药师应在药品不良反应监测中发挥作用

目的 药品不良反应是危害人们生命安全的重要因素之一,应拓展药师职能,加强其在药品不良反应报告和监测中的作用.方法 药师要加强业务学习,注意与患者的沟通,增强与医护人员的交流.结果 提高医护人员对药品不良反应的认知度,药师参与有其有利条件.结论 医院药师应将药品不良反应监测工作作为责无旁贷之己任.     

药师在药品不良反应监测中的作用

近年来，随着激烈的市场竞争，各家医院为了确保可持续发展，又为解决“看病难、看病贵”这一社会问题而努力奋斗着。然而作为药师，不单是发药、供应工作，提供优质的药学服务，制定合理的用药方案，指导患者用药等已成为药师的重要职责。为了保障患者用药安全，对药品进行再评价，淘汰药品，必须要对药品不良反应（ADR）进行报告、监测。而在这一过程中，作为药师应全程参与，正确、合理地协助医护人员完成ADR的处理和登记，发挥其作用。     

药师在药品不良反应报告与监测中的作用

随着我国医药技术的不断发展,药品质量检测工作得到了人们越来越多的关注,药品反应报告与药品的检测地位进一步的提升。《药品不良反应报告和检测管理办法》的颁布,对药品的生产制造过程、药品企业的日常经营管理、医疗机构依法对药品不良反应的监测等有着详细的规定,并明确了其各自的相关职责、药品不良反应报告单位等。由于临床医生日常工作     

药师在药品不良反应监测中的作用

为了加强上市药品的安全监管,严格药品不良反应(ADR)监测工作的管理,确保人体用药安全有效．根据《中华人民共和国药品管理法》的有关规定．制定了《药品不良反应监测管理办法》对药品生产、经营、使用单位纳入监测管理范围,有利于提高药品生产质量,遏制不合理用法,减少药品不良反应的发生,确保人民用药安全有效。药品不良反应监测工作是一项系统工程。     

临床药师在医院临床药品不良反应监测工作中的作用

目的:探究临床药师在医院临床药品不良反应(ADR)监测工作中的作用。方法:抽取医院药品不良反应监测中心2017年1月—2018年12月期间的ADRs报告175份,分析其临床药师参与临床药品不良反应监测工作前后的ADR监测情况。结果:175份ADRs报告中,2017年上报ADRs报告78例(其中严重的4例),2018年上报ADRs报告97例(其中严重的11例);临床药师参与ADRs监测前后,涉及可疑的药物种类、给药途径、报告的ADRs临床表现均有明显不同,其中临床药师参与临床ADRs监测后比较明显地发现了许多隐藏的和因不合理给药引起的ADRs。结论:通过临床药师积极参与ADRs监测,有效提高了ADRs监测的上报率,并根据监测结果及时建议临床给药方案的调整,确保了患者用药的安全性、有效性。     

临床药师在我院药品不良反应监测中的作用

医疗机构开展药品不良反应（adverse drug reactions,ADR）监测是一项法定义务,是一项利国利民的善事,也是上级卫生主管部门对医疗机构的一项重要考核内容。同时,医疗机构开展ADR监测,自身也是受益方。     

临床药师在药品不良反应监测中的重要作用

目的：对临床药师在药品不良反应监测中的重要作用进行探析。方法：临床资料选自本院及社区卫生服务中心（包括佛山市第一人民医院禅城医院及南庄镇社区卫生服务中心）2013年1月～2015年6月800份不良反应监测报告,其中监测前400份,监测后400份,对比药品不良反应监测前后的不良反应发生率。结果：监测后,新的以及严重的药品不良反应的总发生率是15%,监测前是28.25%,差异明显（P＜0.05）。监测前临床药师提交的监测报告占10.5%,监测后,占28%,差异显著（P＜0.05）。监测前后,药品种类中的抗感染药、心血管药、中药制剂、内分泌系统药等所占比例变化较大,差异显著（P＜0.05）。结论：临床药师在药品不良反应监测中发挥的作用不可替代,能够全程监测药品不良反应,为药品的后续使用与改进提供可靠的数据资料。     

临床药师在我院药品不良反应监测中的作用

目的根据我院消化科药品不良反应（ADR）报表,分析临床药师在药品不良反应监测中的作用。方法从我院药品不良反应监测中心调取2008年11月～2009年10月ADR报告,对临床药师参与临床常规工作前后的ADR情况进行回顾性分析。结果临床药师参与临床常规工作前（第一阶段）ADR报表为5例。临床药师参与临床常规工作后（第二阶段）ADR报表增至38例。43份ADR涉及的可疑药物以质子泵抑制剂和抗感染居多,均占23.3%;静脉途径给药发生的ADR占总计的72.1%。结论临床药师参与临床常规工作后,提高了ADR的监测水平,有助于及时应对ADR,促进合理用药。     

