左乙拉西坦不良反应分析

doi:10.19803/j.1672-8629.20220719

摘要/Abstract

摘要： 目的分析左乙拉西坦致药品不良反应（ADR）情况和临床特点,为临床安全用药提供参考。方法检索中国知网、维普网、万方数据、中国生物医学文献数据库、PubMed、Embase、Web of Science等数据库,检索时限为1999年1月1日至2022年11月1日,对左乙拉西坦致ADR的个案报道进行分析。结果共获得文献77篇,纳入患者85例,其中男性37例,女性48例。使用左乙拉西坦后出现ADR最短时间为用药后5 min,最长为4年,63.53%发生在用药后30 d内。左乙拉西坦致ADR主要涉及精神异常（28.42%）、皮肤及其附件损害（17.89%）、血液和淋巴系统异常（13.68%）。在85例患者中,55例患者仅作停药处理后痊愈或好转。结论左乙拉西坦可引发一些新的及严重的ADR,需提高医务工作者对其所致ADR的认知,加强其用药过程监测,保障患者用药安全。

关键词: 左乙拉西坦, 精神异常, 皮肤及其附件损害, 血液和淋巴系统异常, 药品不良反应

Abstract: Objective To analyze the occurrence and clinical characteristics of adverse drug reactions (ADR) induced by levetiracetam and to promote rational clinical drug use. Methods Case reports about ADR induced by levetiracetam in Chinese and English databases between January 1, 1999 and November 1, 2022 were collected and analyzed. Results A total of 77 articles about ADR caused by levetiracetam were retrieved and 85 patients (37 men and 48 women) were included. ADR mainly occurred within 30 days (63.53%) of therapy. The top three adverse drug reactions were respectively mental disorders (28.42%), skin and its appendage damage (17.89%) and blood and lymphatic system abnormalities (13.68%). Conclusion Levetiracetam can cause some new and serious ADR. It is necessary to raise the awareness of ADR caused by levetiracetam while medication should be monitored more rigorously to ensure the safety and efficacy of drug use.

Key words: levetiracetam, mental disorders, skin and its appendage damage, blood and lymphatic system abnormalities, adverse drug reaction

中图分类号:

R971.6
R994

梁栋, 罗莉, 程均祥. 左乙拉西坦不良反应分析[J]. 中国药物警戒, 2023, 20(9): 1054-1059.

LIANG Dong, LUO Li, CHENG Junxiang. Adverse reactions caused by levetiracetam[J]. Chinese Journal of Pharmacovigilance, 2023, 20(9): 1054-1059.

