ST LOUIS (MD Consult) - Following a review of updated clinical data, the US Food and Drug Administration (FDA) has determined that treatment with zonisamide can cause metabolic acidosis in some patients.

Zonisamide is indicated as adjunctive therapy in the treatment of partial seizures in adults with epilepsy.

Metabolic acidosis is a disturbance in the body's acid-base balance that results in excessive acidity of the blood. It is diagnosed by laboratory tests measuring the serum bicarbonate level in the blood to determine the presence and severity of metabolic acidosis.

Metabolic acidosis can result in hyperventilation and nonspecific symptoms such as fatigue and anorexia, or more severe symptoms including cardiac arrhythmias or stupor. Chronic metabolic acidosis can have adverse effects on the kidneys and on bones, and can retard growth in children. Patients with predisposing conditions or therapies, including renal disease, severe respiratory disorders, diarrhea, surgery, ketogenic diet, or certain other drugs may be at greater risk for developing metabolic acidosis after treatment with zonisamide. The risk of zonisamide-induced metabolic acidosis appears to be more frequent and severe in younger patients.

The FDA recommends that health care professionals measure serum bicarbonate before starting treatment and periodically during treatment with zonisamide, even in the absence of symptoms. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing zonisamide (using dose tapering), and modifying the patient's antiepileptic treatment as appropriate. If the decision is made to continue patients with metabolic acidosis on zonisamide, then alkali treatment should be considered.

The FDA is working with the makers of zonisamide to revise the product labeling to reflect this new safety information.
 

基于对最新临床资料的总结分析，美国食品与药物管理局（FDA）得出结论称，唑尼沙胺治疗可导致某些患者发生代谢性酸中毒。

唑尼沙胺目前用于辅助治疗成人癫痫患者的部分性发作。

代谢性酸中毒是一种最终导致血液中酸过多的体内酸碱平衡紊乱。代谢性酸中毒的存在与否以及严重程度通过检测血清碳酸氢盐水平的实验室检查来诊断。

代谢性酸中毒可导致肺换气过度和乏力、厌食等非特异性症状，也可导致心律失常、昏迷等较严重症状。慢性代谢性酸中度可对肾脏或骨骼产生不良影响，并可导致儿童发育迟缓。有某些基础疾病（包括肾病、严重呼吸系统疾病和腹泻）或接受某些治疗（手术、生酮饮食或服用某些其他药物）的患者在经唑尼沙胺治疗后更易发生代谢性酸中毒。唑尼沙胺诱导的代谢性酸中毒似乎在年轻患者中发病率更高，症状也更严重。

FDA建议，在患者开始唑尼沙胺治疗之前，医护人员应检测其血清碳酸氢盐水平，而在唑尼沙胺治疗期间，即使没有代谢性酸中毒的症状，也应定期监测其碳酸氢盐水平。一旦发生代谢性酸中毒且代谢性酸中毒持续存在，应考虑唑尼沙胺减量或停用（停用时应减停），并适当调整患者的抗癫痫治疗方案。如果确定要继续给予代谢性酸中毒患者唑尼沙胺治疗，应考虑同时给予碱治疗。

FDA目前正与唑尼沙胺的生产厂家合作修改该药品的标签，以反映上述新的安全信息。

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