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Torsemide Injection is a diuretic of the pyridine-sulfonylurea class. Its chemical name is 1-isopropyl-3-[(4-rn-toluidino-3-pyridyl) sulfonyl]urea and its structural formula is:

Its molecular formula is C,sH;!ON4 0 3S, its pKa is 6.42, and its molecular weight is 348.42.Torsemide is a white to off-white c rys ta lline powder. Torsemide vials for intravenous injection contain asterile solution of torsemide (10 mglmL), polyethylene g lycal-400, tromethamine, and sodium hydroxide(as needed to adjust p H ) in water for injection.

Mechanism of ActionMicropuncture studies in anima ls have shown that torsemide acts from within the lumen of the thickascending portion of the loop of Henle, where it inhibits the Na'JK'/2CI'-carrier system. Clinicalpharmacology studies have confirmed this site of action in humans, and effects in other segments ofthe nephron have not been demonstrated. Diuretic activity thus correlates better with the rate of drugexcretion in the urine than with the concentration in the blood.Torsemide increases the urinary excretion of sodium, chloride, and water, but it does not significantlyalterglomerular filtration rate, renal plasma flow, or acid-base balance. Pharmacokinetics and MetabolismThe volume of distribution of torsemide is 12 liters to 15 liters in normal adults or in patients with mildto moderate renal failure or congestive heart failure. In patients with hepatic cirrhosis, the volume ofdistribution is approximately doubled.In normal subjects the elimination half- life of torsemide is approximately 3.5 hours. Torsemide is clearedfrom the circulation by both hepatic metabolism (approximately 80% of total clearance) and excretioninto the urine (approximately 20% of total clearance in patients w ith normal renal function). The majormetabolite in humans is the carboxylic acid derivative, which is biologically inactive. Two of the lessermetabolites possess some diuretic activity, but for practical purposes metabolism terminates the actionof the drug.Because torsemide is extensively bound to plasma protein (> 990/0), very little enters tubular urine viaglomerular filtration. Most renal clearance of torsemide occurs via active secretion of the drug by theproximal 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 totalclearance of torsemide is approximately 50% of that seen in healthy volunteers, and the plasma half-lifeand AUG a re correspondingly increased. Because of reduced renal clearance, a smaller fraction of anygiven dose is delivered to the intraluminal site of action, so at any given dose there is less natriuresis inpatients with congestive heart failure than in normal subjects.In patients with renal failure, renal clearance of torsemide is markedly decreased but total plasmaclearance is not significantly altered. A smaller fraction of the administered dose is delivered to theintraluminal site of action, and the natriuretic action of any given dose of diuretic is reduced. A diureticresponse in renal failure may still be achieved if patients are given higher doses. The total plasmaclearance and elimination half-life of torsemide remain normal under the conditions of impaired renalfunction because metabolic elimination by the liver remains intact.In patients with hepatic cirrhosis, the volume of distribution, plasma half-life, and renal clearance are allincreased, but total clearance is unchanged.The pharmacokinetic profile of torsemide in healthy elderly subjects is similar to that in young subjectsexcept for a decrease in renal clearance related to the decline in renal function that commonly occurswith aging. However, total plasma clearance and elimination half-life remain unchanged. Clinical EffectsThe diuretic effect s of torsemide begin within 10 minutes of intravenous dosing and peak within the firsthour. With intravenous administration diuresis lasts about 6 to 8 h ours. In healthy subjects given singledoses, the dose-response relationship for sodium excretion is linear over the dose range o f 2.5 mg to 20mg. 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 o f 20 mg. Congestive Heart FailureTorsemide has been studied in controlled trials in patients with New York Heart Association Class II toClass IV congestive heart failure . Patients who received 10 mg to 20 mg o f daily torsemide in thesestudies achieved significantly greater reductions in weight and edema than did patients who receivedplacebo. Nonanuric Renal FailureIn single-dose studies in patients with nonanuric renal failure, high doses of torsemide (20 mg to 200mg) caused marked increases in water and sodium excretion . In patients with nonanuric renal failure,severe enough to require hemodialys is, chronic treatment with up to 200 mg of daily torsemide hasnot been shown to change steady-state fluid retention . When patients in a study of acute renal failurereceived total daily doses of 520 mg to 1200 m g o f to rsemide, 1 9% experienced seizures. Ninety-sixpatients were treated in this study; 6/32 treated with torsemide experienced seizures, 6/32 treatedwith comparably high doses of furosemide experienced seizures, and 1/32 treated with placeboexperienced a seizure. Hepatic CirrhosisWhen given with aldosterone antagonists, torsemide also caused increases