参考文献

[1] STOPPA A, ANMELLA G, DELGADO L, et al.A manic episode with psychotic features associated with levetiracetam: a case report, a proposal of prodromal and discriminative symptoms and a possible pathophysiological mechanism[J]. J Clin Psychopharmacol, 2022, 42(3): 316-317.
[2] NARANJO CA, BUSTO U, SELLERS EM, et al.A method for estimating the probability of adverse drug reactions[J]. Clinical Pharmacology and Therapeutics, 1981, 30(2): 239-245.
[3] Chinese Journal of Pharmacovigilance. System-organ code search involved in the WHO adverse drug reaction terminology set[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2008, 5(4): 255-256.
[4] Ministry of Health of the People's Republic of China. Administrative Measures on Reporting and Monitoring of adverse drug reaction (药品不良反应报告和监测管理办法)[EB/OL]. (2011-05-04) [2011-05-24]. https://www.gov.cn/zhengce/2011-05/24/content_2603398.htm.
[5] ZOU X, HONG Z, ZHOU D.Hair loss with levetiracetam in five patients with epilepsy[J]. Seizure, 2014, 23(2): 158-160.
[6] SELVARAJ V, MADABUSHI JS, GUNASEKAR P, et al.Levetiracetam associated acute hepatic failure requiring liver transplantation: case report[J]. J Neurol, 2016, 263(4): 814-815.
[7] GOHIL JR, AGARWAL TS.Levetiracetam adverse drug reaction: pancytopenia[J]. J Pediatr Neurosci, 2018, 13(1): 116-117.
[8] THURMAN DJ, FAUGHT E, HELMERS S, et al.New-onset lesional and nonlesional epilepsy in the US population: Patient characteristics and patterns of antiepileptic drug use[J]. Epilepsy Res, 2019, 157: 106210.
[9] China Anti-Epilepsy Association Expert Group. Expert consensus on the application of antiepileptic drugs after craniocerebral surgery (trial implementation)[J]. Chinese Journal of Neurosurgery(中华神经外科杂志), 2012, 27(7): 751-754.
[10] SIRSI D, SAFDIEH JE.The safety of levetiracetam[J]. Expert Opin Drug Saf, 2007, 6(3): 241-250.
[11] BOU NASIF M, VARADE S, KOUBEISSI MZ.Multifocal myoclonus as a presentation of levetiracetam toxicity[J]. Clin Neurophysiol Pract, 2021, 6: 281-284.
[12] KAPOOR P, MCCABE P, KOTHARI MJ.Levetiracetam induced polyneuropathy: a case report[J]. Electromyogr Clin Neurophysiol, 2005, 45(1): 15-17.
[13] CHOUINARD MJ, NGUYEN DK, CLÉMENT JF, et al. Catatonia induced by levetiracetam[J]. Epilepsy Behav, 2006, 8(1): 303-307.
[14] HWANG ES, SIEMIANOWSKI LA, SEN S, et al.Levetiracetam: an unusual cause of delirium[J]. Am J Ther, 2014, 21(6): e225-e228.
[15] EKINCI N, GÜNEŞ S, EKINCI Ö, et al. Levetiracetam-related mania-like symptoms: an adolescent case[J]. Clin Neuropharmacol, 2019, 42(3): 97-98.
[16] TURATI M, GLARD Y, AFONSO D, et al.Osteochondral alteration in a child treated with levetiracetam: a rare case of juvenile osteochondritis dissecans of the talar head[J]. J Pediatr Orthop B, 2017, 26(2): 189-192.
[17] JADHAV P, KULKARNI T, JADHAV J, et al.Levetiracetam-induced systemic lupus erythematosus[J]. J R Coll Physicians Edinb, 2021, 51(1): 58-60.
[18] CHAU K, YONG J, ISMAIL K, et al.Levetiracetam-induced severe acute granulomatous interstitial nephritis[J]. Clin Kidney J, 2012, 5(3): 234-236.
[19] KARADAG AS, BILGILI SG, CALKA O, et al.A case of levetiracetam induced bullous pemphigoid[J]. Cutan Ocul Toxicol, 2013, 32(2): 176-178.
[20] FUJIKAWA M, KISHIMOTO Y, KAKISAKA Y, et al.Obsessive-compulsive behavior induced by levetiracetam[J]. J Child Neurol, 2015, 30(7): 942-944.
[21] XIONG N, HOU L, LU N, et al.Probable levetiracetam-related serum alkaline phosphatase elevation[J]. BMC Neurol, 2012, 12: 97.
[22] JU J, ZOU LP, SHI XY, et al.Levetiracetam: probably associated diurnal frequent urination[J]. Am J Ther, 2016, 23(2): e624-e627.
