Elephant specific information, if available, is in blue.

Chemistry – A loop diuretic related structurally to the sulfonamides, furosemide occurs as an odorless, practically tasteless, white to slightly yellow, fine, crystalline powder. Furosemide has a melting point between 203° – 205° with decomposition, and a pKa of 3.9. It is practically insoluble in water, sparingly soluble in alcohol and freely soluble in alkaline hydroxides. The injectable product has its pH adjusted to 8 – 9.3 with sodium hy­droxide. Furosemide may also be known as frusemide.

 

Storage/Stability/Compatibility – Furosemide tablets should be stored in light-resistant, well-closed containers. The oral solution should be stored at room temperature and protected from light and freezing. Furosemide injection should be stored at room temperature. A precipitate may form if the injection is refrigerated, but will resolubolize when warmed without alteration in potency. The human injection (10 mg/ml) should not be used if it is a yellow-color. The veterinary injection (50 mg/ml) normally has a slight yellow color. Furosemide is unstable at an acid pH, but is very stable under alkaline conditions.

 

Furosemide injection (10 mg/ml) is reportedly compatible with all commonly used intravenous solutions and the following drugs: amikacin sulfate, cimetidine HCl, kanamycin sulfate, tobramycin sulfate and verapamil.

 

It is reportedly incompatible with the following agents: ascorbic acid solutions, dobutamine HCl, epinephrine, gentamicin sulfate, netilmicin sulfate and tetracylines. It should generally not be mixed with antihistamines, local anesthetics, alkaloids, hypnotics, or opiates.

 

Pharmacology – Furosemide reduces the absorption of electrolytes in the ascending section of the loop of Henle, decreases the reabsorption of both sodium and chloride and increases the excretion of potassium in the distal renal tubule, and directly effects electrolyte transport in the proximal tubule. The exact mechanisms of furosemide’s effects have not been established. It has no effect on carbonic anhydrase nor does it antagonize aldos­terone.

 

Furosemide increases renal excretion of water, sodium, potassium, chloride, calcium, magnesium, hydrogen, ammonium, and bicarbonate. It causes some renal venodilation and transiently increases glomerular filtration rates (GFR). Renal blood flow is increased and decreased peripheral resistance may occur. Furosemide can cause hyperglycemia, but to a lesser extent than the thiazides.

 

Uses/Indications – Furosemide is used for its diuretic activity in all species. It is used in small animals for the treatment of congestive cardiomyopathy, pulmonary edema, hyper­calcuric nephropathy, uremia, as adjunctive therapy in hyperkalemia and, occasionally, as an antihypertensive agent. In cattle, it is approved for use for the treatment of post-parturient udder edema. It has been used to help prevent or reduce epistaxis (exercise-induced pulmonary hemorrhage; EIPH) in race horses.

 

Pharmacokinetics – The pharmacokinetics of furosemide have been studied in a limited fashion in domestic animals. In dogs, the oral bioavailability is approximately 77% and the elimination half-life approximately 1 – 1.5 hours.

 

In humans, furosemide is 60-75% absorbed following oral administration. The diuretic effect takes place within 5 minutes after IV administration and within one hour after oral dosing. Peak effects occur approximately 30 minutes after IV dosing, and 1-2 hours after oral dosing. The drug is approximately 95% bound to plasma proteins in both azotemic and normal patients. The serum half-life is about 2 hours, but is prolonged in patients with renal failure, uremia, CHF, and in neonates.

 

Contraindications/Precautions – Furosemide is contraindicated in patients with anuria or who are hypersensitive to the drug. The manufacturer states that the drug should be discontinued in patients with progressive renal disease if increasing azotemia and oliguria occur during therapy.

 

Furosemide should be used with caution in patients with preexisting electrolyte or water balance abnormalities, impaired hepatic function (may precipitate hepatic coma) and diabetes mellitus. Patients with conditions that may lead to electrolyte or water balance abnormalities (e.g., vomiting, diarrhea, etc.) should be monitored carefully. Patients hyper­sensitive to sulfonamides may also be hypersensitive to furosemide (not documented in veterinary species).

 

Adverse Effects/Warnings – Furosemide may induce fluid and electrolyte abnormalities. Patients should be monitored for hydration status and electrolyte imbalances (especially potassium, calcium and sodium). Other potential adverse effects include ototoxicity (especially in cats with high dose IV therapy), gastrointestinal disturbances, hematologic effects (anemia, leukopenia), weakness and restlessness.

