opioids for pain control, but indications for opioid prescriptions and the relationship of opioid use to gastroparesis manifestations are undefined. We characterized associations of use of potent vs weaker opioids and presentations of diabetic and idiopathic gastroparesis.
METHODS
We collected data on symptoms, gastric emptying, quality of life, and health care resource use from 583 patients with gastroparesis (>10% 4-h scintigraphic retention) from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Consortium, from January 2007 through November 2016. Patients completed medical questionnaires that included questions about opioid use. The opioid(s) were categorized for potency relative to oral morphine. Symptom severities were quantified by Patient Assessment of Upper Gastrointestinal Disorders Symptoms questionnaires. Subgroup analyses compared patients on potent vs weaker opioids and opioid effects in diabetic vs idiopathic etiologies.
RESULTS
Forty-one percent of patients were taking opioids; 82% of these took potent agents (morphine, hydrocodone, oxycodone, methadone, hydromorphone, buprenorphine, or fentanyl). Abdominal pain was the reason for prescription for 61% of patients taking opioids. Mean scores for gastroparesis, nausea/vomiting, bloating/distention, abdominal pain, and constipation scores were higher in opioid users (P ≤ .05). Opioid use was associated with greater levels of gastric retention, worse quality of life, increased hospitalization, and increased use of antiemetic and pain modulator medications compared with nonusers (P ≤ .03). Use of potent opioids was associated with worse gastroparesis, nausea/vomiting, upper abdominal pain, and quality-of-life scores, and more hospitalizations compared with weaker opioids (tapentadol, tramadol, codeine, or propoxyphene) (P ≤ .05). Opioid use was associated with larger increases in gastric retention in patients with idiopathic vs diabetic gastroparesis (P = .008).
CONCLUSIONS
Opioid use is prevalent among patients with diabetic or idiopathic gastroparesis, and is associated with worse symptoms, delays in gastric emptying, and lower quality of life, as well as greater use of resources. Potent opioids are associated with larger effects than weaker agents. These findings form a basis for studies to characterize adverse outcomes of opioid use in patients with gastroparesis and to help identify those who might benefit from interventions to prevent opioid overuse.
Topics: Abdominal Pain; Adult; Analgesics, Opioid; Female; Gastric Emptying; Gastroparesis; Health Resources; Humans; Male; Prognosis; Quality of Life
PubMed: 30326297
DOI: 10.1016/j.cgh.2018.10.013 -
BMJ Open Sep 2018Dextropropoxyphene (DXP), a step 2 analgesic commonly prescribed in France, was withdrawn from the French market in 2011 following a European decision due to its poor...
OBJECTIVES
Dextropropoxyphene (DXP), a step 2 analgesic commonly prescribed in France, was withdrawn from the French market in 2011 following a European decision due to its poor risk-benefit ratio. The purpose of this study was to explore the perceptions of French general practitioners (GPs) and patients regarding DXP withdrawal.
DESIGN
Qualitative study based on 26 individual semi-structured interviews.
SETTING
Rhône-Alpes region of France.
PARTICIPANTS
Thirteen patients and 13 GPs.
METHODS
Interviews were conducted to collect data concerning the status of DXP, its efficacy and safety, the conditions of DXP's withdrawal and its potential impact. The transcripts were analysed using NVivo software.
RESULTS
DXP was a very popular drug among both patients and GPs. Its withdrawal was a bad experience for patients and many GPs; these misunderstood the reasons for its withdrawal and several contested them. They generally recognised more benefits than risks of DXP and considered alternative drugs unsatisfactory. In the same period, a French court case regarding another drug led to distrust towards the pharmaceutical industry and healthcare institutions, which contributed to the negative feelings reported. However, the experience was positive for the GPs who had been alerted to the poor DXP risk-benefit ratio well before its withdrawal.
CONCLUSIONS
Apart from physicians who were previously informed of its poor risk-benefit ratio, DXP withdrawal was not a good experience for patients and GPs. Better anticipation by the health authorities, in terms of pharmacoepidemiological surveillance and communication to healthcare professionals as well as the general public, should provide better acceptance of such a decision in the future.
