Gloria Cereza

An Intervention to Improve Spontaneous Adverse Drug Reaction Reporting by Hospital Physicians : A Time Series Analysis in Spain

AbstractBackground: Spontaneous reporting of adverse drug reactions (ADRs) in hospitals is scarce and several obstacles to such reporting have been identified previously. Objective: To assess the effectiveness of a multifaceted intervention based on healthcare management agreements for improving spontaneous reporting of ADRs by physicians in a hospital setting. Methods: In 2003, the spontaneous reporting of ADRs was included as one of the objectives of hospital physicians at the Vall d’Hebron Hospital, Barcelona, Spain, within the context of management agreements between clinical services and hospital managers. A continuous intervention related to these management agreements, including periodic educational meetings and economic incentives, was then initiated. We carried out an ecological time series analysis and assessed the change in the total number of spontaneous reports of ADRs, and the number of serious ADRs, unexpected ADRs, and ADRs associated with new drugs between a period previous to the intervention (from 1998 to 2002) and the period during the intervention (from 2003 to 2005). A time series analysis with ARIMA (Auto-Regressive Integrated Moving Average) models was performed. Results: The median number of reported ADRs per year increased from 40 (range 23–55) in the first period to 224 (range 98–248) in the second period. In the first period, the monthly number of reported ADRs was stable (3.47 per month; 95% CI 1.90, 5.03), but in the second period the number increased progressively (increase of 0.74 per month; 95% CI 0.62, 0.86). In the second period, the proportion of reported serious ADRs increased nearly 2-fold (63.1% vs 32.5% in the first period). The absolute number of previously unknown or poorly known ADRs increased 4-fold in the second period (54 vs 13 in the first period). There was also an increase in the absolute number of suspected pharmacological exposures to new drugs (97 vs 28) and in the number of different new drugs suspected of causing ADRs (50 vs 19). Conclusion: A continuous intervention based on healthcare management agreements with economic incentives and educational activities is associated with a quantitative and qualitative improvement of spontaneous reporting of ADRs by hospital physicians.

Effect of an intervention on the features of adverse drug reactions spontaneously reported in a hospital

ObjectivesA continuous intervention based on healthcare management agreements was associated in our hospital with an increase in the absolute number of spontaneous reporting of adverse drug reactions (ADRs), and also with an increase in the number of reports of serious or unexpected ADRs and ADRs associated with new drugs. The objective was to analyse the effect of this intervention on the features of ADRs spontaneously reported in a hospital, the drugs involved and the number of signals identified.MethodsA longitudinal study with two periods, the 1st period without intervention from 1998 to 2002 and the 2nd period with intervention from 2003 to 2005, was carried out in a tertiary teaching hospital. Changes between the two periods with regard to the following variables were analysed: the patients’ characteristics, such as gender and age; the reported ADRs, and the medical assistance required; the suspected drugs involved in the ADRs; the main signals identified.ResultsGender and age distribution of patients described in the spontaneous reports were no different in the two periods. During the second period, spontaneously reported cases requiring hospital admission and those occurring in hospital increased (236 from 2 in the first period and 277 from 99 in the first period respectively) and cases from outpatient hospital consultations began to be reported (13.9% of reports). The spontaneous reporting on all kinds of ADRs and drugs increased during the second period. Cutaneous reactions were the most frequently spontaneously reported ADRs in both periods followed by cardiovascular and neurological reactions in the first period, and haematological and gastrointestinal reactions in the second one. However, during the second period the higher increase was for endocrinological, urinary and hepatic reactions. Systemic antibiotics, anti-thrombotics and cardiac therapy drugs were the most common therapeutic subgroups reported to be suspected drugs in both periods, but in the second period the proportion of immunostimulants, beta blocking agents, immunosuppressants and psychoanaleptics increased. No signals were recognised during the first period; however, two signals and one additional safety concern were identified during the second.ConclusionAn intervention based on healthcare management agreements, was associated with an important increase in spontaneous reporting of ADRs by hospital physicians and also with a change in terms of the type of ADRs identified affecting different organs or systems, and the therapeutic groups of drugs involved. Future studies should analyse the effect of different types of intervention on the spontaneous reporting of ADRs in hospitals.

Drug points: Dysgeusia and burning mouth syndrome by eprosartan

Eprosartan is an angiotensin II receptor antagonist. Dysgeusia and burning mouth syndrome attributed to angiotensin converting enzyme inhibitors have been reported.1 Several case reports related to angiotensin II receptor antagonists have also been published. We report the case of a patient in whom oral eprosartan induced reversible taste disturbance and burning mouth sensation on two occasions. This case was reported to the Catalan pharmacovigilance centre. A 48 year old woman with a 10 year history of essential hypertension was being treated with valsartan 160 mg daily. …

Association of musculoskeletal complaints and gliptin use: review of spontaneous reports

Gliptins are new oral antidiabetic drugs that increase insulin levels through dipeptidyl peptidase‐4 inhibition. Recently, the association of serious musculoskeletal (MSk) adverse effects with the gliptin use has been suggested. The aim is to describe and analyze the characteristics of spontaneous reports related to these adverse effects and gliptin use.

