Fluoroquinolone-associated anaphylaxis in spontaneous adverse drug reaction reports in Germany: differences in reporting rates between individual fluoroquinolones and occurrence after first-ever use.

BACKGROUND: The frequency of fluoroquinolone-associated anaphylaxis has been estimated to be 1.8-23 per 10 million days of treatment based on spontaneous reports. It is unknown whether there are differences between the reporting rates of anaphylaxis with individual fluoroquinolones. According to pathophysiology, anaphylaxis may be immune mediated (anaphylactic) or not (anaphylactoid). The latter may occur after first-ever intake since no sensitisation phase is necessary. OBJECTIVE: To analyse spontaneous reports of fluoroquinolone-associated anaphylaxis contained in the spontaneous adverse drug reaction database of the Federal Institute for Drugs and Medical Devices in Germany with regard to differences in reporting rates between various fluoroquinolones, the previous intake and the time to onset of the reaction. METHODS: All fluoroquinolone-associated cases of anaphylaxis, anaphylactic shock, and anaphylactic/anaphylactoid reaction spontaneously reported to the Federal Institute for Drugs and Medical Devices between 1 January 1993 and 31 December 2004 were identified and assessed with regard to the correctness of the diagnosis of anaphylaxis, the causal relationship with the drug, the previous intake of fluoroquinolones and the time to onset of the reaction. RESULTS: In 166 of 204 cases identified, the diagnosis of anaphylaxis and a causal relationship with the drug were considered at least possible. Moxifloxacin, levofloxacin, ciprofloxacin and ofloxacin accounted for 90 (54%), 25 (15%), 21 (13%) and 16 (10%) of the 166 cases, respectively. The corresponding reporting rates per 1 million defined daily doses based on crude estimates of exposure were 3.3, 0.6, 0.2 and 0.2 for moxifloxacin, levofloxacin, ciprofloxacin and ofloxacin, respectively. The occurrence of anaphylaxis after the first dose or within the first three days was reported in 71 of 166 (43%) cases, but no information on prior exposure with this or any other fluoroquinolone was provided with these reports. In 21 of 166 (13%) cases, the reaction occurred within the first 3 days and it was stated that the particular fluoroquinolone had never been taken before. CONCLUSIONS: Anaphylaxis appears to be associated with the fluoroquinolone class of antibacterials. Observed differences in reporting rates should be further investigated. Fluoroquinolone-associated anaphylaxis may occur after first-ever intake of the agent.     

Drug-induced anaphylaxis : case/non-case study based on an italian pharmacovigilance database.

OBJECTIVE: To identify the number of cases of anaphylaxis reported in association with different classes of drugs and compare it with other reports contained in the same database. METHODS: The data were obtained from a database containing all of the spontaneous reports of adverse drug reactions (ADRs) coming from the Italian regions of Emilia Romagna, Lombardy and the Veneto, which are the main contributors to the Italian spontaneous surveillance system. The ADRs reported between January 1990 and December 2003 with a causality assessment of certainly, probably or possibly drug related (according to the WHO criteria) were analysed using a case/non-case design. The cases were defined as the reactions already coded by the WHO preferred terms of 'anaphylactic shock' or 'anaphylactoid reaction' (this last term also included anaphylactic reaction) and those with a time of event onset that suggested an allergic reaction and involved at least two of the skin, respiratory, gastrointestinal, CNS or cardiovascular systems; the non-cases were all of the other ADR reports. The frequency of the association between anaphylaxis and the suspected drug in comparison with the frequency of anaphylaxis associated to all of the other drugs was calculated using the ADR reporting odds ratio (ROR) as a measure of disproportionality. RESULTS: Our database contained 744 cases (including 307 cases of anaphylactic shock with 10 deaths) and 27 512 non-cases. The percentage of anaphylaxis cases reported in inpatients was higher than that among outpatients (59.1% vs 40.9%). This distribution is significantly different from that of the other ADR reports that mainly refer to outpatients. After intravenous drug administrations, anaphylactic shock cases were more frequent than anaphylactoid reactions or other ADRs, but more than one-third of these reactions were caused by an oral drug. Blood substitutes and radiology contrast agents had the highest RORs. Among the systemic antibacterial agents, anaphylaxis was disproportionally reported more often for penicillins, quinolones, cephalosporins and glycopeptides, but diclofenac was the only NSAID with a significant ROR. As a category, vaccines had a significantly lower ROR, thus indicating that anaphylaxis is reported proportionally less than other ADRs. CONCLUSIONS: Anaphylaxis is a severe ADR that may also occur with commonly used drugs. It represents 2.7% of all of the ADRs reported in an Italian spontaneous reporting database.     

