Septra, Bactrim Linked to 'Serious' Side Effects By Michael Smith, North American Correspondent, MedPage Today Published: October 11, 2011 Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Trimethoprim-sulfamethoxazole (TMP-SMX) 又称 Septra, Bactrim 等 (译按： 或者在台湾常听到的 - Baktar )，是一种被广泛使用的抗生素，而根据文献回顾 指出，此品可能与轻微甚至是潜在致死性的副作用有关。 Trimethoprim-sulfamethoxazole -- a widely used antibiotic sold as Septra, Bactrim, and others -- has a set of adverse reactions that range from minor to potentially fatal, according to a literature review. 此品於 1968 年现世，并由於其价格便宜、有效与容易使用而广受欢迎。 - Joanne Ho, MD, and David Juurlink, MD, PhD, both of the University of Toronto The drug was introduced in 1968 and is popular because it's cheap, effective and familiar, according to Joanne Ho, MD, and David Juurlink, MD, PhD, both of the University of Toronto. 虽然病人对 TMP-SMX 通常具有良好的耐受性，但其可能与许多潜在性的严重药物 不良反应有关。 - Ho and Juurlink reported online in Canadian Medical Association Journal, CMAJ. Although the drug is usually well tolerated, it is "associated with several potentially serious adverse reactions," Ho and Juurlink reported online in CM. 临床医师应该充分认知其潜在风险，并在投予 TMP-SMX 之治疗期间监测病人之药 物不良反应发生情形，或在适当的状况下改用其他替代抗生素进行治疗。 "Clinicians should be cognizant of the potential consequences of prescribing trimethoprim-sulfamethoxazole, monitor patients for adverse events during therapy, or use an alternate antibiotic when appropriate," they concluded. 纵然在这几十年间， TMP-SMX 是如此不可思议的被广泛使用着，但另一方面，它 的缺陷同样广为周知。 - According to Brad Spellberg, MD, an expert on antibiotic issues at the University of California Los Angeles. On the other hand, trimethoprim-sulfamethoxazole "has been an incredibly useful workhorse antibiotic for decades" and its limitations are well known, according to Brad Spellberg, MD, an expert on antibiotic issues at the University of California Los Angeles. 此药物的价位并不昂贵，而它能广泛分布於身体各个组织中，并对许多型态的感染 症都具有相当好的疗效。而其副作用发生率是较低的。 Spellberg 表示：「我用它治疗过好多好多病人啊~ 在这几十年来，对很多医师来 说，它非常安全又有效的啊~ 」 The compound, "is inexpensive, gets into all body tissues well, and is very effective at treating many types of infections," Spellberg told MedPage Today in an email. And the adverse events are relatively rare, he added. "I have treated many, many patients extremely safely and effectively with this drug, as have tens of thousands of physicians for many decades." 爲探讨 TMP-SMX 的副作用，Ho 与 Juurlink 搜索了 1950 - 2011 年间的医药文献 ，从超过 900 篇的参考文献中筛选至 70 篇，包括病例报告、自愿受试者研究和随 机分配之试验等，以探讨其安全性议题。 To pin down the adverse reactions, Ho and Juurlink conducted a search of medical literature from 1950 to 2011, eventually winnowing more than 900 citations down to 70 articles, including case reports, volunteer studies, observational studies, and randomized trials, that shone light on possible safety issues. 他们发现，最常见的药物不良反应为 rashes, fixed drug eruptions, drug-drug interactions (DDIs) & hyperkalemia。 其中最常见的是 rashes & fixed drug eruptions (3%)。 The most common adverse effects, they found, are rashes and fixed drug eruptions, drug-drug interactions, and hyperkalemia. The rashes and fixed drug eruptions occur in about 3% of patients, the researchers reported, and are some of the most common adverse effects of the drug. 