What are the potential side effects of Furosemide (Lasix)?

From the Guidelines

When taking Lasix (furosemide), it is crucial to monitor for signs of dehydration, electrolyte imbalances, and kidney function, as these are the most significant concerns that can impact morbidity, mortality, and quality of life, as indicated by the most recent guidelines 1.

Key Considerations

• Monitor for dehydration signs such as excessive thirst, dry mouth, dizziness, or decreased urination.
• Watch for electrolyte imbalances, particularly low potassium (hypokalemia), which may cause muscle weakness, cramps, or irregular heartbeat, as noted in the management of ascites in cirrhosis guidelines 1.
• Regularly check blood pressure, as Lasix can cause it to drop too low, especially when standing up quickly.
• Be aware of potential hearing problems, including ringing in the ears or decreased hearing, which require immediate medical attention.

Management and Monitoring

• Take the medication early in the day to avoid nighttime urination disrupting sleep.
• Diabetic patients should monitor blood sugar levels closely as Lasix can affect glucose control.
• The dose of Lasix should be adjusted based on the patient's response, with a maximum dose of 160 mg/day, and consideration of combination therapy with aldosterone antagonists like spironolactone, as recommended in the guidelines for liver cirrhosis management 1.
• Monitor changes in body weight, vital signs, serum creatinine, sodium, and potassium levels periodically, and adjust the diuretic dose accordingly to prevent complications.
• If the serum sodium level decreases below 125 mmol/L, diuretics can be carefully reduced or discontinued, and fluid restriction can be considered, as advised in the clinical practice guidelines for liver cirrhosis 1.

From the FDA Drug Label

ADVERSE REACTIONS Adverse reactions are categorized below by organ system and listed by decreasing severity Gastrointestinal System Reactions hepatic encephalopathy in patients with hepato-cellular insufficiency pancreatitis jaundice (intrahepatic cholestatic jaundice) increased liver enzymes anorexia oral and gastric irritation cramping diarrhea constipation nausea vomiting Systemic Hypersensitivity Reactions Severe anaphylactic or anaphylactoid reactions (e. g with shock) systemic vasculitis interstitial nephritis necrotizing angiitis Central Nervous System Reactions tinnitus and hearing loss paresthesias vertigo dizziness headache blurred vision xanthopsia Hematologic Reactions aplastic anemia thrombocytopenia agranulocytosis hemolytic anemia leukopenia anemia eosinophilia Dermatologic-Hypersensitivity Reactions toxic epidermal necrolysis Stevens-Johnson Syndrome erythema multiforme drug rash with eosinophilia and systemic symptoms acute generalized exanthematous pustulosis exfoliative dermatitis bullous pemphigoid purpura photosensitivity rash pruritis urticaria Cardiovascular Reaction Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates or narcotics Increase in cholesterol and triglyceride serum levels Other Reactions hyperglycemia glycosuria hyperuricemia muscle spasm weakness restlessness urinary bladder spasm thrombophlebitis fever PRECAUTIONS General Excessive diuresis may cause dehydration and blood volume reduction with circulatory collapse and possibly vascular thrombosis and embolism, particularly in elderly patients. As with any effective diuretic, electrolyte depletion may occur during Furosemide tablets therapy, especially in patients receiving higher doses and a restricted salt intake Hypokalemia may develop with Furosemide tablets, especially with brisk diuresis, inadequate oral electrolyte intake, when cirrhosis is present, or during concomitant use of corticosteroids, ACTH, licorice in large amounts, or prolonged use of laxatives.

Key things to look out for with Lasix (furosemide) include:

• Electrolyte imbalance: hypokalemia, hypomagnesemia, hypocalcemia
• Dehydration and blood volume reduction: circulatory collapse, vascular thrombosis, and embolism
• Hypotension: orthostatic hypotension, particularly in elderly patients
• Hypersensitivity reactions: anaphylactic or anaphylactoid reactions, systemic vasculitis, interstitial nephritis, necrotizing angiitis
• Gastrointestinal reactions: hepatic encephalopathy, pancreatitis, jaundice, increased liver enzymes
• Central nervous system reactions: tinnitus, hearing loss, paresthesias, vertigo, dizziness, headache, blurred vision
• Hematologic reactions: aplastic anemia, thrombocytopenia, agranulocytosis, hemolytic anemia, leukopenia, anemia, eosinophilia
• Dermatologic-hypersensitivity reactions: toxic epidermal necrolysis, Stevens-Johnson Syndrome, erythema multiforme
• Cardiovascular reactions: orthostatic hypotension, increase in cholesterol and triglyceride serum levels
• Other reactions: hyperglycemia, glycosuria, hyperuricemia, muscle spasm, weakness, restlessness, urinary bladder spasm, thrombophlebitis, fever 2 2

From the Research

Adverse Reactions and Interactions

• The most common adverse reactions attributable to furosemide therapy are essentially extensions of the therapeutic effects, such as fluid and electrolyte disturbances 3.
• Furosemide can cause acute and delayed tolerance, which is postulated to be due to the intervention of homeostatic mechanisms influencing fluid and electrolyte balances 3.
• The association of furosemide with other diuretics, such as hydrochlorothiazide, can increase the fractional excretions of sodium and chloride, and decrease mean blood pressure 4.
• Furosemide can increase the risk of acute kidney injury and hypokalemia, particularly when used in combination with fluid restriction 5.

Mechanism of Action and Pharmacokinetics

• Furosemide acts at the luminal surface of the ascending limb of the loop of Henle by inhibiting the active reabsorption of chloride 3.
• The response to a given dosage of furosemide is modulated by the fluid and electrolyte balance of the individual 3.
• Furosemide is delivered to its site of action by active secretion via the nonspecific organic acid pump 3.
• The bioavailability of furosemide from oral dosage forms is highly variable, and the poor bioavailability has been hypothesized to be due to the poor solubility of the compound, site-specific absorption, presystemic metabolism, and/or other unknown mechanisms 3.

Clinical Uses and Efficacy

• Furosemide is used in the treatment of oedematous states associated with cardiac, renal, and hepatic failure, and for the treatment of hypertension 3.
• Furosemide is the diuretic of choice for the treatment of hypertension in chronic kidney disease, but its efficacy may be decreased by adaptative changes in the distal nephron 4.
• Furosemide with or without sodium chloride supplementation did not show benefits in correction of hyponatremia compared with treatment with fluid restriction alone in patients with syndrome of inappropriate antidiuresis (SIAD) 5.
• Furosemide can increase urinary water and sodium excretion, and reduce body weight and extracellular water, but may also increase intracellular water and urinary excretion of NKCC2 6.