in sodium and fluidexcretion in patients with edema or ascites due to hepatic cirrhosis. Urinary sodium excretion raterelative 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 ofportal hypertension and ascites). However, because of the increased renal clearance of torsemide inpatients with hepatic cirrhosis, these factors tend to balance each other, and the result is an overallnatriuretic response that is similar to that seen in healthy subjects. Chronic use of any diuretic in hepaticdisease has not been studied in adequate and well-controlled trials. Essential HypertensionIn patients with essential hypertenSion, torsemide has been shown in controlled studies to lower bloodpressure when administered once a day at doses of 5 mg to 10 mg. The antihypertensive effect is nearmaximal after 4 to 6 weeks of treatment, but it may continue to increase for up to 12 weeks. Systolic anddiastolicsupine 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 inblack patients (a low-renin population) than in non black patients.When torsemide is first administered, daily urinary sodium excretion increases for a t least a week. Withchronic administration, however, daily sodium loss comes into balance with dietary sodium intake. Ifthe administration of torsemide is suddenly stopped, blood pressure returns to pretreatment levels overseveral days, without over shoot.Torsemide has been administered together with j3-adrenergic blocking agents, ACE inhibitors, andcalcium-channel blockers. Adverse drug inte rac tio n s have n o t been observed, and special dosageadjustment has not been necessary.

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 ofedema associated w th chronic renal failure. Chronic use of any diuretic in hepatic disease has not beenstudied in adequate and well-controlled trials.Torsemide Injection is indicated when a rapid onset of diuresis is desired or when oral administrationis impractical.Torsemide Injection is indicated for the treatment of hypertension alone or in combination with otherantihypertensive agents.

Torsemide Injection is contraindicated in patients with known hypersensitivity to torsemide or tosulfonylureas.Torsemide Injection is contraindicated in patients who are anuric.

Hepatic Disease With Cirrhosis and AscitesTorsemide should be used with caution in patients with hepatic disease with cirrhosis and ascites, sincesudden 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 hypokalemiaand metabolic alkalosis, analdosteroneantagonist or potassium-sparing drug should be usedconcomitantly with torsemide. OtotoxicityTinnitus and hearing loss (usually reversible) have been observed after rapid intravenous injection ofother loop diuretics and have also been observed after oral Torsemide. It is not certain that these eventswere attributable to torsemide . Ototoxicity has also been seen in animal studies when very high plasmalevels of torsemide were induced. Administered intravenously, torsemide should be injected slowly over2 minutes, and single doses should not exceed 200 mg. Volume and Electrolyte DepletionPatients receiving diuretics should be observed for clinical evidence of electrolyteim balance,hypovolemia, orprerenal azotemia . Symptoms of these disturbances may include one or more of thefollowing: dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle painsor cramps, muscular fatigue , hypotension , oliguria, tachycardia, nausea, and vomiting. Excessivediuresis may cause dehydration, blood-volume reduction , and possibly thrombosis and embolism,especially in elderly patients. In patients who develop fluid and electrolyte imbalances, hypovolemia,orprerenal azotemia, the observed laboratory changes may include hyper-orhypon atremia, hyper -orhypochloremia, hyper- or hypokalemia, acid-base abnormalities, and increased blood urea nitrogen(BUN). If any of these occur, to rsemide should be discontinued until the situation is corrected; torsemidemay be restarted at a lower dose.In controlled studies in the United States, torsemide was administered to hypertensive patients at doseso f 5 mg or 10 mg daily. Afte r 6 weeks at these doses, the mean decrease in serum potassium wasapproximately 0.1 mEq/L. The percentage of patients who had a serum potassium level below 3.5 m Eq/Lat any time during the studies was essentially the same in patients who received torsemide ( 1.5%) as inthose who received placebo (3%) . In patients followed for 1 year, there was no further change in meanserum potassium levels. In patients with congestive heart failure, hepatic cirrhosis, orrena l diseasetreated with torsemide at doses higher than those studied in United States a ntihypertensive trials,hypokalemia was observed with greater frequency, in a dose-related manner.In patients with cardiovascular disease, especially those receiving digitalis glycosides, diuretic-inducedhypokelemia may be a risk factor for the development of arrhythmias. The risk of hypokalemia isgreatest in patients with cirrhosis of the liver, in patients experiencing a brisk diuresis, inpatients whoare receiving inadequate oral intake of electrolytes, and in patients receiving concomitant therapy withcorticosteroids or ACTH.Periodic monitoring of serum potassium and other electrolytes is advised in patients treated withtorsemide.

