Furosemide (Lasix): Drug Whys


Generic name: Furosemide (multiple manufacturers)
Common U.S. brand names: Lasix (Sanofi-Aventis – U.S.)
Popularity: Tenth most commonly prescribed drug between 2002-2006 (U.S.)
Class: Loop diuretic, sulfonamide (contains sulfa), antihypertensive

Treatment Uses – For treatment of edema, including edema associated with heart failure or renal failure. As an adjunct (for use with other medications) for treatment of acute volume overload states associated with heart failure. For treatment of hypertension; most often employed in combination with other antihypertensive agents, although probably effective if used alone. For treatment of ascites in patients with cirrhosis.

 

 

Furosemide is also used to improve pulmonary function in infants with bronchopulmonary dysplasia (BPD). Nebulized furosemide may be beneficial for treatment of asthma in adults and children although the evidence supporting this use is not overwhelming. Likewise, nasally inhaled furosemide has been used for treatment of sinus congestion and for prevention of recurrent nasal polyps. There is also limited data suggesting that nebulized furosemide may provide symptomatic relief of acute shortness of breath in patients with terminal cancer. A small study of elderly men with nocturnal polyuria (frequent nighttime urination) given furosemide six hours before bedtime demonstrated significant reduction in nighttime urination.

Furosemide belongs to a family of drugs called loop diuretics. The differences between loop and thiazide diuretics result from where they act on the kidneys. Loop diuretics work by inhibiting sodium reabsorption from the Loop of Henle (a more significant sodium reabsorption site) while thiazides inhibit reabsorption of sodium in the early part of the kidney's distal tubules. Both cause increased excretion of sodium and water. The loop diuretics produce a more aggressive and shorter lived diuresis; thiazides result in a gentler and more sustained diuretic effect. Thiazides are more effective than loop diuretics for treating hypertension.

While furosemide is still the mainstay for treatment of acutely decompensated heart failure, it is slowly falling out of favor for several reasons. The most important is that patients with heart failure are not uniformly volume overloaded. In fact, 40 percent or more may be intravascularly volume depleted. Second, furosemide does not work as quickly as previously thought in very sick patients. Finally, studies comparing treatment of acutely decompensated heart failure found shorter lengths of hospital stay and fewer deaths in patients not given furosemide.

Dosing and Administration – Usual adult oral dosing ranges from 20 to 80 milligrams per day, titrated to effect up to 600 milligrams (daily). Larger doses are divided into twice daily administration. Single doses are best taken in the morning to avoid sleep disruption from frequent nighttime urination.Intravenous (IV) dosing for edema in adults is 20 to 40 milligrams, administered slowly. IV doses can be increased by 20 milligrams or the same dose can be repeated at two hour intervals until the desired response is achieved. The final individually determined dose can then be given once or twice daily. In acute volume overload states, best practice dosing (found in many heart failure protocols) is a single IV bolus of double the patient's usual daily (24 hour) dose. IV maximums top off at 4,000 milligrams per day. Injection rates faster than 20 mg/min can cause hearing impairment; current literature recommends against administered furosemide any more rapidly than 4 milligrams per minute. One way to slowly deliver any medication is to inject the drug into a proximal IV tubing port and allow the drip rate to slowly deliver the drug to the patient (typical IV tubing administration sets have a 10-20 milliliter fill volume).

It should be noted when attempting to induce diuresis with escalating doses of furosemide that each patient whose kidneys are capable of responding have a threshold below which no diuretic action occurs and a (somewhat higher) threshold above which no greater diuretic effect is seen. Because these thresholds vary from patient to patient and time to time, dosing changes should reflect this understanding. Contemporary critical care practice often utilizes continuous infusions of furosemide to induce, maintain and adjust diuretic response.

Dosing for children and infants is typically 1 milligram per kilogram per dose either orally, IV or IM. Dose titration and repeat administrations is much the same as for adults except that no more than 6 milligrams per kilogram per day should be given to a child.

IV furosemide administered orally has potency similar to oral tablets, hence it can be given orally,, in beverages, through feeding tubes when an oral solution is not readily available. In patients without IV access, IV doses can be given IM, but have slower absorption.

Although most drug references say that furosemide can be taken with food or milk, oral doses taken with meals may result in reduced plasma drug levels. Whether this is clinically significant remains controversial. If nausea occurs with oral furosemide, taking the drug with food should reduce or eliminate this unpleasant side effect. To avoid nocturia (nighttime urination), furosemide should be taken early in the day, and preferably before breakfast (for maximal drug levels).

While no dosing adjustments are recommended for patients with renal insufficiency, it may take considerably higher than normal doses to induce diuresis in patients with renal dysfunction. Patients with liver dysfunction require higher than usual doses of furosemide and also experience prolonged absorption of oral furosemide. If emergency diuresis is needed in patients with liver dysfunction, IV furosemide is preferred. No dosing adjustments are required in the geriatric population.

