Weak Opioid Analgesic Research Articles

Comparisons in analgesic effects between ultrasound-guided erector spinae plane block and surgical intercostal nerve block after video-assisted thoracoscopic surgery: A randomized controlled trial

Study objectiveThis study aimed to compare the analgesic effects of anesthesiologist-administrated erector spinae plane block (ESPB) and surgeon-administrated intercostal nerve block (ICNB) following video-assisted thoracoscopic surgery (VATS). DesignRandomized, controlled, double-blinded study. SettingOperating room, postoperative recovery room and ward in two centers. PatientsOne hundred patients, ASA I-III and scheduled for elective VATS. InterventionsThe anesthesiologist-administrated ESPB under ultrasound guidance or surgeon-administrated ICNB under video-assisted thoracoscopy was randomly provided during VATS. Regular oral non-opioid analgesic combined with intravenous rescue morphine were prescribed for multimodal analgesia after surgery. MeasurementsThe primary outcomes were the pain score and morphine consumption during 48 h after surgery. Postoperative pain intensity were assessed using the 10-cm visual analogue scale at 1 h, 24 h, and 48 h after surgery. Morphine consumption at these time points was compared between the two study groups. Furthermore, oral weak opioid rescue analgesic was also provided at 24 h after surgery. Postoperative quality of recovery at 24 h was also assessed using the QoR-15 questionnaire, along with duration of chest tube drainage and hospital stay were compared as secondary outcomes. Main resultsPatients in the two study groups had comparable baseline characteristics, and surgical types were also similar. Postoperative VAS changes at 1 h, 24 h, and 48 h after surgery were also comparable between the two study groups. Both groups had low median scores (<4.0) at all time points (all p > 0.05). Patients in the ESPB group required statistically non-significant higher 48-h morphine consumption [3 (0–6) vs. 0 (0–6) mg in the ESPB group and ICNB group respectively; p = 0.135] and lower numbers of oral rescue analgesic (0.4 ± 1.2 vs. 1.0 ± 1.8 in the ESPB group and ICNB group respectively; p = 0.059). Additionally, patients in the two study groups had similar QoR15 scores and lengths of hospital stay. ConclusionsBoth anesthesiologist-administered ultrasound-guided ESPB and surgeon-administered VATS ICNB were effective analgesic techniques for patients undergoing VATS for tumor resection.

Patterns of filled prescriptions and the association with risk of drug-induced death. A population-based nested case-control register study.

Opioid analgesics (OA) and other pharmaceuticals have been associated with drug-induced deaths. However, there is a lack of knowledge regarding patterns of use of these pharmaceuticals in the population and regarding such associations. We identify and describe subgroups of people with different patterns of filled prescriptions of OA and other relevant pharmaceuticals and examine associations with drug-induced deaths. In addition, we estimate the proportion of drug-induced deaths with a filled OA prescription and OA as cause of death. A Norwegian population-based nested case-control register study with cases (drug-induced deaths 2010-2018, N = 2388) and population controls matched for age, gender and year of inclusion (N = 21 465). Patterns of filled prescriptions for opioid analgesics (OA), benzodiazepines and benzodiazepine-related drugs, gabapentinoids, ADHD medication and antidepressants/antipsychotics were explored by k-means cluster analysis. Associations with drug-induced deaths were estimated by conditional logistic regression adjusted for sociodemographic characteristics. Overlap of filled OA prescriptions and OA as cause of death was estimated. Five clusters were identified: 'few prescriptions', 'weak OA', 'ADHD medication', 'sedative/psychiatric morbidity' and 'strong OA'. The 'strong OA' cluster had higher socioeconomic status compared to the other groupings. The risk of drug-induced death was also highest in this cluster (OR = 35.5; CI 25.6-49.3) and, for 68% (CI 64-73) of cases, filled prescriptions for OA was indicated as the underlying cause of death. The cluster analysis identified a subgroup with filled prescriptions of OA and other pharmaceuticals and a higher socioeconomic status than other subgroups. This subgroup had a high risk of drug-induced death that needs to be addressed.

Trends in adverse drug reactions related to oral weak opioid analgesics in therapeutic use in adults: A 10-year French vigilances retrospective study.

