Furosemide

Furosemide Injection is a loop diuretic indicated for:

• •The treatment of edema associated with heart failure, cirrhosis of the liver, and renal disease (
  1.1 Edema

  Furosemide Injection is indicated in adults and pediatric patients for the treatment of edema associated with heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome.
  )
• •Acute pulmonary edema as adjunctive therapy (
  1.2 Acute Pulmonary Edema

  Furosemide Injection is indicated as adjunctive therapy in acute pulmonary edema.
  )

• •Initial dose is 20 mg to 40 mg once given intramuscularly or intravenously. The intravenous dose should be administered slowly over 1 minute to 2 minutes (
  2.2 Recommended Dosage for Adults

  Edema

  Individualize therapy according to patient response.

  The usual initial dose of furosemide is 20 mg to 40 mg given as a single-dose, injected intramuscularly or intravenously. Give the intravenous dose slowly (over 1 minute to 2 minutes). If needed, administer another dose in the same manner 2 hours later or increase the dose. The dose may be raised by 20 mg and administered not sooner than 2 hours after the previous dose until the desired diuretic effect has been obtained. Administer this individually determined single-dose once or twice daily.

  If the physician elects to use high-dose parenteral therapy, add the furosemide to either 0.9% Sodium Chloride Injection USP, Lactated Ringer's Injection USP, or Dextrose Injection 5%, USP, after pH has been adjusted to above 5.5, and administer as a controlled intravenous infusion at a rate not greater than 4 mg/min. Furosemide Injection is a buffered alkaline solution with a pH of about 9 and the drug may precipitate at pH values below 7. Care must be taken to ensure that the pH of the prepared infusion solution is in the weakly alkaline to neutral range. Acid solutions, including other parenteral medications (e.g., labetalol, ciprofloxacin, amrinone, milrinone) must not be administered concurrently in the same infusion because they may cause precipitation of the furosemide.

  Acute Pulmonary Edema

  The usual initial dose of furosemide is 40 mg injected slowly intravenously (over 1 minute to 2 minutes). If a satisfactory response does not occur within 1 hour, increase the dose to 80 mg injected slowly intravenously (over 1 minute to 2 minutes).
  )
• •If needed, a second dose may be administered 2 hours after the first dose (
  2.2 Recommended Dosage for Adults

  Edema

  Individualize therapy according to patient response.

  The usual initial dose of furosemide is 20 mg to 40 mg given as a single-dose, injected intramuscularly or intravenously. Give the intravenous dose slowly (over 1 minute to 2 minutes). If needed, administer another dose in the same manner 2 hours later or increase the dose. The dose may be raised by 20 mg and administered not sooner than 2 hours after the previous dose until the desired diuretic effect has been obtained. Administer this individually determined single-dose once or twice daily.

  If the physician elects to use high-dose parenteral therapy, add the furosemide to either 0.9% Sodium Chloride Injection USP, Lactated Ringer's Injection USP, or Dextrose Injection 5%, USP, after pH has been adjusted to above 5.5, and administer as a controlled intravenous infusion at a rate not greater than 4 mg/min. Furosemide Injection is a buffered alkaline solution with a pH of about 9 and the drug may precipitate at pH values below 7. Care must be taken to ensure that the pH of the prepared infusion solution is in the weakly alkaline to neutral range. Acid solutions, including other parenteral medications (e.g., labetalol, ciprofloxacin, amrinone, milrinone) must not be administered concurrently in the same infusion because they may cause precipitation of the furosemide.

  Acute Pulmonary Edema

  The usual initial dose of furosemide is 40 mg injected slowly intravenously (over 1 minute to 2 minutes). If a satisfactory response does not occur within 1 hour, increase the dose to 80 mg injected slowly intravenously (over 1 minute to 2 minutes).
  )

• •Initial dose is 40 mg injected slowly intravenously over 1 minute to 2 minutes (
  2.2 Recommended Dosage for Adults

  Edema

  Individualize therapy according to patient response.

  The usual initial dose of furosemide is 20 mg to 40 mg given as a single-dose, injected intramuscularly or intravenously. Give the intravenous dose slowly (over 1 minute to 2 minutes). If needed, administer another dose in the same manner 2 hours later or increase the dose. The dose may be raised by 20 mg and administered not sooner than 2 hours after the previous dose until the desired diuretic effect has been obtained. Administer this individually determined single-dose once or twice daily.

  If the physician elects to use high-dose parenteral therapy, add the furosemide to either 0.9% Sodium Chloride Injection USP, Lactated Ringer's Injection USP, or Dextrose Injection 5%, USP, after pH has been adjusted to above 5.5, and administer as a controlled intravenous infusion at a rate not greater than 4 mg/min. Furosemide Injection is a buffered alkaline solution with a pH of about 9 and the drug may precipitate at pH values below 7. Care must be taken to ensure that the pH of the prepared infusion solution is in the weakly alkaline to neutral range. Acid solutions, including other parenteral medications (e.g., labetalol, ciprofloxacin, amrinone, milrinone) must not be administered concurrently in the same infusion because they may cause precipitation of the furosemide.

