Loop Diuretic

Aka: Loop Diuretic, Furosemide, Lasix, Bumetanide, Bumex, Torsemide, Demadex, Ethacrynic Acid, Edecrin

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II. Indications

  1. Symptomatically reduce pulmonary and Peripheral Edema
    1. Congestive Heart Failure
    2. Nephrotic Syndrome
    3. Renal Insufficiency (GFR<30%)
      1. Other Diuretics (e.g. Thiazide Diuretics) are ineffective at low GFR
      2. Loop Diuretics (esp. Furosemide) may be used to prevent weight gain between Dialysis runs
  2. Emergency Management of Pulmonary Congestion (Lasix)
    1. Left Ventricular Dysfunction (CHF)

III. Contraindications

  1. Sulfonamide Allergy

IV. Precautions

  1. All Loop Diuretics except Torsemide need to be dosed twice daily for effect
  2. Loop Diuretics are associated with significant Electrolyte abnormalities and volume depletion (FDA black box warning)
  3. Loop Diuretics have a threshold dose, below which they have no effect
  4. Loop Diuretics have a ceiling dose, above which increasing dose has little effect
    1. Better in these cases to increase frequency at the ceiling dose

V. Mechanism

  1. Loop Diuretics are the most potent Diuretics
  2. Potently inhibits reabsorption of Sodium and chloride
    1. Action at ascending loop of Henle in glomerulus (Inhibits Na+/K+/Cl+ co-transporter)
    2. Results in increased urinary Sodium and water excretion
  3. Direct Venodilation in Pulmonary Edema
    1. Reduces venous return (Preload)
    2. Reduces Central Venous Pressure
    3. Synergistic effect with Morphine and Nitroglycerin
  4. Reduces Intravascular Volume
    1. Reduces Cardiac Output
    2. Beware Hypotension in Myocardial Infarction

VI. Preparations: Relative Potency (40 to 20 to 1)

  1. Furosemide (Lasix) 40 mg IV (equivalent to 80 mg oral, but variable Bioavailability)
  2. Torsemide (Demadex) 20 mg IV (equivalent to 20 mg oral)
  3. Bumetanide (Bumex) 1 mg IV (equivalent to 1 mg oral)
  4. References
    1. Pham (2017) Card Fail Rev 3(2):108-122 +PMID: 29387462 [PubMed]

VII. Preparations: Bumetanide (Bumex)

  1. Oral dosing (adults)
    1. Start: 0.5 to 1 mg orally twice daily
    2. Maximum: 10 mg/day
    3. Duration: 4-6 hours
  2. Intravenous dosing (adults)
    1. Start: 1 mg IV/dose (Max: 4-8 mg/dose)
  3. Intravenous Infusion (adults)
    1. Load: 1 mg IV
    2. Rate: 0.5 to 2 mg/hour IV

VIII. Preparations: Furosemide (Lasix)

  1. Precautions
    1. Lasix (named for LAst SIX) is only effective for 6 hours
    2. Optimal dosing is given at least twice daily (patient otherwise is Sodium avid 18 hours/day)
    3. Half-Life: 1 to 1.5 hours
    4. Highly variable Bioavailability on oral ingestion (varies between 10 and 90%)
      1. Increased Bioavailability when taken with meals
      2. Gastrointestinal absorption is markedly decreased in severe edema
      3. Contrast with Torsemide which has excellent and consistent Bioavailability
    5. Higher doses (2-3x) required for Nephrotic Syndrome
    6. Renal dysfunction results in decreased response and increased Half-Life
      1. Only 15-20% of Furosemide dose is delivered to the renal tubule in stage 5 CKD
  2. Oral Dosing (adults)
    1. Start: 20-40 mg orally daily to twice daily
    2. Maximum: 600 mg/day (rare to exceed 400 mg/day)
    3. Peak effect at 1 to 1.5 hours after oral dose
    4. Duration: 6-8 hours
  3. Intravenous Dosing
    1. Intravenous dose is typically one half of oral dose (in exacerbations, the oral dose is often used IV)
    2. Administer slowly over 1-2 minutes
      1. Doses higher than 80 mg should infuse slowly to avoid Ototoxicity
    3. Bolus: 20-40 mg IV (0.5-1.0 mg/kg, max 2 mg/kg)
    4. Infusion: 0.25 to 0.75 mg/kg/hour
    5. Onset: Diuresis starts within 10 minutes
    6. Peak effect in 10-30 minutes
    7. Duration: 6 hours
    8. Peak Diuretic effect of repeat dosing is 25% of the first dose
      1. Compensatory Sodium retention may be overcome by frequent IV doses or continuous infusion
    9. Maximum effective dose (ceiling dose)
      1. Chronic Kidney Disease or Nephrotic Syndrome: 80 to 200 mg
      2. Congestive Heart Failure or Cirrhosis: 40-80 mg
  4. Intravenous Infusion
    1. Background
      1. More effective at maintaining a constant increased Urine Output with less adverse effects (e.g. Ototoxicity)
      2. Maximum diuresis at 3 hours after continuous infusion started
    2. Loading dose: 40-200 mg
      1. Loading doses higher than 80 mg should infuse slowly to avoid Ototoxicity
    3. Infusion dose
      1. Start: 10-20 mg/hour IV
      2. Maximum: 40 mg/hour IV
      3. Very high dose Furosemide infusions (4 mg/min) risk Ototoxicity

