Adverse drug reactions to self‐medication: a study in a pharmacovigilance database

Although self‐medication is widely developed, there are few detailed data about its adverse drug reactions (ADRs). This study investigated the main characteristics of ADRs with self‐medication recorded in the Midi‐Pyrénées PharmacoVigilance between 2008 and 2014. Self‐medication included first OTC drugs and second formerly prescribed drugs later used without medical advice (reuse of previously prescribed drugs). Among the 12 365 notifications recorded, 160 (1.3%) were related to SM with 186 drugs. Around three‐forth of the ADRs were ‘serious’. Mean age was 48.8 years with 56.3% females. The most frequent ADRs were gastrointestinal and neuropsychiatric and main drug classes involved NSAIDs, analgesics, and benzodiazepines. Phytotherapy–homeopathy accounted for 9.1% of drugs.     

A comprehensive 4‐year survey of adverse drug reactions using a network‐based hospital system

What is known and Objective: Spontaneous Adverse Drug Reaction Reporting Systems (ADRRS) provide early warnings or ‘signals’ for adverse drug reactions (ADRs). Our aim was to survey reports of ADRs made through our teaching‐hospital‐based pharmacovigilance system to identify the drugs most commonly associated with allergies and the types of immunological reactions reported. Methods: Adverse drug reactions records were retrieved from our network‐based electronic notification system. Results and Discussion: Four hundred and seventy four reports of adverse drug effects were studied. 37·3% of the reactions were immune‐mediated drug hypersensitivity reactions. True drug hypersensitivity reactions involving IgE‐mediated drug allergies accounted for 15% of all reactions. Of the drug hypersensitivity reactions, more than half (67%) were morbilliform skin eruptions, whereas cases of urticaria accounted for 20%. Antibiotics (33% of cases) were the most commonly reported drug allergies, followed by non‐steroidal anti‐inflammatory drugs (13%) and anti‐epileptic agents (10%). What is new and Conclusions: A hospital‐based ADR reporting system can generate useful data. In our study, antibiotics accounted for the majority of drug allergies, particularly anaphylactic reactions. More cases of drug allergies were owing to cephalosporin allergies than penicillins. Anti‐epileptic agents caused most of the severe drug hypersensitivity syndromes.     

Can drugs induce or aggravate sleep apneas? A case–noncase study in VigiBase®, the WHO pharmacovigilance database

The potential favorizing role of drugs in sleep apnea syndrome (SAS) is unknown. This study investigates drugs associated with SAS in a pharmacovigilance database. SAS recorded as adverse drug reactions (ADRs) in VigiBase^®, the WHO pharmacovigilance database (more than 11 million reports), from 1978 to 2015 was selected. The risk of SAS reports was estimated using the case–noncase method, with cases being SAS and noncases all other recorded ADRs. During this 37‐year period, 3325 ADRs including the word SAS were registered (0.05% of the database). Mean age was 51.2 ± 16.9 years with 52% men. ADRs were ‘serious’ in around 82% of cases. The case–noncase study found an association between SAS and exposition with sodium oxybate, rofecoxib, quetiapine, and clozapine for individual drugs and coxibs, antipsychotics, benzodiazepines, and opium alkaloids for drug classes. The potential role of other drugs is discussed. This study suggests that SAS can be associated with some drugs (mainly psychotropics) that are able to reveal or aggravate such a disease. Physicians should take into account the role of drugs in the etiological appraisal and management of SAS.     

Drug interactions between antihypertensive drugs and non‐steroidal anti‐inflammatory agents: a descriptive study using the French Pharmacovigilance database

Drug–drug interactions (DDIs) between antihypertensive drugs and non‐steroidal anti‐inflammatory drugs (NSAIDs) can lead to adverse drug reactions (ADRs). Guidelines are available to help prescribers deal with these drug associations, but their implementation is not well evaluated. The aims of this study were to assess the prevalence of NSAIDs exposure in patients treated with antihypertensive drugs, using the French Pharmacovigilance database, and explore the ADRs related to DDIs between antihypertensive drugs and NSAIDs. Over the 11, 442 notifications of ADRs recorded in this database in patients treated with oral antihypertensive drugs between 2008 and 2010, 517 (4.5 and 95% CI: 4.1–4.9) also included exposure to NSAIDs. These subjects were more frequently women, took more drugs in general, and were younger and less frequently treated with antiplatelet drugs. In 24.2% of them (125 patients), a DDI between NSAIDs and antihypertensive drugs was potentially the cause of the reported ADR. Acute renal failure caused by DDIs between NSAIDs and angiotensin‐converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or diuretics was the most frequently reported ADR (20.7%). Finally, in the French Pharmacovigilance database, around one‐fourth of associations NSAIDs  +  antihypertensive drugs are associated with a ‘serious’ ADR (mainly acute renal failure), suggesting that this well‐known DDI is not enough taken into account by prescribers.     