临床药师在药品不良反应监测工作的作用分析

目的:探讨临床药师在药品不良反应(ADR)监测工作中的重要作用。方法:收集我院2012年(临床药师干预前)和2013年(临床药师干预后)上报的ADR报告,按报告人、给药途径、患者的年龄与性别、引起ADR的药品品种、药品不良反应累及器官等进行分析、评价、比较。结果:2012年共上报ADR报告343份,其中严重的ADR仅2例,药师上报20例;引起ADR最常见的药物为抗感染药(54.52%)和中药制剂(23.03%);常见的ADR累及器官-系统为皮肤及其附件(54.23%)和消化系统(27.99%)。2013年共上报ADR报告406份,其中严重ADR59例,药师上报ADR 101例;抗感染药和中药制剂ADR报告比例分别为43.84%和13.30%,与2012年相比均有明显下降(P<0.01);ADR受累器官-系统仍以皮肤及其附件(46.55%)为主,但所占比例有明显下降(P<0.001)。结论:临床药师可通过各个方面积极参与ADR监测工作,在提高ADR上报的数量和质量方面发挥重要作用。     

医院药师在药品不良反应监测中的作用

医院药师是提供药品服务的直接参与者和指导者。无论是传统的医院药学,还是现代的药学监护(临床药学、血药浓度监测、药品不良反应监测、药学咨询等),单纯的收方、发药、供应已不再是医院药师工作的全部,开展药学监护,提供优质、高效的药学服务,制定合理用药方案,指导医师、护士、患者用药等已是医院药师的重要职责。据有关文献显示,中国每年有250万人次的患者因药品不良反应(ADR)而入院治疗,约19.2万人死于ADR[1]。ADR已经成为危害人们生命安全的重要因素之一。为此,充分发挥医院药师在ADR报告和监测中的作用,显得尤为重要。为了让更…     

临床药师在危重症患者药品不良反应监测中的作用

临床药师通过收集本院ICU、急诊科的药品不良反应、参与临床查房、关注危重症患者的转归等,从药学角度协助医生分析药品不良反应,并在众多使用药物中判断出可疑药物,进而提出相应处理措施.保障了危重症患者的用药安全,提高了合理用药水平.     

药师在药物不良反应投诉中的沟通技巧

通过药师在药物不良反应投诉处理中的成功案例,总结药师在沟通中的工作体会及经验,探讨药师在参与处理药物不良反应投诉中的沟通技巧显示药师参与药物不良反应投诉处理,减少了医疗纠纷的发生,发挥了药学专业在临床中的作用,建立了药师在患者心中的职业地位.     

药师开展药学服务对减少药品不良反应的效果观察简

目的观察对药师开展药学服务对减少药品不良反应的效果。方法选取120例中药治疗患者随机分成两组,各60例,观察组的药师提供药学服务,而对照组的药师不提供。对两组患者的药品不良反应进行对比。结果观察组的药品不良反应率为3．33％低于对照组的11．67％（P〈0．05）。结论药师开展药学服务可有效降低药品的不良反应率,从而提高患者的治疗效果。     

我国药品不良反应监测工作的现状和对策

药品不良反应 (ＡｄｖｅｒｓｅＤｒｕｇＲｅａｃｔｉｏｎｓ ,ＡＤＲ)是指合格药品在正确用法用量下出现的与用药目的无关的或意外的有害反应。六十年代震惊世界的反应停事件 ,敲响了药物灾难的警钟 ,药品不良反应监测由此应运而生。1970年ＷＨＯ大会决定在瑞士日内瓦建立ＷＨＯ国际药品监测合作中心 ,该中心于 1978年迁址瑞典的乌普萨拉 (Ｕｐｐｓａｌａ)市至今[1] ,目前已有 6 4个国家加入了ＷＨＯ国际药品监测合作计划[2 ] 。我国于 1998年 3月正式加入ＷＨＯ国际药品监测合作计划 ,并开始履行成员国定期向ＷＨＯ国际药品监测合作中心报送…     

中药不良反应不容忽视--从龙胆泻肝丸事件引发的思考

随着药学科学的飞速发展,大量新药不断研制上市,但在药物作用到人体发挥药理作用时,有时也会产生与治疗作用无关的反应,使机体产生某些病理变化,在临床上表现出各种症状,称为"药源性疾病",也叫药品不良反应.只要有药物就会有不良反应产生的可能性.     

咨询药师参与药品不良反应案例的分析实践与价值

摘 要 目的：通过药师参与药品不良反应案例的分析实践,体现药师在解决患者用药问题和用药风险防范中的价值。方法: 药师对4例药品不良反应咨询案例进行分析,并利用专业知识为患者给出合理用药建议。结果: 药师可以识别药品不良反应及用药风险,对患者家属解释用药后出现异常行为的原因,妥善处理发生严重药物不良反应的患者以避免医患纠纷,为发生药品不良反应预后的患者给出合理建议。结论: 药师在用药风险防范中发挥着重要作用,可以承担起药学监护的责任。     

老年人药品不良反应分析

目的分析老年人药品不良反应/事件(ADR/ADE)的发生情况、特点及相关因素。方法收集2011年我市食品药品监督管理局上报的60～85岁老年人ADR/ADE共232例,按照国家药品不良反应监测中心制定的标准进行分析,总结ADR/ADE发生的原因。结果在232例ADR/ADE中,抗生素、中药引起的ADR较多,以皮损及其附件损伤常见,ADR累及人体各系统。结论应加强对老年人用药的关注,合理用药,减少ADR/ADE的发生。     

