Download Can we prescribe digoxin and diuretics in the same

實證醫學報告
• 壢新醫院 家醫科
• 住院醫師 楊豐碩/
楊豐碩/ 指導醫師:
指導醫師: 蕭添木 主任
• 日期：
日期：2010/03/16
Scenario 臨床情境
• 醫院門診電腦有藥物反應不良通報系統，若同時開立
強心劑digoxin 和所有含利尿劑diuretics的藥物時，怕
影響鉀離子K+，會有不可以合併使用之警示並電腦卡
死，無法開立。委員會討論時，有專科醫師反應
digoxin和diuretics合併使用對鉀離子K+的影響並不嚴
重到無法合併的地步，建議取消電腦警示卡死系統，
不要設限。你是委員會EBM負責小組成員,你會向委員
會做什麼建議？
2
1
想法…….
• 臨床情境並未指出病人罹患的疾病和使用
digoxin, diuretics的原因。
• 因此在開始進行EBM研究前, 應先分析這兩種
藥物最常見的適應症。
3
Secondary Data Base
• UpToDate
4
2
Keyword: Digoxin
->Method of digitalization
• Digitalis has important positive inotropic effects
and electrophysiologic actions.
• Digoxin is the most commonly used digitalis
glycoside.
• The primary uses of digoxin are for symptom
control in heart failure and, less often, for rate
control in atrial fibrillation.
5
Keyword: diuretics
-> Mechanism of action of diuretics
• The diuretics are generally divided into 3 major classes,
which are distinguished by the site at which they impair
sodium reabsorption:
• Loop diuretics act in the thick ascending limb of the loop
of Henle.
• Thiazide-type diuretics in the distal tubule and connecting
segment (and perhaps the early cortical collecting tubule)
• Potassium-sparing diuretics in the aldosterone-sensitive
principal cells in the cortical collecting tubule
6
3
Common Indications of Diuretics
• Thiazide-type diuretics (e.g. Trichloromethiazide)
edema, HTN, CFH, diabetes insipidus
• Loop diuretics (e.g. Furosemide): edema, CHF,
fluid overload
• Potassium-sparing diuretics (e.g. Spironolactone):
CHF, ascites, hypokalemia, hyperaldosteronism
7
PICO-1
• Patient or Population:
Congestive heart failure
• Intervention:
Digoxin and diuretics (combination or double therapy)
• Comparison:
Diuretics only (or combines with other medications)
• Outcomes:
Heart failure symptoms improving or worsening
8
4
完整問題描述（
完整問題描述（Question
sentence，
，hypothesis）
）
• Congestive heart failure (CHF) is a common indication of
combination therapy of digoxin and diuretics. For this
reason, we focus on CHF patients treated by diuretics with
or without digoxin.
• We will try to find evidences of benefit or disadvantage in
these treatments and to answer the question: Can we
prescribe digoxin and diuretics in the same time?
9
Secondary Data Base
• UpToDate Keywords: Digoxin, Diuretics,
Congestive heart failure
10
5
Keyword: Digoxin
->Topic: Method of digitalization
• There are a number of important drug interactions.
• Diuretics may increase digitalis toxicity as a result
of a decrease in the glomerular filtration rate (GFR)
and the development of electrolyte abnormalities,
especially hypokalemia.
11
UpToDate
key words: diuretics and digoxin
• Topic: Use of diuretics in heart failure (2009)
• Most patients with CHF and edema are initially
treated with the combination of an oral "loop"
diuretic (such as furosemide) plus a low sodium
diet.
12
6
UpToDate
key words: diuretics and digoxin
• Thiazide diuretics can be added for a synergistic
effect.
• Aldosterone antagonism (e.g.
spironolactone) can be added to loop diuretics
to modestly enhance the diuresis and minimize
potassium loss; more importantly, these drugs
improve survival in certain types of patients.
