用藥安全 Drug Safety 貳案例報告 kg 4 valproate phenytoin piperacillin/tazobatum 7 16 valproate phenytoin valproate 41 mcg/ml phenytoin 18.5

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1 Drug Safety 用藥安全 Valproate 與 Ertapenem 併用引起交互作用之案例報告東元綜合醫院藥劑部藥師楊慧珠羅仁美摘要 valproate phenytoin ertapenem 4 valproate ertapenem ertapenem valproate valproate ertapenem Drug interaction 壹前言 % 13.5% 8.1% 5.4% 5.4% 2.7% 1 (1) (2) (3) 2 藥學雜誌第 107 冊 121

2 用藥安全 Drug Safety 貳案例報告 kg 4 valproate phenytoin piperacillin/tazobatum 7 16 valproate phenytoin valproate 41 mcg/ml phenytoin 18.5 mcg/ml valproate valproate 500 mg bid 500 mg tid 7 19 E-coli (ESBL) piperacillin/ tazobatum piperacillin/tazobatum ertapenem 7 21 ertapenem valproate phenytoin ertapenem valproate phenytoin ( ) valproate 5 mcg/ml phenytoin 19.4 mcg/ ml ( ) valproate 400 mg IV Q8H 7 26 valproate 54 mcg/ml 8 1 表一病患用藥史 7/14 7/15 7/ /19 7/20 7/21 7/22 7/23 7/24 7/25 7/26 7/27-9 7/30 7/31 8/01 Potassium chloride 40 meg/amp IVF 20 ml QD piperacillin/tazobatum 2.25 g/vial IVF 4.5 g Q8H Acetylcysteine 100 mg/pack PO 1 pack QID Magnesium Oxide 1PC PO 1 PC TID 250 mg/tab QID Propafenone 150 mg/tab Procaterol 25 mcg/tab 200 mg / CC Valproate 1PC 400 mg 2CC 2CC 500 mg/tab TID IV Q8H TID BID Theovent 250 mg/cap PO 1 PC QD Benzyl hydrochlorothiazide 4 mg/tab PO 1 PC QD Isosoribide 60 mg/tab PO 0.5 PC QD Phenytoin 100mg 3PC PO 3 PC HS 100 mg/tan IV Q8H HS Bisacodyl 5 mg/ent PO 2 PC HS 122 THE JOURNAL OF TAIWAN PHARMACY Vol.27 No.2

3 Valproate Ertapenem Ipratropium 0.5 mg/2 ml/pc Terbutaline 5 mg/2 ml/pc Dopamine 800 mg/500cc Albumin 25% 50 ml/vial Ertapenem 1 g/vial Metoclopramide 10 mg/amp Tigecycline 50 mg/vial Mosapride 5 mg/tab 7/14 7/15 7/ /19 7/20 7/21 7/22 7/23 7/24 7/25 7/26 7/27-9 7/30 7/31 8/01 INHA 1 PC Q6H 1 P C 1 P C PRN Q6H INHA 1 PC Q6H 1 P C 1 P C PRN Q6H IVF 1BT QD IVF 1g QD IV 1Amp Q8H IVF 50 mg Q12H PO 1 PC TID 表二實驗室檢查值 99/7/14 99/7/15 99/7/16 99/7/17 99/7/19 99/7/21 99/7/23 99/7/24 99/7/26 99/7/29 WBC /ul Neut 45-75% CRP mmol/l Hb 12-16g/dL Hct 36-46% Cr mg/dl BUN 6-26 mg/dl Na mmol/l K mmol/l Eosin 0-6% Albumin 3-5 gm/dl Phenytoin mcg/ml Valproic acid mcg/ml 參藥物介紹 Valproate GABA GABA valproate glucuronide conjugation mitocjondrial -oxidation 30-50% glucuronide conjugation valproate cytochrome P 450 (80-90%) valproate Ertapenem carbapenems 3 藥學雜誌第 107 冊 123

