Analgesic switching in chronic users of dextropropoxyphene in France.

BACKGROUND: The combination dextropropoxyphene/paracetamol (DXP/P) was the most prescribed opioid analgesic until its withdrawal in 2011. OBJECTIVES: This study investigated dispensations of analgesics in chronic users of DXP/P during the 18 months following its withdrawal. METHODS: A cross-sectional study repeated yearly was conducted by using the French reimbursement database from 2006 to 2015. Chronic DXP/P users were defined as patients who received at least 40 boxes of DXP/P in the year prior to withdrawal. Data on analgesic dispensing were analyzed at DXP/P withdrawal (T0) and then every 6 months for 18 months. RESULTS: A total of 63 671 subjects had a DXP/P reimbursement in the year prior to its discontinuation, of whom 7.1% were identified as chronic users (mean age: 71.5 years, women: 68.7%). Among the patients taking DXP/P alone at T0 (74.6%), one fourth switched to a peripheral analgesic, one fourth to a combination of peripheral analgesic/opioid, one fourth to another opioid, and the others mainly discontinued their treatment (14.1%) or died. During the following 12 months, most of the subjects taking only peripheral analgesics continued this treatment, while half of the subjects with a combination of opioid/peripheral analgesic or taking only an analgesic remained on this type of treatment. CONCLUSION: Eighteen months after DXP/P withdrawal, more than 10% of patients stopped taking an analgesic. Vigilance is required regarding any change in analgesics by regularly reassessing patients' pain and, in the case of opioid treatments, by monitoring the risk of use disorders.

Adverse drug reactions induced by cotrimoxazole: Still a lot of preventable harm.

Owing to a broad spectrum and low cost antimicrobial, cotrimoxazole is largely prescribed. However, its use is associated with various adverse drug reactions (ADRs) that warrant to ensure rational prescribing. This study aimed to describe spontaneous reports of cotrimoxazole ADRs and to evaluate the quality of prescription in patients who had ADRs. Suspected cotrimoxazole-induced ADRs cases reported to the Bordeaux regional pharmacovigilance center (France) during a 5-year period were described. Seriousness was assessed according to international criteria. Quality of prescription was assessed by compliance with the Summary of Product Characteristics (SPC) and relevance of cotrimoxazole indication. Then, an ADR was considered as preventable if the cotrimoxazole indication was not relevant, or potentially preventable if indication was relevant but the prescription was not compliant with the SPC. A total of 96 cases were analyzed: median age was 60.5 years (range: 4-94); 59.4% of patients were male. ADRs were mostly cutaneous disorders (n = 46) and hematological disorders (n = 25). A total of 60 serious ADRs occurred in 55 patients. Prescribers complied with all SPC recommendations in 21.9% of cases. Indication of cotrimoxazole was relevant or highly relevant in 41 cases. In 58% of cases, the occurrence of a cotrimoxazole-induced ADR would have been preventable or potentially preventable. In a context of increasing interest for this antibiotic to treat infections due to resistant bacteria, physicians should be more aware of the potential consequences of inappropriate prescribing cotrimoxazole and reserve its use when there is no alternative and under suitable monitoring.

A 13-Year National Monitoring Study to Assess Narcotic Prescriptions and Indications (2007-2019).

INTRODUCTION: Analgesics are among the most widely used drugs worldwide. This study describes the population treated with narcotic analgesics, their therapeutic indications and how the data have evolved over a decade. METHODS: A cross-sectional, national, multicentre survey study was conducted that included surveys taken every year from 2007 to 2019 in a national sample of 1500 randomly selected dispensing pharmacies. RESULTS: The mean age of patients, mostly women (around 60%), remained stable over the study period (63.2 ± 17.1 years in 2007, 68.2 ± 17.2 years in 2019). The proportion of patients treated for more than 3 months increased from 2007 to 2019. Most prescriptions involved morphine, oxycodone and fentanyl (98.5% of all prescriptions in 2019). Morphine prescriptions dropped dramatically from 49.6% (2007) to 32.3% (2019) of the total narcotic analgesics. Fentanyl prescriptions varied from 40.1% in 2007 to 32.2% in 2019. Prescriptions of oxycodone, regardless of the indication, increased steadily from 2007, from 8.3 to 34% in 2019, becoming the most prescribed narcotic analgesic for the first time since the beginning of the survey. CONCLUSIONS: This study demonstrates how narcotic opioids are prescribed, thanks to the active participation of health professionals, and confirms the striking increase in the prescription of oxycodone.