13
Primary Data Base-Pub Med
•
•
•
•
Limit: human, clinical trail
key words:
(1) Digoxin AND diuretics 237 results
(2) Narrow down results by add third key
words: hypokalemiaresults: 4 itemsno
appropriate or no full text
14
7
• Change key words to: digoxin AND diuretics
AND congestive heart failure
• 202 results
• Add limit: Randomized Controlled Trial
• 139 results
• Change key words to : digoxin, diuretics
combination AND congestive heart failure 44
results
15
Study 1
• Superiority of “Triple” Drug Therapy in
Heart Failure: Insights from the PROVED
and RADIANCE Trials
•
JAMES B. YOUNG. Et. Al. J Am Coll Cardiol 1998;32:686 –92.
• Subject: We sought to study the efficacy of “triple”
therapy with digoxin, diuretic and ACEI compared to
other combinations of these drugs in patients with
symptomatic left ventricular systolic dysfunction.
16
8
Methods:
Including: The PROVED (Prospective
Randomized Study of Ventricular Function and
Efficacy of Digoxin) and RADIANCE
(Randomized Assessment of Digoxin and
Inhibitors of Angiotensin-Converting Enzyme)
trials
17
Methods:
• Both studies were multicenter, double-blind,
randomized, placebo-controlled, parallel group
protocols.
• Sample size: PROVED
88, RADIANCE->178,
total 266 patients.
18
9
19
Statistical methods:
• The two trial populations were pooled and
reanalyzed according to treatment allocation after
baseline characterization and randomization.
• Differences of baseline characteristics: chi-Square test
for categorical data and analysis of variance or
Student’s t test for continuous variables.
20
10
21
Statistical methods:
• Differences of frequency of worsening HF: the chisquare test.
• The Kaplan–Meier life table technique and the Cox
proportional-hazards method: compare time to
treatment failure among the therapeutic groups.
• Differences in maximal treadmill exercise testing and
change in left ventricular ejection fraction:
nonparametric methods and Student’s t test,
respectively.
22
11
Methods
• Patients were withdrawn from either study for
adverse reactions during follow-up or if their
heart failure worsened sufficiently to require
one of the following therapeutic interventions:
augmentation in therapy for heart failure, visit
to an emergency room for increasing heart
failure or hospitalization for heart failure.
23
Main results: Worsening HF occurred in...
• 4 of the 85 patients who continued triple
therapy (4.7%) compared to:
• 18 of the 42 patients (19%) on digoxin and
diuretic therapy (p < 0.009)
• 23 of the 93 patients (25%) on ACEI and
diuretic therapy (p <0.001)
• to 18 of the 46 patients (39%) on diuretic alone
(p < 0.001).
24
12
25
26
13
Conclusion:
• In patients with severe systolic dysfunction, triple
therapy with digoxin, diuretic and ACEI (triple
therapy) significantly reduced the risk of
worsening heart failure and improved exercise
tolerance during short-term follow-up compared to
double therapy with diuretic plus ACEI or digoxin
or monotherapy with diuretic alone.
27
Conclusion:
• Our results suggest consideration of triple therapy
as the initial management of patients with
symptomatic heart failure due to severe systolic
dysfunction.
28
14
Discussion:
• Another rationale for combining digoxin and ACEI
is the tendency for these latter agents to increase
serum potassium which could limit digoxin
toxicity.
29
Critical Appraisal
Title: Superiority of “Triple” Drug Therapy in Heart Failure: Insights from the PROVED and
RADIANCE Trials
Journal
Valid
Apply
to
patient
J Am Coll
Cardiol
Year
1998
Author
JAMES B. YOUNG. Et. Al.
★問題與我的問題吻合嗎? ■ Yes □ No □ can’t tell (和臨床情境部份吻合
和臨床情境部份吻合)
收集適當的研究設計型態的研究嗎? ■ Yes □ No □ can’t tell
值得繼續評估? ■ Yes □ No
納入分析研究是否完整? ■ Yes □ No □ can’t tell
評估個別研究的有效性? □ Yes □ No ■ can’t tell
結果運用於我的病人狀況? ■ Yes □ No □ can’t tell (部份適合)
結論有經過綜合性考量(benefit/ harm/cost)? □ Yes ■ No □ can’t tell
30
15
Appraisal
Superiority of “Triple” Drug Therapy in Heart Failure: Insights from the PROVED and
RADIANCE Trials
期刊
J Am Coll Cardiol
年份
1998
作者
JAMES B. YOUNG. Et.