ISMP Adverse Drug Reactions

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Shuster at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-947-7797; fax: 215-914-1492; e-mail: ude.elpmet@retsuhs.leoj). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

• Hosp Pharm. 2013 Feb; 48(2): 100–103.
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• Aspirin/Clopidogrel-Induced Spontaneous Liver Hematoma

2013 Feb; 48(2): 100–103. Published online 2013 Feb 1. doi: 10.1310/hpj4802-100

Aspirin/Clopidogrel-Induced Spontaneous Liver Hematoma

Joel Shuster, PharmD, BCPP^*

Joel Shuster

^*Clinical Professor of Pharmacy Practice, Temple University School of Pharmacy, Philadelphia, Pennsylvania; Clinical Consultant, Episcopal Hospital, Philadelphia, Pennsylvania; Clinical Advisor, Institute for Safe Medication Practices, Horsham, PennsylvaniaFind articles by Joel ShusterAuthor information Copyright and License information Disclaimer^*Clinical Professor of Pharmacy Practice, Temple University School of Pharmacy, Philadelphia, Pennsylvania; Clinical Consultant, Episcopal Hospital, Philadelphia, Pennsylvania; Clinical Advisor, Institute for Safe Medication Practices, Horsham, PennsylvaniaCopyright notice A 76-year-old man presented to his local emergency department (ED) with a day-long complaint of right upper quadrant pain. He stated that he had not had any trauma. His physical examination was essentially normal except for “mild tenderness in the epigastric area and 2+ pitting edema in both legs.” His medical history included the placement of drug eluting stents after a myocardial infarction 8 years earlier and 3 years after that for unstable angina. One of the stents was coated with heparin and the other was coated with paclitaxel. Other comorbidities included sarcoidosis, pulmonary hypertension, diabetes, and essential hypertension. His medications included aspirin, clopidogrel, glipizide, benazepril, rosuvastatin, allopurinol, prednisone, and omeprazole. He was also using a variety of inhalers for his pulmonary symptoms. He had been taking the clopidogrel and aspirin for 5 years. He did not use nonsteroidal anti-inflammatory drugs.Laboratory testing revealed the hemoglobin and hematocrit to be slightly below normal, while the platelet count was fine. Abdominal ultrasound and follow-up computed tomography (CT) of the abdomen showed a “large hypodense” mass in the right side of the liver. The patient was admitted to the hospital. Because of a suspected hemorrhage, the aspirin and clopidogrel were discontinued. By the following morning, the patient’s hemoglobin had dropped to 8.6 g/dL from 13 g/dL on admission (reference range, 14-18 g/dL), and he was given 2 units of packed red blood cells. The liver transaminases had also increased 5-fold in the first 24 hours. A few days later, a repeat CT scan showed that the first liver lesion had resolved, while a new hypodense lesion had developed. Because of a high white blood cell count, a liver abscess was suspected. “CT-guided aspiration of the lesion revealed 21 mL of dark blood.” The patient was treated with an additional unit of whole blood and was discharged a few days later with a “diagnosis of subcapsular liver hematoma while receiving dual antiplatelet therapy.” The clopidogrel and aspirin were not restarted upon discharge from the hospital, but the patient was placed back on aspirin alone a month later and had no further problems up to a 1-year follow-up.The authors state that liver hematoma from antiplatelet therapy is rare, but we must be cautious in using dual therapy for more than the recommended periods of time after stent placements.Darwish OS, Iqbal E. Dual antiplatelet agent-induced spontaneous liver hematoma. Ann Pharmacother. 2012;46(11):e33.

• Hosp Pharm. 2013 Feb; 48(2): 100–103.
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• Adenosine-Induced Severe Bronchospasm in a Patient Without Pulmonary Disease

2013 Feb; 48(2): 100–103. Published online 2013 Feb 1. doi: 10.1310/hpj4802-100

Adenosine-Induced Severe Bronchospasm in a Patient Without Pulmonary Disease

Copyright and License information DisclaimerCopyright notice An obese 29-year-old man developed frequent episodes of palpitations that were short and self-limiting. When he developed another episode of palpitations that lasted nearly 2 hours, he presented to his local ED. On physical examination, the patient’s heart rate was 210 beats per minute and his blood pressure was 140/90 mm Hg. He complained of “mild chest discomfort” but did not have any difficulty breathing. The electrocardiogram “showed a regular wide QRS tachycardia with a left bundle-branch block morphology, consistent with aberrant supraventricular tachycardia.” The patient underwent carotid massage with no effect. The patient was then given a 6 mg intravenous (IV) bolus of adenosine, which also had no effect. A 12 mg bolus was then administered without effect, but the patient developed a mild cough. Another 12 mg IV bolus of adenosine was given, which “cardioverted the patient to sinus tachycardia.” The patient immediately developed trouble breathing, and his pulse oximetry showed that he was hypoxic at 83% oxygen saturation on room air. Auscultation revealed “diffuse bronchospasm.” An arterial blood gas specimen revealed “hypocapnic respiratory failure,” whereas a chest x-ray was normal. He was treated with oxygen and inhaled beclomethasone, along with an IV bolus of methylprednisolone. When this did not help, an IV infusion of aminophylline was started, which relieved the bronchospasm but caused a recurrence of the supraventricular tachycardia (at a rate of 180 beats per minute). Intravenous flecainide halted the new arrhythmia, and the patient had no further problems with bronchospasm or abnormal rhythms. An accessory pathway was later discovered during electrophysiological studies, and the patient was treated with a radiofrequency ablation procedure.The authors remind us that adenosine is known to cause dyspneic symptoms during cardiac studies, but the symptoms are usually “transient and benign.” There are documented cases of severe bronchoconstriction occurring in patients with prior lung disease, but this is apparently the first such case in a patient with normal pulmonary status.Coli S, Mantovani F, Ferro J, Gonzi G, Zardini M, Ardissino D. Adenosine-induced severe bronchospasm in a patient without pulmonary disease. Am J Emerg Med. 2012;30(9):2082.e3-2082.e5.

