Comparison of Commonly Used Diuretics

THIAZIDE DIURETICS are among the drugs that significantly increase blood glucose. They can also increase triglycerides and cholesterol minimally.¹ Other side effects include hypokalemia, metabolic alkalosis, hyponatremia, and hypomagnesemia.^1,2 Thiazides reduce urinary calcium excretion, an effect that may be beneficial to people at risk of osteoporosis or kidney stones.¹ Contrary to popular belief, thiazides, particularly metolazone, can be effective if CrCl is <30 mL/min.^6,7

Chlorothiazide (oral)

(not available in Canada)

Diuril

250 mg/5 mL, suspension

Edema

0.5-1 g QD to BID

HTN
0.5-1 g QD or divided BID

≤2 hrs

6 to 12 hrs

US: 500 mg: ~$2.50 (brand)

• Brand only.

Chlorothiazide (IV)

(not available in Canada)

500 mg injection (IV)

Edema

0.5-1 g QD to BID

15 min

N/A

US: 500 mg injection:

~$30

• Only thiazide available as an injectable.

Chlorthalidone

HemiClor (US)
12.5 mg tabs

Thalitone (US)
15 mg, 25 mg tabs

25, 50 mg tabs (US);
12.5, 25, 50 mg tabs (Canada)

Edema

50 to 200 mg QD or
100 to 200 mg every other day

(Canada: 50 mg QD, max)

HTN

12.5 to to 100 mg QD
(Canada: 25 to 50 mg QD)

~2.6 hrs

48 to 72 hrs

US:

25 mg tab: ~$0.40

Canada:

50 mg tab: ~$0.15

• Diuretic with most evidence for improved CV outcomes (e.g., used in ALLHAT).¹ Has not been proven to provide better cardiovascular outcomes than hydrochlorothiazide.³ Comparative study ongoning.⁴
• May be more effective in lowering SBP
  (by ~5 mmHg) over a full 24-hour period than hydrochlorothiazide.⁵
• 12.5 mg chlorthalidone ~ hydrochlorothiazide
  25 mg.¹
• In combination products, only available with atenolol or azilsartan.

Hydrochlorothiazide

12.5, 25 mg, 50 mg tabs; 12.5 mg cap (US)

Edema

25 to 100 mg QD or divided (Canada:

25 to 100 mg QD or BID)

HTN

12.5 QD to 50 mg QD or divided BID (Canada:
50 to 100 mg QD or divided)

≤2 hrs

6 to 12 hrs

US:

25 mg tab: ~$0.02

Canada:

25 mg tab: ~$0.02

• Most commonly prescribed thiazide.¹
• Most widely available diuretic in combination products with other antihypertensives.¹

Indapamide

1.25, 2.5 mg tabs

Edema (US only)

2.5 to 5 mg QD

HTN

1.25 to 2.5 mg QD

1 to 2 hrs²

At least

24 hrs²

US:

1.25 mg tab: ~$0.20

Canada:
1.25 mg tab: ~$0.15

• Reduced CV events (heart failure and death from stroke) in hypertensive patients ≥80 years vs placebo.⁸
• May be more effective in lowering SBP
  (by ~5 mmHg) over a full 24-hour period than hydrochlorothiazide.⁹
• In combo product with perindopril (Canada).
• 1.25 mg ~ hydrochlorothiazide 25 mg⁹

Metolazone

Zaroxolyn (Canada)

US: 2.5, 5, 10 mg tabs

Canada: 2.5 mg tabs

Edema

5 to 20 mg QD

HTN

2.5 to 5 mg QD

≤1 hr

≥24 hr (dose-dependent)

US:

2.5 mg tab: ~$0.45

Canada (brand):

2.5 mg tab: ~$0.25

• Absorption is slow and unpredictable.¹⁰
• More effective than other thiazides at
  CrCl <30 mL/min.¹⁰

LOOP DIURETICS are more effective diuretics than thiazides, but lack outcomes data for hypertension.^1,11 They are best reserved for edematous conditions (e.g., heart failure, renal failure).¹ Loops are generally recommended over thiazides for patients with GFR <30 mL/min/1.73 m².⁷ A thiazide can be added to a loop to enhance diuresis.⁷ Like thiazides, loops can cause hypokalemia and metabolic alkalosis.¹¹ Loops are less likely to cause hyponatremia or hypomagnesemia.^11,12 Loops increase excretion of calcium, instead of reducing it like thiazides.¹ Loops can cause dose-dependent ototoxicity (furosemide >bumetanide).¹³ For edematous states, loops are usually dosed intermittently, as needed.

Bumetanide (oral)

Bumex (US)

Burinex (Canada)

US:0.5, 1, 2 mg tabs

Canada: 1, 5 mg tabs

Edema: 0.5 to 2 mg QD. If needed, repeat every

4 to 5 hrs

(max 10 mg/day).