Ten-year trend of opioid and nonopioid analgesic use in the French adult population.

AIMS: Analgesics are the most widely used medicines worldwide. In parallel, opioid abuse has increased and is of major concern. The accessibility of pharmacologically powerful medicines and the addictovigilance signals in France about the risk of opiates addiction call for an overview of analgesic use. The objective of this study was to investigate the use of analgesics reimbursed in France over a 10-year period through its prevalence. METHODS: A cross-sectional study repeated yearly was conducted by using data from the French reimbursement database from 2006 to 2015. Analgesics were classified according to their pharmacological potency: prevalence of use for each category and sociodemographic characteristics of patients treated were analysed. RESULTS: The annual prevalence of analgesic use was high and increased during the study period (59.8%, 253 976 users in 2015). In 2015, prevalence was always higher in women and increased with age, except for those older than 84 years. Peripheral analgesics were the most used (55.3%, 234 739 users). The prevalence of weak analgesic use decreased (21.3%, 90 257 users), mainly due to the definitive withdrawal of dextropropoxyphene in France in 2011, which was not offset by an increase in the consumption of other weak analgesics. For strong analgesics (1.2%, 5129 users), morphine was the most widely used, with a dramatic increase in oxycodone use, especially in the elderly. CONCLUSION: The prevalence of analgesic use is high: approximately 31 million adults had at least 1 analgesic reimbursed in 2015. The most widely used analgesics were peripheral analgesics, far ahead of opioid analgesics.

[Use of synthetic substances in France and in Europe]. / Usages de substances de synthèse en France et en Europe.

This paper aims to present the main information presented at the 9th Meeting about addictovigilance in 2016 by four healthcare professionals and addiction experts on the issue of new psychoactive substance use. A new psychoactive substance (NPS) is defined as a narcotic or psychotropic drug, in pure form or in preparation, that is not controlled by the United Nations drug conventions, but which may pose a public health threat comparable to that posed by substances listed in these conventions. The emergence of NPS consumption is a worldwide concern. Although NPS are less consumed than established drugs, there has been a sharp increase in their use over the last few years, notably of synthetic cathinones, synthetic cannabinoids and, more recently, synthetic opioids. The latter in particular are involved in deaths in Europe. However, "established" drugs (MDMA [methylenedioxymethamphetamine], amphetamines, LSD, methamphetamine) are far from being dethroned by the more recent substances: they are considered "a safe bet" already "tried and tested" by many consumers over the years. MDMA, in particular, also known as ecstasy, which has been used as a recreational drug since the 1990s, saw its consumption decrease until 2010, and then increase again, especially in higher amounts; inexpensive and easily accessible, it is increasingly associated with emergency admissions or deaths in France. The perpetual appearance of new substances on the drug market is obligating to improve knowledge on these products, particularly by focusing on their analytical identification, and also by monitoring their use and harms.

Identifying Drugs Inducing Prematurity by Mining Claims Data with High-Dimensional Confounder Score Strategies.

BACKGROUND: Pregnant women are largely exposed to medications. However, knowledge is lacking about their effects on pregnancy and the fetus. OBJECTIVE: This study sought to evaluate the potential of high-dimensional propensity scores and high-dimensional disease risk scores for automated signal detection in pregnant women from medico-administrative databases in the context of drug-induced prematurity. METHODS: We used healthcare claims and hospitalization discharges of a 1/97th representative sample of the French population. We tested the association between prematurity and drug exposure during the trimester before delivery, for all drugs prescribed to at least five pregnancies. We compared different strategies (1) for building the two scores, including two machine-learning methods and (2) to account for these scores in the final logistic regression models: adjustment, weighting, and matching. We also proposed a new signal detection criterion derived from these scores: the p value relative decrease. Evaluation was performed by assessing the relevance of the signals using a literature review and clinical expertise. RESULTS: Screening 400 drugs from a cohort of 57,407 pregnancies, we observed that choosing between the two machine-learning methods had little impact on the generated signals. Score adjustment performed better than weighting and matching. Using the p value relative decrease efficiently filtered out spurious signals while maintaining a number of relevant signals similar to score adjustment. Most of the relevant signals belonged to the psychotropic class with benzodiazepines, antidepressants, and antipsychotics. CONCLUSIONS: Mining complex healthcare databases with statistical methods from the high-dimensional inference field may improve signal detection in pregnant women.

