藥物不良反應的評估及處置 - cgmh.org.tw · 藥物不良反應定義...

嘉義長庚藥劑科林佩姿2014/04/29

藥物不良反應的評估及處置

1

大綱1.

藥物不良反應定義及影響

2.

全國及本院藥物不良反應通報

3.

藥物不良反應評估技巧及原則4.

藥物不良反應的處置

5.

臨床案例討論16.

臨床案例討論2

7.

如何實際應用於工作環境中8.

藥物不良反應評估實際演練

2

藥物不良反應定義

根據ICH與WHO對不良反應的定義

基於證據、或是可能的因果關係

判定在任何劑量下

對藥品所產生之有害的、非蓄意的個別反應

3

藥物不良反應影響

藥物不良反應導致住院的比率

Br J Clin Pharmacol. Mar 1998; 45(3): 301–308. 4


住院中藥物不良反應發生率

Br J Clin Pharmacol. Mar 1998; 45(3): 301–308.

5


對醫療花費和住院天數的影響

JAMA. 1997;277:307‐311

6


增加整體醫療花費

JAMA. 1997;277:307‐311

7

院內通報路徑 1安全通報安全通報

9

院內通報路徑 1

10


藥品不良反應提報藥品不良反應提報

12

院內通報路徑 3 & 4

藥物諮詢與用藥指導服務

藥物諮詢與用藥指導服務

ADR提報ADR提報

13


不良反應提報不良反應提報

14

院內HIS通報畫面

15

查詢/確認通報案件

回覆藥品不良反應提報回覆藥品不良反應提報

16

全國藥物不良反應通報系統

https://adr.fda.gov.tw/Manager/WebLogin.aspx

可申請帳號進行線上通報

可申請帳號進行線上通報

18

線上通報

19

紙本通報

通報表填寫須知

文宣品

通報表填寫須知

文宣品

21

全國 102 /103年前10大不良反應通報藥品

2013 2012

藥品通報件數藥品通報件數

1 Ketorolac 339 Diclofenac 395

2 Diclofenac 335 Ketorolac 296

3 Iopromide 274 Iopromide 255

4 Acetylsalicylic acid 228 Acetylsalicylic acid 235

5 Metoclopramide 184 Vancomycin 199

6 Iohexol 181 Cefazolin 194

7 Levofloxacin 152 Piperacillin+sulbactam 167

8 Piperacillin+sulbactam 151 Phenytoin 162

9 Amoxicillin+Clavulanic acid

150 Metoclopramide 149

10 Cefazolin 149 Amoxicillin+Clavulanic acid

149

22

本院 102 年度不良反應通報藥品

藥品通報件數

Desmopressin 12

Allopurinol 9

Warfarin 8

Cisplatin、Vancomycin 6

Doxazosin、

Oxybutynin 5

Cefazolin、Ceftriaxone、Celecoxib、Ibuprofen、 Methocarbamol、Methotrexate、Metoclopramide、