IX. Preparations: Torsemide (Demadex)

  1. Background
    1. Oral Bioavailability 80-90% consistently, even in severe edema (contrast with Furosemide)
    2. Once daily dosing (contrast with all other Loop Diuretics)
    3. Half-Life: 3 to 4 hours (doubled in hepatic dysfunction)
  2. Oral Dosing (adults)
    1. Start: 10-20 mg orally daily
    2. Maximum: 200 mg/day
    3. Duration: 12-16 hours
  3. Intravenous Dosing (adults)
    1. Start: 10 mg IV
    2. Maximum: 100-200 mg/day
  4. Intravenous Infusion (adults)
    1. Load: 20 mg
    2. Rate: 5-20 mg/hour

X. Preparations: Ethacrynic Acid (Edecrin)

  1. Oral Dosing
    1. Start: 25 mg orally daily
    2. Maximum: 200-400 mg divided 2-3 times daily
  2. Intravenous Dosing
    1. Start: 0.5 to 1 mg/kg IV up to 100 mg/dose

XI. Adverse Effects

  1. Risk of central volume depletion (Dehydration, Hypotension and contraction alkalosis)
  2. Renal dysfunction
    1. Minimize dosage when starting an ACE Inhibitor
    2. Avoid NSAIDs
  3. Hypersensitivity (esp. Sulfonamide)
    1. Ethacrynic Acid is the only non-sulfonamide Loop Diuretic
  4. Electrolyte abnormalities
    1. Metabolic Alkalosis
    2. Hypokalemia
    3. Hypomagnesemia
    4. Hypocalcemia
    5. Hyponatremia
    6. Hyperosmolality
  5. Ototoxocity
    1. Typically reversible (but permanent Deafness may occur)
    2. Risk Factors
      1. Higher Loop Diuretic serum concentrations (esp. high dose Furosemide)
      2. Renal dysfunction
      3. Concurrent Aminoglycoside use
      4. More common with Ethacrynic Acid

XII. Mechanism: Loop Diuretic Resistance

  1. Renal Insufficiency
    1. Renal Toxin (e.g. NSAID) decreases GFR
    2. NSAIDs
  2. Decreased Diuretic oral absorption
  3. Structural changes in the Kidney
    1. Normal aging
    2. Distal tubular hypertrophy (long term use)
      1. Consider adding a Thiazide Diuretic
      2. Counters distal tubular reabsorption
      3. Significantly boosts Loop Diuretic effect
  4. Increased Dietary Sodium intake
    1. CHF patient is an avid Sodium retainer
    2. Sodium is common in most foods
      1. Chicken Noodle soup = 1200 meq
      2. Milk 122 meq
      3. Big Mac 1010 meq
      4. Canned Spinach 910 meq

XIII. Drug Interactions

  1. Warfarin
    1. Furosemide displaces Warfarin from Protein binding and increases Warfarin levels and INR
  2. Cyclosporine
    1. Cyclosporine decreases Uric Acid excretion, and increased gout risk when used with Furosemide

XIV. References

  1. Won Oh (2015) Electrolyte Blood Press 13(1):17-21 +PMID: 26240596 [PubMed]

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Related Studies

Cost: Medications

furosemide (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
FUROSEMIDE 10 MG/ML SOLUTION Generic $0.09 per ml
FUROSEMIDE 20 MG TABLET Generic $0.03 each
FUROSEMIDE 40 MG TABLET Generic $0.03 each
FUROSEMIDE 80 MG TABLET Generic $0.05 each
bumetanide (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
BUMETANIDE 0.5 MG TABLET Generic $0.22 each
BUMETANIDE 1 MG TABLET Generic $0.23 each
BUMETANIDE 2 MG TABLET Generic $0.42 each
torsemide (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
TORSEMIDE 10 MG TABLET Generic $0.08 each
TORSEMIDE 100 MG TABLET Generic $0.27 each
TORSEMIDE 20 MG TABLET Generic $0.08 each
TORSEMIDE 5 MG TABLET Generic $0.07 each
ethacrynic acid (on 11/23/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
ETHACRYNIC ACID 25 MG TABLET Generic $2.53 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

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