4 用藥安全 Drug Safety (1) (2) (3) ESBL (extended-spectrum -lactamase) AmpC -lactamase Ertapenem Pseudomonas aeruginosa Acinetobacter spp ertapenem 4 肆討論 ertapenem ertapenem % ertapenem valproate valproate 5,6 valproate ertapenem valprate - Valproate carbapenems valproate (1) carbapenems valproic acid valproic acid (2) carbapenems -glucurronidase valproic acid glucuronide valproic acid ( ) (3) valproic acid glucuronidation UDP-glucuronosyltransferase (UGT) uridine 5'-diphosphate -glucuronic acid (UDPGA) carbapenems UDPGA valproic acid glucuronide carbapenems mutlidrug resistance associated protein valproic acid erythrocytes carbapenems valproic acid 2,7,9-11 valproate carbapenems carbapenems valproate valproate valproate carbapenems valproate valproate 8 valproate ertapenem ertapenem valproate valproate valproate 5-7 伍結論 % carbamazepine phenytoin valproate 2 9 % carbamazepine valproate valproate carbapenems 124 THE JOURNAL OF TAIWAN PHARMACY Vol.27 No.2

5 Valproate Ertapenem 參考資料 : l. Chen CC, Chen TF, Hwang YC, et al: Population-based survey on prevalence of adult patients with epilepsy in Taiwan. Epilepsy Res 2006; 72: Ertapenem (2) David S.Tatro Drug interaction facts.america, Facts and Comparisons, lunde JL, Nelson RE, Storanolt HE. Acute seizures in a patient receiving divalproex sodium after stating ertapenem therapy. Pharmacotherapy 2007; 27(8): Mori H, Takahashi K, Mizutani T. Interaction between valproic acid and carbapenem antibiotics. Drug metabolism reviews 2007; 39(4) Mancl EE, Gidal BE. The effect of carbapenem antibiotics on plasma concentrations of valproic acid. Ann Pharmacother Dec; 43(12): Epub 2009 Nov Nakajima Y, Mizobuchi M, Nakamura M, Takagi H, Inagaki H, Kominami G, et al: Mechanism of the drug interaction between valproic acid and carbapenem antibiotics in monkeys and rats. Drug Metab Dispos 2004; 32(12): Hitomi M, Takaharu M. In vitro activation of valproate glucuronidation by carbapenem antibiotics. Journal of health science, (3) Drug Interactions between Valproate and Ertapenem Hui-Chu Yang, Lo-Jen Mei Pharmacist, Ton Yen General Hospital Abstract Seizures are the clinical manifestation of sudden abnormal electrical discharge of cortical neurons. It can arise spontaneously or from an unknown cause; other causes include head injury, CNS infections, or lesions, cerebrovascular accidents, related to pregnancy. We want to present a case of a patient recently living under the care of a nursing home, diagnosed previously with post stroke seizure. Her seizure had been controlled for many years with valproate and phenytoin as medications. The patient had been confined to a hospital recently for respiratory and urinary tract infection, empirical treatment with IV antibiotics ertapenem started. After 4 days of antimicrobial therapy, seizure developed. We are considering this seizure as a drug-drug interaction induced by concomitant use of ertapenem IV antimicrobial with valproate. Ertapenem cause a decrease in serum level of valproate triggering a seizure episode. After shifting to other antimicrobial, improvement noted, the patient did not develop any seizure episodes. 藥學雜誌第 107 冊 125

middle cerebral artery infarct) 16:43 rt-pa 5 mg 1 41 mg (muscle power, MP) (right middle cerebral artery infarct) diltiazem 15 mg TID PO 10

middle cerebral artery infarct) 16:43 rt-pa 5 mg 1 41 mg (muscle power, MP) (right middle cerebral artery infarct) diltiazem 15 mg TID PO 10 臨床藥物治療學缺血性腦中風的治療之案例報告中國醫藥大學藥學系江尚德台大醫院雲林分院藥劑部藥師張有邑莊謹如廖玲巧摘要 (recombinant tissue plasminogen activator, rt-pa) rt-pa rt-pa 壹前言 (7.3 %) (29.0 %) (11.5%) 1 67.9 % 2 (recombinant tissue plasminogen activator,

用藥安全 Drug Safety 貳 案例報告 kg 4 valproate phenytoin piperacillin/tazobatum 7 16 valproate phenytoin valproate 41 mcg/ml phenytoin 18.5

用藥安全 Drug Safety 貳案例報告 kg 4 valproate phenytoin piperacillin/tazobatum 7 16 valproate phenytoin valproate 41 mcg/ml phenytoin 18.5