What are the adult indications, dosing regimen, contraindications, precautions, and monitoring recommendations for furosemide?

Furosemide: Adult Indications, Dosing, Contraindications, Precautions, and Monitoring

Indications

Furosemide is FDA-approved for treating edema associated with congestive heart failure, cirrhosis of the liver, renal disease (including nephrotic syndrome), and hypertension in adults. 1

• Loop diuretics like furosemide are the preferred diuretic agents for most patients with heart failure and are recommended in all patients with HFrEF who have evidence of fluid retention to improve symptoms 2
• In cirrhosis with ascites, furosemide is typically combined with spironolactone as first-line therapy 3
• For nephrotic syndrome with severe edema, furosemide addresses fluid overload when conservative measures fail 3
• Furosemide may be used alone or combined with other antihypertensive agents for hypertension, though patients inadequately controlled on thiazides will likely not respond to furosemide monotherapy 1

Dosing Regimen

Oral Dosing for Edema

The usual initial dose is 20 to 80 mg given as a single dose, with the dose increased by 20 or 40 mg increments every 6 to 8 hours until the desired diuretic effect is achieved. 1

• Once the effective single dose is determined, administer once or twice daily (e.g., at 8 AM and 2 PM) 1
• The dose may be carefully titrated up to 600 mg/day in patients with clinically severe edematous states 1
• When doses exceeding 80 mg/day are given for prolonged periods, careful clinical observation and laboratory monitoring are particularly advisable 1
• Edema may be most efficiently and safely mobilized by giving furosemide on 2 to 4 consecutive days each week 1

Disease-Specific Oral Dosing

For heart failure: Start with 20-40 mg orally once daily in the morning, targeting weight loss of 0.5-1.0 kg daily during active diuresis 2, 3, 4

For cirrhosis with ascites: Start with furosemide 40 mg combined with spironolactone 100 mg as a single morning dose, maintaining the 100:40 ratio and increasing both drugs simultaneously every 3-5 days if weight loss is inadequate 3, 4

• Maximum furosemide dose in cirrhosis is 160 mg/day; exceeding this indicates diuretic resistance requiring large volume paracentesis 3

For nephrotic syndrome: Initial dose is 0.5-2 mg/kg per dose, up to 6 times daily, with a maximum of 10 mg/kg per day 3, 4

Intravenous Dosing for Acute Presentations

For acute heart failure or pulmonary edema, administer 20-40 mg IV bolus over 1-2 minutes for diuretic-naïve patients, or use a dose at least equivalent to the patient's chronic oral dose. 3, 4

• For patients with prior diuretic exposure or severe volume overload, initial doses of 40-80 mg IV are appropriate 3
• Total dose limits are <100 mg in the first 6 hours and <240 mg in the first 24 hours, though higher doses may occasionally be used with close monitoring 2, 3
• If urine output remains <0.5 mL/kg/h after 2 hours, double the dose but never exceed 160-200 mg per individual bolus 3
• For continuous infusion: start with 40 mg IV loading dose followed by 5-10 mg/hour (maximum rate 4 mg/min) 3

Oral Dosing for Hypertension

The usual initial dose for hypertension is 80 mg, usually divided into 40 mg twice a day. 1

• When adding furosemide to other antihypertensive agents, reduce the dosage of other agents by at least 50% to prevent excessive blood pressure drop 1
• As blood pressure falls under the potentiating effect of furosemide, further reduction or discontinuation of other antihypertensive drugs may be necessary 1

Geriatric Dosing

In elderly patients, start at the low end of the dosing range (typically 20 mg) and titrate more slowly because older adults have a 2-3-fold longer furosemide half-life, increased risk of orthostatic hypotension, and reduced renal clearance. 3, 1

Contraindications

Absolute Contraindications

Do not administer furosemide in patients with anuria. 2, 3

Severe hyponatremia (serum sodium <120-125 mmol/L) is an absolute contraindication. 2, 3, 4