Overview of adverse reactions to nefopam: an analysis of the French Pharmacovigilance database

Nefopam is widely used for the relief of moderate acute pain. Its safety profile remains to be specified. The objective of the study was to review adverse reactions to nefopam spontaneously reported to the French Pharmacovigilance system. All cases of adverse drug reactions (ADRs) associated with nefopam, registered in the French Pharmacovigilance database from January 1, 1995 to December 31, 2004, were reviewed. For each reported ADR, information about patient (age, gender, medical history), drug exposure (suspected and concomitantly used drugs), characteristics of ADRs (imputability score, time of onset, seriousness, outcome) were collected. A total of 114 ADRs with an imputability rated from 'plausible' (I2) to 'likely' (I3) and 'very likely' (I4) was analysed. The most frequent ADRs included 'expected' ADRs such as sweating, nausea, tachycardia, malaise or vomiting; 61 ADRs were 'unexpected. No overdose was reported; 26 ADRs (23%) were considered as 'serious'. Most of them were 'unexpected', including neuropsychiatric (hallucinations, convulsions) or cutaneous (pruritus, erythema, urticaria) ADRs. Six cases of anaphylactic ADRs (two angioedema and four anaphylactic shocks) were reported, all occurring shortly after use of nefopam during the post-operative period. Physicians should be aware of the possible occurrence of some serious ADRs when using nefopam such as convulsions and anaphylactic shocks, especially when the drug is used in special medical conditions, like post-operative periods.     

Idiosyncratic reactions to antidepressants: a review of the possible mechanisms and predisposing factors.

Antidepressants, a widely used group of drugs, are associated with a range of idiosyncratic reactions affecting in particular the liver, skin and both the hematological and central nervous systems. These reactions seem to be mediated by chemically reactive metabolites formed by the cytochrome P450 enzyme system, the toxicity occurring either directly or indirectly via an immune mechanism. Individual susceptibility is determined by factors, both genetic and environmental, which result in inadequate detoxication of the chemically reactive metabolite. Prevention of such reactions will depend on either the development of new compounds which are not converted to toxic metabolites or by prediction of individual susceptibility prior to drug administration.     

Adverse drug reactions causing admission to a paediatric hospital: a pilot study

What is known and Objective: It is known that adverse drug reactions (ADRs) cause admission to hospital in adults and children. A recent adult study showed that ADRs are an important and frequent cause of hospital admission. The objective of this study is to develop methodology to ascertain the current burden of ADRs through a prospective analysis of all unplanned admissions to a paediatric hospital. Methods: Prospective observational study over a 2‐week period. Results and Discussion: There were 19 admissions to the main hospital wards related to an ADR, giving an estimated incidence of 4%, with the ADR directly leading to the admission in 71% of cases. There were no deaths attributable to ADR. 33% of the reactions were possibly avoidable. The drugs most commonly implicated in causing admissions were anti‐neoplastic agents. The most common reactions were neutropenia, vomiting and diarrhoea. The health burden of ADRs in the paediatric population is likely to be significant. This pilot study will be used to inform a much larger prospective study providing more detailed evidence of the burden of ill‐health from ADRs in children. This larger study will add to a body of research aiming to identify drug‐related problems within children to aid paediatric pharmacovigilance. What is new and Conclusion: This study provides knowledge regarding the methodology to be used for a larger study investigating ADRs in children. The study will allow authors who wish to replicate the study in their own populations (internationally) to avoid some of the pitfalls in planning a large epidemiological study of paediatric ADRs. The study also provides an estimate of the incidence and problem of admissions caused by ADRs in a UK paediatric population.     

Mania associated with ranitidine: a case report and review of literature

H2 receptor antagonists can be associated with central adverse drug reactions (ADRs), like confusion, delirium, hallucinations, slurred speech or headaches. We report here a ‘serious’ case of severe mania leading to hospitalization in a 42‐year‐old alcohol‐dependent man, 4 days after ranitidine introduction. Review of literature showed that this ‘very rare’ ADR occurs mainly in patients with predisposing factors: age, decrease in renal and/or hepatic function, polymedication, alcohol. Knowledge of this ADR can be particularly important for these drugs widely used as self‐medication.     

