Torsemide (injection)
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adeel Jamil, M.D. [2]
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Overview
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Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
- Torsemide Injection is indicated for the treatment of edema associated with congestive heart failure, renal disease, or hepatic disease. Use of torsemide has been found to be effective for the treatment of edema associated with chronic renal failure. Chronic use of any diuretic in hepatic disease has not been studied in adequate and well-controlled trials.
- Torsemide Injection is indicated when a rapid onset of diuresis is desired or when oral administration is impractical.
- Torsemide Injection is indicated for the treatment of hypertension alone or in combination with other antihypertensive agents.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Torsemide (injection) in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Torsemide (injection) in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Torsemide (injection) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Torsemide (injection) in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Torsemide (injection) in pediatric patients.
Contraindications
- Torsemide Injection is contraindicated in patients with known hypersensitivity to torsemide or to sulfonylureas.
- Torsemide Injection is contraindicated in patients who are anuric.
Warnings
Hepatic Disease with Cirrhosis and Ascites
- Torsemide should be used with caution in patients with hepatic disease with cirrhosis and ascites, since sudden alterations of fluid and electrolyte balance may precipitate hepatic coma. In these patients, diuresis with torsemide (or any other diuretic) is best initiated in the hospital. To prevent hypokalemia and metabolic alkalosis, an aldosterone antagonist or potassium-sparing drug should be used concomitantly with torsemide.
Ototoxicity
- Tinnitus and hearing loss (usually reversible) have been observed after rapid intravenous injection of other loop diuretics and have also been observed after oral Torsemide. It is not certain that these events were attributable to torsemide. Ototoxicity has also been seen in animal studies when very high plasma levels of torsemide were induced. Administered intravenously, torsemide should be injected slowly over 2 minutes, and single doses should not exceed 200 mg.
Volume and Electrolyte Depletion
- Patients receiving diuretics should be observed for clinical evidence of electrolyte imbalance, hypovolemia, or prerenal azotemia. Symptoms of these disturbances may include one or more of the following: dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, nausea, and vomiting. Excessive diuresis may cause dehydration, blood-volume reduction, and possibly thrombosis and embolism, especially in elderly patients. In patients who develop fluid and electrolyte imbalances, hypovolemia, or prerenal azotemia, the observed laboratory changes may include hyper- or hyponatremia, hyper- or hypochloremia, hyper- or hypokalemia, acid-base abnormalities, and increased blood urea nitrogen (BUN). If any of these occur, torsemide should be discontinued until the situation is corrected; torsemide may be restarted at a lower dose.
- In controlled studies in the United States, torsemide was administered to hypertensive patients at doses of 5 mg or 10 mg daily. After 6 weeks at these doses, the mean decrease in serum potassium was approximately 0.1 mEq/L. The percentage of patients who had a serum potassium level below 3.5 mEq/L at any time during the studies was essentially the same in patients who received torsemide (1.5%) as in those who received placebo (3%). In patients followed for 1 year, there was no further change in mean serum potassium levels. In patients with congestive heart failure, hepatic cirrhosis, or renal disease treated with torsemide at doses higher than those studied in United States antihypertensive trials, hypokalemia was observed with greater frequency, in a dose-related manner.
- In patients with cardiovascular disease, especially those receiving digitalis glycosides, diuretic-induced hypokalemia may be a risk factor for the development of arrhythmias. The risk of hypokalemia is greatest in patients with cirrhosis of the liver, in patients experiencing a brisk diuresis, in patients who are receiving inadequate oral intake of electrolytes, and in patients receiving concomitant therapy with corticosteroids or ACTH.
- Periodic monitoring of serum potassium and other electrolytes is advised in patients treated with torsemide.
PRECAUTIONS
=====Laboratory Tests Potassium
See WARNINGS.
Calcium
Single doses of torsemide increased the urinary excretion of calcium by normal subjects, but serum calcium levels were slightly increased in 4 to 6 week hypertension trials. In a long-term study of patients with congestive heart failure, the average 1 year change in serum calcium was a decrease of 0.1 mg/dL (0.02 mmol/L). Among 426 patients treated with torsemide for an average of 11 months, hypocalcemia was not reported as an adverse event.
Magnesium
Single doses of torsemide caused healthy volunteers to increase their urinary excretion of magnesium, but serum magnesium levels were slightly increased in 4 to 6 week hypertension trials. In long-term hypertension studies, the average 1 year change in serum magnesium was an increase of 0.03 mg/dL (0.01 mmol/L). Among 426 patients treated with torsemide for an average of 11 months, one case of hypomagnesemia (1.3 mg/dL [0.53 mmol/L]) was reported as an adverse event.