To describe the symptoms, patient demographics, and trends over time of adverse drug reactions (ADRs) related to weak opioid analgesics reported to the French vigilance networks. Retrospective study of data from French Poison Control Centers and Pharmacovigilance Centers databases of weak opioid analgesics-related ADRs cases, with high causality score, in adults, in therapeutic analgesic use, without co-exposure, between 2011 and 2020. The number of cases was 388 in the Poisonings database and 155 in the Pharmacovigilance database; ratio of the number of these cases to all reported cases during the study period was 0.02% and 0.03%, respectively. Tramadol was most often involved (74% and 56.1%, respectively), followed by codeine (26% and 38.7%, respectively). There was no significant variation in the number of cases reported. Cases most often involved young adults (median age: 40 years) and mostly women (76%). Gastrointestinal symptoms were mostly reported (80% and 65%, respectively) as described in the Summary of Products Characteristics. Patterns of ADRs were comparable in both databases, except for codeine-associated acute pancreatitis and anaphylaxis that were reported in the Pharmacovigilance database. No fatality was observed. Severity was more often observed in the Pharmacovigilance database (30%) than in the Poisonings database (moderate toxicity: 7%). ADRs mostly occurred among young women using tramadol, without significant variation in the number of reported cases over time. Serious ADRs were more frequently reported to the Pharmacovigilance database, particularly for codeine. Women seemed to be at greater risk of ADRs.

Analgesic effect of oral paracetamol 1000 mg/ibuprofen 400 mg, paracetamol 1000 mg/codeine 60 mg, paracetamol 1000 mg/ibuprofen 400 mg/codeine 60 mg, or placebo on acute postoperative pain: a single-dose, randomized, and double-blind study

PurposeCombining analgesics with different mechanisms of action may increase the analgesic efficacy. The multidimensional pharmacodynamic profiles of ibuprofen 400 mg/paracetamol 1000 mg, ibuprofen 400 mg/paracetamol 1000 mg/codeine 60 mg, and paracetamol 1000 mg/codeine 60 mg and placebo were compared.MethodsA randomized, double-blind, placebo-controlled, parallel-group, single-centre, outpatient, and single-dose study used 200 patients of both sexes and homogenous ethnicity after third molar surgery (mean age 24 years, range 19–30 years). Primary outcome was sum pain intensity over 6 h (SPI). Secondary outcomes were time to analgesic onset, duration of analgesia, time to rescue drug intake, number of patients taking rescue drug, sum pain intensity difference (SPID), maximum pain intensity difference, time to maximum pain intensity difference, number needed to treat, prevent remedication and harm values, adverse effects, and patient-reported outcome measure (PROM).ResultsAnalgesia following ibuprofen and paracetamol combination with or without codeine was comparable. Both were better than paracetamol combined with codeine. Secondary variables supported this finding. Post hoc analysis of SPI and SPID revealed a sex/drug interaction trend in the codeine-containing groups where females experienced less analgesia. PROM showed a significant sex/drug interaction in the paracetamol and codeine group, but not in the other codeine-containing group. Especially females reported known and mild side effects in the codeine-containing groups.ConclusionCodeine added to ibuprofen/paracetamol does not seem to add analgesia in a sex-mixed study population. Sex may be a confounding factor when testing weak opioid analgesics such as codeine. PROM seems to be more sensitive than traditional outcome measures.Trial registrationClinicalTrials.gov June 2009 NCT00921700.

Parkinson's Disease with Intolerable Painful Dyskinesia: Standard Treatment and Subsequent Tips

The pathogenesis of pain related to dyskinesia in Parkinson disease is thought to be based on hypersensitivity to pain. To relieve symptoms, it is essential to reduce dyskinesia and alleviate symptoms. Frequent small doses of levodopa, dopamine agonists, MAOB inhibitors, and amantadine are effective. If improvement is insufficient, device-aided therapy should be considered. In addition, antidepressants, weak opioid analgesics, benzodiazepines, gabapentin, botulinum toxin injections, and exercise therapy are also worth trialing.

