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奥曲肽相关性中性粒细胞减少症

Octreotide-Associated Neutropenia.

作者信息

Tse Stacy S, Kish Troy

机构信息

Geriatric Research Education and Clinical Centers, James J. Peters VA Medical Center, Bronx, New York.

Department of Pharmacy Practice, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York.

出版信息

Pharmacotherapy. 2017 Jun;37(6):e32-e37. doi: 10.1002/phar.1942.

Abstract

Drug-induced neutropenia and agranulocytosis are rare adverse events but can be fatal. Neutropenia can be induced by a myriad of drugs from almost every pharmacologic class. Octreotide is a somatostatin analog that has been used to treat variceal bleeding, acromegaly, and severe diarrhea associated with metastatic tumors, and to reduce symptoms in the setting of malignant bowel obstruction and pseudoobstruction. The most common adverse effects associated with octreotide include pain at the injection site and gastrointestinal effects such as loose stools, cramping, and nausea; neutropenia is not currently listed as an adverse effect of the drug. We describe the case of an 87-year-old man who developed neutropenia immediately after administration of three doses of subcutaneous octreotide. He presented to the hospital with a history of constipation and straining for 3 days. He was admitted, and laxatives, suppositories, and enemas were administered over the next 3 days to induce a bowel movement; however, they were ineffective. Bowel obstruction secondary to a mass was confirmed by computed tomography; the mass was eventually diagnosed as colon cancer. Octreotide 100 µg subcutaneously every 8 hours was started for the obstruction on the evening of hospital day 4. After the patient had received 3 doses of octreotide, his white blood cell count (WBC) had decreased from 4.1 × 10 /mm (neutrophils 75.4%, absolute neutrophil count [ANC] 3.1 × 10 /mm ) on admission to 1.6 × 10 /mm (neutrophils 62%, ANC 0.99 × 10 /mm ) on day 5. Given the temporal relationship of octreotide and neutropenia as well as the lack of a reasonable alternative cause, it was suspected that octreotide was the most likely culprit of the patient's neutropenia. Octreotide was subsequently discontinued, and his WBC increased to 4.9 × 10 /mm (neutrophils 66.3%, ANC 3.2 × 10 /mm ) the next day. The remainder of the patient's hospitalization was not significant for any further hematologic abnormalities. His WBC and ANC (WBC 6.7 × 10 /mm , neutrophils 83.2%, ANC 5.6 × 10 /mm ) remained stable 30 days after the incident. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 5) between the patient's development of neutropenia and octreotide therapy. To our knowledge, this report highlights the first case of octreotide-associated neutropenia. Although the frequency of drug-induced neutropenia remains rare outside of cytotoxic chemotherapy, the importance of recognizing this adverse effect cannot be understated given the mortality risks for neutropenic patients.

摘要

药物性中性粒细胞减少症和粒细胞缺乏症是罕见的不良事件,但可能致命。几乎每一类药物都能诱发中性粒细胞减少症。奥曲肽是一种生长抑素类似物,已被用于治疗静脉曲张破裂出血、肢端肥大症以及与转移性肿瘤相关的严重腹泻,并减轻恶性肠梗阻和假性肠梗阻的症状。与奥曲肽相关的最常见不良反应包括注射部位疼痛和胃肠道反应,如腹泻、绞痛和恶心;目前中性粒细胞减少症未被列为该药物的不良反应。我们报告一例87岁男性,在皮下注射三剂奥曲肽后立即出现中性粒细胞减少症。他因便秘和用力排便3天入院。入院后,给予泻药、栓剂和灌肠剂,持续3天以促进排便,但均无效。计算机断层扫描证实为肿块继发肠梗阻;该肿块最终被诊断为结肠癌。在住院第4天晚上,因肠梗阻开始每8小时皮下注射100μg奥曲肽。患者接受3剂奥曲肽后,白细胞计数(WBC)从入院时的4.1×10⁹/mm³(中性粒细胞75.4%,绝对中性粒细胞计数[ANC]3.1×10⁹/mm³)降至第5天的1.6×10⁹/mm³(中性粒细胞62%,ANC 0.99×10⁹/mm³)。鉴于奥曲肽与中性粒细胞减少症的时间关系以及缺乏合理的其他病因,怀疑奥曲肽是该患者中性粒细胞减少症最可能的病因。随后停用奥曲肽,第二天他的白细胞计数升至4.9×10⁹/mm³(中性粒细胞66.3%,ANC 3.2×10⁹/mm³)。患者住院期间其余时间未出现任何进一步的血液学异常。事件发生30天后,他的白细胞计数和绝对中性粒细胞计数(白细胞计数6.7×10⁹/mm³,中性粒细胞83.2%,绝对中性粒细胞计数5.6×10⁹/mm³)保持稳定。使用Naranjo药物不良反应概率量表评估显示,患者中性粒细胞减少症的发生与奥曲肽治疗之间可能存在关联(评分为5分)。据我们所知,本报告首次强调了奥曲肽相关性中性粒细胞减少症的病例。尽管在细胞毒性化疗之外,药物性中性粒细胞减少症的发生率仍然很低,但鉴于中性粒细胞减少症患者的死亡风险,认识到这种不良反应的重要性不容小觑。

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