臨 床 藥 物 治 療 學 Therapeutics of Clinical Drugs 抗 癲 癇 藥 品 引 起 嚴 重 藥 物 不 良 反 應 高 雄 長 庚 紀 念 醫 院 藥 劑 部 藥 師 李 浩 銓 王 嘉 珍 摘 要 14 phenytoin carbamazepine 9 ( ) drug reaction with eosinophilia and systemic symptoms 壹 前 言 (drug reaction with eosinophilia and systemic symptoms; DRESS) 1940 hydantoin 1959 Saltztein drug-induced pseudolymphoma carbamazepine (anticonvulsant hypersensitivity syndrome; AHS) sulfonamide allopurinol AHS (drug-induced hypersensitivity syndrome; DIHS) 1996 ( ) DRESS ( phenytoin carbamazepine primidone phenobarbital ) 1/1000-1/10000 貳 案 例 報 告 14 161 72 2010 8 10 B valproate phenobarbital clonazepam 2010 10 14 phenobarbital (30 mg) 2.5 # q12h clonazepam (0.5 mg) 1# q8h 3-4 10 20 10 27 carbamazepine (200 mg) 1/2# tid haloperidol (1 mg) 1/2# tid 2010 11 23 96 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.3 Sep. 30 2012
10 phenytoin ( 350 mg 100 mg q12h) carbamazepin 1# tid 11 25 phenytoin phenytoin carbamazepine 450 mg 900 mg phenytoin 11 29 phenytoin 300 mg levetiracetam 11 30 ceftibuten 12 2 ceftriaxone teicoplanin 12 5 (1) ( - ) (2) C3 ( C4) (3) (4) (18%) 12 5 12 6 carbamazepine phenytoin midazolam dexamethasone 12 8 (55-65 bpm) (80-90 mmhg/40-50 mmhg) dopamine dobutamine ST troponin-i CK (creatine kinase )-MB 39.16 ng/ml 61.6 ng/ml VA mode ECMO (venous-artery mode extracorporeal membrane oxygenation) ECMO 12 9-11 methylprednisolone pulse 12 14-15 12 21 12 24 ECMO 100 1 21 表 一 病 人 住 院 期 間 實 驗 室 檢 查 值 (99.11.23-100.1.21) 11/22 11/25 11/30 12/2 12/7 12/8 12/10 12/13 12/17 12/22 1/6 1/14 BUN (mg/dl) 5-20 15 10 7 14 18 16 18 9 7 Cr (mg/dl) 0.2-1 0.45 0.47 0.28 0.42 0.43 0.39 0.31 0.41 0.3 AST (U/L) 13-40 30 27 433 309 305 77 37 33 ALT (U/L) 7-40 14 16 280 241 169 63 31 39 direct bilirubin (mg/dl) <0.5 0.27 0.86 0.66 total bilirubin (mg/dl) 0.1-0.2 0.6 1.7 1.6 CK (U/L) 15-30 42 959 2826 429 106 24 14 16 CK-MB (ng/ml) 0.6-6.3 61.6 239 8.3 2.3 3.7 28 3 Sep. 30 2012 藥 學 雜 誌 第 112 冊 97
臨 床 藥 物 治 療 學 Therapeutics of Clinical Drugs 11/22 11/25 11/30 12/2 12/7 12/8 12/10 12/13 12/17 12/22 1/6 1/14 troponin-i (ng/ml) 0.06 18.7 51 25 1.39 0.3 0.06 Procalcitonin (ng/ml) 2 sepsis like <0.09 0.91 0.7 0.12 <0.09 CRP (mg/l) <5 15.1 8.3 58 39 16 58 13 62.3 12.6 WBC (1000/cmm) 3.9-10.6 9.4 7.8 6.1 2.9 3 2.9 6.9 10.9 7.1 6.9 6 3.4 Segment (%) 42-74 81 78 80 89 89 63 53 69 70 74 81 76 Eosinophil (%) 0-5 2 2.9 2 0 0 0 0 0 0 0 0 0 atypical-lymphocyte (%) 0 1 2 4 1 0 0 Phenytoin (ug/ml) 10-20 4.57 21.7 19.3 19.6 Carbamazepine (ug/ml) 8-12 3.85 3.92 5.5 表 二 病 人 住 院 期 間 用 藥 記 錄 (99.11.23-100.1.21) 11/23 11/25 11/29 11/30 12/2 12/5 12/6 12/7 12/9 12/12 12/20 12/24 12/25 12/29 1/21 carbamazepine 200 mg 1/2# tid 1.5# tid DC (12/5) clonazepam 2 mg 3/4# tid 1/2#tid haloperidol 1 mg 1/2# tid DC (11/29) phenytoin Inj. 250 mg 100 mg q12h DC (11/25) phenytoin 100 mg 1.5# tid 1#tid DC (12/6) levetiracetam 500 mg 1/3# tid DC 1/2# tid 1# tid ceftibuten 100 mg 2# bid DC(12/2) ceftriaxone Inj. 500 mg 1 g q12h DC (12/5) teicoplanin Inj. 200 mg 340 mg qd DC (12/12) ceftazidime Inj. 500 mg 1500 mg q8h DC (12/12) dexamethasone Inj. 5 mg 5 mg q8h DC (12/9) midazolam Inj. 1 mcg/kg/min DC (12/31) topiramate 100 mg 1/2# bid 2/3# tid dobutamine Inj. 250 mg 5-9 mcg/kg/min DC (12/29) dopamine Inj. 200 mg 6-10 mcg/kg/min DC (12/25) milrinone Inj. 0.5 mcg/kg/min DC (12/25) methylprednisolone Inj. 1 g gd DC (12/11) captopril 25 mg 1/2# q8h 1/2#q12h digoxin 0.25 ng 1/4# qd furosemide 40 mg 1/2# qd 參 討 論 11 3 0 (collagen vascular disease) 98 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.3 Sep. 30 2012