• Hosp Pharm. 2013 Feb; 48(2): 100–103.
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• Paclitaxel-Induced Acral Erythema

2013 Feb; 48(2): 100–103. Published online 2013 Feb 1. doi: 10.1310/hpj4802-100

Paclitaxel-Induced Acral Erythema

Copyright and License information DisclaimerCopyright notice A 66-year-old woman was started on paclitaxel as neoadjuvant therapy for ductal breast cancer. After receiving 3 IV doses at 80 mg/m², the patient developed “a nonpruritic, 1-cm confluent erythematous patch over several metacarpophalangeal joints” bilaterally. Continued treatment with the antineoplastic agent caused new areas of discomfort. The new lesions were seen “primarily over her right lateral heel and toes.” The erythematous areas became “tender yellow plaques with scaling.” Even though there was a reduction in the dose of paclitaxel, the patient presented with pain and swelling in the right foot after the 11th dose. She had developed multiple lesions and had significant swelling of toes on both feet that caused significant pain. A biopsy of a lesion on the patient’s right foot showed “epithelial acanthosis with prominent compact orthokeratotic hyperkeratosis and areas of parakeratosis.” She was treated with topical silver sulfadiazine for the open wound areas and received triamcinolone and emollients to the right foot. All lesions and plaques were completely resolved a month after the paclitaxel therapy had been completed.The authors state that skin rashes are common with paclitaxel, but this type of acral erythema, pertaining to peripheral parts of the body, is not commonly seen. Acral lesions are more commonly seen with other chemotherapeutic agents, such as fluorouracil, cytarabine, or doxorubicin.Richards KN, Ivan D, Rashid RM, Chon SY. Paclitaxel-induced acral erythema. Arch Dermatol. 2012;148(11):1333-1334.

• Hosp Pharm. 2013 Feb; 48(2): 100–103.
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• Acute Laryngeal Dystonia Associated with Aripiprazole

2013 Feb; 48(2): 100–103. Published online 2013 Feb 1. doi: 10.1310/hpj4802-100

Acute Laryngeal Dystonia Associated with Aripiprazole

Copyright and License information DisclaimerCopyright notice A 16-year-old girl with a history of rape, sexual molestation, aggressive behaviors, and cutting was admitted to a psychiatric hospital after getting into a fight at school with a female peer. The admitting diagnosis was bipolar disorder not otherwise specified with borderline traits.Four months before admission, she was given aripiprazole 5 mg daily that had been added to topiramate 25 mg twice daily, which was being used for mood lability. She had been treated in the past with a variety of medications that caused weight gain, oversedation, or other adverse effects that caused her to stop taking the medications. She was also getting naproxen 375 mg twice daily for pain caused by recent cutting attempts. Three days before admission to the hospital, her dose of aripiprazole was increased to 10 mg daily. She was continued on the aripiprazole, topiramate, and naproxen upon admission.On the third hospital day, 6 days after the increase in dose of the aripiprazole, the woman was found on the floor of the hospital gymnasium “with dyspnea, dysphonia, tongue and throat tightening, cogwheel rigidity, and dizziness.” The oxygen saturation varied from 92% to 100%. She was treated with a stat dose of benztropine 2 mg intramuscularly and oral diazepam 5 mg, which caused rapid improvement of her breathing and rigidity. The aripiprazole was halted. Over the next 3 days, benztropine was used orally and there was not a recurrence of symptoms.The patient had an acute dystonic reaction involving her laryngeal musculature, which was easily treated with the anticholinergic agent, benztropine. The authors state that this is only the second published report of acute laryngeal dystonia occurring with the “newer” or “atypical” antipsychotic agents marketed over the past 20 years or so. It is likely that many such cases have not been reported. With the increased use of some of the antipsychotic agents as adjuncts to antidepressant therapy, we must be aware of such possible episodes of extrapyramidal side effects.Goga JK, Seidel L, Walters JK, Khushalani S, Kaplan D. Acute laryngeal dystonia associated with aripiprazole. J Clin Psychopharmacol. 2012;32(6):837-839.

