QUININE-INDUCED CUTANEOUS VASCULITIS

We report a 60-year-old woman who developed severe cutaneous vasculitis three weeks after commencing quinine sulphate (300 mg at night) for nocturnal cramps. The patient died despite immunosuppressive treatment with prednisolone and cyclophosphamide. We review three previous cases and conclude that cutaneous vasculitis is a rare but life-threatening complication of treatment with this widely-prescribed drug. Quinine sulphate is prescribed frequently for nocturnal cramps, although its efficacy is unsupported by stringently controlled clinical trials. Adverse reactions to the drug are unusual. We describe a 60-year-old woman with fatal cutaneous vasculitis related to quinine treatment.     

Effectiveness of quinine in treating muscle cramps: a double-blind,placebo-controlled,parallel-group,multicentre trial

To determine the efficacy and safety of quinine in treating nocturnal muscle cramps we performed a double-blind, placebo-controlled, parallel-group, multicentre trial in 17 general practice centres in Germany. Ninety-eight patients aged 18-70 years with more than six muscle cramps in two weeks were enrolled. A two-week run-in period without treatment was followed by two weeks of treatment with 400 mg quinine or placebo per day and a wash-out period of two weeks without treatment. The primary outcome measure was the reduction in the number of muscle cramps between the run-in and treatment periods. The intensity of cramps, number of nights with cramps, sleep disturbance and intensity of pain were recorded as secondary outcome measures. At baseline the median number of cramps was 12 in two weeks in both groups. The median reduction between the run-in and therapy phases was eight (95% CI 7-10) versus six (95% CI 3-7) muscle cramps during quinine and placebo treatment; 36 (80%) participants in the quinine group and 26 (53%) in the placebo group had a reduction of at least 50% in the number of muscle cramps. Frequency, intensity and pain at night showed a statistically significant difference in favour of quinine. The improvement was more evident according to physician assessment than patient assessment; this is corroborated by the high placebo response rate. No significant differences were found between the two groups with respect to side-effects. Short term treatment with 400 mg quinine per day can effectively prevent nocturnal leg cramps in adults without relevant side-effects.     

Nurse reporting of adverse events caused by medicines

Even though all drugs are extensively tested before marketing, the need for continuous postmarketing surveillance is now greater than ever. In 2002, 16,176 adverse drug reaction reports were received, of which 67 per cent related to reactions categorised as 'serious'. Nurse reporting of adverse drug reactions has almost doubled in the past year since nurses were officially allowed to participate in the yellow-card scheme for identifying adverse drug reactions (NT Clinical news, 2 December, p7). Nurses, through their close contact with patients, are ideally placed to be a key source of information on adverse drug reactions in the UK's yellow-card scheme.     

2014年我院120例药品不良反应报告分析

目的:了解我院药品不良反应(ADR)发生的特点及ADR报告情况,促进临床合理用药。方法 :对我院2014年上报的120例药品不良反应报告进行回顾性统计分析。结果:120例ADR报告中,涉及药物共有70个品种,其中抗微生物药引起的ADR最多,约占44.4%;ADR以皮肤及其附件损害最为常见;静脉给药方式引发的ADR最多,约占81.7%。结论:应加强ADR的监测,重视安全合理用药,以避免和减少药品不良反应发生。     

Unity from diversity: the evidential use of anecdotal reports of adverse drug reactions and interactions

Anecdotal case reports contribute about one-third of the published literature on adverse drug reactions and interactions, but are regarded as providing poor-quality evidence. However, they can occasionally provide proof of cause and effect, and there are many other reasons for publishing them. Because an anecdote is a narrative, narratological paradigms from literature, art, and music can show how we can make evidential use of anecdotes. Useful paradigms are the dramatic unities (of time, place, and action), comprehensive catalogues, and pattern formations. Here I give examples of each of these types of paradigm and show how they can be used to interpret anecdotes about adverse drug reactions and interactions. The dramatic unities show how a proper classification of adverse drug reactions can be achieved, according to dose-relation, time-course, and susceptibility factors; use of this classification should improve the evidential use of anecdotal reports. A high background incidence of the effect (the medical equivalent of subplots, which violate the unity of action) makes it more difficult to detect adverse drug effects using anecdotal reports. To make best evidential use of the corpus of anecdotal reports of adverse drug reactions, comprehensiveness is important: each suspected adverse reaction should be reported in detail and reactions should be reported in sufficient numbers for proper classification and for patterns to be recognized. One form of pattern recognition, teleoanalysis of data, should, when possible, include not only randomized controlled trials and observational studies, but also case series and anecdotal reports.     