Al.
■Yes □No
Blinding ■Yes □No
Measure: gold standard ■ Yes □ No
Follow-up: ? %
ITT analysis □ Yes ■ No (?)
Randomized
Valid
Sample size: intervention group 85,93,42; control group: 46
Impact
Group
% of
HF
worsen
Hazard Ratio
(95%CI)
P
Relative Risk
Reduction
(RRR)
Absolute
Risk
Reduction
(ARR)
Number
Needed to
Treat
(NNT)
Triple Tx
4.7
-
-
0.879
34.3%
2.91
ACEI+Diur
25
5.8 (2.02-16.9)
0.001
0.358
14%
7.14
Dig+Diur
19
4.2(1.2-13.8)
0.02
0.512
20%
5
Diur. Only
39
10.2(3.45-30.1)
<0.001
-
-
-
31
文章可能存在偏差
• Short duration of follow-up (150 days)
• No detail data about adverse effects, serum
potassium level and digoxin toxicity
• 作者認為使用digoxin時, 併用ACEI可增加 鉀
離子濃度,進而減少digoxin toxicity 。 但論文中
並沒有鉀離子和digoxin toxicity的數據。
32
16
小結論-1
• For CHF due to systolic dysfunction: triple
therapy> (digoxin +ACEI or digoxin+diuretics)>
diuretics only
• 並沒有指出不能併用digoxin
+ diuretics
併用
•
•
Note: in this study: Serum [digoxin] mean: 1.0-1.2ng/ml
Diuretics (furosemide) dose mean: 74-79mg
33
小結論-2
• No data mentioned about hypokalemia,
hyperkalemia or adverse effect due to combimation
of digoxin and diuretics in this paper.
34
17
下一步呢?
• 臨床情境:醫院門診電腦系統，因擔心利尿劑
影響鉀離子,故無法合併使用digoxin
• 想法:接下來可探討利尿劑對鉀離子的影響
35
PICO-2
• Patient or Population:
Congestive heart failure or hypertension
• Intervention
Diuretics
• Comparison
Placebo or other agents
• Outcomes
Hypokalemia
36
18
UpToDate: Diuretic+Hypokalemia
• Topic: Diuretic-induced hypokalemia (Burton D.R.
UpToDate 2009)
• Hypokalemia is a relatively common problem with diuretic therapy.
• The decrease in [k+] after prolonged administration of 50 mg/day
of hydrochlorothiazide is ~ 0.5 meq/L
• ** Co-Diovan (160): 含hydrochlorothiazide 12.5mg
• ** Behyd: Benzyl Hydrochlorothiazide 4mg (HTN dose: 12.550mg/day)
37
UpToDate: Dose-dependence of
thiazide-induced side effects
•
Metabolic complications induced by bendrofluazide in relation to daily dose (multiply
by 10 to get equivalent doses of hydrochlorothiazide). Increasing the dose led to
progressive hypokalemia and hyperuricemia and a greater likelihood of a mild
elevation in the fasting blood glucose (FBG), all without a further reduction in the
systemic blood pressure. Each treatment group contained approximately 52 patients.
Data from Carlsen, JE, Kober, L, Torp-Pedersen, C, Johannsen, P, BMJ 1990;
300:975.
38
19
UpToDate: Diuretic-induced hypokalemia
• Time course — In stable patients on a fixed diuretic dose,
K+ loss, occurs only during the first two weeks of therapy
before a new steady state is established.
• Thus, a stable pt with a normal [K+] at 3 weeks is not at
risk of late hypokalemia unless the diuretic dose is
increased, extrarenal K+ losses increase, or dietary K+
intake is reduced.
39
UpToDate: Diuretic-induced hypokalemia
• Prophylactic therapy to prevent hypokalemia is an
important issue in patients with CHF and cirrhosis.