• Hosp Pharm. 2013 Feb; 48(2): 100–103.
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• Incidence of Thrombocytopenia During Heparin Prophylaxis

2013 Feb; 48(2): 100–103. Published online 2013 Feb 1. doi: 10.1310/hpj4802-100

Incidence of Thrombocytopenia During Heparin Prophylaxis

Copyright and License information DisclaimerCopyright notice This report is a follow-up to a study published in 2008 that showed that patients receiving prolonged unfractionated heparin for a variety of reasons developed thrombocytopenia at an extremely high rate of 33%.¹ In this new report, a total of 1,017 patients were included in the analysis of patients receiving heparin solely for prophylaxis of venous thromboembolism. The investigation showed that 190 patients (18.7%) developed thrombocytopenia as a result of being placed on heparin prophylaxis. Thrombocytopenia “was defined as a nadir platelet count <150 x 10⁹/L or a platelet count decrease ≥50% from admission levels.” Half of the patients had only nadir counts below 150 x 10⁹/L, while 11% of the patients saw their admitting platelet counts fall below 50% of the first measured values. The other 39% of the patients had platelet counts below the cutoff point, and their counts were more than halved from admission. Forty percent of the cases of thrombocytopenia were caused by low-molecular-weight heparins, although the risk was certainly smaller with these agents.The authors conclude that almost 1 in 5 patients develop thrombocytopenia during heparin prophylaxis, and this high number still seems to be “under-recognized.” They suggest more vigilant platelet monitoring, especially in patients at higher risk.Wang TY, Honeycutt EF, Tapson VF, Moll S, Granger CB, Ohman EM. Incidence of thrombocytopenia among patients receiving heparin venous thromboembolism prophylaxis. Am J Med. 2012;125(12):1214-1221.

• Hosp Pharm. 2013 Feb; 48(2): 100–103.
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• Oral Fluoroquinolones and the Risk of Retinal Detachment

2013 Feb; 48(2): 100–103. Published online 2013 Feb 1. doi: 10.1310/hpj4802-100

Oral Fluoroquinolones and the Risk of Retinal Detachment

Copyright and License information DisclaimerCopyright notice An article was published in the JAMA in early April 2012 that concluded that treatment with oral fluoroquinolone antibiotics caused an increased risk of retinal detachment.² “The absolute risk in the risk of a retinal detachment was 4 per 10,000 person-years (number needed to harm = 2500 computed for any use of fluoroquinolones).”² I had not seen that original publication, but I recently found this editorial in the American Journal of Ophthalmology that pointed out some potential problems with just a superficial observation of the original analysis.The authors discuss the fact that tendinitis and/or tendon ruptures may occur in 1 out of 1,000 patients treated with fluoroquinolones, yet we still use the fluoroquinolones in all manner of patients. Is the risk of a rhegmatogenous retinal detachment something to be feared? Please take a look at both of these publications, which may be used for a good discussion in a journal club.Albini TA, Karakousis PC, Abbey AM, Bartlett JG, Flynn HW. Association between oral fluoroquinolones and retinal detachment. Am J Ophthalmol. 2012;154(6):919-921.

• Hosp Pharm. 2013 Feb; 48(2): 100–103.
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• Prenatal Exposure to Antidepressants: How Safe are They?

2013 Feb; 48(2): 100–103. Published online 2013 Feb 1. doi: 10.1310/hpj4802-100

Prenatal Exposure to Antidepressants: How Safe are They?

Copyright and License information DisclaimerCopyright notice A prospectively collected database looked at 4 groups of children. Two of the groups included women who took either venlafaxine or selective serotonin reuptake inhibitors (SSRIs) during their pregnancies. Another group included depressed pregnant women who were not treated, and the final group was made up of nondepressed, healthy women. The children of these women were followed to ages 3.5 to 6 years and were given intelligence tests and other tests for neurodevelopment.The study showed that exposure to antidepressants did not affect the children’s intellectual or behavioral outcomes. Untreated depression certainly led to a much higher risk of postpartum depression. The data also showed “that fetal and childhood exposure to maternal depression were significant predictors of child behavior problems and may represent risk for long-term child psychopathology.”A well-referenced accompanying editorial in the same issue of the American Journal of Psychiatry looks at other reports where prenatal exposure to antidepressants was studied.³Nulman I, Koren G, Rovet J, et al. Neurodevelopment of children following prenatal exposure to venlafaxine, selective serotonin reuptake inhibitors, or untreated maternal depression. Am J Psychiatry. 2012;169(11):1165-1174.

• Hosp Pharm. 2013 Feb; 48(2): 100–103.
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• Proton Pump Inhibitors: The Good, The Bad, and The Unwanted

2013 Feb; 48(2): 100–103. Published online 2013 Feb 1. doi: 10.1310/hpj4802-100

Proton Pump Inhibitors: The Good, The Bad, and The Unwanted

Copyright and License information DisclaimerCopyright notice This column has previously reported on uncommon adverse effects associated with proton pump inhibitors (PPIs). Last month (January 2013), we reviewed a case of agranulocytosis brought on by exposure to PPIs.⁴This report is a 60-reference review of adverse effects associated with PPIs. A good discussion is included about “usage issues” with this class of drugs. Too many hospitalized patients are placed on these agents without good reason. The takeaway lesson from this review is that PPIs should only be used for accepted indications and their long-term use should be reevaluated on a regular basis.Chubineh S, Birk J. Proton pump inhibitors: the good, the bad, and the unwanted. Southern Med J. 2012;105(11):613-618.     