1 12 7 2 haloperidol clonazepam levetiracetam acetaminophen carbamazepin phenytoin cephalosporin haloperidol haloperidol clonazepam levetiracetam acetaminophen cephalosporin carbamazepine phenytoin DRESS 2-6 10% ( ) 3 DRESS T- IgE cytochrome P450 arene oxide arene oxide microsomal epoxide hydroxylase (MEH) MEH arene oxide antigen-presenting cell T human herpes virus (HHV)-5,-6, -7 DRESS 4 90% 1-2 5,6 1-2 1 7 8 carbamazepine phenytoin Bocquet DRESS (1) (2) eosinophilia ( 1.5 X 10 9 eosinophils/l) (3) ( 2 ) ( 2 ) 3 11/30 12/2 12/4 12/7 12/9 G a v e n a carbamazepine DRESS 3-4 9 carbamazepine DRESS phenytoin (carbamazepine phenytoin 4 5 2 4 DRESS) 10 Bessmertny 28 3 Sep. 30 2012 藥 學 雜 誌 第 112 冊 99
臨 床 藥 物 治 療 學 Therapeutics of Clinical Drugs 20 86% 5 14 11 Bohan 6 12 4 carbamazepine phenytoin 41 7 carbamazepine phenytoin Chen 10 DRESS phenytoin carbamazepine 12 5 P h e n y t o i n c a r b a m a z e p i n e phenobarbital 70%-80% lamotrigine DRESS phenytoin DRESS carbamazepine DRESS phenytoin DRESS benzodiazepine gabapentin topiramate vigabatrin Valproate DRESS 13,14 肆 結 論 DRESS 參 考 資 料 : 1. Ravelli A, Martini A: Juvenile idiopathic arthritis. Lancet 2007; 369: 767-778. 2. Burns JC, Glode MP: Kawasaki syndrome. Lancet 2004; 364: 533-544. 3. Kano Y, Shiohara T: The variable clinical picture of druginduced hypersensitivity syndrome/drug rash with eosinophilia and systemic syndroms in relation to the eliciting drug. Immunol Allergy Clin N Am 2009;29:481-501. 4. Bohan KH, Mansuri TF, Wilson NM: Anticonvulsant hypersensitivity syndrome: implications for pharmaceutical care. Pharmacotherapy 2007; 27: 1425-1439. 5. Morkunas MR: Anticonvulsant hypersensitivity syndrome. Critical care clinics 1997; 13: 727-739. 6. Schlienger RG, Shear NH : Antiepileptic drug hypersensitivity syndrome. Epilepsia 1998; 39: S3-7. 7. Shapiro L, Shear N: Mechanisms of drug reactions: the metabolic track. Semin Cutan Surg 1996; 15: 217-227. 8. Knowles SR, Shapiro LE, Shear NH: Anticonvulsant hypersensitivity syndrome: incidence, prevention and management. Drug Saf 1999; 21: 489-501. 9. Ganeva M, Gancheva T, Lazarova R, et al: Carbamazepine-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: report of four cases and brief review. Int J Dermatol 2008; 47: 853-860. 10. Mansur AT, Yasar SP, Goktay F: Anticonvulsant hypersensitivity syndrome:clinical and laboratory features. Int J Dermatol 2008; 47: 1184-1189. 11. Bessmertny O, Hatton RC, Gonzalez-Peralta RP: Antiepileptic hypersensitivity syndrome in children. Ann Pharmacother 2001; 35: 533-8. 12. Chen YC, Chiu HC, Chu CY: Drug reaction with eosinophilia and systemic symptoms. Arch Dermatol 2010;16: E1-E7. 13. Klassen BD, Sadler RM: Induction of hypersensitivity to a previously tolerated antiepileptic drug by a second antiepileptic drug. Epilepsia 2001;42:433-435. 14. Kaminsky M, Moreno M, Diaz M, et al: Anticonvulsant hypersensitivity syndrome. Int J Dermatol 2005; 44: 594-598. 100 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.3 Sep. 30 2012
Antipeileptics Causing Serious ADRs Lee Haw-Chyuan, Wang Chia-Chen Department of Pharmacy Administration, Kaoshiung Chang Gung Memorial Hospital Abstract We reported a 14-year-old boy treated with phenytoin and carbamazepine for seizure. On hospital day 9, the patient developed skin rash and fever. His clinical condition worsened with progressive lymphadenopathy, hepatitis, and myocarditis. We suspected that is an anticonvulsant induced DRESS (drug reaction with eosinophilia and systemic symptoms). We reminded the medical staff to pay attention to such adverse drug reactions. Only early detection and immediate withdrawal will minimize the adverse drug reactions (ADRs). 禁 藥 (Doping) 專 有 名 詞 介 紹 ( ) ( ) ( ) / / 28 3 Sep. 30 2012 藥 學 雜 誌 第 112 冊 101