• Among patients with CHF, hypokalemia may precipitate
serious arrhythmias. It is recommended that the serum [K+]
be maintained between 4.0 and 5.0 meq/L.
40
20
EBM Data Base-Cochrane Library
• key words: Diuretic AND Hypokalemia only
one result
• Continuous infusion versus bolus injection of loop
diuretics in congestive heart failure.
•
Salvador DRK, Punzalan FE, Ramos GC Cochrane Database of Systematic
Reviews 2005, Issue 3.
41
Study-2: Main Results
• Eight RCT trials involving 254 pt were included.
Electrolyte disturbances (hypokalemia,
hypomagnesemia) were recorded in 3 trial (71pt):
• No detail data of hypokalemia.
42
21
Primary Data Base-Pub Med
• Limit: human, clinical trail
• key words: Diuretic AND Hypokalemia ->279
results
• Switch limit from clinical trail to RCT 168
results
• Add key word: Thiazide 96 results
• Limit: full text 19 results
43
Study-3
• Long-Term Antihypertensive Efficacy and Safety
of the Oral Direct Renin Inhibitor Aliskiren: A 12Month Randomized, Double-Blind Comparator
Trial With Hydrochlorothiazide
Roland E. et. al. Circulation 2009;119;417-425;
44
22
Methods:
• Including : outpatients > 18 y/o with essential
HTN.
• Patients with a history of severe
cardiovascular or cerebrovascular disease or
other severe lifethreatening medical conditions
were excluded.
45
Study Design
• This randomized, double-blind, parallel-group,
active-controlled, dose-titration study was
performed at 132 study centers in Belgium
(11), Finland (6), Germany (34), Italy (43), the
etherlands (20), and Spain (18).
46
23
47
48
24
49
50
25
Results
• Serum [K+] < 3.5 mmol/L were more frequent (P<0.0001)
with hydrochlorothiazide than with the aliskiren regimen
(17.9% versus 0.9%)
• The incidence of [K+] > 5.5 mmol/L was higher with the
aliskiren regimen than with the hydrochlorothiazide regimen
(6.5% versus 3.7%, P< 0.05).
• 無詳細數據(如 [K+]平均下降值…等)
• 使用hydrochlorothiazide (25mg QD) 之 hopokalemia發
生率: 17.9%, hyperkalemia: 3.7%
51
Study-4
• Hydrochlorothiazide – amiloride versus
hydrochlorothiazide alone for essential
hypertension: effects on blood pressure and
serum potassium level
• Pierre Larochelle. Et. Al. CAN MED ASSOC J, VOL. 132, APRIL 1,
1985
•
*** Hydrochlorothiazide – amiloride (5,50mg/tab )
商品名: Moduretic, dose: 1-2# QD
52
26
Methods:
• Including : The study was limited to ambulant
patients of either sex between 18 ~ 70 y/o with
essential hypertension who after not being treated
for at least 2 weeks prior to the study had a DBP
while supine of 95 to 109 mm Hg and a [K+] >= 3.5
mmol/L.
53
Methods:
• The patients were drawn from 42 centres across
Canada; 26 centres (62%) accounted for 272 (80%)
of the 338 patients who entered the study.
54
27
Methods:
• Excluding: serum [K+] < 3.5 mmol/L at the end of the
screening period; a hx of hyperkalemia; evidence of
significant renal or hepatic disease, 2nd HTN, AMI
within 6 months or a hx of >= 2 AMI, angina; a hx of
arrhythmia requiring therapy; a history of CVA or
hypertensiveencephalopathy;
• Excluding: medication with digitalis, anticoagulants
or psychotropic drugs; pregnancy; and other
concurrent severe disease that would have
precluded participation or survival.
55
Study Design
• The study was divided into 3 phases: a singleblind
prerandomization screening period of 2 to 4
weeks‘ duration; a double-blind "titration" period
of 4 weeks‘ duration, in which the patients were
randomly assigned to one of two forms of
treatment; and a maintenance period, during which
the patients continued to receive the assigned
treatment for a further 4 weeks 'at the dosage
established during the titration period.