Patterns of opioid analgesic prescribing in cancer outpatients during the last year of life in France: A pharmacoepidemiological cohort study based on the French health insurance database

Cancer pain management with adequate analgesics for cancer outpatients can be particularly challenging. This representative retrospective cohort study aimed to investigate the prevalence and timing of weak and strong opioid analgesic prescriptions in cancer outpatients during their last year of life, with a focus on factors associated to potential late strong opioid initiation. Factors associated with late strong opioid initiation were investigated through multivariate logistic regression analyses stratified by place of death. A retrospective cohort of cancer outpatients, who died between 2014 and 2016, was identified from the general sample of beneficiaries. Among N=4704 cancer patients (median age 76 years, 42.7% women), 3002 (63.8%) were prescribed and dispensed ≥1 weak or strong opioid analgesic during their last year of life; of whom, 2458 (52.3%) received ≥1 weak opioid analgesic (tramadol as single-ingredient accounting for 25.9%) and 1733 (36.8%) ≥1 strong opioid analgesic dispensation (fentanyl 21.6%). Median interval between the first prescription for any strong opioid and death was 18 weeks (interquartile range: 8-38), and for weak opioids 33 weeks (interquartile range: 20-47). Among weak opioid users, 1229 (50.0%) patients had received ≥1 weak opioid analgesic dispensation during the year n-2 before death. Among strong opioid users, 986 (56.9%) patients had received ≥1 weak opioid analgesic dispensation during the year n-2 before death and 381 (21.9%) patients ≥1 strong opioid analgesic dispensation. Patients with an outpatient death were more likely to have a late strong opioid initiation compared to patients with an inpatient death. Late strong opioid initiation (<18 weeks before death) was significantly associated with a lower number of hospitalization days and prior weak opioid exposure for patients with an inpatient death and, with older age, social, prior weak opioid exposure, and a prescription initiation by general practitioner for patients with an outpatient death. Our gained knowledge of opioid prescribing patterns in cancer patients during the last year of life might help to progress opioid analgesic treatment and to improve patient outcomes.

Pain Evaluation and Treatment Techniques Designed Specially for Hospital Nurses in Order to Provide High-Quality Health Care Services

The purpose of this research was to examine the pain evaluation and treatment procedures used by practicing nurses. The research is a descriptive cross-sectional research that was conducted on 146 nurses who were directly engaged in patient care, were not on leave throughout the data collecting period, and volunteered to participate in the research using the convenience sample methodology. The data collection instrument was a pretested self-structured questionnaire with a 0.9 reliability value. Sorting, coding, entering, and analyzing data were performed using the SPSS version 23.0 software program at a 5% level of significance. The majority of respondents, 136 (93.1 percent), were female, while just 10 (6.9 percent) were male. 48 (23.9 percent) of respondents were SNOs, 86 (58.9 percent) of respondents had 6–10 years of experience, 120 (82.2 percent) were married, and 140 (95.9 percent ) were Christians. Concerning respondents' degree of knowledge regarding pain assessment techniques, 28 (19.2 percent) had inadequate knowledge, 44 (30.1 percent) had acceptable knowledge, and 74 (50.7 percent) had enough information. Self-reported pain management strategies included patient positioning and movement, massage, breathing exercises, diversional therapy, the use of warm or hot compresses, encouraging rest and relaxation, the use of both weak and strong opioid analgesics, and the administration of non-opioid analgesics. Using chi-square analysis, it was shown that there is no statistically significant relationship between nurses' knowledge and use of pain assessment instruments (p-value =0.15).

A nation-wide Swedish study of opioid analgesic prescribing patterns during pregnancy and associated preexisting mental health conditions