Laboratory ValuesPotassiumSee WARNINGS. CalciumSingle doses of torsemide increased the urinary excretion of calcium by normal subjects, but serumcalcium levels were slightly increased in 4 to 6 week hypertension trials . In a long-term study of patientswith congestive heart failure, the average 1 year change in serum calcium was a decrease of 0 .1 mgJdL(0.02 mmoIlL). Among 426 patients treated with torsemide for an average o f 11 months, hypocalcemiawas not reported as an adverse event. MagnesiumSingle doses of torsemide caused healthy volunteers to increase the ir urinary excretion of magnesium,but serum magnesium levels were slightly increased in 4 to 6 week hypertension trials. In long-termhypertension studies, the average 1 year change in serum magnesium was an increase of 0.03 mgJdL(0.01 mmoIlL). Among 426 patients treated with torsemide for an average of 11 months, one case ofhypomagnesemia (1 .3 m gJdL [0.53 mmollLJ) was reported as an adverse event .In a tong- term clinical study of torsemide in patients with congestive heart failure, the estimatedannual change in serum magnesium was an increase of 0.2 mg/dL (0.08 mmoI/L), but these data areconfounded by the fact that many of these patients received magnesium supplements. In a 4 weekstudy in which magnesium supplementation was not given, the rate of occurrence of serum magnesiumlevels below 1.7 mg/dL (0.7 mmollL) was 60/0 a nd 9% in the groups receiving 5 mg a nd 10 mg oftorsemide, respectively. Blood Urea Nitrogen (BUN), C reatinin e a nd Uric AcidTorsemide produces small dose-related increases in each of these laboratory values. In hypertensivepatients who received 10 mg o f torsemide daily for 6 weeks, the mean increase in blood urea nitrogenwas 1 .8 mg/dL (0.6 mmo IJL) , the mean increase in serum creatinine was 0.05 mg/dL (4 mmo t/ L) , andthe mean increase in serum uric acid was 1 .2 m gJdL (70 mmoIJL). Little further change occurred withlong-term treatment, and all changes reversed when treatment was discontinued.Symptomatic gout has been reported in patients receiving torsemide, but its incidence has been similarto that seen in patients receiving placebo. GlucoseHypertensive patients who received 10 m g of daily torsemide experienced a mean increase in serumglucose concentration o f 5.5 mg/dL (0.3 mmot/L) after 6 weeks of therapy, with a further increase of1 .8 mgldL (0.1 mmollL) during the subsequent year. In long-term studies in diabetics, mean fastingglucose values were not significantly changed from baseline. Cases of hyperglycemia have beenreported but are uncommon. Serum LipidsIn the controlled short-term hypertension studies in the United States, daily doses of 5 mg, 10 mg, and20 mg of torsemide were associated with increases in total plasma cholesterol of 4, 4 , and 8 mg/dL (0.1to 0.2 mmoIlL ), respectively. The changes subsided during chronic therapy.In the same short- term hypertension studies, daily doses of 5 mg, 10 m g and 20 mg of torsemide wereassociated with mean increases in plasma triglycerides of 16, 13, and 71 mg/dL (0. 15 to 0.8 mmoIlL) ,respectively.In long-term studies of 5 mg to 20 mg of torsemide daily, no clinically significant differences frombaseline lipid values were observed after 1 year of therapy. OtherIn long-term studies in hypertensive patients, torsemide has been associated with small meandecreases in hemoglobin, hematocrit , and erythrocyte count and small mean increases in white bloodcell count, platelet count, and serum alkaline phosphatase. Although statistically significant, all of thesechanges were medically inconsequential. No significant trends have been observed in any liver enzymetests other than alkaline phosphatase.