Nightmares induced by montelukast in children and adults

To the Editors: Montelukast, a leukotriene receptor antagonist, was approved in Spain in 1998 for the treatment of asthma in both adults and children. Sleep disturbances, including nightmares, related to leukotriene receptor antagonists have not been described in clinical trials. However, several cases of sleep abnormalities, including nightmares, have been reported in post-marketing experience in patients treated with montelukast [1]. Up to December 2011, the Spanish System of Pharmacovigilance had gathered 24 reports of nightmares in patients (17 children, seven adults) treated with montelukast (table 1). Of the 24 patients, 15 were males and nine were females. 14 patients presented with other concomitant psychiatric symptoms: insomnia (n=5), nervousness (n=4), hallucinations (n=3), aggressiveness (n=2), irritability (n=2) and anxiety (n=1). Cases with aggressiveness were rated as serious. In all cases the only suspect medicine was montelukast. Six patients had taken other medicines concomitantly, although on a long-term basis. In 18 patients the nightmares appeared within the first …

Primeras notificaciones espontáneas de sospechas de reacciones adversas a los nuevos antiinflamatorios selectivos sobre la ciclooxigenasa-2

BACKGROUND: [corrected] The new selective cyclooxygenase 2 non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with a lower incidence of adverse gastrointestinal effects. MATERIAL AND METHOD: The first Yellow Cards received at the Catalan Centre of Pharmacovigilance reporting adverse effects of rofecoxib and celecoxib were reviewed and compared to those attributed to non-selective NSAIDs. RESULTS: Most frequent adverse effects of rofecoxib were gastrointestinal and cardiovascular; those of celecoxib were mostly cutaneous and gastrointestinal; and those of non-selective NSAIDs were gastrointestinal and neuropsychiatric. CONCLUSIONS: Rofecoxib and celecoxib are not devoid of gastrointestinal toxicity; they may also induce cardiovascular adverse effects.

Lack of essential information in spontaneous reports of adverse drug reactions in Catalonia—a restraint to the potentiality for signal detection

PurposeThe aim of this study is to analyze the quality of the information contained in the adverse drug reactions (ADR) reports and to describe the magnitude and characteristics of the lacking information.MethodsAll reports of serious ADR received by the Catalan Center of Pharmacovigilance in 2014 were analyzed using the VigiGrade and a more clinical and qualitative approach.ResultsUp to 824 reports describing serious ADR were included in the study; of them, 503 (61.0%) were sent by health care professionals (HPs) and the remaining 321 (39.0%) came from pharmaceutical companies (PhC). More than 80% of missing variables such as ‘onset date’ or ‘time-to-onset’ of the ADR were from PhCs reports. ‘Onset of treatment date’ was not filled in 28 (22.2%) of the reports including an ‘additional monitoring’ medicine, and ‘end of treatment’ date was not completed in 53 of those reports (42.1%). In summary, 39% of the reports involving a black triangle medicine sent by PhCs lacked some essential information such as the onset date of treatment.ConclusionsMore than one third of the reports coming from manufacturers did not include information that is considered a limiting factor to evaluate any causal relationship, and can be an issue for the detection of safety signals. To take advantage of this huge amount of potentially important information that is almost useless at present, data mining tools and new algorithms should be developed and tested with the aim of finding formulas to deal with a huge amount of low quality data without losing it, nor generating a number of false associations.

Dronedarone and renal impairment: evaluation of Spanish postmarketing reports and review of literature

Background: Renal impairment associated with dronedarone use is hardly known. Our aim is to describe the characteristics of spontaneous reports involving renal adverse reactions with use of dronedarone. Methods: In the Spanish Pharmacovigilance database, reports with renal reactions and dronedarone until May 2014 were retrieved and analyzed. Also, a review of case reports of renal failure and dronedarone was conducted in MEDLINE. Results: Dronedarone was found as a suspected drug in 192 reports, 10 (5.2%) of these reports described renal reactions. Renal reactions appeared until 3 months after the onset of dronedarone treatment. In 5 out of 10 cases, dronedarone was withdrawn and the patient recovered. The Reporting Odds Ratio was 2.88 [95% CI 1.52 – 5.46; p < 0.05]. Additionally, eight cases were found in the medical literature. In five of them, the patient outcome was described as recovered. One patient had to undergo hemodialysis for the treatment of their renal impairment. Conclusions: The effect of dronedarone on the renal function is supported by limited information; therefore, the cases from spontaneous reporting system and those from the medical literature could give relevant additional information. Our analysis shows a potential relationship between dronedarone use and renal impairment. Further studies are needed to confirm these findings.