Oxcarbazepine、Piperacillin +Tazobactam、 Propiverine

4

Aceclofenac、Acetaminophen、 Amoxycillin+Clavulanic

acid、Carvedilol、

Valproate、Digoxin、Itraconazole、 Metronidazole、Pilocarpine、Silodosin、

Sulfamethoxazole 、Terbinafine

3

23

藥物不良反應評估技巧及原則

24


整體評估

非只評估病患或醫生告知的藥品

事件前、後相關之檢查資料

懷疑藥品之血中濃度

考慮併用藥品的可能性

病患本身因素

是否有藥物過敏史

相關疾病

藥物-藥物或藥物-食物交互作用

時序性

回顧疑似藥品使用前後處方之藥物

ADR發生時間一定在用藥後

25


文獻的查證

藥品仿單

醫學書籍

醫學資料庫

Micromedex 、UpToDate、PubMed

、案例報告

ADR發生後的處置方式

停藥後症狀是否緩解或改善

26


訪視住院病患

瞭解用藥情形

疾病進展程度

給予照護衛教

醫護人員討論及回饋

聽取專家意見：會診結果，和照護醫師討論

排除相關疾病

瞭解治療預後

藥師意見回饋

評估表

Naranjo scale、WHO‐UMC causality categories

27

Naranjo score評估問題是否不知

1 關於此種不良反應，以前是否有確定之研究報告? +1 0 0

2 此種不良反應是否發生於服藥之後? +2 -1 0

3 當停藥或服用此藥之解藥，不良反應是否減輕? +1 0 0

4 停藥一段時間再重新服用，同樣的不良反應是否再度發生? +2 -1 0

5 有沒有其他原因(此藥除外)可以引起同樣之不良反應? -1 +2 0

6 當給予安慰劑時，此項不良反應是否也會再度發生? -1 +1 0

7 此種藥物之血中濃度是否達到中毒劑量? +1 0 0

8 藥物劑量與病人的不良反應程度是否成正向關係? +1 0 0

9 病人過去對同樣或類似藥物是否也產生同樣的不良反應? +1 0 0

10 此項不良反應是否有任何的客觀證據可證實? +1 0 0

≦0 分，存疑；1-4 分，可能； 5-8 分，極有可能：≧

9 分，確定

28

WHO‐UMC causality categories因果關係

相關性服藥與ADR發生有合理的時序性

ADR 與病人本身疾病或併用藥物有關

停藥後 ADR減輕

確定

極有可能

可能

存疑

資料不全資料不全，須補充進一步資料才能做評估無法評估資料不全且無法提供更詳盡資料

29


停止造成不良反應的疑似藥物

症狀危及生命或不能忍受

繼續使用造成病人的狀況惡化

有其他替代藥品可供選擇

停止該藥物對疾病的治療是安全的

繼續給予造成不良反應的疑似藥物:

症狀是輕微的，且隨著使用時間慢慢改善

為疾病必須的治療療藥物

沒有替代藥品可以選擇

考慮再次給藥 (rechallenge) 或減敏治療 (desensitization)

30


給予支持或緩解的藥物治療

Hydration, glucocorticoids, warm / cold

compresses, analgesics, antipruritics• 追蹤後續情況

未改善

重新評估

簡化藥物、停止非必要的治療藥物

紀錄

31

臨床案例討論

33

臨床案例討論 1

Na

怎麼那麼低阿?

Type 2 Diabetes mellitus、Chronic hepatitis C、Benign prostate hypertrophy

2013/02/03

No pitting edema34

2013/02/03 、77y/o、♂ 、60kg

我頭暈好久一陣子、昨天吐了三次

項目檢驗值

BUN (B) 11.7

mg/dL

Cr (B) 0.48

mg/dL

ALT/GPT 26

U/L

Calcium 8.3

mg/dL

K 3.48

mEq/L

Na

(134‐148 ) 116.3

mEq/L

Osmolality(B) 249

mosm/KgH2O

Osmolality(U) 434

mosm/KgH2O

Na (U) 110.6

mEq/L

Hyponatremia

35

Plasma sodium < 134 mEq/L

Symptoms

Mild:130‐135 mEq/L: asymptomatic

Moderate :125‐130 mEq/L: nausea、malaise

Severe: < 115‐120 mEq/L

Headache、lethargy、restlessness、disorientation

、

fatigue

、dizziness

、gait disturbances

、 forgetfulness

、confusion

、muscle cramps

Seizures、coma、respiratory arrest

Severe

or rapid

onset hyponatremia

More prominent with large

or rapid

decreases in serum

sodium concentration

Hyponatremia

36

Hyponatremia

Hyponatremia

37

Hyponatremia

38

Hypertonic

hyponatremia (increased serum osmolarity)

Hyperglycemia

↑ Serum glucose 100 mg/dL→↓1.6 mEq/L

Hypertonic infusion (glucose or mannitol)

Isotonic hyponatremia (normal serum osmolarity)

Hyperproteinemia

Hyperlipidemia

Transurethral resection of the prostate (TURP)

Pseudohyponatremia

Hyponatremia

~ hypotonic

39

Hypotonic hyponatremia (decreased serum osmolarity)

Hypervolemic (increased extracellular volume)

Heart failure、cirrhosis、nephrotic syndrome、acute

renal failure 、chronic kidney disease、pregnancy

Hyponatremia

~ hypotonic

40

Euvolemic

(normal extracellular fluid volume)

60% in hyponetramia

Syndrome of Inappropriate AntiDiuretic Hormone (SIADH)

Adrenal insufficiency

Hypothyroidism、water intoxication、thiazide‐type

diuretics、 decreased intake of solutes

Plasma UrineSodium < 134 mEq/L > 30 mEq/LOsmolality < 270 mOsm/kg > 100 mOsm/kg

Patient

Hyponatremia

~ hypotonic

41

Hypovolemic

(decreased extracellular fluid volume)

Renal

sodium loss

Diuretics、osmotic

diuresis (glucose, urea,

mannitol)、ketonuria、bicarbonaturia、adrenal insufficiency 、salt‐wasting nephropathy、cerebral

salt wasting (CSW)

Extrarenal sodium loss

Dermal losses (for example, sweating or burns)、

Gastrointestinal

(GI) losses (for example, diarrhea or vomiting)、blood

loss、fluid sequestration ('third

spacing')