某三级甲等医院2012—2013年度568例药品不良反应报告分析

目的综合分析评价某三级甲等医院2012-2013年度药品不良反应（ADR）呈报的基本情况,掌握该院药品不良反应特点、规律和临床表现,为临床合理用药提供依据。方法将ADR报告表填写项目录入Microsoft Excel XP电子表格,根据统计药品ADR发生的患者年龄、ADR表现的分布情况等情况进行归纳分析。结果 568份报告中,其中ADR发生较高的分别是抗菌药物、抗肿瘤、中药注射剂,给药途径以静脉注射引起ADR最为常见,临床表现主要以皮肤及附件损害为主,占33.63%,其次是消化系统,占23.24%。结论临床应加强ADR监测力度,增强ADR呈报意识,提高合理用药水平,保障患者用药安全。     

Herbal remedies: drug-herb interactions

Controlled clinical studies are needed to clarify and determine the clinical importance of drug-herb interactions. However, it is unlikely that this information will be forthcoming except as anecdotal reports. Patients taking drugs with a narrow therapeutic index (cyclosporine, digoxin, hypoglycemic agents, lithium, phenytoin, procainamide, theophylline, tricyclic antidepressants, and warfarin) should be discouraged from using herbal products. All drugs with a narrow therapeutic index may either have increased adverse effects or be less effective when used in conjunction with herbal products. More research is required to define the interactions. When adverse reactions are experienced with drug therapy, patients must always be queried as to their intake of herbal products: what they are taking in pills and tincture form, what they are drinking as teas, and what they are eating from their garden.     

Is it quinine TTP/HUS or quinine TMA? ADAMTS13 levels and implications for therapy

Thrombocytopenia with or without microangiopathy following quinine is often referred to as quinine “hypersensitivity.” When schistocytes are present it is frequently termed “quinine‐associated TTP/HUS.” A severe deficiency of the vWF‐cleaving protease, ADAMTS13, is associated with idiopathic TTP. A previous study of patients with “quinine‐associated TTP/HUS” found that ADAMTS13 activities were not abnormal in 12/12 patients. A retrospective review of TTP patients with quinine‐associated thrombotic microangiopathy (TMA) for whom ADAMTS13 was measured before plasma exchange was performed. Six patients were identified. All were females (age range: 43 to 73, mean = 61.7 years) and had taken quinine for leg cramps. Four of the six experienced renal failure requiring dialysis. Five of the patients had D‐Dimers levels measured, all were elevated. In four patients the levels were ≥18 times the upper limit of normal. ADAMTS13 was normal in four patients and mildly decreased in two patients. We conclude that while thrombocytopenia and schistocytosis can be seen in quinine‐associated TTP/HUS, the pathophysiology seems to be distinct from that seen in most cases of idiopathic TTP (i.e., severely decreased ADAMTS13 with an inhibitor). We recommend that a TMA in association with quinine be consistently referred to as quinine‐associated thrombotic microangiopathy (quinine‐TMA) to better distinguish this entity from idiopathic TTP. The use of plasma exchange in quinine‐TMA is called into question. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

Postmarketing surveillance: accuracy of patient drug attribution judgments

Data from two samples of ambulatory patients participating in a postmarketing surveillance study, one receiving antibiotics and another receiving tricyclic antidepressant agents, are presented, indicating that patients appear to be capable of correctly discriminating probable adverse drug reactions from other adverse clinical events. However, attribution accuracy depended both on the surveillance method and on how reports of the adverse clinical events were obtained. Discrimination was better when patients were reporting adverse clinical events spontaneously than when the interviewer probed for recall in a systematic inquiry. Discrimination was also better when the adverse clinical events were obtained from a staff-initiated surveillance method than from a self-monitoring, patient-initiated telephone-reporting method--probably because the latter method generates an excessively strong tendency to report mainly those adverse clinical events suspected of being drug related.     