In patients with essential hypertension, torsemide has been administered together with beta-blockers,ACE inhibitors, and calcium-channel blockers, In patients with congestive heart failure, torsemide hasbeen administered together with digitalis glycosides, ACE inhibitors, and o rganic nitrates. None of thesecombined uses was associated with new or unexpected adverse events.Torsemide does not affect the protein binding of glyburide or of wartarin, the anticoagulant effect ofphenprocoumon (a related coumarin derivative), or the pharmacokinetics of digoxin or carvedilol (avasodilator/beta-blocker). In hea lthy subjects, coadministration of torsemide was associated withsignificant reduction in the renal clearance of spironolactone, with corresponding increases in the AUC.However, clinical experience indicates that dosage adjustment of either agent is not required ,Because torsemide and salicylates compete fo r secretion by rena l tubules, patients receiving highdoses of salicylates may experience salicylate toxicity when torsemide is concomitantly administe red ,Also, although possible inte ractions between torsemide and nonsteroidal anti-inflammatory agents(including aspirin) have not been studied, coadministration of these agents with another loop diuretic(furosemide) has occasionally been associated with renal dysfunction,The natriuretic effect of torsemide (like that of many other diuretics) is partially inhibited by theconcomitant administration of indomethacin. This effect has been demonstrated for torsemide underconditions of dietary sodium restriction (50 mEq/day) but not in the presence of normal sodium intake(150 mEq/day).The pharmacokinetic profile and diuretic activity of torsemide are not altered by cimetidine ors pironolactone, Coadministration of digoxin is reported to increase the area under the curve fortorsemide by 50%, but dose adjustment of torsemide is not necessary.Concomitant use of torsemide and cholestyramine has not been studied in humans but, in a studyin animals, coadministration of cholestyramine decreased the absorption of orally administeredtorsemide. If torsemide and c holestyramine are used concomitantfy, simultaneous administration isnot recommended.Coadministration of probenecid reduces secretion of torsemide into the proximal tubule and therebydecreases the diuretic activity of torsemide.Other diuretics are known to reduce the renal clearance of lithium, inducing a high risk of lithiumtoxicity, so coadministration of lithium and diuretics should be undertaken with great caution, if at all.Coadministration of lithium and torsemide has not been studied.Other diuretics have been reported to increase the ototoxic potential of aminoglycoside antibiotics andof ethacrynic acid, especially in the presence of impaired renal function. These potential interactionswith torsemide have not been studied.Carcinogenesis, Mutagenesis, Impairment of FertilityNo overall increase in tumor incidence was found when torsemide was given to rats and micethroughout their lives at doses up to 9 mg/kg/day (rats) and 32 mg/kg/day (mice). On a body-weightbasis, these doses are 27 to 96 times a human dose of 20 mg; on a body-surface-area basis, they are5 to 8 times this dose. In the rat study, the high-dose female group demonstrated renal tubular injury,interstitial inflammation, and a statistically significant increase in renal adenomas and carcinomas. Thetumor incidence in this group was, however, not much higher than the incidence sometimes seen inhistorical controls. Similar signs of chronic non· neoplastic renal injury have been reported in high·doseanimal studies of other diuretics such as furosemide and hydrochlorothiazide.No mutagenic activity was detected in any of a variety of in vivo and in vitro tests of torsemide andits major human metabolite. The tests included the Ames test in bacteria (with and without metabolicactivation), tests for chromosome aberrations and sister-chromatid exchanges in human lymphocytes,tests for various nuclear anomalies in cells found in hamster and murine bone marrow, tests forunscheduled DNA synthesis in mice and rats, and others.In doses up to 25 mg/kg/day (75 times a human dose of 20 mg on a body-weight basis; 13 times thisdose on a body·surface·area basis), torsemide had no adverse effect on the reproductive performanceof male or female rats.PregnancyTeratogenic EffectsPregnancy Category B.There was no fetotoxicity or teratogenicity in rats treated with up to 5 mg/kg/day of torsemide (on amg/kg basis, this is 15 times a human dose of 20 mg/day; on a mg/m2 