ISMP Adverse Drug Reactions

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: ude.elpmet@onacnamm). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

• Hosp Pharm. 2013 Apr; 48(4): 270–273.
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• Statin-Induced Lung Injury

2013 Apr; 48(4): 270–273. Published online 2013 Apr 3. doi: 10.1310/hpj4804-270

Statin-Induced Lung Injury

Michael A. Mancano, PharmD^*

Michael A. Mancano

^*Chair and Clinical Professor, Department of Pharmacy Practice, Temple University School of Pharmacy, Philadelphia, Pennsylvania; Clinical Advisor, Institute for Safe Medication Practices, Horsham, PennsylvaniaFind articles by Michael A. MancanoAuthor information Copyright and License information Disclaimer^*Chair and Clinical Professor, Department of Pharmacy Practice, Temple University School of Pharmacy, Philadelphia, Pennsylvania; Clinical Advisor, Institute for Safe Medication Practices, Horsham, PennsylvaniaCopyright notice Statin-induced lung injury (SILI) is an uncommon but serious pulmonary complication of statin therapy. SILI was initially reported in the medical literature in 1995¹ and additional case reports followed. In 2007 an analysis of the US Food and Drug Administration (FDA) Adverse Reporting System data concerning statin use and SILI was performed.² The findings demonstrated a group of disorders with similar pathological findings including cellular infiltration, scarring and/or architectural disruption of the pulmonary parenchyma involving alveolar lining cells, small and large airways, endothelial basement membranes, and occasionally the pleura. This group of pulmonary effects was found to occur in 0.01% to 0.4% of patients treated with statins and demonstrates that the clinical features of SILI vary widely.The authors completed an investigation of 12 previously reported cases of SILI as well as 4 cases diagnosed at their institution. The authors’ analysis demonstrated that simvastatin was the most common statin reported to cause lung injury; however, of the 4 patients at their institution, 3 patients received rosuvastatin and 1 received atorvastatin. The most common symptoms patients reported were fever, dyspnea, and cough. The onset of lung injury varied widely from the start of statin treatment, ranging from 0.25 to 120 months. Upon onset of symptoms, statins were discontinued and steroids were administered in 15 of the 16 patients. Clinical or radiologic improvement was noted in 10 patients receiving steroids. Because of severe lung injury, rechallenge with statins was not performed. However, 1 patient experienced increased dyspnea 1 week after inadvertent re-administration of rosuvastatin prescribed by a physician with no knowledge of the patient’s history of SILI. Of the remaining 6 patients with unfavorable outcome, 2 had slowly progressive disease complicated by persistent dyspnea. Four patients died from respiratory or cardiac failure, including 1 patient who received continuous simvastatin therapy.The authors’ analysis indicates that the patients with clinical symptoms of cough and/or fever had a favorable outcome. It may be that the presence of such acute symptoms prompts the patient to seek medical help and avoid delay in diagnosis and treatment. However, these clinical symptoms, in addition to thoracic radiological findings, may mimic pulmonary infection and confuse physicians who are unaware of SILI. The authors recommend a high index of suspicion of SILI; the presence of pulmonary phospholipidosis, shown by a foamy appearance of the majority of alveolar macrophages which stain positive for Sudan black in bronchoalveolar lavage fluid, may be of considerable value in diagnosing SILI. In addition, the high-resolution CT (HRCT) findings in SILI are nonspecific but may be of prognostic value. Alveolar infiltrates, especially ground-glass opacity, indicate favorable outcome, whereas fibrosis shown on HRCT suggests an unfavorable outcome.The authors outline the current research questions concerning SILI that remain: What are the underlying mechanisms of SILI? What are the risk factors for the occurrence of SILI? How can health care professionals become more aware of SILI in their clinical practice?Huang LK, Tsai MJ, Tsai HC, et al. Statin-induced lung injury: diagnostic clues and outcome. Postgrad Med. 2013;89:14-19.

• Hosp Pharm. 2013 Apr; 48(4): 270–273.
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• Colchicine-Induced Rhabdomyolysis Caused by Interaction with Clarithromycin