56
28
No. of hypokalemia after 8 weeks of treatment
57
Results: The mean [K+] ↓ after 8
weeks treatment of...
• Hydrochlorothiazide (HCTZ 50mg 1-2 # QD)
alone: [K+]: 4.15+-0.46 3.75+-0.46 (-0.4 mmol/L)
hypokalemia: 37 (29%) of the 129 patients
• HCTZ-amiloride (50/5mg 1-2# QD):
[K+]: 4.31+-0.35 4.11+-0.44 (-0.2 mmol/L)
hypokalemia: only 18 (14%) of the 133 patients
58
29
小結論
• 使用hydrochlorothiazide (25mg QD) 之
hopokalemia發生率: 17.9%, hyperkalemia: 3.7%
• Hydrochlorothiazide (HCTZ 50mg 1-2 # QD)
alone: [K+] 平均下降: 0.4 mmol/L
hypokalemia發生率: 29%
• HCTZ-amiloride (50/5mg 1-2# QD):
[K+] 平均下降: 0.2 mmol/L
hypokalemia:發生率14%
59
Study 5
• Cardiac arrhythmias induced by
hypokalaemia and potassium loss during
maintenance digoxin therapy
• E. Steiness and K. H. Olesen. British Heart Journal, 1976,
38, 167-172.
60
30
Methods:
Including: 12 pt with advanced CHF and 1) received
maintenance digoxin therapy for >= 1 month and
showed normal [digoxin], 2) in a stable situation on
maintenance diuretics treatment, and 3) the subjects
presented normal [K+] and were apparently in stable
K+ balance while receiving a standard supplement of
KCl of 3g/day or a K sparing drug additional diuretic
if required.
61
Methods
• Hold KCl or K-sparing drug
• digoxin (0.125-0.5mg/day) + Lasix 80160mg/day, diet with 30meqK+/day for 7 days
• collect 24hr urine, check serum [K+] and body
weight QD
• check serum digoxin at beginning and end of the
study
62
31
1.186 ng/ml
1.318ng/ml
63
64
32
65
66
33
Results
•
•
•
•
•
Mean digoxin dose: 0.3mg +- 0.06mg
Mean serum [digoxin]: 1.19ng/mL
Lasix dose: 80-160mg/dL
Mean serum [K+] decrease: 0.96 mmol/L
本實驗結果無法確定arrhythmia是因低血鉀所導
致或是併用digoxin and diuretics的結果
67
Study 6
• Digoxin and reduction in mortality and
hospitalization in heart failure: a
comprehensive post hoc analysis of the
DIG trial
• Ali Ahmed et. Al. European Heart Journal (2006) 27,
178–186
68
34
Study Design
• The DIG trial was a randomized controlled trial to
evaluate the effects of digoxin on mortality and
hospitalization in 7788 ambulatory adults with
chronic HF and normal sinus rhythm.
• Patients received digoxin (0.125, 0.25, 0.375, and
0.50 mg/day) or matching placebo on the basis of
age, sex, weight, and serum creatinine level. Most
patients were receiving ACEI and diuretics.
69
70
35
71
72
36
73
Suggestions
• On the basis of our observations, we
suggest that for young men with
clinically stable HF (no pulmonary
congestion by chest X-ray and not
receiving diuretics) and normal renal
function, a daily digoxin dose of 0.25
mg would be therapeutic.
74
37
Discussion
• In contrast, for HF patients who are
elderly, women, have pulmonary
congestion or receiving diuretics, or
have renal impairment, a daily dose of
0.125 mg would probably be more
appropriate.
75
Discussion
• Pts with multiple risk factors for high SDC,
such as an elderly woman with CKD or a
woman with pulmonary congestion receiving
a non-potassium-sparing diuretic,
digoxin should be started at a daily dose of
0.0625 mg. When possible, SDC should be
monitored to guide therapy for these patients.