Topics: Adult; Aged; Analgesics, Opioid; Attitude of Health Personnel; Dextropropoxyphene; Female; France; General Practitioners; Humans; Interviews as Topic; Male; Middle Aged; Patients; Perception; Qualitative Research; Risk Assessment; Substance Withdrawal Syndrome; Trust; Withholding Treatment
PubMed: 30244207
DOI: 10.1136/bmjopen-2018-021582 -
Scandinavian Journal of Pain Oct 2018Background and aims Dextropropoxyphene (DXP) is a synthetic opioid that was prescribed worldwide for mild to moderate pain. It was withdrawn from the European market in... (Observational Study)
Observational Study
Background and aims Dextropropoxyphene (DXP) is a synthetic opioid that was prescribed worldwide for mild to moderate pain. It was withdrawn from the European market in 2009. In this study we aim to investigate the effect of the market withdrawal of dextropropoxyphene in Norway on overall use of opioids and other analgesics at an individual level. Methods Data were collected from the nationwide Norwegian Prescription Database (NorPD). It covers all prescription of drugs from 01 January 2004 from Norwegian pharmacies dispensed to individuals outside institutions. The study period was divided in two 2-year periods from 01 September 2008 to 31 August 2010, and from the market withdrawal of DXP on 01 September 2010 to 31 August 2012. We included every individual that filled at least one prescription of dextropropoxyphene in the first 2-year period in our study population. In this study dextropropoxyphene, codeine and tramadol are defined as "weak opioids", and all other opioids are termed "strong opioids". Results Nine thousand one hundred and seventy-one individuals were included in our study population. Four thousand two hundred and ninety filled a prescription of DXP only once and were classified as "single users", 2,990 were users with prescriptions of up to 200 defined daily doses (DDD) over the first 2-year period, or "sporadic users", and 1,886 were classified high users with over 200 DDDs over a 2-year period. After the market withdrawal 8,392 continued to be prescribed analgesics or benzodiazepines. In the single user group, the proportion of users of weak opioids decreased from 69.5% to 57.6%, whereas the proportion of users of strong opioids was unchanged. Among the sporadic user group, the proportion of users of weak opioids went from 69.7% to 71.0%, the proportion using tramadol from 39.1% to 43.9%, and the users of strong opioids from 25.8% to 31.3%. In the high user group, there was an increase in the number of users of strong opioids from 37.8% to 51.4%. The amount of strong opioids prescribed in the high user group increased from a mean of 262.5 DDD to a mean of 398.3 DDD in the following 2 years. The amount of tramadol increased in all groups and was 3 times as high in the high user group after market withdrawal of DXP. Conclusions Our study showed that the withdrawal of DXP lead to an increase in prescription of other analgesics. The proportion of users increased in all three groups and so did the prescribed amount of other analgesics. Both the proportion of users of other opioids and the amount prescribed increased considerably. However, 1 in 10 earlier users of DXP stopped using prescribed analgesics altogether in the following 2 years. The increase in use among earlier high users of DXP was most striking. Implications This study documents markedly increased prescriptions of other opioids after withdrawal of dextropropoxyphene due to its high risk of serious complications. However, consequences of the increased use of opioids among earlier high users of DXP such as changes in risk of poisonings, accidental deaths and suicides remain to be investigated.
Topics: Analgesics, Opioid; Databases, Factual; Dextropropoxyphene; Drug Prescriptions; Female; Humans; Longitudinal Studies; Male; Middle Aged; Norway; Pain; Product Recalls and Withdrawals; Prospective Studies; Tramadol
PubMed: 30145581
DOI: 10.1515/sjpain-2018-0103 -
European Journal of Pain (London,... Jan 2019While data from USA and Canada demonstrate an opioid overdose epidemic, very little nation-wide European studies have been published on this topical subject.
BACKGROUND
While data from USA and Canada demonstrate an opioid overdose epidemic, very little nation-wide European studies have been published on this topical subject.