  Acute Pulmonary Edema

  The usual initial dose of furosemide is 40 mg injected slowly intravenously (over 1 minute to 2 minutes). If a satisfactory response does not occur within 1 hour, increase the dose to 80 mg injected slowly intravenously (over 1 minute to 2 minutes).
  )
• •If needed, a second dose is 80 mg injected intravenously slowly in 1 minute to 2 minutes (
  2.2 Recommended Dosage for Adults

  Edema

  Individualize therapy according to patient response.

  The usual initial dose of furosemide is 20 mg to 40 mg given as a single-dose, injected intramuscularly or intravenously. Give the intravenous dose slowly (over 1 minute to 2 minutes). If needed, administer another dose in the same manner 2 hours later or increase the dose. The dose may be raised by 20 mg and administered not sooner than 2 hours after the previous dose until the desired diuretic effect has been obtained. Administer this individually determined single-dose once or twice daily.

  If the physician elects to use high-dose parenteral therapy, add the furosemide to either 0.9% Sodium Chloride Injection USP, Lactated Ringer's Injection USP, or Dextrose Injection 5%, USP, after pH has been adjusted to above 5.5, and administer as a controlled intravenous infusion at a rate not greater than 4 mg/min. Furosemide Injection is a buffered alkaline solution with a pH of about 9 and the drug may precipitate at pH values below 7. Care must be taken to ensure that the pH of the prepared infusion solution is in the weakly alkaline to neutral range. Acid solutions, including other parenteral medications (e.g., labetalol, ciprofloxacin, amrinone, milrinone) must not be administered concurrently in the same infusion because they may cause precipitation of the furosemide.

  Acute Pulmonary Edema

  The usual initial dose of furosemide is 40 mg injected slowly intravenously (over 1 minute to 2 minutes). If a satisfactory response does not occur within 1 hour, increase the dose to 80 mg injected slowly intravenously (over 1 minute to 2 minutes).
  )

• •The initial dose in pediatric patients is 1 mg/kg body weight once given slowly intramuscularly or intravenously. If needed, dosage may be increased by 1 mg/kg not sooner than 2 hours after the previous dose, until the desired diuretic effect has been obtained. Doses greater than 6 mg/kg body weight are not recommended (
  2.3 Recommended Dosage for Pediatric Patients

  The usual initial dose of Furosemide Injection (intravenously or intramuscularly) in pediatric patients is 1 mg/kg body weight administered slowly (over 1 minute to 2 minutes). If the diuretic response to the initial dose is not satisfactory, dosage may be increased by 1 mg/kg not sooner than 2 hours after the previous dose, until the desired diuretic effect has been obtained. Doses greater than 6 mg/kg body weight are not recommended.

  The maximum dose for premature infants should not exceed 1 mg/kg/day

  [see Use in Specific Populations ]

  .
  )

Injection: Furosemide Injection, USP is supplied as a sterile, colorless solution as

• •20 mg/2 mL (10 mg/mL) in a single-dose vial
• •40 mg/4 mL (10 mg/mL) in a single-dose vial
• •100 mg/10 mL (10 mg/mL) in a single-dose vial

Available data from published observational studies, case reports, and postmarketing reports, from decades of use, have not demonstrated a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes with furosemide use during pregnancy. Untreated congestive heart failure and cirrhosis of the liver can lead to adverse outcomes for the mother and the fetus

In animal reproduction studies, furosemide has been shown to cause unexplained maternal deaths and abortions in rabbits when administered orally during organogenesis at 4 times a human i.v. dose of 80 mg based on body surface area (BSA) and oral bioavailability corrections, presumably secondary to volume depletion

The estimated background risk for major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

• •
  Fluid, Electrolyte, and Metabolic Abnormalities
  : Monitor serum electrolytes, CO₂, BUN, creatinine, glucose, and uric acid (
  5.1 Fluid, Electrolyte, and Metabolic Abnormalities

  Furosemide may cause fluid, electrolyte, and metabolic abnormalities such as hypovolemia, hypokalemia, azotemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypocalcemia, hyperglycemia, or hyperuricemia, particularly in patients receiving higher doses, patients with inadequate oral electrolyte intake, and in elderly patients. Excessive diuresis may cause dehydration and blood volume reduction with circulatory collapse and possibly vascular thrombosis and embolism, particularly in elderly patients. Serum electrolytes, CO₂, BUN, creatinine, glucose, and uric acid should be monitored frequently during furosemide therapy.

  In patients with hepatic cirrhosis and ascites, sudden alterations of fluid and electrolyte balance may precipitate hepatic encephalopathy and coma. Treatment in such patients is best initiated in the hospital with small doses and careful monitoring of the patient's clinical status and electrolyte balance.
  )
• •
  Worsening Renal Function
  : Monitor for dehydration and azotemia. (
  5.2 Worsening Renal Function

  Furosemide can cause dehydration and azotemia. If increasing azotemia and oliguria occur during treatment of severe progressive renal disease, furosemide should be discontinued

  [see Clinical Pharmacology ]

  .