In a long-term clinical study of torsemide in patients with congestive heart failure, the estimated annual change in serum magnesium was an increase of 0.2 mg/dL (0.08 mmol/L), but these data are confounded by the fact that many of these patients received magnesium supplements. In a 4 week study in which magnesium supplementation was not given, the rate of occurrence of serum magnesium levels below 1.7 mg/dL (0.7 mmol/L) was 6% and 9% in the groups receiving 5 mg and 10 mg of torsemide, respectively.
Blood Urea Nitrogen (BUN), Creatinine and Uric Acid
Torsemide produces small dose-related increases in each of these laboratory values. In hypertensive patients who received 10 mg of torsemide daily for 6 weeks, the mean increase in blood urea nitrogen was 1.8 mg/dL (0.6 mmol/L), the mean increase in serum creatinine was 0.05 mg/dL (4 mmol/L), and the mean increase in serum uric acid was 1.2 mg/dL (70 mmol/L). Little further change occurred with long-term treatment, and all changes reversed when treatment was discontinued.
Symptomatic gout has been reported in patients receiving torsemide, but its incidence has been similar to that seen in patients receiving placebo.
Glucose
Hypertensive patients who received 10 mg of daily torsemide experienced a mean increase in serum glucose concentration of 5.5 mg/dL (0.3 mmol/L) after 6 weeks of therapy, with a further increase of 1.8 mg/dL (0.1 mmol/L) during the subsequent year. In long-term studies in diabetics, mean fasting glucose values were not significantly changed from baseline. Cases of hyperglycemia have been reported but are uncommon.
Serum Lipids
In the controlled short-term hypertension studies in the United States, daily doses of 5 mg, 10 mg, and 20 mg of torsemide were associated with increases in total plasma cholesterol of 4, 4, and 8 mg/dL (0.1 to 0.2 mmol/L), respectively. The changes subsided during chronic therapy.
In the same short-term hypertension studies, daily doses of 5 mg, 10 mg and 20 mg of torsemide were associated with mean increases in plasma triglycerides of 16, 13, and 71 mg/dL (0.15 to 0.8 mmol/L), respectively.
In long-term studies of 5 mg to 20 mg of torsemide daily, no clinically significant differences from baseline lipid values were observed after 1 year of therapy.
Other
In long-term studies in hypertensive patients, torsemide has been associated with small mean decreases in hemoglobin, hematocrit, and erythrocyte count and small mean increases in white blood cell count, platelet count, and serum alkaline phosphatase. Although statistically significant, all of these changes were medically inconsequential. No significant trends have been observed in any liver enzyme tests other than alkaline phosphatase.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Torsemide (injection) Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Torsemide (injection) Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Torsemide (injection) Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Torsemide (injection) in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Torsemide (injection) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Torsemide (injection) during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Torsemide (injection) in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Torsemide (injection) in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Torsemide (injection) in geriatric settings.
Gender
There is no FDA guidance on the use of Torsemide (injection) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Torsemide (injection) with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Torsemide (injection) in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Torsemide (injection) in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Torsemide (injection) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Torsemide (injection) in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Torsemide (injection) Administration in the drug label.
Monitoring
There is limited information regarding Torsemide (injection) Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Torsemide (injection) and IV administrations.
Overdosage
There is limited information regarding Torsemide (injection) overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Torsemide (injection) Pharmacology in the drug label.
Mechanism of Action
- Micropuncture studies in animals have shown that torsemide acts from within the lumen of the thick ascending portion of the loop of Henle, where it inhibits the Na+/K+/2Cl--carrier system. Clinical pharmacology studies have confirmed this site of action in humans, and effects in other segments of the nephron have not been demonstrated. Diuretic activity thus correlates better with the rate of drug excretion in the urine than with the concentration in the blood.
- Torsemide increases the urinary excretion of sodium, chloride, and water, but it does not significantly alter glomerular filtration rate, renal plasma flow, or acid-base balance.
Structure
Torsemide Injection is a diuretic of the pyridine-sulfonylurea class. Its chemical name is 1-isopropyl-3-[(4-m-toluidino-3-pyridyl)sulfonyl] urea and its structural formula is:
Pharmacodynamics
There is limited information regarding Torsemide (injection) Pharmacodynamics in the drug label.
Pharmacokinetics
- The volume of distribution of torsemide is 12 liters to 15 liters in normal adults or in patients with mild to moderate renal failure or congestive heart failure. In patients with hepatic cirrhosis, the volume of distribution is approximately doubled.
- In normal subjects the elimination half-life of torsemide is approximately 3.5 hours. Torsemide is cleared from the circulation by both hepatic metabolism (approximately 80% of total clearance) and excretion into the urine (approximately 20% of total clearance in patients with normal renal function). The major metabolite in humans is the carboxylic acid derivative, which is biologically inactive. Two of the lesser metabolites possess some diuretic activity, but for practical purposes metabolism terminates the action of the drug.
- Because torsemide is extensively bound to plasma protein (>99%), very little enters tubular urine via glomerular filtration. Most renal clearance of torsemide occurs via active secretion of the drug by the proximal tubules into tubular urine.