此外因为 TMP-SMX 会影响 cytochrome P-450 的两个 isoforms ，可能会减少或增 强其他经由相同路径代谢之药物的代谢，影响范围包括了口服降血糖药 (oral hypo- glycemic agents, OHAs) 和 Warfarin，因此，药物交互作用是 TMP-SMX 的一个大 问题。 译按：TMP-SMX 会影响 CYP3A4 和 2C9/10 这两个 isoenzymes Some drug-drug interactions occur because trimethoprim-sulfamethoxazole affects two isoforms of the cytochrome P450 enzyme system, and may reduce or enhance the effects of other drugs that are metabolized by the enzymes, including oral hypoglycemic agents and warfarin. 举例来说，TMP-SMX 会增加 sulfonylureas (SUs) 的血中浓度，从而增加 insulin 的分泌而造成低血糖。此外，相较於其他抗生素，当 TMP-SMP 并服 warfarin 时， 则可能会导致肠胃道出血机率增加。 TMP-SMX 也会影响包含 methotrexate (MTX) 在内的许多药物在肾脏之清除率。 For instance, trimethoprim-sulfamethoxazole increases levels of sulfonylureas, leading to an increased release of insulin and hypoglycemia. As well, taking the drug with warfarin leads to increased risk of gastrointestinal hemorrhage compared with other antibiotics. Trimethoprim-sulfamethoxazole also affects renal clearance of several drugs, including methotrexate. 在一篇随机分派研究中，约有 6% 的病患接受 TMP-SMX 治疗後出现高血钾的症状 (定义为血中钾离子浓度高於 5.5 mmol/L)，此外有高达 81.5% 的病人出现血中 钾离子浓度增高的状况，指出钾离子浓度过高是 TMP-SMX 用於治疗时可能预期的 潜在性之致命药物不良反应。 Excess of potassium is a "predictable and potentially fatal adverse effect of treatment with trimethoprim-sulfamethoxazole," the researchers argued, noting that in a randomized trial, 6% of patients experienced hyperkalemia -- defined as serum potassium greater than 5.5 mmol/L -- and 81.5% had an increase in serum potassium. 研究指出这些病人的高血钾大部分是在数天内发生，并合并有其他风险因子如糖尿 病、肾功能不良、年龄较长者、AIDS 和并服某些会抑制钾离子排除的药物，如 ACEIs 和 ARBs 等。 The hyperkalemia takes several days to build up, and risk factors include diabetes, renal insufficiency, older age, AIDS, and drugs that inhibit excretion of potassium, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, they reported. 其他较不常见或罕见的药物不良反应包括： - 神经学症状：无菌性脑膜炎，幻觉，震颤和步态不稳 - 降低氧气的携带能力和其他血液学异常：血色素变性和恶质血液 - 药物过敏：发烧，皮疹并可能侵犯内脏器官等。而临床人员很容易误解此发烧是 因为感染症所致而误判。 - 生殖毒性：高胆红素血症，出生体重较低之婴儿 (SGA) 以及畸胎。 - 肾功能 ：急性肾间质肾炎，阻塞性肾小管病变与低血钠。 Uncommon and rare adverse reactions include: - Neurologic events, including aseptic meningitis, delirium, tremor, and gait disturbances - Decreased oxygen- carrying capacity and other hematologic abnormalities, including methemoglobinemia and blood dyscrasia - Drug hypersensitivity, with fever, rash and internal organ involvement. The fever can fool clinicians into thinking they are dealing with infection. - Reproductive toxicity, including such effects as hyperbilirubinemia, small-for-gestational-age babies, and structural malformations - Kidney effects, such as acute interstitial nephritis, obstructive tubulopathy, and hyponatremia Primary source: CMAJ Source reference: Ho JMW, and Juurlink D "Considerations when prescribing trimethoprim– sulfamethoxazole" CMAJ 2011; DOI: 10.1503/cmaj.111152 Linkage of Original Article: http://0rz.tw/1gxpt MedPage News: http://www.medpagetoday.com/PrimaryCare/PreventiveCare/28976 -- ┌ 暗恋--->时间久---->痛苦--->结束 朋友---->喜欢─┤ ┌ 失败--->避不见面--->痛苦-->结束 (常在一起) └ 表白 ┤ ┌ 恋爱-->日久无趣-->痛苦-->结束 (挣扎) └ 成功 ├ 恋爱-->移情别恋-->痛苦-->结束 └ 恋爱-->结婚-->更大的痛苦-->无法结束 --

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