[From psychoactive medicines to addictovigilance in French Public Health Code (1990-2017)]. / Du médicament psychoactif à l'addictovigilance dans le Code de la santé publique en France (1990­2017).

Addictovigilance in the French Public Health Code, in the section related to poisonous substances, refers to a monitoring system developed since 1990: control of psychoactive substances and products, with medicinal use or not, was completed by a specific system focused on evaluation and information on pharmacodependance in 1999. The French medicines agency (Agence du médicament) created in 1993 was involved in this monitoring system; pharmacodependance evaluation was added by law to the missions of the agencies that followed: the Agence française de sécurité sanitaire des produits de santé missions (AFSSAPS, 1998) and the Agence nationale de sécurité du médicament et des produits de santé (ANSM, 2011). "Addictovigilance" first appears in French Law in 2017 whereas it was used by pharmacodependance centers and AFSSAPS since 2007. Legal definition of addictovigilance in the French Public Health Code testified to public authorities action against addictive behavior whatever products status, legal or not. The visibility of addictovigilance is growing on the Internet as well (ANSM website, web portal for reporting adverse health events).

[Psychoactive substances use in Réunion Island and Mayotte, French departments in Indian Ocean]. / Consommation de substances psychoactives à la Réunion et à Mayotte, départements français de l'Océan Indien.

INTRODUCTION: The government plan for the fight against drugs and addictive behaviors 2013-2017 includes several actions concerning French overseas territories, in particular to strengthen information on drug addiction. The Interministerial mission for combating drugs and addictive behaviors (MILD&CA) has commissioned the Bordeaux addictovigilance center to strengthen exchanges on addictovigilance with Réunion Island and Mayotte and to make an inventory of problematic drug use in these two French departments of Indian Ocean. METHOD: Two pharmacologists went on an assignment 4.5 days in Reunion and 2 days in Mayotte and met more than fifty people involved in addictology. RESULTS: In Reunion Island, alcohol is the psychoactive substance by far the most used, followed by zamal, the local name for cannabis. There is a strong tradition of medicines diversion, including trihexyphenidyl, barbiturates and more recently, benzodiazepines. Heroin and cocaine are rarely available. Poly drug use is common. In Mayotte, bangué, the local name for cannabis, is the most used psychoactive substance. The use of "chimique" has emerged in 2012-2013. It is used mainly by teenagers and young adults, causing numerous cases of hospitalizations and consultations in addictology in 2015. These could be synthetic cannabinoids bought on the Internet. DISCUSSION: It is important to report new or serious cases to better take into account the particularities of these two departments in the French addictovigilance data and to enable analysis of substances consumed.

Tamper-resistant prescription forms for narcotics in France: Should we generalize them?

In France, prescription of narcotics must be written on a tamper-resistant prescription form with specific technical particularities. Dosage and daily dose of medicines shall be written out entirely in letters. These prescription forms are also mandatory for buprenorphine, clorazepate, clonazepam, tianeptine, buccal midazolam and zolpidem owing to traffic, abuse or diversion. In 2012, to assess the use of standard and tamper-resistant prescription forms and the acceptability of the generalization of the latter to all medicines, a national opinion survey was performed, with a postal questionnaire, within three randomized samples of 1500 prescribers (physicians, dentists and midwives). Of the 403 participating prescribers (participation rate of 26.8%), 373 were physicians, 14 dentists and 16 midwives. Tamper-resistant prescription forms were used by 76.2% of prescribers, but only by 5.1% in a computerized version, whereas for standard prescription forms, 61% used computer assisted prescription software. The main reason was the inability of the prescription software to print these forms or to respect the mandatory prescription rules for narcotics. Theft and falsification of prescriptions had ever occurred (working life). Most prescribers (62.5%) were against the generalization of tamper-resistant prescription forms. Those in favour were for a generalization to all medicines (65%) and not only to psychotropic agents. Generalization of tamper-resistant prescription forms is not a consensual solution to prevent medicines' diversion. Some prescribers alluded to the possibility of dematerialization and electronic transmission of prescription forms, which could avoid theft, forgery or falsification.

Adverse drug reactions of analgesic medicines: analysis of the Romanian pharmacovigilance database.