51例药源性过敏性休克药师分析

目的：了解我院药源性过敏性休克发生的情况和特点,分析药源性过敏性休克发生的可能因素,为医院安全、合理用药提供参考信息。方法：对我院51例过敏性休克不良反应报告以及过敏性休克住院患者病历进行回顾性统计和分析。结果：发生过敏性休克患者年龄、性别没有显著差异;涉及药物以抗菌药物为主,其中又以β-内酰胺类和氟喹诺酮类为主;涉及静脉、肌内、口服和外用四种给药方式,以静脉给药为主;患者临床表现都以血压的变化合并皮肤及其黏膜系统、呼吸系统、神经系统、心血管系统、消化系统的表现为主。结论：加强药源性过敏性休克的报告与监测工作,及时分析相关信息可以提高医院安全用药风险能力,提高医院药物警戒工作水平。     

Drug-induced anaphylaxis: a decade review of reporting to the Portuguese Pharmacovigilance Authority

Purpose

Anaphylaxis is a potentially fatal systemic adverse drug reaction (ADR). It is an unpredictable and mostly dose-independent event that occurs suddenly following exposure to the causative drug. Our objective was to characterize a case series of anaphylactic reactions reported to the Portuguese Pharmacovigilance authority during the past decade. Patients’ demographic data and implicated drugs were analyzed as well as the severity of the ADR and time trends.

Methods

This study was a retrospective analysis of episodes of anaphylaxis, defined according to the Second Symposium on the Definition and Management of Anaphylaxis Criteria, reported to the Portuguese Pharmacovigilance System between 1 January 2000 and 1 November 2010

Results

Amongst the 16,157 ADR reported to the Portuguese Pharmacovigilance System during the 10-year study period, we found 918 (6 %) cases of anaphylaxis that met the proposed criteria. The age of the patients varied from 7 days to 91 years, with 87 cases (9 %) of anaphylaxis involving patients under 18 years of age. There was an overall female predominance (67 %), but the majority of pediatric patients were male (56 %). There was a trend toward increased reporting as the decade progressed, and 31 % (284) of all anaphylaxis cases were reported during the last 2 years of the study period. Of the anaphylaxis episodes reported, 19 % led to hospitalization and 24 (3 %) had a fatal outcome. Antibiotics were responsible for most cases (17 %) followed by nonsteroidal anti-inflammatory drugs/acetaminophen (13 %), antineoplastic/cytotoxic drugs and immune-modulators. Vaccines and radiographic contrast media were also important contributors to an anaphylactic event.

Conclusions

In this series of drug-related anaphylaxis, we found that most of the reported episodes were associated with widely used drugs, such as antibiotics and analgesics. Anaphylaxis can occur at any age. The female gender was more highly represented, with the exception of pediatric patients.     

多西他赛和紫杉醇致严重不良反应对比分析

目的：分析多西他赛和紫杉醇致严重不良反应的特点,为临床安全用药提供参考。方法收集2004年1月至2013年1月我省药品不良反应监测中心收到的多西他赛和紫杉醇引起的严重不良反应报告,比较2种药物所致严重不良反应临床表现及转归。结果共收集多西他赛和紫杉醇严重不良反应报告31份,涉及患者31例,不良反应33例次。31例患者中男性9例,女性22例;年龄31～76岁,平均年龄53岁。紫杉醇引起的严重不良反应17例次,主要临床表现为过敏性休克（70.59%）、过敏样反应（11.76%）、白细胞减少（11.76%）、骨髓抑制（5.88%）;多西他赛引起的严重不良反应16例次,主要临床表现为过敏样反应（31.25%）、骨髓抑制（18.75%）、白细胞减少（18.75%）、腹泻（6.25%）、过敏性休克（6.25%）、胃肠道出血（6.25%）、背痛（6.25%）、胸闷（6.25%）。停药及对症治疗后均好转或痊愈。结论多西他赛与紫衫醇致严重不良反应临床表现有所不同,与多西他赛相比,紫衫醇过敏性休克所占比例较高,使用时更应加强用药指导和监测。     