  Furosemide use in the first year of life, especially in patients born pre-term, may precipitate nephrocalcinosis/nephrolithiasis. Therefore renal function must be monitored and renal ultrasonography performed in this age group

  [see Use in Specific Populations ]

  .
  )
• •
  Ototoxicity:
  Avoid rapid injection and higher than recommended doses. (
  5.3 Ototoxicity

  Cases of tinnitus and reversible or irreversible hearing impairment and deafness have been reported. Reports usually indicate that furosemide ototoxicity is associated with rapid injection, severe renal impairment, the use of higher than recommended doses, hypoproteinemia or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If the physician elects to use high-dose parenteral therapy, controlled intravenous infusion is advisable (for adults, an infusion rate not exceeding 4 mg furosemide per minute has been used)

  [see Drug Interactions ]

  .

  Hearing loss in neonates, including premature neonates has been associated with the use of Furosemide Injection

  [see Use in Specific Populations ].
  ,
  7.1 Effects of Furosemide on Other Drugs

  Drug/Substance Class or Name	Drug Interaction Effect	Recommendations
  Aminoglycoside antibiotics	Furosemide may increase the ototoxic potential of aminoglycoside antibiotics, especially in the presence of impaired renal function [see Warnings and Precautions ].	Avoid combination except in life-threatening situations.
  Ethacrynic acid	Possibility of ototoxicity [see Warnings and Precautions ].	Avoid concomitant use with ethacrynic acid.
  Salicylates	May experience salicylate toxicity at lower doses because of competitive renal excretory sites.	Monitor for symptoms of salicylate toxicity.
  Cisplatin Cisplatin and nephrotoxic drugs	There is a risk of ototoxic effects if cisplatin and furosemide are given concomitantly [see Warnings and Precautions ]. Nephrotoxicity	Administer furosemide at lower doses and with positive fluid balance when used to achieve forced diuresis during cisplatin treatment. Monitor renal function.
  Paralytic agents	Furosemide has a tendency to antagonize the skeletal muscle relaxing effect of tubocurarine and may potentiate the action of succinylcholine.	Monitor for skeletal muscle effect.
  Lithium	Furosemide reduces lithium's renal clearance and add a high-risk of lithium toxicity.	Avoid concomitant use with lithium.
  Angiotensin converting enzyme inhibitors or angiotensin II receptor blockers	May lead to severe hypotension and deterioration in renal function, including renal failure.	Monitor for changes in blood pressure and renal function and interrupt or reduce the dosage of furosemide, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers if needed.
  Antihypertensive drugs	Furosemide may add to or potentiate the therapeutic effect of other antihypertensive drugs.	Monitor for changes in blood pressure and adjust the dose of other antihypertensive drugs if needed.
  Adrenergic blocking drugs or peripheral adrenergic blocking drugs	Potentiation occurs.	Monitor for changes in blood pressure and adjust the dose of adrenergic blocking drugs if needed.
  Norepinephrine	Furosemide may decrease arterial responsiveness (vasoconstricting effect) to norepinephrine.	Monitor blood pressure (or mean arterial pressure).
  Chloral hydrate	In isolated cases, intravenous administration of furosemide within 24 hours of taking chloral hydrate may lead to flushing, sweating attacks, restlessness, nausea, increase in blood pressure, and tachycardia.	Concomitant use with chloral hydrate is not recommended.
  Methotrexate and other drugs undergoing renal tubular secretion	Furosemide may decrease renal elimination of other drugs that undergo tubular secretion. High-dose treatment of furosemide may result in elevated serum levels of these drugs and may potentiate their toxicity.	Monitor serum levels of drugs undergoing renal tubular secretion and adjust the dose if needed.
  Cephalosporin	Furosemide can increase the risk of cephalosporin-induced nephrotoxicity even in the setting of minor or transient renal impairment.	Monitor for changes in renal function.
  Cyclosporine	Increased risk of gouty arthritis secondary to furosemide-induced hyperuricemia and cyclosporine impairment of renal urate excretion.	Monitor serum urate levels.
  Thyroid hormones	High-doses (> 80 mg) of furosemide may inhibit the binding of thyroid hormones to carrier proteins and result in transient increase in free thyroid hormones, followed by an overall decrease in total thyroid hormone levels.	Monitor the total thyroid hormone levels.
  )
• •
  Acute Urinary Retention
  : Monitor patients with symptoms of urinary retention. (
  5.4 Acute Urinary Retention

  In patients with severe symptoms of urinary retention (because of bladder emptying disorders, prostatic hyperplasia, urethral narrowing), the administration of furosemide can cause acute urinary retention related to increased production and retention of urine. Thus, these patients require careful monitoring, especially during the initial stages of treatment.
  )