Microsoft Word - 05藥物血中濃度監測注意事項_10101修訂_.doc

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1 藥物血中濃度監測 (TDM) 注意事項 (10101 修訂 ) 藥物有效治療濃度範圍 Toxic level 適當抽血時間再抽血時間注意事項 Amikacin life-threatening infection: mcg/ml serious infection: mcg/ml urinary tract infection: mcg/ml trough < 8 mcg/ml > 40 mcg/ml > 10 mcg/ml 30 分鐘靜脈輸注結束後, 再等 30 分鐘抽血 ( 即靜脈輸注開始後一小時抽血 ) 1-2 天 1. The American Thoracic Society(ATS) recommends trough levels of <4-5 mcg/ml for patients with hospital-acquired pneumonia. 2. Nephrotoxicity may occur from amikacin peak concentrations persistently greater than 20 to 35 mcg/ml and trough concentrations greater than 8 mcg/ml. Gentamicin Vancomycin Carbamazepine life-threatening infection: 8-10 mcg/ml serious infection: 6-8 mcg/ml urinary tract infection: 4-6 mcg/ml Synergy against gram-positive organisms : 3-5 mcg/ml life-threatening infection: 1-2 mcg/ml serious infection: mcg/ml Peak : mcg/ml at least > 10 mcg/ml( 避免發生抗藥性 ) mcg/ml( 確定或高度懷疑以下感染 : bacteremia, HAP, endocarditis, osteomyelitis) 4-12 mcg/ml > 12mcg/mL > 2 mcg/ml >80 mcg/ml (Toxicity is reported at levels sustained above 80 to 100 mcg/ml) > 15 mcg/ml 30 分鐘靜脈輸注結束後, 再等 30 分鐘抽血 ( 即靜脈輸注開始後 1 小時抽血 ) 靜脈輸注完後 1 個小時抽血 ; 目前已不建議抽測 peak. 到達穩定狀態的抽血時間大約是四個劑量之後, 即第 5 個劑量. 2~5 天後 1-2 天 2 天 2-5 天 1. Obtain drug levels after the third dose unless renal dysfunction/toxicity suspected 若是腎功能異常者, 初次採血時間為第三次給藥前即可抽血檢驗 2. The American Thoracic Society(ATS) recommends trough levels of < 1 mcg/ml for patients with hospital-acquired pneumonia. 3. Nephrotoxicity may occur from gentamicin with persistent peak serum concentrations of more than 12 mcg/ml or trough concentrations more than 2 mcg/ml. 1. Therapeutic levels: 10 mcg/ml. For pathogens with an MIC 1 mcg/ml, the minimum trough concentration should be 15 mcg/ml to meet target AUC/MIC of 400(*1). 2. bacteremia, endocarditis, osteomyelitis, meningitis, and hospital-acquired pneumonia caused by S. aureus), trough concentrations of mcg/ml are recommended to improve penetration and improve clinical outcomes (Liu, 2011; Rybak, 2009). 3. The American Thoracic Society (ATS) guidelines for hospital-acquired pneumonia and the Infectious Disease Society of America (IDSA) meningitis guidelines also recommend trough concentrations of mcg/ml. 1. Patient who requires higher level of 8-12 mcg/ml,should be watched closely. CNS side effects(ataxia and nystagmus, 12 mcg/ml) occur commonly at higher dosage levels. 2. If other anticonvulsants are given therapeutic

