目的： 我們報導6 位疑似因為服用clozapine 後所造成的肺炎或上呼吸道感染的案例並探討可能藥物交互作用及相關致病機轉。
方法： 本研究為個案例系列 (case series) 分析。我們收集疑似clozapine 使用後引起上呼吸道感染或肺炎的案例進行病例回顧 (chart review) 研究。進一步，利用Spearman’s 相關係數探討clozapine 使用期間及使用劑量與Naranjo score 之間的相關性。
結果： 某南部精神專科教學醫院從2011 年1 月至2014 年11 月，相關於clozapine 的藥物不良反應通報案件共有21 件，其中有6 位病人 (28.6%) 疑似使用clozapine 後導致肺炎而被通報。clozapine 平均使用劑量為212.5 ± 143.0 mg，使用時間為46.7 ± 26.9 個月。最常併用藥品為valproic acid (83.3%)；其次為鎮靜安眠藥 (66.7%)；其中有1 位併用CYP1A2 強效抑制劑 ( 如：fluvoxamine)。而使用clozapine 越久的個案與發生證據等級越高的藥物不良反應具有強烈的相關性 (ρ = 0.80, p = 0.05)。
結論： 身心科病人常會併用多種抗精神病、抗憂鬱劑及鎮靜安眠藥。併用時也容易發生多種藥物與藥物交互作用的發生，因而嚴重影響藥物療效或是發生不良反應。對於clozapine 的使用為了減少肺炎或上呼吸道感染的發生，如果病人：一、併用CYP1A2 強效抑制劑 ( 如: fluvoxamine) 或是誘導劑( 如: carbamazepine、抽菸)；二、初始使用clozapine 時；三、併用valproic acid 或是多種鎮靜安眠藥，我們必須要小心監測病人是否有可能會發生肺炎或是上呼吸道感染的可能。
Objective: We reported 6 cases that were suspected of clozapine-induced pneumonia or upper respiratory tract infection (URI). The possible mechanisms and drug-drug interactions involving clozapine among 6 patients were investigated.
Methods: This is a case-series and retrospective chart review study. Patients suspected of clozapine toxicity resulting in pneumonia or URI were collected in a southern psychiatric hospital.Moreover, Spearman’s rank correlation was used to calculate the correlations between the duration and dose of clozapine and Naranjo score.
Results: Twenty-one cases associated with clozapine adverse reactions are reported from January 2011 to November 2014 in a southern psychiatric hospital. Among 21 cases, there were 6 patients (28.6%) that developed pneumonia or URI. Average doses and duration of clozapine are 212.5 ±143.0 mg and 46.7 ± 26.9 months, respectively. The most comorbid medication with clozapine is valproic acid (83.3%), and then hypnotics (66.7%). Particularly, one patient also included fluvoxamine, which is a strong CYP1A2 inhibitor. In addition, the duration of clozapine and Naranjo score were significantly correlated (ρ = 0.80, p = 0.05).
Conclusions: Patients always combined with several antipsychotics, antidepressants, and hypnotics in psychiatric department. Sometimes, some severe adverse reactions were developed after those complicated comorbid medications. In order to decrease the risk of whom using clozapine resulting in pneumonia or URI, we should be aware of: (1) combining with strong CYP1A2 inhibitors (e.g., fluvoxamine) or inducers (e.g., carbamazepine or cigarette); (2) at the beginning of clozapine; (3) comedications with valproic acid or many hypnotics.