76
38
臨床運用
• 根據上述文獻回顧結果,Thiazide and loop
diuretics確實會有導致低血鉀的可能性。而且其
發生率和藥物種類與劑量相關。因此CHF病人最好
將其[K+]保持在4~5mmol/L之間比較安全。若利尿
劑劑量種類改變或病人臨床狀況改變時應特別注
意[K+] 。
77
臨床運用
• 無證據顯示digoxin絕對不能和利尿劑併用。
• 合併使用這兩種藥物治療CHF時,應對危險因子(eg.
elderly woman with CKD or a woman with pulmonary
congestion receiving a non-potassium-sparing
diuretic )仔細評估。調整digoxin劑量以保持低的
digoxin血中濃度(0.5-0.9ng/mL)可降低死亡率。
• Digoxin合併使用利尿劑和ACEI(Triple therapy)可
降低CHF惡化比例。
78
39
去醫療化的話語回答
• 門診病人會同時使用Digoxin (商品名:Lanoxin
隆我心錠)和利尿劑的常見適應症是心衰竭
(CHF)。
• 根據上述文獻回顧結果顯示:門診常用的兩類利
尿劑(Thiazide (例如hydrochlorothiazide) 及loop
diuretics (例如Furosemide適泄錠))確實會有
導致血中鉀離子濃度([K+])下降或過低的可能
性。而且其發生率和藥物種類與劑量相關。
79
去醫療化的話語回答
• 每天使用利尿劑hydrochlorothiazide 25mg低血
鉀的發生率約 : 18% (若增加到50-100 mg, 低血
鉀的發生率約 : 29 %, [K+]平均下降: 0.4 mmol/L)
• 每天使用利尿劑來適泄錠(Furosemide, Lasix)
80-160mg 平均使[K+]下降0.96 mmol/L.
80
40
去醫療化的話語回答
• 心衰竭病人如果血中鉀離子濃度過低時,容易發
生心律不整。有文獻指出鉀離子濃度過低也會
增加digoxin中毒的可能性。
• 因此CHF病人最好將其[K+]保持在4~5mmol/L之
間比較安全。若利尿劑劑量種類改變或病人臨
床狀況改變時應特別注意[K+] 。
81
去醫療化的話語回答
• 無證據顯示digoxin絕對不能和利尿劑併用。
• 合併使用這兩種藥物治療CHF時,應對危險因子
(例如:老年人,腎功能異常, 肺鬱血, 使用非保鉀
型利尿劑等 )仔細評估。適度調整digoxin劑量以
保持低的digoxin血中濃度(0.5-0.9ng/mL), 可降
低CHF死亡率。
• Digoxin合併使用利尿劑和ACEI(Triple therapy)
可降低CHF惡化比例。
82
41
去醫療化的話語回答
• 建議醫院門診電腦系統改成:若為CHF病人同時
開立強心劑digoxin 和含利尿劑藥物時提醒醫
師和藥師注意病人的鉀離子濃度、digoxin濃度
及危險因子(腎功能、年齡及臨床狀況等)，適
度調整digoxin劑量以保持低的digoxin血中濃度
(0.5-0.9ng/ml), 可降低CHF死亡率。
• 併用ACEI可以減少血中鉀離子濃度過低的危
險， 也可降低CHF惡化比例。
83
其他相關資料
42
壢新醫院標準值
•
•
•
•
Digoxin: 0.8 - 2.0 ng/mL
K+: 3.4 –4.8 meq/L
Na: 134 – 148 meq/L
Creatinine: 0.4 – 1.4 mg/dL
85
Keyword: Digoxin
->Method of digitalization
• INITIATION OF THERAPY — The electrolyte
and renal status should be ascertained before
treatment and periodically after treatment.
• Hypokalemia, for example, may promote the
development of digitalis-induced arrhythmias.
• Renal dysfunction, on the other hand, may result in
higher than anticipated serum drug levels
86
43
UpToDate
• Time course of the diuresis and associated
complications — The fall in cardiac output
induced by diuretic therapy has important
implications for the time course of the diuresis.
