Tapentadol Versus Tramadol: A Narrative and Comparative Review of Their Pharmacological, Efficacy and Safety Profiles in Adult Patients.

We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical interest of tapentadol in adult patients. Tapentadol and tramadol share a mixed mechanism of action, including both mu-agonist and monoaminergic properties. Tapentadol is approximately two to three times more potent than tramadol and two to three times less potent than morphine. It has no identified analgesically active metabolite and is not significantly metabolised by cytochrome P450 enzymes, thus overcoming some limitations of tramadol, including the potential for pharmacokinetic drug-drug interactions and interindividual variability due to genetic polymorphisms of cytochrome P450 enzymes. The toxicity profiles of tramadol and tapentadol are similar; however tapentadol is likely to result in less exposure to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) but cause more opioid adverse effects (constipation, respiratory depression, abuse) than tramadol. The safety of tapentadol in real-world conditions remains poorly documented, particularly in at-risk patient subgroups and also in the ability to assess the risk associated with its residual serotonergic activity (serotonin syndrome, seizures). Because of an earlier market introduction, more real-world safety data are available for tramadol, including data from at-risk patient subgroups. The level of evidence on the efficacy of both tramadol and tapentadol for the treatment of chronic pain is globally low. The trials published to date show overall that tapentadol does not provide a clinically significant analgesic improvement compared to existing treatments, for which the safety profile is much better known. In conclusion, tapentadol is not a first-line opioid but represents an additional analgesic in the therapeutic choices, which some patients may benefit from after careful examination of their clinical situation, co-morbidities and co-medications.

[Monoaminergic opioids: which one should we choose?] / Opioïdes monoaminergiques : lequel choisir ?

Tapentadol shares with tramadol a mixed mechanism of action. It has no identified analgesically active metabolite and is not significantly metabolised by CYP450, thus overcoming some limitations of tramadol, including potential for pharmacokinetic drug-drug interactions and inter-individual variability due to genetic polymorphisms of CYP450. It is likely to expose less to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) and more to opioid adverse effects (constipation, respiratory depression, abuse) than tramadol. The level of evidence on the efficacy of both tramadol and tapentadol for the treatment of chronic pain is globally low. As a conclusion, tapentadol represents an additional analgesic which some patients may benefit from after careful examination of their clinical situation, comorbidities and comedications.

Le tapentadol partage avec le tramadol un mode d'action mixte. Il n'a pas de métabolite actif identifié et n'est pas significativement métabolisé par le cytochrome P450 (CYP450), ce qui lui permet de contourner certaines limites du tramadol (interactions pharmacocinétiques, variabilité due aux polymorphismes génétiques du CYP450). Il expose potentiellement moins aux effets indésirables sérotoninergiques (nausées, vomissements, hypoglycémie) et davantage aux effets opioïdergiques (constipation, dépression respiratoire, abus) que le tramadol. Le niveau de preuve des données disponibles sur l'efficacité du tramadol et du tapentadol dans les douleurs chroniques est globalement faible. Le tapentadol représente un antalgique supplémentaire dont certains patients peuvent bénéficier après un examen attentif de leurs comorbidités, de leurs comédications et de la situation clinique.

[Drug treatment of inpatients with chronic kidney disease in the acute care ward of a Swiss regional hospital]. / Prise en charge médicamenteuse des patients insuffisants rénaux chroniques hospitalisés en soins aigus dans un hôpital régional suisse.

INTRODUCTION: Optimal drug treatment may slow down the progression of chronic kidney disease (CKD) and reduce the associated complications. We conducted a study to assess the drug treatment of inpatients with CKD at their discharge. METHODS: We retrospectively collected patient data from the electronic medical record of a Swiss regional hospital for two non-consecutive months. Patients were eligible if their glomerular filtration rate at discharge ranged between 15 and 60 mL/min/1.73 m2. Primary outcome was optimal CKD management, defined by drug treatment conforming to the following 3 criteria: (i) appropriate medication dosage relative to kidney function, (ii) absence of contraindicated medication, and (iii) treatment of any comorbidity/complication related to CKD; or alternatively by the recommendation of a kidney-specific follow-up. RESULTS: The primary outcome was achieved by 45.1% of the 71 patients included. A total of 29.6% had at least one inappropriate medication dosage at discharge, 9.9% left with a drug contraindicated in case of CKD, and 73.2% presented at least one untreated comorbidity/complication at discharge. The most common untreated comorbidity was anaemia. A proposition for a specific follow-up was lacking in 39 of the 56 patients discharged with a non-optimal treatment. CONCLUSION: Drug treatment of patients with CKD may be improved in our setting, especially the treatment of comorbidities/complications related to CKD and the specific ambulatory follow-up.