basis, the animal dose is 10times the human dose), or in rabbits, treated with 1.6 mg/kg/day (on a mg/kg basis, 5 times the humandose of 20 mg/kg/day; on a mg/m2 basis, 1.7 times this dose). Fetal and maternal toxicity (decrease inaverage body weight, increase in fetal resorption and delayed fetal ossification) occurred in rabbits andrats given doses 4 (rabbits) and 5 (rats) times larger. Adequate and well-controlled studies have notbeen carried out in pregnant women. Because animal reproduction studies are not always predictive ofhuman response, this drug should be used during pregnancy only if clearly needed.Labor and DeliveryThe effect of torsemide on labor and delivery is unknown.Nursing MothersIt is not known whether torsemide is excreted in human milk. Because many drugs are excreted inhuman milk, caution should be exercised when torsemide is administered to a nursing woman.Pediatric UseSafety and effectiveness in pediatric patients have not been established.Administration of another loop diuretic to severely premature infants with edema due to patent ductusarteriosus and hyaline membrane disease has occasionally been associated with renal calcifications,sometimes barely visible on X-ray but sometimes in staghorn form, filling the renal pelves. Some ofthese calculi have been dissolved, and hypercalciuria has been reported to have decreased, whenchlorothiazide has been coadministered along with the loop diuretic. In other premature neonates withhyaline membrane disease, another loop diuretic has been reported to increase the risk of persistentpatent ductus arteriosus, possibly through a prostaglandin-E-mediated process. The use of torsemidein such patients has not been studied.Geriatric UseOf the total number of patients who received torsemide in United States clinical studies, 24% were 65or older while about 4% were 75 or older. No specific age· related differences in effectiveness or safetywere observed between younger patients and elderly patients.

At the time of approval, torsemide had been eva luated for safety in approximately 4000 subjects: over800 of these subjects received torsemide for at least 6 months, and over 380 were treated for morethan 1 year. Among these subjects were 564 who received torsemide during United States-based trialsin which 274 other subjects received placebo.The reported side effects of torsemide were generally transient, and there was no relationship betweenside effects and age, sex, race, or duration of therapy. Discontinuation of therapy due to side effectsoccurred in 3.5% of United States patients treated with torsemide and in 4.4% of patients treated withplacebo. In studies conducted in the United States and Europe, discontinuation rates due to side effectswere 3% (38/1250) with torsemide and 3.4% (13/380) with furosemide in patients with congestive heartfailure, 2% (81409) with torsemide and 4.8% (11/230) with furosemide in patients with renal insufficiency,and 7.6% (13/170) with torsemide and 0% (0/33) with furosemide in patients with cirrhosis.The most common reasons for discontinuation of therapy with torsemide were (in descending orderof frequency) dizziness, headache, nausea, weakness, vomiting, hyperglycemia, excessive urination,hyperuricemia, hypokalemia, excessive thirst, hypovolemia, impotence, esophageal hemorrhage, anddyspepsia. Dropout rates for these adverse events ranged from 0.1 % to 0.5%.The side effects considered possibly or probably related to study drug that occurred in United Statesplacebo-controlled trials in more than 1% of patients treated with torsemide are shown in Table 1.Table 1 Reactions Possibly or Probably Drug-Related United States Placebo-ControlledTable 1 Reactions Possibly or Probably Drug-Related United States Placebo-ControlledStudies Incidence (Percentages of Patients) I Torsemiae I PlaceDo(N=564) (N=274)Headache 7.3 9.1Excessive Urination 6.7 2.2Dizziness 3.2 4.0Rhinitis 2.8 2.2Asthenia 2.0 1.5Diarrhea 2.0 1.1ECG Abnormality 2.0 0.4Cough Increase 2.0 1.5Constipation 1.8 0.7Nausea 1.8 0.4Arthralgia 1.8 0.7Dyspepsia 1.6 0.7Sore Throat 1.6 0.7Myalgia 1.6 1.5Chest Pain 1.2 0.4Insomnia 1.2 1.8Edema 1.1 1.1Nervousness 1.1 0.4 The daily doses of torsemide used in these trials ranged from 1.25 mg to 20 mg, with most patientsreceiving 5 mg to 10 mg; the duration of treatment ranged from 1 to 52 days, with a median of 41 days.Of the side effects listed in the table, only "excessive urination" occurred significantly more frequentlyin patients treated with torsemide than in patients treated with placebo. In the placebo-controlledhypertension