Cutaneous reactions to drugs. An analysis of spontaneous reports in four Italian regions

AIMS: Cutaneous manifestations are frequently reported in association with drug use. The aim of this study was to analyse the skin reactions reported to the spontaneous surveillance systems of four Italian regions (Friuli Venezia Giulia, Lombardy, Sicily and the Veneto), and correlate the reports with estimated drug consumption during the same period, paying particular attention to the reactions to antimicrobial agents and nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: All of the adverse drug reactions (ADRs) reported spontaneously between January 1996 and December 1997 to the surveillance systems of four Italian regions (a total population of about 20 million people) were analysed by a panel of experts including dermatologists. On the basis of the Critical Term List of the World Health Organization (WHO), the reactions were classified as either serious or nonserious events. Drug consumption was expressed as a daily defined dose (DDD)/1000 inhabitants/day. RESULTS: A total of 2224 adverse skin reaction reports (44.7% of all of the reported ADRs) were identified, making a reporting rate of about 5.5 per 100 000 inhabitants/year. The female/male ratio was 1.58, and the reporting rate progressively increased with age. The drug categories with the highest number of cutaneous reactions were antimicrobials, followed by NSAIDs, analgesics and radiology contrast media. There was a total of 372 (16.9%) serious reaction reports, the most frequent being angioedema (171 cases), erythema multiforme (68 cases) and photosensitivity (37 cases). Co-trimoxazole, followed by the cephalosporins and fluoroquinolones, were associated with the highest consumption-related reporting rate among the antimicrobials, and aspirin and dipyrone among the NSAIDs and analgesics. CONCLUSIONS: Spontaneous reports from four Italian regions revealed that the skin was the organ most frequently affected by ADRs. The paper shows the validity of a regional decentralized system in Italy.     

Glafenine-associated anaphylaxis as a cause of hospital admission in the Netherlands

Summary In 1981 generalized anaphylaxis was registered on 166 occasions in Dutch general and academic hospitals. Clinical details of 120 of those patients revealed that in 107 anaphylaxis was either probable (n=90) or possible (n=17), whereas in 13 cases some other reaction than anaphylaxis had occurred. The series of confirmed cases contained 46 men and 61 women, with mean ages of 47 y and 48 y, respectively.There was a complete recovery in 102 patients and two patients died. Hypotension was present in 79 cases (74%), dyspnoea in 34 cases (32%) and a skin reaction, mainly urticaria, erythema or angioedema, was mentioned in 62 cases (58%). Most cases of anaphylaxis were drug-induced (76%), the main causes being the analgesic glafenine and contrast media. Glafenine was mentioned as the cause in 36% of all admissions for drug-induced anaphylaxis. Only 3.7% of cases had been reported to the voluntary reporting scheme of the Netherlands Centre for Monitoring of Adverse Reactions to Drugs.On the basis of reimbursement data, the risk of developing severe anaphylaxis to glafenine was estimated at 11.7–19.3-fold relative to indomethacin, and 13.4–20.2-fold relative to oral penicillins.     

Fatal cases of gabexate mesilate-induced anaphylaxis

Gabexate mesilate, ethyl-4-(6-guanidinohexanoyloxy) benzoate monomethanesulfonate (C16H23N3 O4CH4O3S: M.W. 417.48), is a synthetic protease inhibitor and was introduced for clinical use in 1978. It rarely induces anaphylaxis, and patients with gabexate mesilate-induced shock had been reported to survive with appropriate treatments including respiratory support. However, there were increasing reports on fatal cases in recent years: 6 cases have been reported to develop fatal anaphylaxis following dripping infusions of gabexate mesilate. All the fatal cases rapidly developed anaphylaxis (within 5 minutes), whereas 7 out of 11 in recovered cases developed it 5 or more minutes after the injection. Venous access should be kept for at least 30 minutes to prepare for and to treat this fatal reaction in patients receiving gabexate mesilate repeatedly.     