The results of national safety studies are essential for decision-making at the regulatory level and have also educational implications for prescribing patterns. The aim of this study was to analyze the adverse drug reactions (ADRs) of analgesic medicines spontaneously reported to Pharmacovigilance and Risk Management Service of the Romanian National Agency for Medicines and Medical Devices between 2011 and 2015. For the 71 reports, patients had a mean age of 39.8 years; 60.6% of patients were female, and 38% male and 1.4% were unknown. Reporters were mainly physicians (74.7%), and 52.1% of ADR reports were transmitted through marketing authorization holders. Of the serious ADRs (32.4%), 34.7% led to hospitalization or prolonged hospitalization. The most frequent ADRs reported were skin and subcutaneous tissue disorders (25.8%) and general disorders and administration site conditions (19.2%). Metamizole, alone or in combination, was the main analgesic suspected in almost 15.5% of the cases and remains one of the most popular analgesics in Romania. Ten cases were assessed as preventable or potentially preventable (14%), of which two cases were serious. Even if the level of reporting is still low, this study conducted on ADRs of analgesics reported to the national pharmacovigilance center represents an essential step toward promoting the rational use of analgesics in Romania.

Rhabdomyolysis after co-administration of a statin and fusidic acid: an analysis of the literature and of the WHO database of adverse drug reactions.

Following a severe case of rhabdomyolysis in our University Hospital after a co-administration of atorvastatin and fusidic acid, we describe this interaction as this combination is not clearly contraindicated in some countries, particularly for long-term treatment by fusidic acid. All cases of rhabdomyolysis during a co-administration of a statin and fusidic acid were identified in the literature and in the World and Health Organization database, VigiBase® . In the literature, 29 cases of rhabdomyolysis were identified; mean age was 66 years, median duration of co-administration before rhabdomyolysis occurrence was 21 days, 28% of cases were fatal. In the VigiBase® , 182 cases were retrieved; mean age was 68 years, median duration of co-administration before rhabdomyolysis was 31 days and 24% of cases were fatal. Owing to the high fatality associated with this co-administration and the long duration of treatment before rhabdomyolysis occurrence, fusidic acid should be used if there is no appropriate alternative, as long as statin therapy is interrupted for the duration of fusidic acid therapy, and perhaps a week longer. Rarely will interruption of this sort have adverse consequences for the patient.

Parachuting psychoactive substances: Pharmacokinetic clues for harm reduction.

BACKGROUND: Parachuting, also called bombing, is a way to ingest psychoactive substances wrapped into cigarette paper, toilet paper, etc. There is little data describing parachuting in terms of substances use, context of use and, most importantly, the motivations for using such wrappers, although some authors hypothesized that parachute could be used for pharmacokinetic reason. However, inconsistently, some authors report that parachutes are used for sustained-release whereas others report that users are looking for an immediate effect. RESEARCH DESIGN AND METHODS: Considering parachute as a "home-made" dosage form, we have applied the dissolution testing to characterize the dissolution performance of a substance wrapped into a parachute and to characterize whether a parachute represents an immediate-release form or not. RESULTS: This in-vitro study provides the first pharmacokinetic data for drugs wrapped in parachutes. It shows that parachute acts as sustained-release form when made with a cigarette paper wrapper, but as immediate release form in the presence of alcohol or if wrapped with toilet paper. CONCLUSIONS: An important message to harm reduction is that users must be aware that a parachute can have unexpected pharmacokinetics and have to avoid taking another parachute in the absence of an immediate-effect to avoid overdose.

Impact of Medicine Withdrawal on Reporting of Adverse Events Involving Therapeutic Alternatives: A Study from the French Spontaneous Reporting Database.