Overdoses of furosemide generally result in volume depletion, hypotension and electrolyte imbalances. Treatment should be supportive. Hypotension will respond to fluids. There is no specific antidote for furosemide overdoses. Hemodialysis is ineffective in removing furosemide from the body.

Pharmacology/Pharmacokinetics/Stability – Following oral administration, diuresis occurs within 30 to 60 minutes, peaks in one to two hours, and tapers off after six to eight hours. The brand name Lasix® connotes that furosemide "lasts" for "six hours." When given IV, the effect is thought to be faster, with diuresis starting after two to five minutes, peaking in 30 minutes, and tapering after twp hours. With IM furosemide, diuresis occurs in about 30 minutes. Recent studies suggest that effects of IV furosemide are considerably delayed in critically ill patients, especially those with significant volume overload states. One highly touted effect of furosemide was a supposed vasodilatory effect believed to occur within 10 minutes of oral dosing and within seconds of IV administration. This vasodilatory effect is very poorly documented and probably does not actually occur.

During several national shortages of furosemide in the past, many EMS systems substituted bumetanide (Bumex), another loop diuretic, for IV furosemide. Forty milligrams of furosemide is approximately equal to 1 milligram of bumetanide.

The kidneys excrete about 60 to 90 percent of furosemide. Feces contain 7 to 9 percent of furosemide and an additional 6 to 9 percent is eliminated in bile. Furosemide is not removed by hemodialysis.

During pregnancy, diuretic use is generally avoided due to risk of decreased placental perfusion. Furosemide does cross the placenta; increased fetal urine production and fetal electrolyte disturbances have been reported. Whether furosemide is excreted in breast milk is uncertain. The World Health Organization suggests women taking furosemide avoid breastfeeding.

Depending on manufacturer, furosemide comes in 20, 40 and 80 milligram tablets. Colors, shapes and sizes vary by manufacturer. Tablets expire five years and solutions expire 42 months from manufacture date. Injection solutions of furosemide are manufactured in a 10 milligram per milliliter concentration with vials or ampules containing 2, 4, 8 and 10 milliliters. Furosemide is extremely light sensitive (hence, packaging in darkly colored vials, ampules,and bottles). Exposure to light may cause discoloration; do not use furosemide solutions or tablets with a yellow color. Refrigeration may result in drug crystallization or precipitation. Rewarming may be performed without affecting the drug's stability. Infusions solutions of furosemide mixed in NS or D5W are stable for 24 hours at room temperature. Oral solutions of furosemide come in 10 milligrams per milliliter orange flavor and 40 milligrams per 5 milliliter pineapple-peach flavor. Furosemide should be stored at room temperature between 59 – 86 F.

Cautions and Warnings – Furosemide should not be given to patients allergic to drugs containing sulfa.

Important Side Effects and Interactions – Side effects of furosemide are mostly related to diuretic effects, the most significant of which are hypotension and decreased blood potassium levels (hypokalemia). Patients should be instructed to rise slowly from sitting or lying positions to minimize lightheadedness or dizziness associated with diuretic effects. Blood pressure and electrolyte levels should be checked frequently. Potassium supplementation may be necessary. For reasons poorly understood, furosemide also has a tendency to increase blood glucose levels in patients with diabetes. Nausea occurs occasionally with oral furosemide and can usually be reduced or eliminated by taking the drug with food.

Incredibly for such a frequently used drug, there are virtually no published frequencies of side effects. Cases of reversible and permanent hearing loss (ototoxicity) have been reported with furosemide. These have usually been associated with rapid injection, administration to patients with renal failure, doses exceeding several times the recommended maximums or administration with other ototoxic drugs.

There are 190 drugs are reported to interact with furosemide. Few of these could not be surmised from the therapeutic actions of furosemide. Furosemide may increase the ototoxic effects of aminoglycoside antibiotics and high dose salicylates. It may potentiate the action of succinycholine. There is a high risk of lithium toxicity from reduced clearance of lithium when taken with furosemide. There may be a tendency towards worsening of chronic renal insufficiency when furosemide is used in conjunction with NSAIDs.

Average Costs – U.S.
• 40 mg/4 ml vial for injection (generic)
ALS Service cost: $1.42 each
Large Hospital cost: $0.65 each

• 40 mg tablet (generic)
Patient cost: $0.14 each*
Large Hospital cost: $0.04 each
*($4.00 at Wal Mart® and Target for one month supply)


References

 

 

  • MICROMEDEX® Healthcare Series: Thomson Micromedex, Greenwood Village, Colorado (accessed February, 2008).
  • Albany Medical Center Pharmacy, Albany, New York.

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