Introduction Research has consistently shown individuals with mental health conditions are more likely to be prescribed opioid analgesic medications and to engage in heavier utilization. However, it is unclear whether these findings apply to pregnant women. Study design We explored opioid analgesic prescription in 689,400 pregnancies occurring in Sweden between 2007 and 2013. We investigated prescription patterns across time and type of source clinic for any opioid analgesic and for strong and weak opioid analgesics. We further evaluated the extent to which receipt of opioid analgesic medications was associated with previous mental health diagnoses and prescriptions of other psychoactive medications. Results The prevalence of pregnant women who filled prescriptions for opioid analgesics (4.5%) was relatively stable across the assessed years. However, among pregnant women who filled opioid analgesic prescriptions, there was a large increase in strong opioid analgesic prescriptions–from 6.1% in 2007 to 17.1% in 2013. The main source of opioid analgesic prescriptions were primary care and obstetrics and gynecology clinics–38.7% of all filled prescriptions originated from primary care providers and 25.3% from obstetrics and gynecology practitioners. Compared to pregnant women who did not fill any opioid analgesic prescriptions, those who did were more likely to have a wide range of preexisting mental health diagnoses (e.g. anxiety disorder odds ratio [OR] = 3.13, 95% confidence interval [CI]:2.98,3.29) and to utilize a wide range of other psychoactive medications (e.g. benzodiazepines OR = 4.26, 95% CI:4.10,4.43). Similarly, those who received strong opioids were more likely to have a wide range of mental health diagnoses and be prescribed a wide range of psychoactive medications compared to those who received weak opioids. Conclusions These results highlight the need for physicians treating pregnant women and women of childbearing age for painful conditions to obtain detailed histories of mental health problems, screen for symptoms of mental health problems, and facilitate integrated care and evidence-based mental health interventions if needed.

Characterizing tramadol users with potentially inappropriate co-medications: A latent class analysis among older adults.

BackgroundAlthough tramadol is an effective weak opioid analgesic, careful monitoring of potential central nervous system adverse reactions in older adults is needed, especially when used with concomitant medications which may trigger the adverse effects. We aimed to characterize tramadol users with potentially inappropriate co-medications in older adults using a latent class analysis (LCA).MethodPatients aged 65 years or older using tramadol and receiving potentially inappropriate co-medications were included from a nationwide healthcare claims database. We defined antidepressants, first-generation antihistamines, and anxiolytics as potentially inappropriate co-medications. We applied an LCA for grouping tramadol users based on the common characteristics of medication use and healthcare utilization, and each patient was probabilistically assigned to a class. Patients’ characteristics in different latent classes were compared. Potential adverse drug reactions (ADRs) was defined as the any visits for emergency department after the occurrence of potentially inappropriate co-medications. Logistic regression analysis was used to examine the association between latent classes and potential ADRs.ResultsWe identified four distinct latent classes of tramadol users representing different patterns of co-medications: multiple potential drug-drug interaction (pDDI) combination users, antihistamines-tramadol users, antidepressants-tramadol users, and anxiolytics-tramadol users. Multiple pDDI combination users showed high proportion of regular tramadol use, tended to visit more medical institutions, and had a high Charlson comorbidity score. The duration of use of potentially inappropriate co-medications with tramadol was the longest in multiple pDDI combination users and the shortest in antihistamines-tramadol users.When compared with antihistamines-tramadol users, increased potential ADR risk was observed in multiple pDDI combination users (adjusted odds ratio (OR), 1.81; 95% confidence interval (CI), 1.75–1.88), antidepressants-tramadol users (1.24; 1.19–1.29), and anxiolytics-tramadol users (1.04; 1.00–1.08).ConclusionsFour distinct classes were identified among older adults using tramadol and potentially inappropriate co-medications. Differences in potential ADR risk were observed between these classes. These findings may help to identify patients at a high risk for ADRs owing to potentially inappropriate co-medications with tramadol.

Tramadol sensing in non-invasive biological fluids using a voltammetric electronic tongue and an electrochemical sensor based on biomimetic recognition.

Tramadol (TRA) is a weak opioid analgesic, prescribed to relieve mild to moderately severe pain. However, side effects of TRA overdoses, including vomiting, depression, tachycardia, convulsions, morbidity and mortality are often reported. In this study, an electrochemical sensor based on molecularly imprinted conductive polymer was firstly developed for the quantitative and non-invasive detection of TRA. Secondly, a voltammetric electronic tongue (VE-Tongue) combined with chemometric methods was used for the qualitative analysis. The MIP sensor was constructed by self-assembling a poly-aniline layer coated with silver nanoparticles (PANI-AgNPs) on a screen-printed gold electrode (Au-SPE). Then, 2-amino-thiophenol was polymerised in the presence of TRA. The electronic device exhibits, under optimal conditions, responses proportional to TRA concentrations (0.01-100µg/mL) with detection and quantification limits of 9.42µg/mL and 28.55µg/mL, respectively. Moreover, its selectivity was proven by insignificant interferences of substances (paracetamol and citric acid). Spiked saliva and urine samples were used for the sensor practical application with a significant recovery above 90% and standard deviations below 4.5%. Besides, urine samples' analyses using VE-Tongue and pattern recognition methods show good discrimination, classification, and prediction results with scores above 95%. Correspondingly, both electro-analytical devices could be viable for monitoring drugs in biological matrices.