 

Overdosage – The LD50 in dogs after oral administration is > 1000 mg/kg and after IV injection > 300 mg/kg. Chronic overdosing at 10 mg/kg for six months in dogs led to development of calcification and scarring of the renal parenchyma.

 

Acute overdosage may cause electrolyte and water balance problems, CNS effects (lethargy to coma and seizures) and cardiovascular collapse.

 

Treatment consists of emptying the gut after recent oral ingestion, using standard protocols. Avoid giving concomitant cathartics as they may exacerbate the fluid and electrolyte imbalances that can occur. Aggressively monitor and treat electrolyte and water balance abnormalities supportively. Additionally, monitor respiratory, CNS, and cardiovascular status. Treat supportively and symptomatically if necessary.

 

Drug Interactions – Pharmacologic effects of theophylline may be enhanced when given with furosemide. Ototoxicity and nephrotoxicity associated with the aminoglycoside antibiotics may be increased when furosemide is also used. If used concomitantly with corticosteroids, corticotropin or amphotericin B, furosemide may increase the chance of hypokalemia development. Furosemide-induced hypokalemia may increase chances of digitalis toxicity.  Patients on aspirin therapy may need dosage adjustment as furosemide competes for re­nal excretory sites. Furosemide may inhibit the muscle relaxation qualities of tubocurarine, but increase the effects of succinylcholine. Enhanced effects may occur if furosemide is used concomitantly with other diuretics. The uricosuric effects of probenecid or sulfinpyrazone may be inhibited by furosemide. Furosemide may alter the requirements of insulin or other anti-diabetic agents in diabetic patients.

 

Doses –

Horses:

As a diuretic:

a)   0.25 – 1.0 mg/kg IV (Muir and McGuirk 1987)

b)   1 mg/kg IV (Robinson 1987)

 

For epistaxis prevention:

a)   0.3 – 0.6 mg/kg 60-90 minutes prior to race. (Robinson 1987) (Note: Refer to state guidelines for use of furosemide in racing animals)

 

Elephants:

a) Furosemide: 300-500 mg/animal IM (Cheeran et.al. 1995).

 

Elephant References:

a) Cheeran,J.V., Chandrasekharan,K., and Radhakrishnan,K., 1995. Principles and Practice of Fixing Dose of Drugs for Elephants. In: Daniel,J.C. (Editor), A Week with Elephants; Proceedings of the International Seminar on Asian Elephants. Bombay Natural History Society; Oxford University Press, Bombay, India pp. 430-438

 

Monitoring Parameters –

1)   Serum electrolytes, BUN, creatinine, glucose

2)   Hydration status

3)   Blood pressure, if indicated

4)   Symptoms of edema, patient weight, if indicated

5)   Evaluation of ototoxity, particularly with prolonged therapy or in cats

 

Client Information – Clients should contact veterinarian if symptoms of water or electrolyte imbalance occur. Symptoms such as excessive thirst, lethargy, lassitude, restlessness, oliguria, GI distress or tachycardia may indicate electrolyte or water balance problems.

 

Dosage Forms/Preparations/FDA Approval Status/Withholding Times –

 

Veterinary-Approved Products:

Furosemide Tablets 12.5 mg, 50 mg ; Lasix®  (Hoechst); Generic; (Rx)  Approved for use in dogs and cats.

 

Furosemide Oral Solution: 10 mg/ml in 60 ml btls; Lasix® (Hoechst) (Rx)  Approved for use in dogs.

 

Furosemide 2 gram  boluses; Lasix® (Hoechst); (Rx)  Approved for use in cattle. A 48 hour withdrawal time has been assigned for both milk and slaughter for cattle.

 

Furosemide 50 mg/ml (5%) for Injection in 50 ml vials; Lasix® (Hoechst), Diuride®  (Anthony), Generic  (Rx) Approved for use in dogs, cats, horses not intended for food, and cattle. Milk withdrawal time = 48 hours; slaughter withdrawal = 48 hours.

 

Human-Approved Products:

Furosemide Tablets  20 mg, 40 mg, 80 mg; Lasix®  (Hoechst Marion Roussel); Generic (Rx)

 

Furosemide Oral Solution: 8 mg/ml in 5, 10, & 500 ml btls; 10 mg/ml in 60 ml & 120 ml bottles; Lasix® (Hoechst Marion Roussel); Generic (Rx)

 

Furosemide 10 mg/ml for Injection in 2, 4, & 10 ml amps, vials and syringes; Lasix® (Hoechst Marion Roussel); Generic (Rx)