130例不良反应报告分析及合理用药建议

目的:对130例临床药物不良反应报告进行回顾性分析,得出我院不良反应发生的特点,并对合理用药进行建议,以减少我院不良反应发生率。方法:对130例不良反应从性别、年龄、给药途径、药物分类等方面进行统计分析。结果:我院不良反应特点是在老年人和儿童中发生率较高,分别为33.08%和16.15%;女性(66.15%)多于男性(33.85%);发生不良反应最高的药物种类依次为抗菌药物(38.46%)、中成药(37.69%)及营养药物(6.92%),发生率较高品种为阿奇霉素、头孢呋辛、血塞通、生脉、痰热清、热毒宁,且20岁以下抗菌药物不良反应发生率高(42.00%),育龄期妇女中成药不良反应发生率高(30.61%)。结论:在合理用药中,建议我院应重点监护儿童中抗菌药物使用,育龄期女性中成药使用,老年人中成药和抗菌药物使用,并对阿奇霉素、头孢呋辛、血塞通、生脉、热毒宁、痰热清、疏血通7个品种建立重点监测制度,降低不良反应发生率。     

格列本脲的不良反应文献分析

目的：调查格列本脲的10年来不良反应情况为临床上合理使用格列本脲提供参考。方法：检索近10年（1999～2009）维普中文科技期刊数据库报道的格列本脲的不良反应文献,进行统计、分析。结果：格列本脲不良反应表现较多,机制复杂,最常见的是低血糖,其次是肝功能损伤。结论：临床上应该重视格列本脲的不良反应情况,针对不同病人合理用药。     

Novel statistical tools for monitoring the safety of marketed drugs

Robust tools for monitoring the safety of marketed therapeutic products are of paramount importance to public health. In recent years, innovative statistical approaches have been developed to screen large post-marketing safety databases for adverse events (AEs) that occur with disproportionate frequency. These methods, known variously as quantitative signal detection, disproportionality analysis, or safety data mining, facilitate the identification of new safety issues or possible harmful effects of a product. In this article, we describe the statistical concepts behind these methods, as well as their practical application to monitoring the safety of pharmaceutical products using spontaneous AE reports. We also provide examples of how these tools can be used to identify novel drug interactions and demographic risk factors for adverse drug reactions. Challenges, controversies, and frontiers for future research are discussed.     

Adverse events induced by ceftriaxone: a 10-year review of reported cases to Iranian Pharmacovigilance Centre

What is known and Objectives: Ceftriaxone, a third‐generation cephalosporin antibiotic, is used for a vast variety of infectious diseases. Different types of adverse reactions are reported to be induced by ceftriaxone; however, there is limited published information on spontaneous adverse reactions collected by a national pharmacovigilance centre. This study was conducted to evaluate ceftriaxone‐induced adverse drug events, registered in the Iranian pharmacovigilance database during a 10‐year period, and to identify preventive measures for reducing ceftriaxone‐induced adverse events. Method: All adverse events registered in the Iranian pharmacovigilance database from 1998 through 2009 were screened for ceftriaxone‐related adverse events. The extracted data were categorized based on patients’ demographics and previous history of allergic reactions to antibiotics. Assessment of system–organ classes, seriousness and causality of reactions was performed according to World Health Organization scale. The preventability was analysed based on Schumock questionnaire. Results and Discussion: Ceftriaxone was responsible for the highest number of deaths in our database (49 cases). Of 20 877 reports, 1205 (5·8%) were related to ceftriaxone; 357 reports (30%) are categorized as serious including cardiac arrest, anaphylactic and anaphylactoid reactions. The high number of serious cases makes it necessary to develop preventive measures for reducing those adverse events. Unlabelled use of the drug (2·9%) is identified as one of the risk factors for adverse events. Evaluation of the 1030 intravenous injections of the drug shows that rapid intravenous injection of ceftriaxone is another risk factor. One hundred and sixteen patients (9·6%) had a previous history of allergic reaction to ceftriaxone, penicillin or both. We recommend an alternative antibiotic, if possible, in the case of a positive history of allergic reaction to cephalosporins, penicillins and/or other beta‐lactam antibiotics. What is new and Conclusion: Severe and life‐threatening adverse reactions induced by ceftriaxone are of great concern. Rapid intravenous injection, unlabelled use and previous patient history of allergic reactions to cephalosporins or penicillins are risk factors that should be guarded against.     