0.5 to 1 hr

4 to 6 hrs (dose-dependent)

U.S.:

1 mg tab: ~$0.40

Canada (brand):

1 mg tab: ~$0.90

• Well-absorbed¹³
• 1 mg oral bumetanide = 40 mg oral furosemide¹³
• Canadian labeling recommends a max dose of 5 mg in patients with hepatic failure.

Bumetanide (IV or IM)

(not available in Canada)

0.25 mg/mL injection

Edema

0.5 to 1 mg. If needed, repeat every 2 to 3 hrs (max 10 mg/day).

IV: minutes

IM:

40 min.¹⁴

3 to 6 hrs¹⁴

US: 1 mg injection: ~$0.65

• 1:1 IV to PO conversion¹³

Ethacrynic acid (oral)

Edecrin

25 mg tab

Edema

50 mg QD to

50 to 100 mg BID

Take after a meal.

30 min

6 to 8 hr

US:

25 mg tab: ~$2.15

Canada (brand):

25 mg tab: $1.30

• Useful in patients resistant to other diuretics (Canada).
• 50 mg oral ethacrynic acid ~ 40 mg oral furosemide¹⁵
• More ototoxic than other loops.⁷
• Only loop without a sulfa group.⁷ May be useful for patients with allergic reaction to other loops or thiazides. See our chart, Sulfa Drugs and the Sulfa-Allergic Patient, for more information.

Ethacrynate sodium (IV)

Sodium Edecrin (US)

50 mg injection

Edema

50 mg x 1 (or 0.5 to
1 mg/kg; max 100 mg). May repeat (at a different site to avoid phlebitis) if needed.

5 min

2 hrs¹⁴

US: 50 mg:

~$1,900

Canada: 50 mg:

$480

• Not for IM or subcutaneous injection.
• More ototoxic than other loops.⁷
• Only loop without a sulfa group.⁷ May be useful for patients with allergic reaction to other loops or thiazides. See our chart, Sulfa Drugs and the Sulfa-Allergic Patient, for more information.

Furosemide (oral)

Lasix

20, 40, 80 mg tabs;
10 mg/mL oral solution; 40 mg/5 mL oral solution (US);

Lasix Special* (Canada)

*see comments section

Edema

20 to 80 mg (Canada:

40 to 80 mg). May repeat, or increase by 20 to 40 mg, in 6 to 8 hrs. (max

600 mg/day; Canada:

200 mg/day). When effective dose reached, give QD or divide BID (morning and early afternoon; Canada: may repeat one to three times daily)

HTN

40 mg BID (Canada:

20 to 40 mg BID)

<1 hr

6 to 8 hr

US:

40 mg tab: ~$0.05

Canada:

40 mg tab: ~$0.04

• Loop with poorest oral absorption (~50% [range 10% to 100%].¹³
• Lasix Special* is a high-dose oral formulation
  (500 mg tab) of furosemide, for hospitalized patients with GFR 5 to 20 mL/min/1.73 m² not responding to usual furosemide doses. Initial dose is guided by the IV dose found to be effective. Or, in patients who do not respond adequately to
  80 to 160 mg of oral furosemide, the initial dose is 250 mg. After 4 to 6 hrs, if response is inadequate, dose may be increased to 500 mg. Max daily dose 1,000 mg.

Furosemide (subcutaneous)

(not available in Canada)

Furoscix

8 mg/mL subcutaneous solution

Edema

The single-dose infuser delivers 30 mg over the first hour, then
12.5 mg/hour for four hours (80 mg over 5 hrs).

Rapid¹⁶

≥8 hrs after initiation of dosing

US: ~$950

• Furoscix is a wearable patch pump with furosemide solution buffered to pH 7.4 to allow for subcutaneous administration.¹⁶
• Similar diuretic efficacy to two doses of furosemide 40 mg IV two hours apart.¹⁶

Furosemide (IV or IM)

10 mg/mL injection

Edema 

20 to 40 mg. May repeat, or increase by

20 mg, in 2 hrs. (Canada: max 100 mg/day).

Once effective dose reached, give QD or divide BID. For pulmonary edema, dose is 40 mg, increased to 80 mg in 1 hr if needed (Canada: 40 mg, repeated in to 1.5 hrs if needed.)

IV:

≤5 min

IV: ~2 hr

US: 20 mg/2 mL vial: ~$1

Canada:
20 mg/2 mL amp: ~$1.308

• When switching to/from oral furosemide, keep in mind that oral furosemide bioavailability is ~50% (range 10% to 100%).¹³
• Administer over one to two minutes (bolus) or as a continuous infusion at ≤4 mg/min).