Hyponatremia ~

medication

44

Arginine vasopressin analogsDesmopressin、oxytocin、

vasopressin

45

ADH在視上核和室旁核形成

ADH儲存在此

1.當Osm> 280 mOsm/kg or ECF 滲透壓上升2%，對刺激ADH釋放

2. 當全身循環量減少8~10%，會刺激baroreceptor，增加ADH釋放

和遠端腎元底側端細胞膜(basolateral

membrne)上的V2結合，增加遠端腎小管後

段和集尿管對水的通透性，增加水被再吸收


整體評估

2013/1/16

2012/11/28

47


文獻查證

48


文獻查證

49


文獻查證

50


文獻查證

51

Patients at risk include those with conditions associated with fluid and electrolyte imbalance (ie, cystic fibrosis, heart failure, and renal

disorders), those with habitual or psychogenic polydipsia, and those who are taking drugs that may cause them to drink more fluids, such as

tricyclic antidepressants, SSRIs, opiate analgesics, NSAIDs, lamotrigine, carbamazepine, chlorpromazine, and oxybutynin. Fluid restriction is

recommended and patients should be monitored closely to prevent water intoxication and hyponatremia, particularly children and elderly

patients. Symptoms

associated with hyponatremia include headache, nausea,

vomiting, weight gain, restlessness, fatigue, disorientation, depressed reflexes, muscle weakness, spasms, or cramps, decreased

consciousness, and confusion. Severe symptoms may include seizure, coma, and respiratory arrest,

which may rarely be preceded by an

extreme decrease in plasma osmolality


文獻查證

52


文獻查證

53

Hyponatremia: Use may rarely lead to hyponatremia and extreme

decreases in plasma osmolality, resulting in seizures, coma, and death.

Risk factors

for hyponatremia with desmopressin use include cystic fibrosis, renal dysfunction, heart failure,

young age, advanced age, inappropriate high fluid intake with desmopressin administration, a larger than

recommended dose, and concomitant use of medications known to either increase thirst or cause

syndrome of inappropriate ADH secretion (SIADH). Fluid restriction during use is recommended.


文獻查證

54


文獻查證

55


時序性

2011/09/14

開始服用

Desmopressin 0.1mg/tab

1pc HS

2013/02/03 ADR

病患本身因素

Adrenal insufficiency

2/4 Cortisol : 2.98 ug/dl (PM3‐5:3.1‐16.7)

Vomiting

56

Hyponatremia

~ therapy

57

Goals of therapy

↑ < 10 mEq/L in 24 hours ，↑ < 18 mEq/L in 48 hours

Better in practice

↑ 4 to 6 mEq/L: reverse the most severe manifestations

↑ < 9 mEq/L in any 24‐hour period

The first day's goal may be achieved in the first few

hours (within 6 hours)

Osmotic demyelination syndrome

(橋腦中央髓鞘溶解症)

Dysarthria, dysphagia, paraparesis, behavioral disturbances,

lethargy, confusion, disorientation, obtundation, coma, seizures

The daily rate rather than the hourly rate of correction is

associated with osmotic demyelination

syndrome

Hyponatremia

~ therapy

58

Fluid restriction

(except hypovolemic)

Urine (K+Na) / serum Na ration

>1: <500 ml/day( restriction is less effect)

=1: 500‐700 ml/day

<1: <1000 ml/day

Sodium supplement

(IV or oral)

Vasopressin receptor antagonist

Tolvaptan

Underlying disease control

Stop offending medication

Hyponatremia

~ therapy

60

Loop diuretic

Urine to serum electrolyte ratio >2

Inhibiting sodium chloride reabsorption in the thick

ascending limb of the loop of Henle

Interferes with the countercurrent mechanism and

induces a state of ADH resistance

Resulting less concentrated urine and increased water

loss excretion

Reduce

treatment‐induced extracellular fluid

volume

expansion

In hypovolemic

patient: do not

use furosemide until

volume status corrected

Hyponatremia

~ therapy

61

Acute (< 48 hours) Chronic (> 48 hours)hypo‐

volemic• Stop any diuretics• Correct volume depletion with

IV 0.9% NS • If severe

symptoms

• IV 3% NS• Do not use furosemide until

volume status corrected

• Stop any diuretics• Correct volume depletion with IV

0.9% NS until blood pressure restored and euvolemia

Hyper‐ volemic

‐ • Treat underlying condition• Restrict dietary sodium• Diuretics

• Loop diuretics for HF• Combination spironolactone

with loop diuretic for cirrhosis with ascites

Hyponatremia

~ therapy

62

Acute (< 48 hours) Chronic (> 48 hours)Eu‐volemic

(SIADH)