[Developing a terminology in the French language for clinical practice and research in drug safety]. / Iatrogénie médicamenteuse : contribution à l'uniformisation de la terminologie en langue française pour la pratique de soins et la recherche clinique.

While several attempts have been made to clarify the English terminology of drug-related iatrogeny, a consensus has still not been reached in the French language. We set up a multidisciplinary task force to propose a terminology that differs from the one used in pharmacovigilance and risk management. We prefer the term "adverse drug event" (ADE) over "adverse drug reaction", and recommend avoiding the term "adverse event", which is too general. We propose to classify ADEs as "direct drug effect" or "drug involvement in a multifactorial pathological condition", taking into account the close relationship commonly found between drug and non-drug etiologies of a pathology. The consistent association between the notions "error" and "preventability" is also questionable, and we suggest assessing the "ameliorability" of ADEs rather than their "preventability". "Misuse" (i.e., the non-respect by the patient of the drug label) must be distinguished from "off-label use or substance abuse".

Establishing a pharmacy presence in the emergency department: opportunities and challenges in the French setting.

Overview of clinical pharmacy practice around the world shows that pharmaceutical services in emergency departments (EDs) are far less common in Europe than in North America. Reported experiences have shown the impact of a clinical pharmacy service on drug utilisation and safety issues. This commentary presents the implementation of a pharmacy presence in the ED of a French tertiary care hospital. Our experience helps to define the role of the clinical pharmacist in the ED, including patient interviewing, providing medication reconciliation, promoting drug safety, and supporting specific interventions to improve quality of care and patient safety. The role of ED pharmacists in the improvement of quality of care is not necessarily limited to drug therapy, e.g. by helping outpatients to access care and treatment facilities as best suits their needs. Challenges of implementing ED pharmacy services have been identified well, but still require developing strategies to be overcome.

Adverse drug event nonrecognition in emergency departments: an exploratory study on factors related to patients and drugs.

BACKGROUND: Many adverse drug events (ADEs) are not identified by emergency physicians. Research has been done to study risk factors for ADEs and help emergency physicians diagnose ADEs. However, no research has specifically examined the causes underlying a lack of attribution of ADEs to medications in emergency department (ED) patients. OBJECTIVE: We conducted an exploratory study in a medical ED to search for the factors associated with ADE nonrecognition that are related to ED patients and ADEs. METHODS: We conducted an observational study in the medical ED of a French tertiary care hospital between January and December 2009. The study focused on all ADEs, whether or not they were related to the patient's chief complaint. ADEs were identified by an expert physician and pharmacist based on National Electronic Injury Surveillance System criteria. An ADE was considered "attributed" if any evidence of ADE suspicion, ADE diagnosis, or ADE management was documented on ED charts. Factors associated with ADE nonrecognition were identified using multiple logistic regression analysis. RESULTS: Of the 465 included patients, 90 experienced an ADE at ED visit (19.4%; 95% confidence interval [CI] 15.9%-23.2%). Emergency physicians correctly recognized 36 of these cases (40.0%; 95% CI 29.8%-50.9%). On multivariate analysis, ADE nonrecognition was significantly associated with the following variables: nonrelation between the ADE and the patient's chief complaint; daily prescription of four drugs or more; and hospitalization ADE severity category. CONCLUSIONS: Our results emphasize the importance of searching for ADEs in patients with daily polypharmacy or whose chief complaint does not seem to be drug related.

Frequency and severity of adverse drug reactions due to self-medication: a cross-sectional multicentre survey in emergency departments.