87
UpToDate
• In general, the diuresis and kaliuresis in stable
patients are maximal on the first few days
(typically on the first dose) and are complete by
two weeks; at this time, the diuretic will maintain
the fluid loss that has been attained but will not
induce further fluid loss unless the dose is
increased or a second type of diuretic is added.
88
44
UpToDate
• For similar reasons, the fluid and electrolyte
complications of diuretic therapy (eg, volume
depletion, hypokalemia with loop diuretics, and
hyperkalemia with spironolactone) are essentially
complete at two to three weeks in stable patients.
89
UpToDate
• Thus, assuming that the diuretic dose remains
constant, that no other medications that affect
hemodynamics are added, and that the severity of
the heart disease does not change, the BUN and
plasma concentrations of sodium, potassium, and
uric acid are likely to remain stable after the initial
period.
90
45
UpToDate
• Thus, repeated monitoring in such patients is not
necessary unless some change occurs, such as
progression of the HF, or concurrent medications
that may affect hemodynamics or renal function
are added.
91
Title Cardiac Glycosides / Thiazide
Diuretics
• Risk Rating B: No action needed
• Summary: Thiazide Diuretics may enhance the
adverse/toxic effect of Cardiac Glycosides. This by
increasing the risk of hypokalemia. Severity:
Moderate
92
46
Title Cardiac Glycosides / Thiazide
Diuretics
• Patient Management Monitor for increased toxic
effects of cardiac glycosides if a thiazide diuretic is
initiated or the dose is increased. The use of a
potassium-sparing diuretic might be considered to
minimize potassium loss. Likewise, potassium
supplementation, along with careful monitoring of
serum potassium and possibly glycoside
concentrations, might be helpful.
93
Title Cardiac Glycosides / Thiazide
Diuretics
• Discussion The risk of digitalis toxicity increases in the
presence hypokalemia (and possibly hypomagnesemia),
such as may be caused by potassium-depleting diuretics
(eg, loop and thiazide diuretics). Data correlating the
toxicity risks do not always support this presumption,
possibly because serum potassium concentrations may not
correlate with body potassium stores. The mechanism of
this interaction is not clearly established.
94
47
Title Digoxin / Spironolactone
• Risk Rating C: Monitor therapy
• Spironolactone may increase [Digoxin].
Spironolactone may also interfere with the assays
used to determine [Digoxin] , falsely ↑or ↓
[Digoxin]. Severity: Moderate
95
Title Digoxin / Spironolactone
• Monitor patients closely for s/s of digoxin toxicity
when using digoxin and spironolactone in
combination. Additional monitoring of [Digoxin]
may also be warranted, but note that
spironolactone may interfere with the performance
of many different commerical digoxin assays,
complicating the interpretation of [Digoxin]
measurement.
96
48
Title Digoxin / Spironolactone
• Of note, the safe use of spironolactone and digoxin
together for the treatment of severe heart failure
has been described in the clinical trial setting,
where 75% of the 822 patients randomized to
spironolactone were also receiving digoxin.
97
Title Cardiac Glycosides / Loop
Diuretics
• Risk Rating B: No action needed
• Loop Diuretics may enhance the adverse/toxic
effect of Cardiac Glycosides. This by increasing
the risk of hypokalemia. Severity: Moderate
98
49
Title Cardiac Glycosides / Loop
Diuretics
• Monitor for increased toxic effects of cardiac glycosides if
a loop diuretic is initiated or the dose is increased. The use
of a potassium-sparing diuretic might be considered to
minimize potassium loss. Likewise, potassium
supplementation, along with careful monitoring of serum
potassium and possibly glycoside concentrations, might be
helpful.
• Cardiac Glycosides Interacting Members Digitoxin;
Digoxin*
99
Title Cardiac Glycosides / Loop
Diuretics
• The risk of digitalis toxicity increases in the presence
hypokalemia (and possibly hypomagnesemia), such as
may be caused by potassium-depleting diuretics (eg, loop
and thiazide diuretics). Data correlating the toxicity risks
do not always support this presumption, possibly because
serum potassium concentrations may not correlate with
body potassium stores. The mechanism of this interaction
is not clearly established.
100
50