METHODS
Using a nationally representative sample of the French Claims database (>700,000 patients), the exhaustive nationwide hospital discharge database, and national mortality registry, all patients dispensed at least one prescription opioid (PO) in 2004-2017 were identified, to describe trends in PO analgesic use, shopping behaviour, opioid-related hospitalizations and deaths. Annual prevalence of PO use and shopping behaviour (≥1 day of overlapping prescriptions from ≥2 prescribers, dispensed by ≥3 pharmacies) was estimated.
RESULTS
In 2004-2017, the annual prevalence of weak opioid use codeine, tramadol and opium rose by 150%, 123%, and 244%, respectively (p < 0.05). Strong opioid use increased from 0.54% to 1.1% (+104%, p < 0.05), significantly for oxycodone (+1950%). Strong opioid use in chronic noncancer pain rose by 88% (p < 0.05) and 1180% for oxycodone. Opioid shopping increased from 0.50% to 0.67% (+34%, p < 0.05), associated with higher mortality risk HR = 2.8 [95% confidence interval (CI): 1.2-6.4]. Opioid-related hospitalizations increased from 15 to 40 per 1,000,000 population (+167%, 2000-2017), and opioid-related deaths from 1.3 to 3.2 per 1,000,000 population (+146%, 2000-2015).
CONCLUSIONS
This study provided a first European approach to a nationwide estimation with complete access to several national registries. In 2004-2017 in France, PO use excluding dextropropoxyphene more than doubled. The increase in oxycodone and fentanyl use, and nontrivial increasing trend in opioid-related morbidity-mortality should prompt authorities to closely monitor PO consumption in order to prevent alarming increases in opioid-related morbidity-mortality.
SIGNIFICANCE
In 2004-2017, prescription opioid use in France at least doubled and oxycodone use increased particularly, associated with a nontrivial increase in opioid-related morbidity-mortality. Although giving no indication for an 'opioid epidemic,' these findings call for proper monitoring of opioid use.
Topics: Adult; Aged; Analgesics, Opioid; Chronic Pain; Codeine; Databases, Factual; Dextropropoxyphene; Female; Fentanyl; France; Humans; Male; Middle Aged; Mortality; Opioid-Related Disorders; Opium; Oxycodone; Prevalence; Proportional Hazards Models; Tramadol
PubMed: 30051548
DOI: 10.1002/ejp.1291 -
Indian Journal of Pharmacology 2018Tapentadol is a centrally acting opioid analgesic which has partial opioid agonistic and norepinephrine reuptake inhibitor action similar to its nearest congener and...
Tapentadol is a centrally acting opioid analgesic which has partial opioid agonistic and norepinephrine reuptake inhibitor action similar to its nearest congener and tramadol though with a relatively higher μ-affinity. It has abuse potential, is a scheduled drug, yet currently is not known to be an opioid widely misused in India. However, under the current drug abuse legislation in India, where common prescription opioids such as dextropropoxyphene have been banned, tapentadol may take the center stage of pharmaceutical opioid abuse in the near future. We present a series of two cases where the opioid use started with codeine, dextropropoxyphene, and buprenorphine but moved on to tapentadol and tramadol due to ease of access and cost. These cases highlight the potential of tapentadol in replacing dextropropoxyphene as the widespread prescription opioid of abuse and also emphasize the current controversies regarding opioid control policies in India.
Topics: Adult; Analgesics, Opioid; Buprenorphine; Codeine; Dextropropoxyphene; Drug Substitution; Humans; India; Male; Narcotic Antagonists; Opioid-Related Disorders; Phenols; Tapentadol
PubMed: 29861527
DOI: 10.4103/ijp.IJP_21_17 -
BMC Health Services Research Apr 2018In 2009, the European Medicines Agency recommended withdrawal of dextropropoxyphene (DXP); in March 2011 it was withdrawn from the market in France. Up until that time...
BACKGROUND
In 2009, the European Medicines Agency recommended withdrawal of dextropropoxyphene (DXP); in March 2011 it was withdrawn from the market in France. Up until that time the combination dextropropoxyphene-paracetamol (DXP/PC) was widely used for analgesia. At withdrawal, French regulators recommended that DXP/PC be replaced by other step 2 analgesics, i.e. tramadol, codeine, or opium-containing drugs, or by PC for a weak level of pain. To investigate prescribing behaviours after DXP/PC withdrawal, dispensations of analgesics before and after withdrawal were analysed.