BACKGROUND: Little is known about the relation of adverse drug reactions (ADRs) to self-use of medications. OBJECTIVE: The aim of this study was to determine the frequency and severity of ADRs related to self-medication (ADR-SM) among emergency department (ED) patients and to describe their main characteristics. METHODS: A prospective, cross-sectional, observational study was conducted over a period of 8 weeks (1 March to 20 April 2010), in the ED of 11 French academic hospitals. Adult patients presenting to the ED during randomization periods were included, with the exception of cases of self-drug poisoning, inability to complete self-medication questionnaire, or refusal. Clinical outcomes were assessed as well as history of self-medication behaviours and all drugs taken. All doubtful files and those related to ADR-SM were systematically reviewed by an expert committee. RESULTS: A total of 3,027 of 4,661 patients presenting to the ED met the inclusion criteria. Of these, 84.4 % declared a self-medication behaviour, 63.7 % took at least one non-prescribed drug during the previous 2 weeks and 59.9 % took a prescribed medication. A total of 296 patients experienced an ADR (9.78 %), of which 52 (1.72 %) were related to self-medication. Those ADRs related to self-medication included prescribed drugs (n = 19), non-prescribed drugs (n = 17), treatment discontinuation (n = 14), and interactions between non-prescribed and prescribed drugs (n = 2). The ADRs attributed to non-prescribed drugs represented 1 % of all patients taking non-prescribed drugs (n = 1,927). ADR severity was significantly lower for those related to self-medication (p = .032). CONCLUSION: Self-medication is frequent; its potential toxicity should not be neglected, taking into account the rate of adverse drug reactions in about 1 % of ED patient.

Assessment of adverse drug event recognition by emergency physicians in a French teaching hospital.

OBJECTIVES: The frequency and the severity of drug-related visits in emergency department (ED) make the improvement of adverse drug event (ADE) recognition a crucial issue. As part of a research project aiming to improve the diagnosis and the management of ADEs in ED, the authors conducted a pilot study whose primary objective was to assess ADE recognition by emergency physicians. METHODS: The patients presenting to the ED were included at randomised time periods between 1 October 2007 and 31 March 2008 in this prospective cross-sectional study. The primary outcome was the frequency of ADEs that were attributed to a medication-related problem by the emergency physician. RESULTS: A total of 423 patients met the inclusion criteria, of which 95 experienced an ADE (22.5%; 95% CI 18.6% to 26.7%). Emergency physicians correctly attributed 33 of these cases (34.7%; 95% CI 25.3% to 45.2%) to a medication-related problem. Of the 28 cases in which the ADE was considered as a 'direct drug effect' (29.5%; 95% CI 20.6% to 39.7%), 16 were correctly identified by emergency physicians (57.1%; 95% CI 37.2% to 75.5%). Of the 67 cases in which the ADE was considered as a 'drug involvement in a multifactorial pathological condition' (70.5%; 95% CI 60.3% to 79.4%), 17 were correctly attributed (25.4%; 95% CI 15.5% to 37.5%). CONCLUSIONS: ADEs are frequent in EDs and are not well recognised by emergency physicians, especially when the drug is involved in a multifactorial pathological condition.

A questionnaire to document self-medication history in adult patients visiting emergency departments.

PURPOSE: To develop the first questionnaire to obtain a complete medication history by documenting self-medication history in adult patients admitted to a medical emergency department (ED). METHODS: A Questionnaire to document Self-Medicating Behaviours (QSMB) was developed between January and September 2008 (reference period), tested and refined between October and December 2008, and used routinely between January and December 2009 (routine period) in a tertiary care medical ED. The rate of SMBs measured with QSMB during the routine period was compared to the SMB rate measured with a spontaneous reporting method during the reference period. As survey teams changed every trimester, we also analysed the evolution of SMB rate over time. RESULTS: QSMB is divided into two parts. The first part consists of 20 closed-ended questions exploring all indications and dimensions of self-medication. The second part assesses the characteristics of each medication mentioned by the patient in the first 20 questions. The patients interviewed during reference and routine periods did not significantly differ. The routine period patients reported a third more SMBs (89.8% vs 57.6%, respectively; p < 0.0001) and twice more self-medication drugs than the reference period patients. SMB rate was significantly different between the survey teams during the reference period (p < 0.0001), but not during the routine period (p = 0.078). CONCLUSIONS: This questionnaire complements the traditional tools that are already available to collect medication histories of prescribed drugs. It may improve the recognition of iatrogenic conditions related to self-medication, and provide support to public health efforts and research programs on self-medication.