引起过敏性休克死亡的药物及防治

目的：探讨药源性过敏性休克死亡的发生原因、规律、特点,避免或减少药源性过敏性休克死亡的发生。方法：收集与分析中国生物医学文献数据库及中国医院数字图书馆期刊全文库（1994-01～2009-08）药物所致过敏性休克死亡相关的医药期刊查找原文,对文献资料进行整理、汇总,并进行分析。结果：166例过敏性休克中≤10min有82例,≤30min有37例,共119例,占总数的71.69%。患者使用引起过敏性休克死亡的药物,发生例数按药物种类排序前4位为：抗菌药物97例（占58.43%）、循环系统用药17例（占10.24%）、神经系统用药10例（占6.02%）、疫苗类7例（占4.22%）。发生例数按药品排序前3位的是：青霉素类35例、头孢菌素类20例、低分子右旋糖酐10例。结论：严格用药指征,用药前详细询问过敏史,特别是老年患者更应注意其基础疾病,密切观察用药后反应,确保用药安全。     

Adverse reactions induced by NSAIDs and antibacterials: analysis of spontaneous reports from the Sicilian regional database.

OBJECTIVES: To (i) evaluate the suspected adverse drug reactions (ADRs) related to NSAIDs and antibacterials that were reported to Sicilian local health officers by healthcare professionals; and (ii) to detect new or serious potential signals of alarm related to these two widely used drug categories. METHODS: We selected all the spontaneous reports of ADRs sent between January 1998 and June 2004 and analysed those attributed to NSAIDs and systemic antibacterials, applying proportional reporting ratio (PRR) methodology. PRRs >2, chi(2) >4 and >3 ADRs were regarded as signals. RESULTS: During the period considered, 1585 reports of ADRs were received overall (42.6% serious), with an annual reporting rate of approximately 49.1 reports per million inhabitants on average; 351 referred to systemic antibacterials, and 179 to NSAIDs. There were 174 (49.6%) reports of serious ADRs associated with antimicrobials and 108 (60.3%) associated with NSAIDs. Disproportionality was observed, in particular for anaphylactic shock induced by ceftriaxone (all reports were associated with off-label use of the drug), photosensitivity reaction induced by lomefloxacin (administered in the summer), hepatitis induced by nimesulide (three cases leading to liver transplantation) and vasculitis induced by nimesulide. CONCLUSION: Our analysis highlighted several signals of alarm deserving further investigation or measures to influence prescribing. This study underlines the value of a regional centre in identifying local factors (such as prescribing patterns) that may increase the prevalence of serious ADRs.     

骨瓜提取物致过敏性休克36例文献分析

目的：探讨骨瓜提取物致过敏性休克的临床特点及发生规律,为临床合理用药提供参考。方法：以“骨瓜提取物”、“休克”、“过敏反应”为关键词进行检索,对文献中的有关数据进行统计与分析。结果：检索到骨瓜提取物致过敏性休克文献29篇,病例36例。骨瓜提取物在近两年引起过敏性休克25例,占69.4%,75.0%的过敏性休克发生在首次用药过程中,66.7%发生在用药开始后的10 min内。结论：骨瓜提取物注射剂导致过敏性休克发生时间短,病情危重,应引起临床高度重视。     

86例药源性过敏性休克不良反应分析

摘要：目的 分析药源性过敏性休克发生的一般规律及抢救措施,为临床用药合理提供参考。方法 对济南市药品不良反应监测中心2007-2008年收到的86例过敏性休克病例报告进行回顾性分析。结果 过敏性休克病例男性多于女性;大多数发生在用药后5分钟内;主要累及和损害循环、中枢神经、呼吸系统及全身。结论 临床应重视药源性过敏性休克的发生,注意用药全程的监护,一旦出现不良反应及时停药,并采取适当措施予以对症抢救治疗。     

1994年～2004年磷霉素致过敏性休克文献分析

目的:探讨磷霉素致过敏性休克的一般规律。方法:对1994年～2004年国内医药学术期刊报道的有关磷霉素致过敏性休克病例进行统计分析。结果:10年间国内公开报道的磷霉素致过敏性休克共36例,其中死亡3例。结论:磷霉素可致过敏性休克,应引起临床高度重视。     

1230例药物致过敏性休克不良反应报告分析

目的:探讨药物致过敏性休克不良反应的发生规律和特点,为临床防范严重药品不良反应提供参考。方法:采用回顾性分析方法,收集军队不良反应监测中心2009–2019年过敏性休克不良反应报告1230例,对患者性别、年龄、药品种类、给药途径、关联性评价及转归等进行统计、分析。结果:抗感染药物、血液系统药、诊断用药、中药制剂、抗肿瘤药相关过敏性休克依次占比28.54%、14.63%、10.98%、9.76%、8.70%;静脉用药导致过敏性休克发生率最高,占90.57%;70.90%的过敏性休克发生在用药中或用药后的30 min内。结论:临床用药前应细询过敏史,严格用药指征,选择合适的给药途径;警惕抗感染药物、造影剂、中药制剂所致的过敏性休克;用药期间及后仔细观察,做好及时抢救准备。     