INTRODUCTION: The consequences of the withdrawal of marketing authorisation of drugs have mostly been studied considering drug prescription patterns for the therapeutic alternatives of the withdrawn drugs. The potential concomitant changes in the reporting of adverse reactions concerning these alternatives have been studied less often. OBJECTIVE: The objective of this study was to analyse the changes in the reporting of adverse events (AEs) for therapeutic alternatives after the withdrawal of three medicines (dextropropoxyphene, pioglitazone and tetrazepam) from the market for safety reasons. METHODS: This study was performed using both the French pharmacovigilance database and the Echantillon Généraliste des Bénéficiaires (a random sample of French health insurance affiliates). For dextropropoxyphene, pioglitazone and tetrazepam alternatives, the number and types of case reports were studied for both the year preceding the first official safety warning and the year following the withdrawal. Reporting rates expressed per 10,000 reimbursements (RRReimb) and per 10,000 treated patients (RRPat) were also compared for the two periods. RESULTS: After dextropropoxyphene withdrawal, case reports and reimbursements increased for tramadol (case reports: +23%, reimbursements: +13%) and codeine (case reports: +74%, reimbursements: +47%), RRPat being significantly increased for tramadol (0.92 vs. 1.06, p = 0.02). After pioglitazone withdrawal, case reports increased for dipeptidyl peptidase-4 (DPP-4) inhibitors, glinides, and glucagon-like peptide 1 (GLP-1) analogues (+84%, +22% and +5%, respectively) and reimbursements (+55, +11 and +50%, respectively); both decreased for sulfonylureas (case reports: -6%, reimbursements: -2%). RRPat increased for DPP-4 inhibitors (1.63 vs. 2.26, p = 0.008). After tetrazepam withdrawal, case reports increased for diazepam, methocarbamol and thiocolchicoside (+110, +86 and +157%, respectively), as lesser did reimbursements. RRPat increased for diazepam (1.78 vs. 2.41, p = 0.054) and thiocolchicoside (0.14 vs. 0.24, p = 0.013). CONCLUSION: For the three drug withdrawals investigated, the number of case reports involving alternatives increased to a larger extent than the numbers of prescriptions. This could relate to a higher occurrence of AEs in new users of alternatives who switched from the withdrawn medicines or to an increased awareness of possible AEs.

Which psychoactive substances are used by patients seen in the healthcare system in French overseas territories? Results of the OPPIDUM survey.

Addiction to illicit substances or medicines is influenced by cultural, religious, ethnic factors as well as local availability. The purpose of this study was to evaluate the profile of drug users and characteristics of the psychoactive substances used in French overseas territories, using data from the OPPIDUM survey. OPPIDUM is an annual, nationwide, multicentric, cross-sectional study based on specialized care centres that included subjects presenting a drug addiction or under opiate maintenance treatment. The current study includes data from the 2012 and 2013 surveys and focuses on patients included by drug addiction centres located in French overseas departments and territories: French Pacific Ocean (French Polynesia, New Caledonia), French Americas (Guadeloupe, Saint Martin, French Guiana) and Reunion Island. Data from metropolitan France (2013 survey) were included as reference. Two hundred and forty-five patients were included. The sex ratio was 3.7 for the Pacific Ocean, 3.5 for the French Americas and 3.3 for Reunion Island. Cannabis was consumed in all the territories, from 50.8% in Reunion Island to 81.7% in Pacific Ocean. Cocaine was most frequently consumed in the French Americas (61%), mainly in the 'freebase' form (91%), whereas 6.5% of cocaine users in metropolitan France did so. Problematic use of medicines was most frequent in Reunion Island. Heroin seems rarely used in all overseas territories. This study highlights the complexity of substances used in French overseas territories, which often differ from that in mainland France. The relative difference between different areas provides valuable information for future investigations and possible interventions.

Causality assessment in pharmacovigilance: The French method and its successive updates.

The methods for causality assessment of adverse drug reactions were developed in the 1970s and 1980s, alongside the development of pharmacovigilance. The French method is one of the earlier of these, following on from the pioneering works by Irey and Karch and Lasagna. Initially published in 1978, it was updated in 1985, and again in 2011. The main alterations to the original method are presented in tables annexed to this paper. The successive versions improved the presentation, provided more formalised definitions of the criteria for assessing causality, while at the same time ensuring the method remained easy to use. Causality assessment enables the causal link between a drug and the occurrence of an adverse reaction to be formalised and explained. It contributes to diagnosis, and to determining the action to be taken in case of an adverse drug reaction. It can contribute to the quality and the relevance of the data stored in pharmacovigilance databases.

Illicit drugs or medicines taken by parachuting.

Parachuting (also called bombing) is a method of drug delivery where illicit drugs or medicines are ingested after wrapping the substance. There are little data describing parachuting in the literature. To provide a description of this practice, all cases of parachuting reported to the national addictovigilance network up to 31 December 2014 were identified from spontaneous reports and specific surveillance programs. Cases were described according to the type of substance used, patient age and gender, type of complications, context of use and year of the event. Forty-five cases of parachute use were identified and most (n = 43) occurred after 2011. Patients were mostly men (60%), and mean age was 28.9 years. The context of use, known in 19 cases, was mostly recreational. Complications were present in 24 cases, of which eight were serious. The substance was supposed to be 3,4-methylenedioxymethamphetamine (MDMA) in the majority of cases (64.4%); research chemicals were more involved in the most recent years. The physical form was mainly granular (51.6%). The wrappers were a cigarette paper (nine cases) and in one case plastic package; in the other cases, the term of parachute was used without further details. The reason for use was not explained in the majority of cases; two patients indicated using a parachute for faster effect than with a methadone capsule. Clinicians should be aware of this delivery form as the results suggest that it is common and can involve a great variability of drugs.