[Self-medicating behaviours in patients admitted to a medical emergency department]. / Étude des comportements d'automédication chez les patients admis dans un service d'urgences médicales.

OBJECTIVE: To describe the self-medicating behaviours (SMBs) in patients admitted to a tertiary care medical emergency department (ED); to study the factors associated with SMBs. METHODS: Observational cross-sectional study conducted in 2009. Included patients were interviewed about their SMBs using a standardized questionnaire. The search for factors associated with SMBs used multivariate logistic regression analysis. RESULTS: Among the 315 patients who were interviewed, 239 (75.9%) reported one SMBs or more in their lives and 105 (43.9%) within 7 days of admission to the ED. Some of the medications reported during interviews are known to be associated with adverse drug events. After adjustment, SMBs were conversely associated with an age ≥80 years, a number of prescribed medications ≥4 and a social vulnerability condition. CONCLUSION: The description of SMBs and the analysis of their determinants are necessary to improve the recognition of adverse events related to self-medication in ED patients.

Implementing a clinical pharmacy survey of adverse drug events in a French emergency department.

BACKGROUND: The prevalence of adverse drug events (ADEs) occurring in the ambulatory setting is high, requiring the development of a coherent and comprehensive patient-safety policy framework. Former experiences demonstrated that emergency department (ED) surveillance can help characterise the burden of outpatient ADEs. We developed a clinical pharmacy programme called the clinical pharmacy survey of adverse drug events (CPSA) to support interventions and research projects in the area of ADE prevention and management. OBJECTIVE: To design a survey to identify and describe ADEs in patients visiting the medical ED of our tertiary care hospital. We report the results of the first 2 years of CPSA implementation and an assessment of its performance. SETTING: The medical ED of a French 3,000-bed tertiary care hospital. METHOD: Between January 2008 and December 2009, adult patients visiting our medical ED were included during randomised time slots. Data were collected by pharmacy students. ADEs were documented by a trained physician pharmacist team using the chart review method. MAIN OUTCOME MEASURE: The primary outcome was the number of patients visiting our ED with an ADE. The CPSA attributes were assessed on the basis of the Centers for Disease Control and Prevention's 2001 updated guidelines for evaluating public health surveillance systems. RESULTS: Of the 1,035 included patients, 201 experienced an ADE at the ED visit (19.4 %; 95 % confidence interval 15.8-23.0 %). Forty-seven ADEs (23.4 %) were unrelated to the patient's chief complaint. An ADE was the leading cause of 154 in the 1,035 admissions (14.9 %). The assessment of our method on the basis of the Centers for Disease Control and Prevention guidelines showed good performances in terms of data quality, stability, flexibility, timeliness, and acceptability, but not in terms of simplicity and representativeness. The profile of patients with an ADE at admission and detected ADEs did not significantly differ between years 2008 and 2009. CONCLUSION: Our experience demonstrates that clinical pharmacists can successfully implement a survey process of ADEs in an ED over time. Our method seems basic enough to suit most health care facilities with pharmacy students.

[Grapefruit consumption and food-drug interaction hazard]. / Consommation de jus de pamplemousse et risque d'interactions médicamenteuses : étude transversale dans un service d'urgences médicales.

OBJECTIVE: To estimate the prevalence of grapefruit consumption in patients admitted to a tertiary care emergency department (ED) and its potential impact on the risk of fruit-drug interaction. METHODS: Observational cross-sectional study conducted in a medical ED between July and December 2009. Data analysis searched for the main drugs which can dramatically interact with grapefruit and for adverse drug events (ADEs). Among the 162 patients who were interviewed, 59 (36%) reported grapefruit consumption (regardless form or frequency) and 11 (7%) were prescribed a treatment with a risk of fruit-drug interaction. No ADE could be related to an interaction with grapefruit. Calcium channel blockers and HMG-coA-reductase inhibitors mostly accounted for drugs at risk of interaction in grapefruit consumers. CONCLUSION: These results give evidence of the sizeable risk of grapefruit-drug interaction in the prescriptions of patients admitted to a medical ED, with a high proportion of commonly used medicines but poor clinical consequences.