- In patients with decompensated congestive heart failure, hepatic and renal clearance are both reduced, probably because of hepatic congestion and decreased renal plasma flow, respectively. The total clearance of torsemide is approximately 50% of that seen in healthy volunteers, and the plasma half-life and AUC are correspondingly increased. Because of reduced renal clearance, a smaller fraction of any given dose is delivered to the intraluminal site of action, so at any given dose there is less natriuresis in patients with congestive heart failure than in normal subjects.
- In patients with renal failure, renal clearance of torsemide is markedly decreased but total plasma clearance is not significantly altered. A smaller fraction of the administered dose is delivered to the intraluminal site of action, and the natriuretic action of any given dose of diuretic is reduced. A diuretic response in renal failure may still be achieved if patients are given higher doses. The total plasma clearance and elimination half-life of torsemide remain normal under the conditions of impaired renal function because metabolic elimination by the liver remains intact.
- In patients with hepatic cirrhosis, the volume of distribution, plasma half-life, and renal clearance are all increased, but total clearance is unchanged.
- The pharmacokinetic profile of torsemide in healthy elderly subjects is similar to that in young subjects except for a decrease in renal clearance related to the decline in renal function that commonly occurs with aging. However, total plasma clearance and elimination half-life remain unchanged.
Nonclinical Toxicology
There is limited information regarding Torsemide (injection) Nonclinical Toxicology in the drug label.
Clinical Studies
Clinical Effects
- The diuretic effects of torsemide begin within 10 minutes of intravenous dosing and peak within the first hour. Diuresis lasts about 6 to 8 hours. In healthy subjects given single doses, the dose-response relationship for sodium excretion is linear over the dose range of 2.5 mg to 20 mg. The increase in potassium excretion is negligible after a single dose of up to 10 mg and only slight (5 mEq to 15 mEq) after a single dose of 20 mg.
Congestive Heart Failure
- Torsemide has been studied in controlled trials in patients with New York Heart Association Class II to Class IV congestive heart failure. Patients who received 10 mg to 20 mg of daily torsemide in these studies achieved significantly greater reductions in weight and edema than did patients who received placebo.
Nonanuric Renal Failure
- In single-dose studies in patients with nonanuric renal failure, high doses of torsemide (20 mg to 200 mg) caused marked increases in water and sodium excretion. In patients with nonanuric renal failure, severe enough to require hemodialysis, chronic treatment with up to 200 mg of daily torsemide has not been shown to change steady-state fluid retention. When patients in a study of acute renal failure received total daily doses of 520 mg to 1200 mg of torsemide, 19% experienced seizures. Ninety-six patients were treated in this study; 6/32 treated with torsemide experienced seizures, 6/32 treated with comparably high doses of furosemide experienced seizures, and 1/32 treated with placebo experienced a seizure.
Hepatic Cirrhosis
- When given with aldosterone antagonists, torsemide also caused increases in sodium and fluid excretion in patients with edema or ascites due to hepatic cirrhosis. Urinary sodium excretion rate relative to the urinary excretion rate of torsemide is less in cirrhotic patients than in healthy subjects (possibly because of the hyperaldosteronism and resultant sodium retention that are characteristic of portal hypertension and ascites). However, because of the increased renal clearance of torsemide in patients with hepatic cirrhosis, these factors tend to balance each other, and the result is an overall natriuretic response that is similar to that seen in healthy subjects. Chronic use of any diuretic in hepatic disease has not been studied in adequate and well-controlled trials.
Essential Hypertension
- In patients with essential hypertension, torsemide has been shown in controlled studies to lower blood pressure when administered once a day at doses of 5 mg to 10 mg. The antihypertensive effect is near maximal after 4 to 6 weeks of treatment, but it may continue to increase for up to 12 weeks. Systolic and diastolic supine and standing blood pressures are all reduced. There is no significant orthostatic effect, and there is only a minimal peak-trough difference in blood pressure reduction.
- The antihypertensive effects of torsemide are, like those of other diuretics, on the average greater in black patients (a low-renin population) than in nonblack patients.
- When torsemide is first administered, daily urinary sodium excretion increases for at least a week. With chronic administration, however, daily sodium loss comes into balance with dietary sodium intake. If the administration of torsemide is suddenly stopped, blood pressure returns to pretreatment levels over several days, without overshoot.
- Torsemide has been administered together with β-adrenergic blocking agents, ACE inhibitors, and calcium-channel blockers. Adverse drug interactions have not been observed, and special dosage adjustment has not been necessary.
How Supplied
There is limited information regarding Torsemide (injection) How Supplied in the drug label.
Storage
There is limited information regarding Torsemide (injection) Storage in the drug label.
Images
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Patient Counseling Information
There is limited information regarding Torsemide (injection) Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Torsemide (injection) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Torsemide (injection) Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Torsemide (injection) Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.