Multiple drug exposure as a risk factor for the seriousness of adverse drug reactions

macedo a.f., alves c., craveiro n. & marques f.b. (2011) Journal of Nursing Management  19, 395–399
Multiple drug exposure as a risk factor for the seriousness of adverse drug reactions Aim The aim of the present study was to validate the hypothesis that multiple drug exposure is an independent risk factor for serious adverse drug reactions (ADRs). Background Adverse drug reactions (ADRs) are an important cause of iatrogenic disease, the majority being preventable. Multiple drug exposure, ageing and female gender have been identified as important risk factors for an increased incidence of ADRs. Method ADR reports received by the central Portugal Regional Pharmacovigilance Unit, between January 2001 and December 2009, were studied. Results Nearly half (47.4%) of ADRs reports were considered serious, from which 66.7% reported multiple drug exposure (mean 3.07 ± 2.2; maximum 13). After adjusting for gender, simultaneous exposure to three or more drugs was significantly associated with an increased risk of serious ADRs [odds ratio (OR) 1.23; 95% confidence interval (CI) 1.02–1.51]. Conclusions The present results support that multiple drug exposure is an independent risk factor for serious ADRs. Such findings are of importance in both medicines benefit/risk ratio evaluations and patient safety monitoring. Implications for nursing management A new level of nursing involvement is needed in both the detection of ADRs and prevention of serious outcomes, particularly in high-risk patients.     

小汤山医院680例SARS患者药品不良反应分析

目的 研究小汤山医院SARS患者用药过程中药品不良反应的发生情况.方法通过制定和下发合理用药手册,成立临时药品不良反应监测小组等方式指导合理用药,跟踪随访并实时收集所有不良反应报告.采用WHO不良反应分级、分类标准,参考解放军总医院医院信息系统(Hospital Information System,HIS)的原始数据,回顾性系统分析不良反应的发生情况及规律.结果小汤山医院680例SARS患者中,共发生药品不良反应193例(251例次,男性87例,女性106例),发生率28.38%.女性和老年SARS患者的不良反应发生率高于男性和青年患者;重症和原有糖尿病的SARS患者更易发生不良反应;大剂量和合并用药更易引起药品不良反应;激素类药物是本次SARS治疗中引起药品不良反应的主要因素;而且注射剂比各种口服制剂引起的不良反应发生率更高.本次发生的各种药品不良反应主要集中在血液系统异常、胃肠系统异常和内分泌异常.结论 SARS药物治疗涉及品种多、剂量大,不良反应的发生率较高,SARS治疗需慎重使用激素类药物.     

High risk of cross-reactivity between vancomycin and sequential teicoplanin therapy

What is known and Objective: Teicoplanin and vancomycin show similar clinical and bacteriological efficacy in clinical trials. Teicoplanin has been reported to have a lower adverse drug reaction (ADR) rate than vancomycin. Cross‐reactivity between these two glycopeptides is controversial. Our aim was to study the cross‐reactivity between teicoplanin and vancomycin through an assessment of all the reported ADRs of these drugs in our University hospital. Methods: Over a period of 2 years, 170 cases of vancomycin therapy, which were closely monitored by doctors and clinical pharmacists, were used to analyse ADRs. Teicoplanin therapy was used as an alternative in cases of vancomycin intolerance. When an ADR related to vancomycin or teicoplanin was suspected, specialists were consulted to confirm if these were true ADR and to determine whether the implicated drug should be stopped. All ADRs for the two glycopeptides were assessed for causality using the Naranjo probability scale. Results and Discussion: Thirty‐eight of 170 patients (22·4%) treated with vancomycin developed ADRs. Twenty‐four patients were switched to teicoplanin. However, 14 of those 24 patients (58·3%) developed ADRs. The time of onset of ADRs involving vancomycin was 12·7 ± 10·9 days (range, 1–46 days). The time of onset of sequential teicoplanin‐induced ADRs was 11·7 ± 4·7 days (range, 2–20 days). Of the 14 patients with ADRs related to sequential teicoplanin therapy, six showed cross‐reactivity between vancomycin and teicoplanin. The incidence of vancomycin‐induced neutropenia was 4·7% (8/170), whereas the incidence of teicoplanin‐induced neutropenia subsequent to vancomycin intolerance was as high as 33·3% (8/24). Furthermore, 71·4% (10/14) of the teicoplanin‐induced ADRs were associated with haematological abnormalities such as neutropenia, thrombocytopenia or leucopenia. What is new and Conclusion: Teicoplanin, used as an alternative in cases of vancomycin intolerance, was associated with a high incidence of ADRs and haematological reactions, most notably neutropenia. This high rate of ADRs suggests cross‐reactivity between the two glycopeptides.     