Drinking or weak opioid analgesic has an influence on a continuation rate of the once-weekly teriparatide

Drinking or weak opioid analgesic has an influence on a continuation rate of the once-weekly teriparatide

Tramadol Use Increases Risk for Hypoglycemia Hospitalization

In recent years, tramadol use has increased substantially in primary care and emergency department settings, probably because it is a weak opioid analgesic that is perceived to be safer than traditional opioids. Observational studies and case reports suggest that clinically significant hypoglycemia can occur in the first few …

Tramadol for Noncancer Pain and the Risk of Hyponatremia

BackgroundCase reports have signaled a possible association between tramadol, a weak opioid analgesic, and hyponatremia. The objective of this study was to determine whether the use of tramadol is associated with an increased risk of hyponatremia, when compared with codeine. MethodsUsing the UK Clinical Practice Research Datalink and Hospital Episodes Statistics database, a population-based cohort of 332,880 patients initiating tramadol or codeine was assembled from 1998 through 2012. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of hospitalization for hyponatremia associated with the use of tramadol, compared with codeine, in the first 30 days after initiation. A similar analysis was conducted within a highly restricted sub-cohort, which additionally excluded patients with any serum sodium level abnormality in the year before cohort entry. All models were adjusted for propensity score quintiles. ResultsThe incidence rates of hospitalization for hyponatremia were 4.6 (95% CI, 2.4-8.0) and 1.9 (95% CI, 1.4-2.5) per 10,000 person-months for tramadol and codeine users, respectively. In the adjusted model, the use of tramadol was associated with a 2-fold increased risk of hospitalization for hyponatremia, compared with codeine (adjusted HR 2.05; 95% CI, 1.08-3.86). In the highly restricted sub-cohort, the use of tramadol was associated with an over 3-fold increased risk of hospitalization for hyponatremia, compared with codeine (adjusted HR 3.54; 95% CI, 1.32-9.54). ConclusionsIn this first population-based study, the use of tramadol was associated with an increased risk of hyponatremia requiring hospitalization.

Topical Review on the Abuse and Misuse Potential of Tramadol and Tilidine in Germany

ABSTRACT. Background: Tramadol and tilidine (in combination with naloxone) are used as weak opioid analgesics in Germany. Tramadol is not scheduled in the German Narcotic Drugs Act. Tilidine is scheduled, whereas Tilidine in fixed combinations with naloxone is exempt from some of the provisions of the Narcotic Drugs Act. Recent reports on misuse of both substances led to an evaluation of their potential for misuse, abuse, and dependency by the expert advisory committee established by the German Federal Government, resident at the Federal Institute for Drugs and Medical Devices. Methods: A subcommittee formulated key questions and identified available data sources for each of these questions. Additional information was solicited where necessary, including a survey among a panel of pharmacists, a survey in an addiction clinic, analysis of prescription patterns, and information from the boards of pharmacists of the federal states and the Federal Bureau of Criminal Investigation. Results: Analgesic efficiency in the treatment of acute and chronic pain has been proven for both tramadol and tilidine/naloxone. For tramadol, high evidence has been confirmed in systematic reviews, and tramadol is listed in national and international guidelines on acute and chronic pain management. Animal and human studies found a low potential for misuse, abuse, and dependency for both substances. Information from 2 tramadol safety databases allowed calculation of the incidence of abuse or dependency as 0.21 and 0.12 cases per million defined daily dosages (DDDs), with lower incidences in recent years. For tilidine/naloxone, the incidence was calculated as 0.43 cases per million DDDs for oral solution and 0.18 for slow-release tablets. In an online survey among German pharmacies as well as in the reports from state pharmacy boards, fraud attempts were repeated more frequently with tilidine/naloxone than with tramadol in the last 2 years. The Federal Bureau of Criminal Investigations reported prescription fraud only with tilidine/naloxone and predominantly in the region of Berlin. Dependency on tramadol or tilidine/naloxone is reported only rarely from addiction counseling centers. One third of the patients surveyed in an addiction clinic reported experiences with tramadol or tilidine/naloxone, but mostly with duration of less than 4 weeks and with a medical prescription based on a reasonable indication. Also, occasional illegal use of opioid analgesics as a substitute of heroin was reported. An evaluation of pooled data from statutory health insurance companies found 2.5% of persons receiving at least 1 prescription of tramadol or the combination of tilidine and naloxone in 2009 (1.6% with tramadol and 1.0% with tilidine/naloxone). High usage with more than 180 DDDs per year was found in 8.6% of patients treated with tramadol and 17.2% of patients with tilidine/naloxone. Conclusions: In conclusion, the subcommittee of the expert advisory committee found a low potential for misuse, abuse, and dependency for tramadol, and a low prevalence in clinical practice. Considerable less information is available for the combination of tilidine and naloxone. However, the cumulation of evidence indicated a higher risk of misuse, abuse, and dependency for tilidine/naloxone solution, but not for slow-release tablets.