小金丸中成药制剂临床不良反应分析

目的:分析小金丸中成药制剂临床不良反应特点及原因。方法:检索CNKI、万方数据,采集小金丸中成药制剂临床研究及不良反应病例报道,分别分析其不良反应发生率、表现特点,并通过关键词共现网络分析其成因。结果:纳入单独应用小金丸并报道了不良反应的临床研究文献14篇,小金丸不良反应病例报道21篇,小金丸中成药制剂不良反应发生率0.73%,以皮肤损害和胃肠道症状为主要表现,且多发生于用药1周以内;毒性药材及动物源性药材的应用,临床超适应症使用,药品说明书安全性警示不充分是其不良反应的主要因素。结论:小金丸不良反应多发生于用药早期,遵循药品说明及辨证施治合理应用、药品必要警示是减少其不良反应的重要途径。     

Phase IV study and post-marketing surveillance of ofloxacin in Japan

Data derived from phase IV clinical trials of ofloxacin in 13,850 patients show that the incidence of adverse drug reactions was 2.6%. Gastrointestinal symptoms topped other symptoms in order of frequency, followed by neuropsychiatric and hypersensitivity symptoms. On the other hand, we received 155 spontaneous reports on ofloxacin adverse reactions, including severe convulsions and shock. Examination of various cases of adverse drug reactions suggested that both severe renal dysfunction and a predisposition to epilepsy were risk factors contributing to the onset of convulsions, and a predisposition to allergy was also a risk factor in hypersensitivity reactions including shock. Data from phase IV trials aimed at efficacy analysis show a high efficacy rate. The usefulness of ofloxacin was confirmed by the data obtained after its marketing.     

Cinchonism in a Patient Taking Quinine for Leg Cramps

Quinine is often used as a treatment for benign nocturnal cramps. The use of Quinine remains controversial with conflicting studies regarding its efficacy. Quinine has a side effect profile that cannot be ignored. Cinchonism, or quinine toxicity, includes nausea, vomiting, and tinnitus. Many other side effects have been reported in the literature. A case report demonstrating the side effects of quinine is presented. We briefly review the literature on quinine and alternative medications.     

Impact of depression mood disorder on the adverse drug reaction incidence rate of anticancer drugs in cancer patients

The aim of this study was to explore the impact of depression mood disorder on the incidence of adverse drug reactions of anticancer drugs in cancer patients. The Hamilton Depression Scale 17 was used to evaluate the depression mood disorder level in 73 cancer patients before chemotherapy. Pharmacists monitored adverse drug reactions during the chemotherapy period. The relationship between depression mood disorder level and the incidence of adverse drug reactions was analysed. The frequency and extent of total adverse drug reactions were not related to depression mood disorder level. The frequency and extent of subjectively experienced adverse drug reactions such as anorexia, nausea and fatigue were related to depression mood disorder level. In conclusion, psychological support and intervention should be provided to cancer patients in order to improve patient adherence and cancer chemotherapy effectiveness, and to decrease the incidence of adverse drug reactions.     

Muscle cramps in the cancer patient: causes and treatment

Muscle cramps may occur in healthy individuals without any apparent cause; these are regarded as benign cramps. Cramps may also develop as a symptom of a systemic disease, such as uremia. Cramps probably originate in the distal portion of the motor nerve. It is unclear whether the nerve terminals are hyperexcitable or prone to repetitive activity in the various related conditions. In the cancer patient, muscle cramps may not be a benign complaint because they often represent an unsuspected underlying pathologic condition associated either with the neoplastic process or the undesirable side effects of therapy. Initial evaluation with a detailed neurologic examination, a complete biochemical profile with magnesium levels and muscle enzymes, and electrodiagnostic examination will lead to the diagnosis in the majority of these patients. Recognized etiologies of cramps may be related to neurologic abnormalities or to nonneurologic causes. Treatment decisions should be oriented according to the following classification: (1) reversible causes; (2) potentially reversible causes and (3) irreversible causes. Whereas the remedy in the first category is to attack the underlying process, if possible, pharmacologic suppression of cramps is the primary approach in the others. Membrane-stabilizing agents, such as quinine, phenytoin or carbamazepine, may be selected according to either nocturnal or daytime predominant occurrence of cramps.