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 30 2.7 64.9% 13.5% 8.1% 5.4% 5.4% 2.7% 1 (1) (2) (3) 2 藥學雜誌第 107 冊 121
用藥安全 Drug Safety 貳 案例報告 85 46.2 kg 4 valproate phenytoin 2010 7 14 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 7/16-18 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
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 7/16-18 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 3.5-11 10 3 /ul 5950 6150 4320 4920 4900 5360 5980 4790 Neut 45-75% 79.6 80.1 58.5 62 49 57.7 54.7 CRP 0-0.5 mmol/l 10.60 13.47 6.982 4.02 2.80 1.34 Hb 12-16g/dL 12.1 12.2 10 10 10 10.4 10.2 9.5 Hct 36-46% 34.5 34.4 28.9 29.6 30.9 31.3 30.7 29 Cr 0.4-1.3 mg/dl 0.48 0.51 0.51 0.38 0.41 BUN 6-26 mg/dl 10 7 9 22 12 Na 134-148 mmol/l 118 127 129 136 136 K 3.5-5.3 mmol/l 3 3.4 4.1 4.4 4.7 Eosin 0-6% 9.6 6 5 6.5 7.9 Albumin 3-5 gm/dl 2.9 3 2.5 Phenytoin 10-20 mcg/ml 18.5 19.4 Valproic acid 50-100 mcg/ml 41 5 54 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
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 0.2-0.5% 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 2004 71% carbamazepine phenytoin valproate 2 9 % carbamazepine valproate valproate carbapenems 124 THE JOURNAL OF TAIWAN PHARMACY Vol.27 No.2
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: 67-74. 2. 10-11. 3. Ertapenem 2010 26(2) 88-94. 4. 2003 239-240. 5. David S.Tatro Drug interaction facts.america, Facts and Comparisons, 2008 1695-1695. 6. 7. lunde JL, Nelson RE, Storanolt HE. Acute seizures in a patient receiving divalproex sodium after stating ertapenem therapy. Pharmacotherapy 2007; 27(8): 1202-1205. 8. Mori H, Takahashi K, Mizutani T. Interaction between valproic acid and carbapenem antibiotics. Drug metabolism reviews 2007; 39(4)647-57. 9. Mancl EE, Gidal BE. The effect of carbapenem antibiotics on plasma concentrations of valproic acid. Ann Pharmacother..2009 Dec; 43(12): 2082-7. Epub 2009 Nov 24. 10. 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): 1383-1391. 11. Hitomi M, Takaharu M. In vitro activation of valproate glucuronidation by carbapenem antibiotics. Journal of health science, 2007 53(3)302-310. 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