2013 Apr; 48(4): 270–273. Published online 2013 Apr 3. doi: 10.1310/hpj4804-270

Colchicine-Induced Rhabdomyolysis Caused by Interaction with Clarithromycin

Copyright and License information DisclaimerCopyright notice A 59-year-old man with a history of pulmonary tuberculosis about 40 years prior presented with generalized myalgia and fever. Behçet disease had been diagnosed 15 months prior, and the patient was treated with methotrexate and colchicine (0.6 mg every 12 hours). Behçet’s disease is a triad of aphthous ulcers, genital ulcerations, and ocular inflammation. Three months prior to his admission, methotrexate was discontinued because of elevated liver enzymes, and his liver function had normalized within 2 months. The patient developed nasal congestion and chronic cough as well as rhinosinusitis. Clarithromycin 500 mg every 12 hours was initiated. Nine days after starting treatment, he developed myalgia and weakness in both legs along with a febrile sensation. Despite treatment with analgesics, his myalgia had worsened and involved other extremities.Upon admission, his liver enzymes were elevated (aspartate aminotransferase, 227 IU/L; alanine aminotransferase, 564 IU/L), but neither cytopenia nor renal impairment was observed. The patient’s creatinine kinase and myoglobin concentrations were markedly elevated at 766 IU/L and 1,393 ng/mL, respectively. After conservative management, his subsequent liver enzymes, myoglobin, and creatinine kinase concentrations decreased while his muscle pain and weakness gradually disappeared within 2 weeks. The patient was discharged without colchicine therapy.According to the FDA’s safety data for colchicine-related deaths, 117 of the 169 fatal cases were within the therapeutic dosage range and more than half were reported in patients concomitantly using clarithromycin.³ Clarithromycin can increase the oral bioavailability of colchicine by increasing its absorption by inhibiting P-glycoprotein in enterocytes and can increase colchicine accumulation by decreasing the activity of CYP3A4, which is involved in colchicine metabolism. The authors warn that pharmacologic interactions between colchicine and clarithromycin and other drugs that inhibit CYP3A4 and/or P-glycoprotein can cause serious adverse reactions. Health professionals should be vigilant for these potentially life-threatening interactions.Kim JB, Kim S, Yoon SY, et al. Colchicine-induced rhabdomyolysis caused by interaction with clarithromycin in a patient with Behçet disease. J Clin Rheumatol. 2012;18(8):453-454.

• Hosp Pharm. 2013 Apr; 48(4): 270–273.
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• Disulfiram Ethanol Reaction Mimicking Anaphylactic, Cardiogenic, and Septic Shock

2013 Apr; 48(4): 270–273. Published online 2013 Apr 3. doi: 10.1310/hpj4804-270

Disulfiram Ethanol Reaction Mimicking Anaphylactic, Cardiogenic, and Septic Shock

Copyright and License information DisclaimerCopyright notice A 65-year-old man was admitted to the intensive care unit (ICU) for shock. The patient had no pertinent past medical history except for alcohol abuse and was asymptomatic until midday when he consumed 500 mL of wine. Within 30 minutes he fainted and was taken to the emergency department. Upon admission, the patient’s consciousness returned to normal but his blood pressure was 80/60 mm Hg, heart rate 110 beats per minute (bpm), respiratory rate 25 breaths per minute, oxygen saturation of 99% on room air, and a temperature of 36°C (96.8°F). The patient displayed diffuse erythema on his chest and face, without mucosal swelling or pruritus. Anaphylaxis was suspected, and the patient immediately received 0.1 mg of intravenous epinephrine along with aggressive fluid resuscitation. Worsening circulatory failure warranted high-dose norepinephrine (0.8 mcg/kg/min) infusion. ECG was suggestive of an acute myocardial infarction but coronary angiography was normal. Because of hypothermia (35.5°C [95.9°F]) and intense shivering, toxic shock syndrome was suspected and intravenous broad-spectrum antibiotics were initiated (ceftriaxone and clindamycin). Upon his admission to the ICU, lab results revealed metabolic acidosis (pH 7.33, bicarbonate 17.2 mmol/L, and arterial blood lactate 8.7 mmol/L), but procalcitonin, high-sensitivity troponin, and other routine lab tests were within normal limits. Blood ethanol concentration was 0.9 g/L measured 6 hours after ingestion.Additional history was elicited from the patient, and it was discovered that he erratically self-medicated with disulfiram and that he had ingested 500 mg of disulfiram 1 hour before his alcohol intake. Within 2 hours after ICU admission, his circulatory status dramatically improved and he was gradually weaned off of norepinephrine. Cutaneous manifestations, lactic acidosis, and ECG abnormalities also resolved within 6 hours. All cultures remained sterile, and antibiotics were discontinued. The patient was discharged to home the next day without any medications. The diagnosis was severe disulfiram ethanol reaction.The disulfiram ethanol reaction is widely known, but the manifestation is expected to be mild but unpleasant with the patient experiencing headache, flushing, and nausea as a deterrent to further ethanol ingestion. Severe vasodilatory shock has been reported rarely in the literature, with only 1 case describing ST-segment depression. This case is unique; the patient experienced effects that mimicked anaphylactic, cardiogenic, and septic shock that resolved relatively rapidly after ICU admission.Moachon L, Arnould MA, Perruche F, et al. Disulfiram ethanol reaction mimicking anaphylactic, cardiogenic and septic shock. Am J Emerg Med. 2013;31(1):270.e1-270.e3.

