Furosemide

Parenteral therapy should be reserved for patients unable to take oral medication or for patients in emergency clinical situations.

Adverse reactions are categorized below by organ system and listed by decreasing severity.

• 1.Hepatic encephalopathy in patients with hepatocellular insufficiency
• 2.Pancreatitis
• 3.Jaundice (intrahepatic cholestatic jaundice)
• 4.Increased liver enzymes
• 5.Anorexia
• 6.Oral and gastric irritation
• 7.Cramping
• 8.Diarrhea
• 9.Constipation
• 10.Nausea
• 11.Vomiting

• 1.Severe anaphylactic or anaphylactoid reactions (e.g. with shock)
• 2.Systemic vasculitis
• 3.Interstitial nephritis
• 4.Necrotizing angiitis

• 1.Tinnitus and hearing loss
• 2.Paresthesias
• 3.Vertigo
• 4.Dizziness
• 5.Headache
• 6.Blurred vision
• 7.Xanthopsia

• 1.Aplastic anemia
• 2.Thrombocytopenia
• 3.Agranulocytosis
• 4.Hemolytic anemia
• 5.Leukopenia
• 6.Anemia
• 7.Eosinophilia

• 1.Exfoliative dermatitis
• 2.Bullous pemphigoid
• 3.Erythema multiforme
• 4.Purpura
• 5.Photosensitivity
• 6.Urticaria
• 7.Rash
• 8.Pruritus
• 9.Stevens-Johnson Syndrome
• 10.Toxic epidermal necrolysis

• 1.Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates or narcotics.
• 2.Increase in cholesterol and triglyceride serum levels.

• 1.Hyperglycemia
• 2.Glycosuria
• 3.Hyperuricemia
• 4.Muscle spasm
• 5.Weakness
• 6.Restlessness
• 7.Urinary bladder spasm
• 8.Thrombophlebitis
• 9.Transient injection site pain following intramuscular injection
• 10.Fever

Whenever adverse reactions are moderate or severe, furosemide dosage should be reduced or therapy withdrawn.

Furosemide should not be used concomitantly with ethacrynic acid because of the possibility of ototoxicity.

Patients receiving high doses of salicylates concomitantly with furosemide, as in rheumatic diseases, may experience salicylate toxicity at lower doses because of competitive renal excretory sites.

There is a risk of ototoxic effects if cisplatin and furosemide are given concomitantly. In addition, nephrotoxicity of nephrotoxic drugs such as cisplatin may be enhanced if furosemide is not given in lower doses and with positive fluid balance when used to achieve forced diuresis during cisplatin treatment.

Furosemide has a tendency to antagonize the skeletal muscle relaxing effect of tubocurarine and may potentiate the action of succinylcholine.

Lithium generally should not be given with diuretics because they reduce lithium's renal clearance and add a high risk of lithium toxicity.

Furosemide combined with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers may lead to severe hypotension and deterioration in renal function, including renal failure. An interruption or reduction in the dosage of furosemide, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers may be necessary.

Furosemide may add to or potentiate the therapeutic effect of other antihypertensive drugs. Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs.

Furosemide may decrease arterial responsiveness to norepinephrine. However, norepinephrine may still be used effectively.

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. Use of furosemide concomitantly with chloral hydrate is therefore not recommended.

Phenytoin interferes directly with renal action of furosemide.

Methotrexate and other drugs that, like furosemide, undergo significant renal tubular secretion may reduce the effect of furosemide. Conversely, furosemide may decrease renal elimination of other drugs that undergo tubular secretion. High-dose treatment of both furosemide and these other drugs may result in elevated serum levels of these drugs and may potentiate their toxicity as well as the toxicity of furosemide.

Furosemide can increase the risk of cephalosporin-induced nephrotoxicity even in the setting of minor or transient renal impairment.

Concomitant use of cyclosporine and furosemide is associated with increased risk of gouty arthritis secondary to furosemide-induced hyperuricemia and cyclosporine impairment of renal urate excretion.

One study in six subjects demonstrated that the combination of furosemide and acetylsalicylic acid temporarily reduced creatinine clearance in patients with chronic renal insufficiency. There are case reports of patients who developed increased BUN, serum creatinine and serum potassium levels, and weight gain when furosemide was used in conjunction with NSAIDs.

Literature reports indicate that coadministration of indomethacin may reduce the natriuretic and antihypertensive effects of furosemide in some patients by inhibiting prostaglandin synthesis. Indomethacin may also affect plasma renin levels, aldosterone excretion, and renin profile evaluation. Patients receiving both indomethacin and furosemide should be observed closely to determine if the desired diuretic and/or antihypertensive effect of furosemide is achieved.