Tramadol/paracetamol fixed-dose combination in the treatment of moderate to severe pain

Pain is the most common reason patients seek medical attention and pain relief has been put forward as an ethical obligation of clinicians and a fundamental human right. However, pain management is challenging because the pathophysiology of pain is complex and not completely understood. Widely used analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen) have been associated with adverse events. Adverse event rates are of concern, especially in long-term treatment or at high doses. Paracetamol and NSAIDs are available by prescription, over the counter, and in combination preparations. Patients may be unaware of the risk associated with high dosages or long-term use of paracetamol and NSAIDs. Clinicians should encourage patients to disclose all medications they take in a “do ask, do tell” approach that includes patient education about the risks and benefits of common pain relievers. The ideal pain reliever would have few risks and enhanced analgesic efficacy. Fixed-dose combination analgesics with two or more agents may offer additive or synergistic benefits to treat the multiple mechanisms of pain. Therefore, pain may be effectively treated while toxicity is reduced due to lower doses. One recent fixed-dose combination analgesic product combines tramadol, a centrally acting weak opioid analgesic, with low-dose paracetamol. Evidence-based guidelines recognize the potential value of combination analgesics in specific situations. The current guideline-based paradigm for pain treatment recommends NSAIDs for ongoing use with analgesics such as opioids to manage flares. However, the treatment model should evolve how to use low-dose combination products to manage pain with occasional use of NSAIDs for flares to avoid long-term and high-dose treatment with these analgesics. A next step in pain management guidelines should be targeted therapy when possible, or low-dose combination therapy or both, to achieve maximal efficacy with minimal toxicity.

Cautions with codeine

Codeine is a weak opioid analgesic. It has to be converted to morphine, but there is significant inter-individual...

Serious morbidity associated with misuse of over‐the‐counter codeine–ibuprofen analgesics: a series of 27 cases

To investigate morbidity related to misuse of over-the-counter (OTC) codeine-ibuprofen analgesics. Prospective case series collected from Victorian hospital-based addiction medicine specialists between May 2005 and December 2008. Morbidity associated with codeine-ibuprofen misuse. Twenty-seven patients with serious morbidity were included, mainly with gastrointestinal haemorrhage and opioid dependence. The patients were taking mean daily doses of 435-602 mg of codeine phosphate and 6800-9400 mg ibuprofen. Most patients had no previous history of substance use disorder. The main treatment was opioid substitution treatment with buprenorphine-naloxone or methadone. Although codeine can be considered a relatively weak opioid analgesic, it is nevertheless addictive, and the significant morbidity and specific patient characteristics associated with overuse of codeine-ibuprofen analgesics support further awareness, investigation and monitoring of OTC codeine-ibuprofen analgesic use.