培门冬酶治疗恶性血液系统疾病的药物不良反应及处置措施研究

目的了解培门冬酶(PEG-Asp)2009年以来的药物不良反应(ADRs)发生情况及其处置措施,为临床安全用药提供依据。方法回顾分析72例PEG-Asp的ADRs报告,统计ADRs的发生特点及处置措施。对不同性别、年龄、给药途径的患者ADRs发生时间、发生类型以及涉及器官系统、临床表现、转归数据进行分析。结果在72例患者中,18岁以下患者最多(24例,33.33%);严重ADRs 17例(23.61%)。典型ADRs包括过敏性休克11例,发生于5 min^3 h内,30 min时最高发,给药途径均为肌内注射;胰腺炎(7例,9.72%)发生于3~19 d;深静脉血栓(6例,8.33%)发生于2~23 d。对PEG-Asp的ADRs进行分析提示,静脉滴注比肌内注射更少报道引起不良事件常用术语标准(CTCAE)≥3级的过敏反应,儿童的ADRs上报比例较高。处置中经过对症治疗或停药后,大部分不良事件结局为好转或痊愈。结论从本ADRs发生时间来看,需要在用药后较长时间内对患者进行监测,静脉滴注引起严重过敏反应的报道更少。在给药前预处理方面,国内尚缺乏统一的标准,建立合理的预处理方法可以降低严重ADRs的发生。     

Comparison of reporting of Stevens-Johnson syndrome and toxic epidermal necrolysis in association with selective COX-2 inhibitors.

BACKGROUND: Stevens-Johnson syndrome and toxic epidermal necrolysis are closely related severe acute life-threatening, drug-induced skin disorders. The US FDA Adverse Events Reporting System (AERS) has received reports of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with the use of the recently introduced selective cyclo-oxygenase (COX)-2 inhibitor NSAIDs, two of which are also sulfonamides. OBJECTIVE: The objective of this study is to review cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported to the FDA associated with the use of the selective COX-2 inhibitor NSAIDs celecoxib, rofecoxib and valdecoxib, and to compare reporting rates of the two conditions associated with these drugs to each other, meloxicam (an oxicam NSAID that came on the US market at a similar time) and the background incidence rate. METHODS: We reviewed all US cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported to the FDA AERS database associated with the use of celecoxib, rofecoxib, valdecoxib and meloxicam since these agents were first marketed. We utilised AERS and drug use data to calculate reporting rates for each drug after the first 2 years of marketing. We obtained the background rate from the medical literature. RESULTS: Up to the end of March 2004, there were 63 cases of Stevens-Johnson syndrome/toxic epidermal necrolysis reported with valdecoxib use, 43 with celecoxib, 17 with rofecoxib (the non-sulfonamide coxib) and none for meloxicam. In the first 2 years of marketing the reporting rate for Stevens-Johnson syndrome/toxic epidermal necrolysis with valdecoxib was 49 cases per million person-years of use, 6 cases per million person-years for celecoxib and 3 cases per million person-years for rofecoxib. The reporting rates for the sulfonamide coxibs were substantially higher than the background rate of 1.9 cases per million population per year, with the valdecoxib rate being 8-9 times that of celecoxib and approximately 25 times that of the background rate. CONCLUSION: There is a strong association between Stevens-Johnson syndrome/toxic epidermal necrolysis and the use of the sulfonamide COX-2 inhibitors, particularly valdecoxib. Physicians should be aware of the possibility of this serious life-threatening event when prescribing these drugs and advise patients to discontinue use at the earliest possible sign or symptom.     