studies whose design allowed side·effect rates to be attributed to dose, excessiveurination was reported by 1% of patients receiving placebo, 4% of those treated with 5 mg of dailytorsemide, and 15% of those treated with 10 mg. The complaint of excessive urination was generallynot reported as an adverse event among patients who received torsemide for cardiac, renal, or hepaticfailure.Serious adverse events reported in the clinical studies for which a drug relationship could not beexcluded were atrial fibrillation , chest pain, diarrhea, digitalis intoxication, gastrointestinal hemorrhage,hyperglycemia, hyperuricemia, hypokalemia, hypotension, hypovolemia, shunt thrombosis, rash, rectalbleeding, syncope, and ventricular tachycardia.Angioedema has been reported in a patient exposed to torsemide who was later found to be allergicto sulfa drugs.Of the adverse reactions during placebo-controlled trials listed without taking into account assessmentof relatedness to drug therapy, arthritis and various other nonspecific musculoskeletal problems weremore frequently reported in association with torsemide than with placebo, even though gout wassomewhat more frequently associated with placebo. These reactions did not increase in frequency orseverity with the dose of torsemide. One patient in the group treated with torsemide withdrew due tomyalgia, and one in the placebo group withdrew due to gout.HypokalemiaSee WARNINGS.

General: Special dosage adjustment in the elderly is not necessary.Because of the high bioavailability of torsemide, oral and intravenous doses are therapeuticallyequivalent, so patients may be switched to and from the intravenous form with no change in dose.Torsemide injection should be administered either slowly as a bolus over a period of 2 minutes oradministered as a continuous infusion.If torsemide is administered through an IV line, it is recommended that, as with other IV injections,the IV line be flushed with Normal Saline (Sodium Chloride Injection) before and after administration.Torsemide injection is formulated above pH 8.3. Flushing the line is recommended to avoid the potentialfor incompatibilities caused by differences in pH which could be indicated by color change, haziness orthe formation of a precipitate in the solution.If torsemide injection is administered as a continuous infusion, stability has been demonstrated through24 hours at room temperature in plastic containers for the following fluids and concentrations:200 mg torsemide (10 mg/mL) added to:250 mL Dextrose 5% in water250 mL 0.9% Sodium Chloride500 mL 0.45% Sodium Chloride50 mg torsemide (10 mg/mL) added to:500 mL Dextrose 5% in water500 mL 0.9% Sodium Chloride500 mL 0.45% Sodium ChlorideBefore administration, the solution of torsemide injection should be visually inspected for discolorationand particulate matter. If either is found, the vial should not be used.Congestive Heart FailureThe usual initial dose is 10 mg or 20 mg of intravenous torsemide. II the diuretic response is inadequate,the dose should be titrated upward by approximately doubling until the desired diuretic response isobtained. Single doses higher than 200 mg have not been adequately studied.Chronic Renal FailureThe usual initial dose of torsemide is 20 mg of intravenous torsemide. If the diuretic response isinadequate, the dose should be titrated upward by approximately doubling until the desired diureticresponse is obtained. Single doses higher than 200 mg have not been adequately studied.Hepatic CirrhosisThe usual initial dose is 5 mg or 10 mg of intravenous torsemide, administered together with analdosterone antagonist or a potassium·sparing diuretic. If the diuretic response is inadequate, the doseshould be titrated upward by approximately doubling until the desired diuretic response is obtained.Single doses higher than 40 mg have not been adequately studied.Chronic use of any diuretic in hepatic disease has not been studied in adequate and well-controlledtrials.HypertenSionThe usual initial dose is 5 mg daily. If the 5 mg dose does not provide adequate reduction in bloodpressure within 4 to 6 weeks, the dose may be increased to 10 mg daily. If the response to 10 mg isinsufficient, an additional anti-hypertensive agent should be added to the treatment regimen.

Torsemide Injection 10 mg/mL, is available as follows:2 mL single dose vials in cartons of 10 - NDC# is 0517-0770-105 mL single dose vials in cartons of 10 - NDC# is 0517-0771-10StorageStore at 200 to 250 C (680 to 7]0 F) (See USP Controlled Room Temperature). DO NOT FREEZE.