• Stop cause SIADH

medications• Fluid restrictions• IV 3% NS

• Severe

symptoms and onset < 48 hours

• ↑ 1‐2 mEq/L/hour• 60kg: 500ml , ↑6mEq/L• 50ml bolus then slower

• Monitor Na levels Q2H during acute therapy

• Stop hypertonic saline for • Symptoms resolved• Sodium ≥

120 mEq/L

• Sodium levels have increased by ≥

18 mEq/L

• Stop cause SIADH

medications• Fluid restrictions• Symptomatic

• 0.9% NS • ↑ 0.5‐2 mEq/L/hour

• Asymptomatic• Monitor Na levels closely to

avoid overcorrection


發生後處置

68

116 to 122 (‐6)6*(30+X)=513*X ; X=327 ml

327‐50(ml bolus)=277277/20(ml/h)=14 h


發生後處置

70


討論及回饋

病人衛教

Desmopression 限制水分攝取

給藥前1小時到給藥後8小時

服藥時間 (HS)

控制血糖

服藥依順性 (Cortisone)

71

Naranjo score

~

案例討論 1

評估問題是否不知











≦0 分，存疑；1-4 分，可能； 5-8 分，極有可能：≧

9 分，確定

72

WHO‐UMC causality categories因果關係 ~

案例討論 1



停藥後 ADR減輕

確定

極有可能

可能

存疑


73


我的病人因為肺栓塞和深層靜脈栓塞

使用warfarin 1mg/tab 3pc HS上次檢查(4/16)INR是1.84

怎麼這次(7/12)會變成 >5.54??

78

y/o、Cr: 0.78 mg/dl1.Pulmonary embolism2.Chronic Obstructive Pulmonary Disease with3.Left leg Deep Vein Thrombosis

74


整體評估

用藥史

神經內科 4/1

心臟科 3/18

75


整體評估

心臟科 4/16 *3月

檢驗值

INR: 4/16 1.84

INR: 7/15 >5.54

76


病患本身因素

藥物‐藥物交互作用:藥歷查閱

藥物‐食物交互作用:病人訪談

疾病影響

文獻查證

Micromedex

UpTodate

77


文獻查證

78


文獻查證

79


文獻查證

80


文獻查證

Probable Mechanism: decreased warfarin metabolism Cimetidine inhibits hepatic metabolism of warfarin (over one to

two weeks) and may increase warfarin levels by 20 to 30%.Clinical Management:Use of cimetidine in patients requiring anticoagulation with

warfarin should be avoided when possible. Alternative H2 antagonist agents such as famotidine

or nizatidine are preferable

in patients requiring antisecretory therapy. If cimetidine is used in combination with warfarin, frequent monitoring of the

prothrombin time is necessary until any response on the anticoagulant effect is manifested and is stabilized at an acceptable level.

81


文獻查證‐處置

82



Warfarin overdose

Correcting excess anticoagulation after warfarin

83



No gum bleeding,no ecchymosis,no abdominal pain,no dyspnea,no tarry stool

84


發生後處置

7/12

Vitamin K(10mg/amp) 1pc STAT

7/13

INR: 1.57

7/15 INR: 1.02

Resume warfarin 1mg 2pc HS

7/22 INR: 1.32

85


討論及回饋

可能因交互作用導致INR升高

Warfarin with cimetidine

Famotidine

or antacids would be better!!!

當INR回到理想範圍內時即可加回 warfarin

86

Naranjo score

~

案例討論 2

評估問題是否不知











≦0 分，存疑；1-4 分，可能；

5-8 分，極有可能：≧

9 分，確定

87

WHO‐UMC causality categories因果關係

~

案例討論 2



停藥後 ADR減輕

確定

極有可能

可能

存疑


88

如何實際應用於工作環境中

89

高度警覺性(神經不要太大條)

掌握藥物不良反應評估技巧及原則

文獻查證技巧

Micromedex, Uptodate, Dynamed

Pubmed, Medline

仿單

練習

The More You Practice, the Better You Get!!

藥物不良反應評估實際演練92★6★★92

2014/04/12 Tazocin/phenytoin (skin rash) 9★335678

2013/09/18 Sevikar(腸病變，sprue‐like enteropathy）

90

謝謝聆聽!!

91

藥物不良反應的評估及處置 - cgmh.org.tw · 藥物不良反應定義...

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Transcript of 藥物不良反應的評估及處置 - cgmh.org.tw · 藥物不良反應定義...