• Hosp Pharm. 2013 Apr; 48(4): 270–273.
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• Weight Gain with Abdominal Enlargement in a Patient Receiving Tocilizumab

2013 Apr; 48(4): 270–273. Published online 2013 Apr 3. doi: 10.1310/hpj4804-270

Weight Gain with Abdominal Enlargement in a Patient Receiving Tocilizumab

Copyright and License information DisclaimerCopyright notice A 56-year-old woman with rheumatoid arthritis (RA) and Sjögren syndrome was initiated on tocilizumab in November 2010 after a long course of disease and failure (due to lack of efficacy or unacceptable adverse effects) of numerous synthetic disease-modifying antirheumatic drugs, 3 anti–tumor necrosis factor (TNF) drugs, and rituximab. Upon initiation of therapy with tocilizumab (Actemra) 320 mg, the patient weighed 43 kg (94.8 lbs; body mass index [BMI] 16.8). The patient also received prednisone 10 mg daily, which had been part of her long-term background regimen. In February 2011, the patient complained of persistent abdominal distention and pain. Abdominal ultrasound, CT, gastroscopy, and colonoscopy did not reveal a cause for the pain. The patient reported no change in her appetite or eating habits and her weight was 52 kg (114.6 lbs; BMI 20.3). The patient experienced moderate improvement in RA activity, and tocilizumab therapy was continued.In May 2011, the patient presented with worsening diffuse abdominal pain and her appearance had changed dramatically. Prominent trunk fat deposition was now apparent and her weight was now 56 kg (123.5 lbs; BMI 21.9). Her anterior abdominal wall was tender and her skin was distended. Ultrasound of the abdominal wall revealed significant diffuse fat deposition in the subcutaneous area. Tocilizumab was discontinued at this time. Three months later (August 2011), the patient noted significant improvement in her abdominal pain and distention and her weight had decreased by 5 kg (11 lbs). However the patient required an increase in her prednisone dose to 20 mg daily to treat her RA. Because of worsening joint disease, the patient agreed to receive another infusion of tocilizumab in November 2011. Two weeks after administration, she presented again with abdominal pain and new weight gain of 3 kg (6.6 lbs). She refused further tocilizumab treatment and was then maintained on prednisone 10 mg/daily. During follow-up, the patient’s abdominal distention gradually diminished and pain disappeared, however her weight did not decrease significantly and remained at 52 kg (114.6 lbs; BMI 20.3) as of September 2012.Tocilizumab is a humanized monoclonal antibody to the interleukin-6 (IL-6) receptor. Although weight gain has been thought to be a potential adverse effect of IL-6 receptor blockade, it has not been reported in patients receiving tocilizumab. This case represents a patient who gained more than 30% of her initial weight as well as significant abdominal fat accumulation. The weight gain also reoccurred upon reintroduction of tocilizumab therapy.Younis S, Rosner I, Rimar D, et al. Interleukin 6 blockade-associated weight gain with abdominal enlargement in a patient with rheumatoid arthritis. J Clin Rheum. 2013;19(1):48-49.

• Hosp Pharm. 2013 Apr; 48(4): 270–273.
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• Nilotinib-Associated Acute Pancreatitis

2013 Apr; 48(4): 270–273. Published online 2013 Apr 3. doi: 10.1310/hpj4804-270

Nilotinib-Associated Acute Pancreatitis

Copyright and License information DisclaimerCopyright notice A 69-year-old Caucasian male was admitted to the hospital for abdominal pain. Six days prior to admission, he began treatment with nilotinib for recently diagnosed chronic myelogenous leukemia (CML). He had been receiving nilotinib 300 mg twice daily. He had no history of smoking or alcohol abuse and no known allergies. He had been receiving simvastatin, aspirin, and enalapril for at least the last 5 years. His abdominal pain had begun after the first dose of nilotinib and gradually worsened prior to admission. The patient denied recent alcohol use or abdominal trauma. Lab test results revealed elevated white blood cell (WBC) count of 33,370/μL, amylase 152 IU/L, serum lipase 308 IU/L, and serum lactate dehydrogenase 308 IU/L. The patient had baseline serum amylase and lipase determined prior to nilotinib inhibition, and they were within normal limits. Serum bilirubin levels were slightly elevated at 1.7 mg/dL and serum triglyceride levels were within normal limits at 121 mg/dL. An abdominal CT scan demonstrated normal liver, a slightly enlarged spleen with normal appearance, and thickening of the pancreatic tail with infiltration of the surrounding fat. All of these findings are consistent with pancreatitis. Nilotinib was immediately discontinued, and the patient had no oral intake for a day and was treated with intravenous fluids and analgesics. The next day, the abdominal pain decreased and serum amylase, lipase, and bilirubin all decreased and returned to normal 2 weeks later.Nilotinib is a second-generation tyrosine kinase inhibitor (TKI). TKI administration has been associated with an increase in serum amylase and/or lipase. This case report describes acute pancreatitis, which was confirmed by clinical, radiologic, and laboratory studies after initiation of nilotinib. Even though the patient had been receiving simvastatin and enalapril and these agents are associated with pancreatitis, it is unlikely that these agents played a part in the development of pancreatitis. He had been receiving these drugs for at least 5 years and was reinitiated on these agents without incident.The authors state that nilotinib should be considered as capable of causing acute pancreatitis. The determination of baseline amylase and lipase serum levels prior to nilotinib initiation should be the standard of care, and clinicians should be alert for this rare phenomenon.Engel T, Justo D, Amitai M, et al. Nilotinib-associated acute pancreatitis. Ann Pharmacother. 2013;47(1):e3.