Safety profile of etifoxine: A French pharmacovigilance survey

Etifoxine chlorhydrate is a benzoxazine derivative approved for the treatment of psychosomatic manifestations of anxiety since 1979. Previously labeled adverse drug reactions (ADRs) only include drowsiness, benign cutaneous reactions, and acute hypersensitivity reactions. The objectives were to examine recent data on etifoxine‐related ADR by reviewing Individual Case Safety Reports (ICSRs) recorded in France especially unexpected ADRs. Etifoxine‐related ICSRs were extracted from the French Pharmacovigilance database from 1 January 2000 to 30 April 2012 and data from the marketing authorization holder up to 31 December 2011 were also obtained. Of the 350 cases retained for analysis, 123 (35%) were considered serious. Dermatological or acute hypersensitivity reactions were the most frequent ADRs (59%) mainly isolated cutaneous eruptions. However, there were 24 cases of severe toxidermia (DRESS in 5, erythema multiforme in 10 and Stevens–Johnson syndrome in 5) with etifoxine as the most suspected drug in 11 patients, and seven cases of vasculitis or serum sickness‐like reaction. Liver disorders were reported in 34 patients of whom 25 developed acute hepatitis with a cytolytic biological pattern in 16. Other unexpected ADRs included 16 reversible cases of metrorrhagia with positive rechallenge in 5, and three cases of biopsy‐proven microscopic colitis of which one recurred after etifoxine re‐administration. Although etifoxine has been marketed for more than 30 years, this survey identified a number of unexpected and sometimes serious ADRs, in particularly severe toxidermia and acute cytolytic hepatitis. A recent update of the French etifoxine summary of the product characteristics (SPC) was based on these findings.     

Drug-induced hypothyroidism: the thyroid as a target organ in hypersensitivity reactions to anticonvulsants and sulfonamides.

Inherited defects in detoxification of reactive metabolites of drugs predispose patients to "hypersensitivity" reactions. Covalent interaction of metabolites with cell macromolecules leads to cytotoxic and immunologic outcomes, manifested clinically by multisystem syndromes with variable organ involvement. Hypothyroidism developed in 5 of 202 patients (age range, 1 to 81 years) we investigated for hypersensitivity reactions to anticonvulsants or sulfonamides shortly after their reaction. None had previous personal or family histories of autoimmune disease. All had low thyroxine levels, elevated levels of thyroid stimulating hormone, and autoantibodies including antimicrosomal antibodies. Patients were 2 to 18 years of age at presentation, and two were male. All returned to a euthyroid state within a year of presentation, and all remain well. The demographics, clinical presentation, and course of the patients is atypical of idiopathic lymphocytic thyroiditis. We investigated the pathogenesis of thyroid toxicity using the hydroxylamine metabolite of sulfamethoxazole as a model. The hydroxyalmine was toxic to thyroid cells in vitro, which did or did not express thyroid peroxidase activity, whereas the parent sulfonamide was toxic only to cells with active thyroid peroxidase. The purified enzyme converted sulfamethoxazole to the hydroxylamine. Formation of reactive drug metabolites by thyroid peroxidase in a host who is genetically unable to detoxify the metabolites may lead directly to cytotoxicity. Covalent binding to macromolecules, including thyroid peroxidase, also may lead to expression of neoantigens and formation of autoantibodies. Patients who have sustained hypersensitivity reactions to drugs should be investigated for possible involvement of the thyroid.     

Gender differences in adverse drug reactions: analysis of spontaneous reports to a Regional Pharmacovigilance Centre in France

The aim of this study was to investigate putative gender-related differences in adverse drug reactions (ADRs). Data were ADRs recorded in the database of the French Midi-Pyrénées Pharmacovigilance Centre in 1998. A total of 927 ADRs were spontaneously reported to the Centre in 1998, of which 53.1% were in females (difference vs. males not statistically significant). There was no statistically significant difference in the incidence of reported ADRs in males (3.6/10,000 inhabitants) vs. females (3.9/10,000 inhabitants) for the total population of the Midi-Pyrénées area. The number of reported ADRs was similar across different age groups (10-year age ranges). However, 'serious' ADRs were more frequently reported in males in the 0-9 and 60-69 age groups (and in females between 20 and 29 years old). There were significantly more neuropsychiatric (69 vs. 43, P = 0.05) and fewer cardiovascular (8 vs. 2, P = 0.05) ADRs reported in females than in males. ADRs were more frequently reported in females for some classes of drugs (such as genito-urinary, sex hormone, antineoplastic, antiparasitic and respiratory drugs). These results confirm that female gender is a risk factor for the development of ADRs.     