Marked hypovolemia or hypotension (systolic blood pressure <90 mmHg) without circulatory support precludes furosemide use. 2, 3, 4

• Furosemide will worsen hypoperfusion and can precipitate cardiogenic shock in hypotensive patients 3

Severe hypokalemia (<3 mmol/L) mandates stopping furosemide. 3

Precautions

Pre-Administration Safety Checks

Before each dose, verify systolic blood pressure ≥90-100 mmHg, exclude severe hyponatremia, confirm the patient is not anuric, and ensure absence of marked hypovolemia. 3, 4

Monitoring During Therapy

Place a bladder catheter in acute settings to monitor urine output hourly and rapidly assess treatment response, targeting >0.5 mL/kg/hour. 3

Monitor daily weights at the same time each day, targeting maximum loss of 0.5 kg/day without peripheral edema or 1.0 kg/day with peripheral edema. 2, 3

Check electrolytes (particularly potassium and sodium) and renal function within 6-24 hours after starting IV furosemide, then every 3-7 days during active titration. 3

• Hypokalemia occurs in approximately 3.6% of furosemide recipients 5
• Intravascular volume depletion occurs in 4.6% of patients 5
• Other electrolyte disturbances occur in 1.5% of cases 5

Ototoxicity Risk

Administer infusions over 5-30 minutes to avoid hearing loss, particularly when doses ≥250 mg are given. 3

• High doses of furosemide (>6 mg/kg/day) should not be given for periods longer than 1 week 3
• Rapid IV administration at doses >1 mg/kg (roughly 70-80 mg) increases the risk of ototoxicity 3

Drug Interactions

Avoid NSAIDs, which block diuretic effects and worsen renal function. 4

Avoid combining high-dose furosemide with aminoglycosides, as this dramatically increases ototoxicity risk. 3

Special Populations

In cirrhotic patients, oral administration is preferred over IV to avoid acute reductions in GFR associated with IV administration. 3

Stop furosemide immediately in cirrhotic patients if worsening hepatic encephalopathy, progressive renal failure, or incapacitating muscle cramps occur. 3

Managing Diuretic Resistance

When inadequate diuresis occurs after 24-48 hours at standard doses, add a second diuretic class rather than escalating furosemide alone beyond 160 mg/day. 2, 3, 4

• Options include hydrochlorothiazide 25 mg PO, spironolactone 25-50 mg PO, or metolazone 2.5-5 mg PO 2, 3
• Sequential nephron blockade is more effective than monotherapy escalation 3
• Consider switching from intermittent boluses to continuous infusion if resistance develops 3

Common Pitfalls to Avoid

Do not administer furosemide to hypotensive patients expecting hemodynamic improvement—it will worsen tissue perfusion. 3

Do not withhold higher-dose furosemide out of fear of mild azotemia; transient renal function worsening is acceptable when the patient remains asymptomatic and volume status improves. 3

Do not persist with 40 mg furosemide when the patient has significant fluid retention; this dose is insufficient and delays euvolemia. 3

Do not exceed 160 mg/day furosemide without adding another diuretic class, as the ceiling effect offers no additional benefit and raises adverse-event risk. 2, 3

Avoid evening doses of furosemide, as they cause nocturia and poor adherence without improving outcomes. 3

Pharmacokinetic Considerations

Furosemide acts at the luminal surface of the ascending limb of the loop of Henle by inhibiting active chloride reabsorption, and it is the urinary concentrations—not plasma concentrations—that determine diuretic effect. 6, 7

• Oral bioavailability is approximately 59% and highly variable 8
• Peak diuretic effect occurs within 1-1.5 hours after oral administration 3
• Duration of action is 6-8 hours for oral furosemide 2
• IV furosemide produces diuresis within minutes 3
• The first dose produces the greatest natriuretic effect; subsequent doses show up to 25% less effect at the same concentration due to compensatory sodium-retention mechanisms 3