Pollak P T, Sketris I S, MacKenzie S L, Hewlett T J
Department of Medicine, Dalhousie University, Victoria General Hospital, Halifax, Nova Scotia, Canada.
Ann Pharmacother. 1995 May;29(5):486-8. doi: 10.1177/106002809502900506.
Clarithromycin is a macrolide antibiotic very similar to erythromycin in structure and spectrum of activity. It has gained increasing use since its release in Canada in May 1992, partly because it is promoted as having less potential for drug interactions and adverse effects. However, as with all new medications, a high degree of vigilance for unreported adverse effects is advisable.
A healthy 53-year-old lawyer was receiving long-term fluoxetine 80 mg hs and nitrazepam 10 mg hs for depression and mild sleep apnea. Subsequent to initiation of treatment with clarithromycin for a respiratory infection, he rapidly developed delirium, which cleared quickly after stopping all 3 medications. The delirium and psychosis did not recur when the infection was treated with erythromycin alone or after restarting fluoxetine and nitrazepam therapy at previous dosages in the absence of antibiotics.
This man's delirium is consistent with fluoxetine intoxication, which appears to have resulted from inhibition of hepatic cytochrome P450 metabolism by clarithromycin. Undiagnosed, this serious drug reaction could have lead to serious medical and social consequences.
As the use of clarithromycin increases, the potential for interactions with other drugs metabolized by the P450 enzyme system may be realized. Clinicians should consider which other medications a patient is receiving before prescribing clarithromycin or any macrolide antibiotic with potential to influence the P450 system.
克拉霉素是一种大环内酯类抗生素,其结构和活性谱与红霉素非常相似。自1992年5月在加拿大上市以来,其使用量不断增加,部分原因是它被宣传为药物相互作用和不良反应的可能性较小。然而,与所有新药一样,对未报告的不良反应保持高度警惕是明智的。
一名53岁健康律师因抑郁症和轻度睡眠呼吸暂停长期服用氟西汀80毫克每晚及硝西泮10毫克每晚。在开始用克拉霉素治疗呼吸道感染后,他迅速出现谵妄,在停用所有三种药物后谵妄迅速消退。当单独用红霉素治疗感染时,或在没有抗生素的情况下按先前剂量重新开始氟西汀和硝西泮治疗后,谵妄和精神病未再复发。
该男子的谵妄与氟西汀中毒一致,这似乎是由于克拉霉素抑制肝细胞色素P450代谢所致。如果未被诊断,这种严重的药物反应可能会导致严重的医疗和社会后果。
随着克拉霉素使用的增加,与其他由P450酶系统代谢的药物发生相互作用的可能性可能会显现出来。临床医生在开具克拉霉素或任何有可能影响P450系统的大环内酯类抗生素之前,应考虑患者正在服用的其他药物。