Torsemide (not available in Canada)

Soaanz, Demadex (brand discontinued)

5 mg, 10 mg, 20 mg,
40 mg (Soaanz), 60 mg (Soaanz), 100 mg tabs

Edema
10 to 20 mg QD
(max 200 mg/day)

HTN

5 to 10 mg QD

≤1 hr

6 to 8 hrs

10 mg tab: ~$0.45

• Bioavailability 80% to 100%.¹³
• 20 mg oral torsemide = 40 mg oral furosemide¹³
• Cirrhosis: start with 5 to 10 mg QD. Doses
  >40 mg/day have not been studied in cirrhosis.

POTASSIUM-SPARING DIURETICS are usually weak antihypertensives, but they can be added to a thiazide to minimize hypokalemia risk.¹ The risk of hyperkalemia is increased in kidney impairment and/or with use of an ACE inhibitor or ARB.¹⁴

Amiloride

Midamor

5 mg tab

5 to 10 mg QD
(max 20 mg)

See comments for indications.

2 hr

~24 hrs

US:

5 mg tab: ~$0.2

Canada (brand):

5 mg tab: ~$0.40

• Weak antihypertensive and diuretic effects that are somewhat additive to those of thiazides.
• Indications: adjunct to thiazide or loop diuretic in patients with heart failure or hypertension, to maintain potassium levels; edema associated with cirrhosis (Canada). Rarely used alone.

Eplerenone

Inspra

25, 50 mg tabs

HFrEF post-MI

25 to 50 mg (target dose) QD

HTN
50 mg QD or BID

Note: HFrEF indication requires dose reduction if potassium level

≥5.5 mEq/mL. Max dose 25 mg QD (HF) or BID (HTN) with moderate CYP3A4 inhibitors.

Not available

Not available

U.S.:

50 mg tab: ~$1.10

Canada:

50 mg tab: ~$2.50

• Eplerenone is an aldosterone antagonist with less progesterone and androgen receptor antagonism than spironolactone.¹⁰
• Option for resistant hypertension.¹
• Benefit in HFrEF (morbidity and mortality reduction) due to RAS suppression.⁷
• Helps offset loop or thiazide diuretic-related potassium and magnesium losses.¹⁷
• Do not use if K >5.5 mEq/L (Canada: >5 mmol/L) at initiation, CrCl ≤30 mL/min (<50 mL/min for HTN), or with strong CYP3A4 inhibitors.

Spironolactone tablets Aldactone

25, 50 (US only),
100 mg tabs

Edema

25 to 200 mg QD or divided (see comments regarding cirrhosis)

HTN

25 to 100 mg QD or divided (Canada: 200 mg max).

HF

25 to 50 mg QD. See comments.

Hypokalemia (Canada)

25 to 100 mg/day

Primary hyperaldosteronism

See comments

Not available

2 to 3 days¹⁴

US:

50 mg tab: ~$0.25

Canada:

25 mg tab: ~$0.04

• Benefit in HFrEF (morbidity and mortality reduction) due to RAS suppression.⁷
• Option for resistant hypertension.¹
• Helps offset loop or thiazide diuretic-related potassium and magnesium losses.¹⁷
• Do not use in severe kidney impairment (Canada) or hyperkalemia.
• HF: consider 25 mg every-other-day if eGFR
  30 to 50 mL/min/1.73 m² or if hyperkalemia develops.
• Primary hyperaldosteronism treatment:
  100 to 400 mg/day pre-op, or lowest effective dose for maintenance.
• Primary hyperaldosteronism diagnosis (Canada)
  400 mg/day x 4 days (short test), or 3 to 4 weeks (long test)
• Cirrhosis: consider a max of 100 mg or 400 mg for Na+/K+ ratio >1 or <1, respectively (Canada)

Spironlactone suspension

Carospir

Edema due to cirrhosis

75 mg to 100 mg QD (initiate in hospital)

HTN

20 to 75 mg QD or divided

HF

20 to 37.5 mg QD

Not available

2 to 3 days¹⁴

US: 20 mg

~$15

• Dosing not equivalent to tablets.
• Benefit in HFrEF (morbidity and mortality reduction) due to RAS suppression.⁷
• Option for resistant hypertension.¹
• Helps offset loop or thiazide diuretic-related potassium and magnesium losses.¹⁷
• Do not use in hyperkalemia.
• HF: reduce dose to 20 mg every-other-day if hyperkalemia occurs on 20 mg QD. Initiate with 10 mg QD if eGFR 30 to 50 mL/min/1.73m².

Triamterene

Dyrenium

50, 100 mg cap

(Only combo products are available in Canada.)

Edema

100 mg BID
(max 300 mg/day)

Take after meals.

2 to 4 hr

7 to 9 hr

US (brand):

50 mg cap: ~$15

• Weak antihypertensive effect.¹