阿莫西林不良反应国内文献回顾性分析

目的:分析国内文献资料中阿莫西林不良反应报告的情况,探索阿莫西林不良反应的发生规律和特点。方法:阿莫西林药物不良反应(ADR)病例通过检索中国生物医学文献数据库和中国医院知识仓库获得,对检索到的符合条件的阿莫西林ADR资料进行计量统计学分析。结果:共检索出175例阿莫西林ADR病例报告,ADR临床表现列前3位的分别是皮肤及其附件损害、全身性损害和泌尿系统损害,共占阿莫西林不良反应的80.58%。有3例过敏性休克病人死亡。结论:过敏反应是阿莫西林最常见的严重不良反应,加强病人药物过敏史、过敏性疾病史的询问和首剂用药的观察对于预防阿莫西林引发过敏反应、减少阿莫西林不良反应的发生具有重要意义。     

乙型脑炎疫苗致过敏性休克个案报道文献分析

目的：分析近10年来国内文献中，乙型脑炎（简称乙脑）有关接种疫苗致过敏性休克的个案报道，为减少乙脑计划免疫所出现的过敏性休克及相关处理提供参考。方法：采取适当检索策略，搜索中国学术期刊全文数据库（1994～2004年）中乙脑疫苗致过敏性休克的个案报道。分别从刊物、作者单位、乙脑疫苗生产厂家、患者年龄、性别、过敏史、接种次数、过敏性休克发生时间、治疗时间等多角度进行分析。结果：共获得文章34篇（36例）。1例为初种时发生，18例为复种时发生，17例接种次数不详。过敏性休克出现的平均时间为22．6min，最早1min，最晚60min。71．2％的过敏性休克伴随其他不良反应，以荨麻疹居多（57．1％）。36例中有5例死亡，其余均治愈，完全治愈所需时间最短为0．5h，最长为11d。结论：乙脑疫苗致过敏性休克的发生可能与免疫次数有关。在乙脑疫苗接种工作中，应该严格执行免疫程序，掌握过敏性休克的抢救知识，做好应对过敏性休克的准备。     

12例细辛脑注射液致儿童过敏性休克文献分析

目的探讨细辛脑注射液致儿童过敏性休克的临床特点及发生规律,为临床合理用药提供参考。方法检索国内有关数据库,对细辛脑注射液致儿童过敏性休克的病例报告进行统计分析。结果细辛脑注射液致儿童过敏性休克12例,给药途径均为静脉滴注,其中男性8例,女性4例,速发型过敏性休克10例,迟发型1例。经抗休克治疗,均恢复正常。结论细辛脑注射液致儿童过敏性休克病程快、危害大,临床医务人员应高度重视。     

Drug-related deaths: an analysis of the Italian spontaneous reporting database.

BACKGROUND: Adverse drug reactions (ADRs) represent a major public health concern, with death as the ultimate adverse drug outcome. Despite the relevance of this, the frequency of fatal ADRs (FADRs) is to a large extent unknown. Although spontaneous reporting data cannot give an exact estimate of the magnitude of drug-related mortality, it may highlight the importance and large dimensions of this public health problem. OBJECTIVE: To describe the types and pattern of reported FADRs by analysing data from the national spontaneous reporting system in Italy. METHODS: The Italian Medicines Agency (AIFA) runs a pharmacovigilance database where all the individual case safety reports (since January 2001) are stored. We selected and then analysed in detail all the case reports (to the end of December 2006) in which death was reported as the outcome. We included in the study only FADR case reports with a probable or possible causality assessment, according to the criteria established by the WHO. In line with the Italian reporting form, we divided FADR reports into two groups: (i) suspected ADRs that caused death; and (ii) suspected ADRs that contributed to death. RESULTS: In the AIFA database 38 507 suspected ADR case reports were collected, of which 641 (1.66%) had a fatal outcome. We analysed 450 case reports (1.17% of total reports), 159 (35.33%) of them causing the patient's death and 291 (64.67%) contributing to death. The annual percentage of FADR reports followed a constant trend during the 6-year period. The majority of fatal reports (79%) were sent by hospital doctors. In total, 222 different drugs were suspected as causes of FADRs. 'Systemic anti-infective drugs' was the drug category associated with the highest percentage of FADRs (21.9%), followed by antineoplastic and immunomodulating agents (18.8%), and then by nervous system drugs (14.8%). Other drug categories involved in the fatal case reports were antithrombotic agents, NSAIDs and contrast media. CONCLUSIONS: The drugs most frequently involved in FADRs were drugs of wide usage with a narrow therapeutic range or those that caused serious skin or systemic allergic reactions. Ceftriaxone, ticlopidine and nimesulide were associated with the highest number of fatal case reports; the related FADRs were already known and recognized for each of these drugs. We highlight some cases reflecting probable inappropriate drug use by Italian physicians. This suggests a need for continued clinical pharmacology training and that many FADRs might be preventable through better medical and prescribing practice.