[23] FAGAN A, FULD J, SOON E.Levetiracetam-induced eosinophilic pneumonia[J]. BMJ Case Rep. 2017, 2017: bcr2016219121.
[24] GUPTA M.Levetiracetam-induced leukocytoclastic vasculitis[J]. Indian J Pharmacol, 2017, 49(1): 124-126.
[25] SEREFLICAN B, KARAPINAR T, DUZCU SE, et al.Disseminated eruptive granuloma annulare induced by levetiracetam[J], Cutan Ocul Toxicol, 2017, 36(3): 300-301.
[26] MCDONALD D, SULTAN R, VISWANATHAN A, et al.A rare case of levetiracetam and drug-induced idiopathic aseptic meningitis in a pediatric patient[J]. Pharmacotherapy, 2019, 39(1): 109-113.
[27] OZDEMIR H, SUMER S, KARABAGLI H, et al.B cell aplasia and hypogammaglobulinemia associated with levetiracetam[J]. Ann Saudi Med, 2018, 38(1): 65-68.
[28] LEVY ZD, SLOWEY M, SCHULDER M. Acute generalized exanthematous pustulosis secondary to levetiracetam and valproic acid use[J]. Am J Emerg Med, 2017, 35(7): 1036.e1-1036.e2.
[29] NEWSOME SD, XUE LY, JENNINGS T, et al.Levetiracetam-induced diffuse interstitial lung disease[J]. J Child Neurol, 2007, 22(5): 628-630.
[30] AKSOY D, CEVIK B, KURT S, et al.Hypokalemia and hypomagnesaemia related to levetiracetam use[J]. J Clin Neurosci, 2014, 21(11): 1989-1990.
[31] BORA İ, DEMIR AB, BAŞKAN EB, et al. A case of mycosis fungoides-like lesions developing after levetiracetam therapy[J]. Epilepsy Behav Case Rep, 2014, 2: 192-195.
[32] ZHANG JF, PIRYANI R, SWAYAMPAKULA AK, et al.Levetiracetam-induced aggression and acute behavioral changes: a case report and literature review[J]. Clin Case Rep, 2022, 10(3): e05586.
[33] DELANTY N, JONES J, TONNER F.Adjunctive levetiracetam in children, adolescents, and adults with primary generalized seizures: open-label, noncomparative, multicenter, long-term follow-up study[J]. Epilepsia, 2012, 53(1): 111-119.
[34] TEINHOFF BJ, STAACK AM.Levetiracetam and brivaracetam: a review of evidence from clinical trials and clinical experience[J]. Ther Adv Neurol Disord, 2019, 12: 1756286419873518.
[35] ALTıNÖZ AE, TOSUN AŞ, GÜZEL BB, et al. Levetiracetam induced hypomania: a case report[J]. Ther Adv Drug Saf, 2019, 10: 2042098619876754.
[36] STOPPA A, ANMELLA G, DELGADO L, et al.A manic episode with psychotic features associated with levetiracetam: a case report, a proposal of prodromal and discriminative symptoms and a possible pathophysiological mechanism[J]. J Clin Psychopharmacol, 2022, 42(3): 316-317.
[37] CHEN B, CHOI H, HIRSCH LJ, et al.Cosmetic side effects of antiepileptic drugs in adults with epilepsy[J]. Epilepsy Behav, 2015, 42: 129-137.
[38] ZOU X, HONG Z, ZHOU D.Hair loss with levetiracetam in five patients with epilepsy[J]. Seizure, 2014, 23(2): 158-160.
[39] CALABRÒ RS, BRAMANTI P, SPINA E, et al.Can zinc depletion play a role in LEV-induced hair loss? Considerations from a case study[J]. Epilepsy Behav, 2013, 29(1): 254-255.
[40] DANESE E, MONTAGNANA M, FAVALORO EJ, et al.Drug-induced thrombocytopenia: mechanisms and laboratory diagnostics[J]. Semin Thromb Hemost, 2020, 46(3): 264-274.
[41] KIM J, SHIN JW.Levetiracetam-induced thrombocytopenia in a patient with status epilepticus[J]. Epileptic Disord, 2017, 19(1): 104-108.
[42] GARCÍA CR, ROMERO BM, OLID-VELILLA M, et al. Pancytopenia associated with levetiracetam in an epileptic woman[J]. BMJ Case Rep, 2016, 7: bcr2016217407.
[43] SINGH T, NIAZI M, KARRI K, et al.A rare case of DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome with cholecystitis in a patient on levetiracetam[J]. Cureus, 2019, 11(3): e4245.
[44] MOINUDDIN IA.Suspected levetiracetam-induced rhabdomyolysis: a case report and literature review[J]. Am J Case Rep, 2020, 21: e926064.