Tramadol dependence: a survey of spontaneously reported cases in Sweden

Tramadol is a weak opioid analgesic, which is generally considered to be safe. However, conflicting data exist on the dependence potential of tramadol. The aim of this study was to investigate occurrence of tramadol dependence and associated risk factors using spontaneously reported adverse drug reactions. The Swedish database for spontaneously reported adverse drug reactions, Swedish Drug Information System (SweDIS), was searched for reports on tramadol dependence from 1 January 1995 until 31 December 2006. Selection was conducted based on the DSM-IV definition of dependence. Available information was scrutinised and registered and then presented descriptively. A total of 104 reports of tramadol dependence were identified, of which 60 (58%) concerned women. The median age (range) was 45 (15-84) years. Information on a history of substance abuse was present in 31 patients (30%) and 41 patients (39%) had a documented past or current use of a drug of abuse. Prescribed doses of tramadol ranged between 50-800 mg/day, and ingested doses between 50-4000 mg/day. Time of onset ranged from some weeks up to 4 years. In 72 (69%) cases the reaction was classified as serious, mainly due to hospitalisations for detoxification or discontinuation of tramadol. There is an occurrence of tramadol dependence in association with analgesic treatment within the recommended dose range. In susceptible patients a severe and serious dependence syndrome may develop. A history of abuse or use of a drug of abuse seems to be an important risk factor.

Dextropropoxyphene withdrawal from a French university hospital: impact on analgesic drug consumption

Dextropropoxyphene is a weak opioid analgesic, widely used as a step 2 analgesic (according to WHO classification) in combination with peripheral analgesics, mainly paracetamol. Recent data have underlined its poor analgesic efficacy (in comparison with paracetamol), risks of serious adverse drug reactions (i.e. hepatic reactions, hallucinations, abuse, withdrawal symptoms, hypoglycaemia), possible lethality after overdose, its risk of accumulation in patients with renal failure or in elderly people and some pharmacokinetic insufficiencies (i.e. different half-lives for dextropropoxyphene and paracetamol). Taking into account these data, the drug committee of the Toulouse University Hospital (France) decided to withdraw dextropropoxyphene from the hospital formulary since 1 June 2005. The aim of our study was to investigate the consequences of this withdrawal by comparing use of analgesic drugs in Toulouse University Hospital before (2004) and after (2006) dextropropoxyphene withdrawal (using defined daily dose for 1000 hospitalization-days as the unit measure). Before withdrawal, dextropropoxyphene (in combination with paracetamol) was the second most used analgesic drug after paracetamol alone. After dextropropoxyphene withdrawal, total consumption of analgesic drugs decreased by 4.6% (2006 vs. 2004). There was a 28% decrease in consumption of step 2 analgesics [with an increase in oral tramadol and a slight decrease in codeine (in combination with paracetamol)]. During the same period, step 1 analgesic consumption increased by 11% (mainly paracetamol) and that of step 3 analgesics slightly decreased (-8%). These results show that dextropropoxyphene withdrawal was not associated with a marked switch in prescriptions towards other analgesic drugs. This paper underlines the interest of a hospital-based drug committee to promote rational drug use. Finally, the present data allow us to discuss putative misuse of dextropropoxyphene.

Propoxyphene (Dextropropoxyphene): A Critical Review of a Weak Opioid Analgesic That Should Remain in Antiquity

Propoxyphene (dextropropoxyphene) is a synthetic weak opioid introduced into the United States in 1957. It is most frequently prescribed in combination with acetaminophen and/or aspirin. After its ubiquitous introductory phase, it was soon discovered that this drug's iatrogenic events (cardiotoxicity, seizures, etc.) far outweighed any perceived therapeutic benefit. Propoxyphene analgesia was equated with that of merely acetaminophen or aspirin independently. The propoxyphenes euphorigenic component has created a problem in its prescribing. Use of this agent in the elderly should be avoided because of its complex pharmacokinetics and pharmacodynamics. The pharmacokinetics, pharmacodynamics, and pharmacology of this drug are discussed thoroughly in this article, including its arrhythmogenicity. Additional noncardiovascular pharmacotherapies that produce QTc prolongation or arrhythmogenicity are described. A list of the cytochrome P450 2D6 pharmacotherapies that will interact with propoxyphene is provided in the article. The use of this agent is highly discouraged. The rationale for this is discussed fully within this article. The toxicity of this drug is partially related to nor-propoxyphene a non-opioid cardiotoxic metabolite. The mere warnings of fatalities within the package insert should alert any cautious prescriber on the dangers of this agent and dampen its prescribing potential.