Demadex (Torsemide): 5 mg, 10 mg, 20 mg, & 100 mg Tablets

By | March 17, 2016

TORSEMIDE (Demadex, Torasemide)

LOOP DIURETIC

Highlights of Prescribing Information

  • Potent loop diuretic potentially useful for adjunctive treatment of CHF in dogs & cats; very little information available on clinical use in veterinary medicine
  • Approximately 10X more potent, longer diuretic action, & more potassium-sparing (in dogs) than furosemide
  • May be more expensive than furosemide, but tablets are now available generically

What Is Drug Used For?

Torsemide is a loop diuretic similar to furosemide, but it is more potent, its diuretic effects persist for a longer period, and it does not cause as much potassium excretion (in dogs). While clinical use in dogs and cats thus far has been minimal, it potentially may be a useful adjunctive treatment for congestive heart failure in dogs and cats, particularly in patients that have become refractory to furosemide.

Pharmacology / Actions

Torsemide, like furosemide inhibits sodium and chloride reabsorption in the ascending loop of Henle via interference with the chloride-binding site of the lNa+, 1K+, 2Cl- cotransport system.

Torsemide increases renal excretion of water, sodium, potassium, chloride, calcium, magnesium, hydrogen, ammonium, and bicarbonate. In dogs, excretion of potassium is affected much less so than is sodium (20:1); this is approximately twice the ratio of Na:K excreted than with furosemide. In cats, torsemide’s effects on potassium excretion appear to be similar to that of furosemide. In dogs, torsemide appears to have differing effects on aldosterone than furosemide. When compared to furosemide, torsemide increases plasma aldosterone levels and inhibits the amount of receptor-bound aldosterone, however, additional research must be performed to determine the clinical significance of these effects.

Pharmacokinetics/Pharmacodynamics

Limited information is available. Oral bioavailability has been reported to be between 80-100% in dogs and cats. Elimination half-life in dogs is about 8 hours which is longer than furosemide. In dogs, diuretic activity begins within one hour of dosing, peaks at about 2 hours and persists for approximately 12 hours.

In cats, peak diuresis occurs about 4 hours post-dose and persists for 12 hours.

Before you take Drug

Contraindications / Precautions / Warnings

Torsemide should not be used in patients with known hypersensitivity to it or other sulfonylureas, or in anuric patients.

Use torsemide cautiously in patients with significant hepatic dysfunction, hyperuricemia (may increase serum uric acid), or diabetes mellitus (may increase serum glucose).

The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance when used in horses.

The injection should be administered IV slowly over a period of 2 minutes. Ototoxicity has occurred in human patients receiving rapid IV administration of other loop diuretics.

Adverse Effects

Adverse effect profiles for dogs and cats have not been established due to the limited use of this drug in veterinary medicine. Furosemide, a related drug, can induce fluid and electrolyte abnormalities. Patients should be monitored for hydration status and electrolyte imbalances (especially potassium, calcium, magnesium and sodium). Prerenal azotemia may result if moderate to severe dehydration occurs. Hyponatremia is probably the greatest concern, but hypocalcemia, hypokalemia, and hypomagnesemia may all occur. Animals with normal food and water intake are much less likely to develop water and electrolyte imbalances than those that do not.

Other potential adverse effects include gastrointestinal disturbances, hematologic effects (anemia, leukopenia), weakness, and restlessness. Torsemide, unlike furosemide, apparently only rarely causes significant ototoxic effects in humans; very high doses in laboratory animals have induced ototoxicity.

Reproductive / Nursing Safety

No effects on fertility were noted when female and male rats were administered up to 25 mg/kg/day.

No adverse teratogenic effects were seen when pregnant rats and rabbits were administered up to 15X (human dose) and 5X (human dose), respectively. Larger doses did increase fetal resorptions, decreased average body weight, and delayed fetal ossification. In humans, the FDA categorizes torsemide as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, hut there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, hut adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters.)

It is unknown if torsemide enters milk, but furosemide is distributed in milk. Clinical significance for nursing offspring is unknown.

Overdosage / Acute Toxicity

In dogs, the oral LD50 is >2 grams/kg. Fluid and electrolyte imbalance is the most likely risk associated with an overdose. Consider gut emptying protocols for very large or quantity unknown ingestions. Acute overdoses should generally be managed by observation with fluid, electrolyte and acid-base monitoring; supportive treatment should be initiated if required.

Drug Interactions

The following drug interactions have either been reported or are theoretical in humans or animals receiving torsemide and may be of significance in veterinary patients:

■ ACE INHIBITORS (e.g., enalapril, benazepril): Increased risks for hypotension, particularly in patients who are volume or sodium depleted secondary to diuretics

■ AMINOGLYCOSIDES (gentamicin, amikacin, etc.): Other diuretics have been associated with increasing the ototoxic or nephrotoxic risks of aminoglycosides. It is unknown if torsemide can also have these effects and if so, what the clinical significance may be.

■ AMPHOTERICIN B: Loop diuretics may increase the risk for nephrotoxicity development

■ DIGOXIN: Can increase the area under the curve of torsemide by 50%, but is unlikely to be of significance clinically; torsemide-induced hypokalemia may increase the potential for digoxin toxicity

■ LITHIUM: Torsemide may reduce lithium clearance

■ NSAIDs: Some NSAIDs may reduce the natriuretic effects of torsemide

■ PROBENECID: Can reduce the diuretic efficacy of torsemide

■ SALICYLATES: Torsemide can reduce the excretion of salicylates

Laboratory Considerations

■ Torsemide can affect serum electrolytes, glucose, uric acid, and BUN concentrations.

How to use Drug

Drug dosage for dogs and cats:

While no referenced dosages were located, torsemide could be considered for use as an alternative to furosemide particularly in those patients that have become refractory to furosemide therapy. Torsemide is approximately 10 times more potent than furosemide, so a starting dose of 10% of furosemide could be considered. As torsemide has a more persistent diuretic effect (approximately 12 hours), dosing frequency may also be reduced.

Monitoring

■ Serum electrolytes, BUN, creatinine, glucose (if diabetic)

■ Hydration status

■ Blood pressure, if indicated

■ Clinical signs of edema, patient weight, if indicated

Client Information

■ Contact veterinarian if clinical signs of water or electrolyte imbalance occur. Signs such as excessive thirst, lethargy, restlessness, increased urination, GI distress or rapid heart rate may indicate electrolyte or water balance problems.

Chemistry / Synonyms

Torsemide is a pyridyl sulfonylurea loop diuretic that occurs as white to off-white, crystalline powder. It is practically insoluble in water and slightly soluble in alcohol. The injection has a pH >8.3.

Torsemide may also be known as torasemide, AC-3525, AC 4464, BM-02.015, TDL-464, and Demadex. International trade names include Torem and Unat.

Storage / Stability / Compatibility

Torsemide tablets and injectable solution should be stored below 40°C; preferably between 15-30°C (59-86°F). Protect from freezing.

Torsemide injection is stable in NaCl 0.9%, NaCl 0.45%, or D5W. When given IV undiluted, the manufacturer recommends flushing the line to avoid incompatibilities with other drugs secondary to torsemide’s high pH.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance.

Human-Labeled Products:

Torsemide Tablets: 5 mg, 10 mg, 20 mg, & 100 mg; Demadex (Roche), generic; (Rx)

Torsemide Injection: 10 mg/mL in 2 and 5 mL amps; Demadex (Roche)

 

Selections from the book: “Plumb’s Veterinary Drug Handbook. Sixth Edition”. 2008