Adverse drug reactions: part II

Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must be effectively practiced by all health care providers in order to avoid ADRs.     

特非那定不良反应的回顾性分析

目的：分析特非那定所致不良反应的临床特征、相关因素,为临床药物治疗中药品不良反应的防治提供参考依据。方法：检索1986～2008年国内文献源特非那定的不良反应资料,并加以分析研究。结果：34例不良反应报告中女性明显多于男性;不良反应以心血管系统损害最多（23例,占67.66%）,其次为皮肤及附件损害（5例,14.70%）;不良反应预后较好。结论：患者的性别、体质、合并用药等因素能影响不良反应的发生,对于引起心律失常不良反应临床应提高警惕,减少不良反应的发生。     

Perception of risk of adverse drug reactions: a 3‐year follow‐up of a cohort of medical students

Previous studies have pointed out the question of effective training and information to health professionals on pharmacovigilance. The lack of training is known to induce inadequate use of drugs and noncompliance of patients. Pharmacology teaching is performed in the third year of medical studies at the Toulouse Faculty of Medicine. The aim of the study was to investigate the perception of risk of adverse drug reactions (ADRs) by medical students at the end of the one year pharmacology course and two years later, after clinical training period. Sixty‐seven students were interviewed in May 2005 and in October 2007. Visual analogue scales were used to define a score of perceived risk of ADRs associated with each drug class (ranking from 0 to 10) before and after pharmacology training. The drug classes evaluated were antibiotics, anticoagulants, antidepressants, aspirin, contraceptive pill, corticosteroids, drugs for arterial hypertension, drugs for diabetes (other than insulin), hypnotics, hypocholesterolaemic drugs, nonsteroidal anti‐inflammatory drugs (NSAIDs), postmenopausal hormone replacement therapy and tranquilisers. After pharmacology courses (May 2005), antidepressants were ranked as the most dangerous drugs by medical students [median score (25th–75th centiles): 7.7 (6.3–8.6)], followed by anticoagulants [7.6 (6.6–8.4)] and hypnotics [7.4 (6.1–8.1)]. Contraceptive pills was listed in the last position [median score [4.7 (2.2–6.7)]. Two years later (October 2007), anticoagulants moved into the first position [8.3 (7.3–9.2)], followed by NSAIDs [6.9 (5.0–8.4)] and aspirin [6.8 (5.8–8.4)]. Contraceptive pills remained in the last position. No change was observed for NSAIDs and aspirin, still ranked as dangerous drugs by medical students after clinical training. Values of perceived risk were significantly increased for anticoagulant (+9.2%, P < 0.01) and hypoglycemiant drugs (+27.7%, P < 0.0001). The perceived risk significantly decreased for hypocholesterolaemic (?14.3%, P < 0.0001) and antidepressant drugs (?19.5%, P < 0.0001), but not for hypnotics. The study shows that the perception of risk of ADRs by medical students was modified after clinical training. They were still aware of potentially serious ADRs associated with anticoagulants, aspirin or NSAIDs, but they remained less cautious for drugs such as antidepressants. Additional pharmacology training at the end of medical studies will be useful.     

氟喹诺酮类抗菌药物不良反应分析

目的 分析我院临床使用的12种氟喹诺酮类抗菌药物(FQNS)的不良反应,为临床用药提供信息.方法 搜集2007年3月至2011年3月门、急诊及住院部使用12种FQNS(诺氟沙星、氧氟沙星、左氧氟沙星、环丙沙星、洛美沙星、培氟沙星、氟罗沙星、莫昔沙星、加替沙星、芦氟沙星、司帕沙星、伊诺沙星)患者的病历资料,分析不良反应.结果 本组192例中男性患者113例(58.9%),高于女性患者79例(41.1%),31～40岁年龄段ADR发生率最高(35.4%),差异有统计学意义(P＜0.05);共涉及12种FQNs,不良反应主要表现在神经、循环、皮肤、泌尿、消化、呼吸、血液等,其中以神经、循环、皮肤系统症状较多也较突出;引起ADR的主要给药途径为静脉给药,共137例(71.4%).结论 FQNS的不良反应在临床使用中应该引起高度重视.