Validation and Reproducibility of the Updated French Causality Assessment Method: an Evaluation by Pharmacovigilance Centres & Pharmaceutical Companies.

OBJECTIVE: Assess the validity and reproducibility of the updated version of the French causality assessment method in conditions approaching real-life use. METHODS: A random sample of 31 drug-event pairs from the French pharmacovigilance database was assessed by the consensual judgement of three experts (gold standard). Separately, a team from a pharmacovigilance centre (PhVC) and another from a pharmaceutical company assessed these pairs using the current method, then with the updated method. To test the inter- and intra-rater reproducibility, two seniors and two juniors from a PhVC and a pharmaceutical company assessed the pairs twice with the updated method. A weighted kappa coefficient was used to measure the agreement of the two causality assessment methods with the consensual expert judgement (validity) as well as the agreement of the updated causality assessment over time (intra-rater reproducibility) and between evaluators (inter-rater reproducibility). RESULTS: Agreement between the current method and consensual expert judgement was fair for the PhVC team (weighted kappa [Kw] 0.33) and moderate for the pharmaceutical company team (Kw 0.41). For the updated method, agreement was better for both the PhVC (Kw 0.58) and the pharmaceutical company (Kw 0.52) teams. The inter- and intra-rater reproducibility of the updated method based on the intrinsic imputability was satisfactory overall (Kw 0.30-0.91). Discrepancies between evaluations from PhVC and pharmaceutical companies were observed with the updated method. CONCLUSION: The updated method performed better than the current one for drug causality assessment, suggesting that it should be used in routine pharmacovigilance.

Signal identification in addictovigilance: the functioning of the French system.

The French addictovigilance network (addictovigilance: surveillance of addiction), composed of 13 Addictovigilance Centres, was set up in 1990 in order to achieve reliable surveillance and evaluation of abuse and dependence cases due to psychoactive substances (alcohol and tobacco excepted). The detection of safety signals is one of the roles of the addictovigilance centres. Signals from spontaneous reports need to be analyzed before further communication. In addictovigilance, signals may be linked to adverse effects (deaths, pathological signs), to products (new psychoactive substances with potentially dangerous effects) or to practices (new administration routes, new contexts of use). These signals are provided by numerous partners among whom the addictovigilance network has to raise awareness about information that may possibly be an alert signal. The watchful attitude of all partners will make it possible that signals will be, after analyze, considered as true alerts. The addictovigilance network collects data, assess the potential for addiction of psychoactive drugs to provide information on the risk of addiction and give opinions for public health decisions (harm reduction or prevention programs, psychoactive substances control, health alerts).

Preventability of adverse effects of analgesics: analysis of spontaneous reports.

OBJECTIVES: The aims of this study were to determine the patterns of analgesic adverse drug reactions (ADRs) and to assess their preventability and contributing factors. METHODS: This is a retrospective, descriptive study conducted on ADRs of analgesics and other drugs indicated as analgesics, spontaneously reported to the Bordeaux pharmacovigilance center from January 2011 to June 2012. RESULTS: The 141 cases selected for the analysis included 16 cases of medication errors (11.3%) and 15 addiction cases (10.6%). In total, 214 ADRs were registered, for which 173 analgesic medicines were suspected. The most frequent ADRs reported were nervous system disorders (26.6%), psychiatric disorders (15.0%), and skin and subcutaneous tissue disorders (12.1%). Tramadol alone or in combination (17.3%), followed by morphine (15%), fentanyl (9.8%), and paracetamol (8.7%) were the most frequently involved analgesics. More than half of the cases (54.6%) were serious and led to hospitalization or prolonged hospitalization. Preventability was determined for 134 cases (95%): 51.5% were considered as preventable, 26.1% not preventable, and 22.4% not assessable. The main contributing factors for the preventable cases included negligence of recommendations for analgesic use and failure to consider patients' risk factors when prescribing. CONCLUSIONS: A significant number of analgesic ADRs could be prevented, and being aware of their contributing factors promotes efficient analgesia with minimum risks to the patients.