METHODS
Aggregated dispensation data of analgesics prescribed between January 2009 and December 2012 in the Rhône-Alpes region were obtained from the general health insurance claims data; changes in analgesic dispensation over time were analysed with the ATC/DDD methodology. Pre (Jan-June 2009) and post-withdrawal (Jan-June 2012) changes of DDDs where computed for each analgesic step.
RESULTS
The dispensations of DXP/PC experienced a two-step decrease until 2011. Over the withdrawal period 2009-2012, there was a 14% decrease in the overall use of analgesic (from 109 to 94 DDDs), while the use of step 2 analgesics declined by 46% (- 22 DDDs, from 47 to 25 DDDs). This latter decline included a cessation of use of DXP/PC (29 DDDs in 2009) that were only in part (+ 7 DDDs, from 18 to 25 DDDs) compensated by increased use of codeine, tramadol and opium, in monotherapy or combined with PC. For step 1 analgesics, use increased with 9%, mostly PC (+ 8 DDDs, from 31 to 39 DDDs). Step 3 analgesics dispensations remained largely unchanged over this period (around 3 DDDs).
CONCLUSIONS
In the Rhône-Alpes region, DXP/PC withdrawal was accompanied in part by an increased use of same level analgesics, and in part by an increased use of PC in monotherapy. The extent of DXP/PC use before withdrawal, and the increased use of PC after DXP withdrawal, underline the complexity of pain management.
Topics: Acetaminophen; Analgesics; Analgesics, Opioid; Codeine; Dextropropoxyphene; Drug Combinations; Drug Prescriptions; France; Humans; Pain; Pain Management; Safety-Based Drug Withdrawals; Tramadol
PubMed: 29609613
DOI: 10.1186/s12913-018-3058-1 -
British Journal of Clinical Pharmacology Jun 2018The aims of the present study were to describe the consumption trends of three groups of analgesics (non-opioids, and mild and strong opioids) between 2006 and 2015 in... (Comparative Study)
Comparative Study
AIMS
The aims of the present study were to describe the consumption trends of three groups of analgesics (non-opioids, and mild and strong opioids) between 2006 and 2015 in France, and compare this pattern of use with six European countries in 2015.
METHODS
Annual drugs sales were extracted from the French national authority's consumption database, and from the IMS Multinational Integrated Data Analysis System and national databases for European countries.
RESULTS
The use of mild opioids in France was found to have decreased by 53% over the past 10 years, owing to the declining use of dextropropoxyphene combinations, along with an increase in the use of non-opioids and strong opioids (from 72 to 93, and 2 to 2.8 defined daily doses/1000 inhabitants/day, respectively). Paracetamol, the most consumed analgesic, increased over this period, particularly for the adult high dose (+140%). The use of tramadol and codeine combinations also increased, by 62% and 42%, respectively. Morphine remained the most used strong opioid, although there were also large increases in the consumption of oxycodone (+613%) and fentanyl (+263% and +72% for transmucosal and transdermal forms, respectively). A comparison of the patterns of use in Europe in 2015 showed a higher consumption of mild and strong opioids in the UK. France ranked first and third place, respectively, for paracetamol and mild opioid consumption, whereas its use of strong opioids was among the lowest.
CONCLUSIONS
Paracetamol consumption is clearly highest in France, whereas its use of strong opioids is among the lowest in Europe, although its consumption of oxycodone has increased significantly. Further studies are required specifically to monitor these drugs.
Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; Commerce; Databases, Factual; Drug Therapy; France; Humans; Practice Patterns, Physicians'; Time Factors
PubMed: 29514410
DOI: 10.1111/bcp.13564 -
Arthritis & Rheumatology (Hoboken, N.J.) May 2018
Topics: Analgesics; Arthritis, Rheumatoid; Dextropropoxyphene; Humans; Interrupted Time Series Analysis; United States
PubMed: 29439294
DOI: 10.1002/art.40446