2 range is 4-8 mcg/ml. Phenobarbital Adults: mcg/ml infants and children: mcg/ml > 40 mcg/ml 10 天後口服後 6~18 小時抽血至少 10 天 1. Toxic concentration: Slowness, ataxia, nystagmus: mcg/ml 2. Coma with reflexes: mcg/ml 3. Coma without reflexes: >100 mcg/ml Phenytoin Valproic acid adults and children: mcg/ml neonates: 8-15 mcg/ml Epilepsy: mcg/ml Mania: mcg/ml Toxic: > 30 mcg/ml Lethal: > 100 mcg/ml 200 mcg/ml (*2; 右側注意事項 ) 一週後 ( 或 5-10 天 ) 口服後 4-8 小時後抽血 ; 給 loading dose: 針劑 1 小時 ; 口服 :4~24 小時. 2~4 天後 6-7 天 2-4 天 1. After a loading dose: If rapid therapeutic levels are needed, initial levels may be drawn after 1 hour (I.V. loading dose) or within 24 hours (oral loading dose) to aid in determining maintenance dose or need to reload. 2. Rapid achievement: Draw within 2-3 days of therapy initiation to ensure that the patient's metabolism is not remarkably different from that which would be predicted by average literature-derived pharmacokinetic parameters; early levels should be used cautiously in design of new dosing regimens 3. Second concentration: Draw within 6-7 days with subsequent doses of phenytoin adjusted accordingly 4. If plasma concentrations have not changed over a 3- to 5-day period, monitoring interval may be increased to once weekly in the acute clinical setting 5. In stable patients requiring long-term therapy, generally monitor levels at 3- to 12-month intervals 6. The acutely hospitalized patient should have serum phenytoin and albumin levels measured every 1 to 3 days when receiving intravenous phenytoin 7. 對於某些病患, 濃度 5-10 mcg/ml 即可得到療效 8. Trough concentrations are generally recommended for routine monitoring. 1. Probability of thrombocytopenia increases with total valproate levels 110 mcg/ml in females or 135 mcg/ml in males. 2. Seizure control: toxicity may occur at mcg/ml

3 3. Mania: risk of toxicity increases at levels >125 mcg/ml Digoxin Congestive heart failure: Arrhythmias: ng/ml (*3; 右側注意事項 ) 5~7 天後其他時機 : 口服後 6~8 小時靜注後 4~6 小時最理想是給藥後的 12 ~24 小時 5-7 天 1. < 0.5 ; probably indicates underdigitalization unless there are special circumstance 2. Digoxin serum concentrations should be obtained within 5-7 days (approximate time to steady-state) after any dosage changes. Continue to obtain digoxin serum concentrations 7-14 days after any change in maintenance dose. Note: In patients with end-stage renal disease, it may take days to reach steady-state.

4 Theophylline Cyclosporine Everolimus Sirolimus Tacrolimus Therapeutic levels: Asthma Adults: 5-15 mcg/ml Children: 5-10 mcg/ml Therapeutic range: Not absolutely defined, dependent on organ transplanted, time after transplant, organ function and CsA toxicity. General range of ( 測定方 :FPIA) Renal transplantation: 3-8 Subependymal giant cell astrocytoma: 5-10 Heart transplantation (unlabeled use): 3-8 (Zuckerman, 2008) (*5) ( 測定方式 :CMIA) Therapeutic range: Not absolutely defined, dependent on organ transplanted, time after transplant, organ function and tacrolimus toxicity. ( 右側 ) 5-20 > 20 mcg/ml(*4) 本院 > 天後,<1 歲者,5 天傳統劑型 : 口服後 2 小時抽血 ; 緩釋劑型 : 口服後 5 小時抽血 ; 靜注停止後 30 分鐘內抽血 3 天後 Steady state occurred within 2 weeks following oral once daily dosing of everolimus 1. The recommended time for collection is 1 hour prior to the next oral dose. 2. Serum drug conc. should be determined 3-4 days after loading doses and 7-14 days after dosage adjustments. 3 天後 2-5 天至少 3 天 5 天 2-3 天 1. Theophylline levels: Serum theophylline levels should be monitored prior to making dose increases; in the presence of signs or symptoms of toxicity; or when a new illness, worsening of a present illness, or medication changes occur that may change theophylline clearance 2. I.V. loading dose: Measure serum concentrations 30 minutes after the end of an I.V. loading dose 3. I.V. infusion: Measure serum concentrations one half-life after starting a continuous infusion, then every hours 1. Method-dependent and specimen-dependent: Trough levels should be obtained: Oral: hours after dose (chronic usage) I.V.: 12 hours after dose or immediately prior to next dose. 2. Toxic level: Not well defined, nephrotoxicity may occur at any level. For renal transplantation, monitor everolimus serum concentrations, especially in patients with hepatic impairment, with concomitant CYP3A4 inhibitors and inducers, and when cyclosporine formulations or doses are changed; monitor cyclosporine concentrations; monitor for proteinuria. Monitoring: Lab Tests 1. sirolimus levels in all patients (especially in pediatric patients, patients 13 years of age weighing <40 kg, patients with hepatic impairment, or on concurrent potent inhibitors or inducers of CYP3A4 or P-gp, and/or if cyclosporine dosing is markedly reduced or discontinued), and when changing dosage forms of sirolimus. 2. LFTs, CBC, cholesterol and triglycerides, serum creatinine, and urinary protein. 1. Heart: Typical whole blood trough concentrations: Months 1-3: Months 4: Kidney transplant: Whole blood trough concentrations: In combination with azathioprine:

5 一般注意事項 : Months 1-3: 7-20 Months 4-12: 5-15 In combination with mycophenolate mofetil/il-2 receptor antagonist (eg daclizumab): Months 1-2: Liver transplant: Whole blood trough concentrations: Months 1-12: Prevention of graft-versus-host disease (unlabeled use): (Uberti, 1999) although some institutions use 5 and an 15 (Przepiorka, 1999; Yanik, 2000) 1. Cyclosporine tacrolimus 及 sirolimus 以紫頭試管送檢, 其他品項皆以紅頭試管送檢檢體量 :3 ml ( 新生兒採血不易可以小試管取血 1 ml) 2. Amikacin sirolimus 與 everolimus 送至外院聯合檢驗所檢驗, 欲先查詢結果, 電話 : (02) Digoxin valproic acid phenytoin 之血中濃度可急作監測 (*) 特殊注意事項 : 1. Although AUC/MIC is the preferred pharmacokinetic-pharmacodynamic parameter used to determine clinical effectiveness, trough serum concentrations may be used as a surrogate marker for AUC and is recommended as the most accurate and practical method of vancomycin monitoring (Liu, 2011; Rybak, 2009).( UpToDate) 2. Valproic acid:some laboratories may report >200 mcg/ml as a toxic threshold, although clinical toxicity can occur at lower concentrations. 3. Digoxin:Critical Values:Toxic: >1.2. The most common manifestations of suspected toxicity are nausea and vomiting, ventricular fibrillation, tachycardia, supraventricular arrhythmia, and second- or third-degree atrioventricular block. Panic value: >3.0.( LEXI-COMP s); Panic level (adult) >2.4 ;Panic level (children) >3 (Stat Ref.2012) 4. Critical Values >20 μg/ml;toxicity can take place at 15 μg/ml. Chronic seizures: μg/ml, Acute toxicity seizures and malignant arrhythmias: >80 μg/ml.( LEXI-COMP s) 5. Concentrations and ranges are dependent on and will vary with assay methodology (chromatographic or immunoassay); assay methods are not interchangeable. ( LEXI-COMP s) 參考資料 : 1. UpToDate 19.3, Micromedex 2, LEXI-COMP s 2012, Lexi-Tox(toxicology):Lab Tests and Diagnostic Procedures, THERAPEUTIC DRUG MONITORING 4. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA 2003 Feb 19;289(7):871-8.

鼠　疫（Plague）

鼠　疫（Plague）鼠疫 (Plague) 一疾病概述 (Disease description) 存在囓齒類及其跳蚤的一種人畜共通傳染病, 並藉跳蚤傳染給各種動物及人類, 其最初反應為跳蚤咬傷部位臨近的淋巴腺發炎, 這就是腺鼠疫, 經常發生於鼠蹊部, 少發生於腋下或頸部,