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Demadex

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Demadex




Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Hypotension And Worsening Renal Function

Excessive diuresis may cause potentially symptomatic dehydration, blood volume reduction and hypotension and worsening renal function, including acute renal failure particularly in salt-depleted patients or those taking renin-angiotensin aldosterone inhibitors. Worsening of renal function can also occur with concomitant use of nephrotoxic drugs (e.g., aminoglycosides, cisplatin, and NSAIDs). Monitor volume status and renal function periodically.

Electrolyte And Metabolic Abnormalities

DEMADEX can cause potentially symptomatic hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, and hypochloremic alkalosis. Treatment with DEMADEX can cause an increase in blood glucose levels and hyperglycemia Asymptomatic hyperuricemia can occur and gout may rarely be precipitated. Monitor serum electrolytes and blood glucose periodically.

Ototoxicity

Tinnitus and hearing loss (usually reversible) have been observed with loop diuretics, including DEMADEX. Higher than recommended doses, severe renal impairment, and hypoproteinemia, appear to increase the risk of ototoxicity.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis And Impairment Of Fertility

No overall increase in tumor incidence was found when torsemide was given to rats and mice throughout their lives at doses up to 9 mg/kg/day (rats) and 32 mg/kg/day (mice). On a body-weight basis, these doses are 27 to 96 times a human dose of 20 mg; on a body-surface-area basis, they are 5 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. The tumor incidence in this group was, however, not much higher than the incidence sometimes seen in historical controls. Similar signs of chronic non-neoplastic renal injury have been reported in high-dose animal 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 and its major human metabolite. The tests included the Ames test in bacteria (with and without metabolic activation), 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 for unscheduled 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 this dose on a body-surface-area basis), torsemide had no adverse effect on the reproductive performance of male or female rats.

Use In Specific Populations

Pregnancy

Risk Summary

There are no available data on use of DEMADEX in pregnant women and the risk of major birth defects or miscarriage. In pregnant rats and rabbits dosed, on a mg/m² basis, with 10 and 1.7 times a human dose of 20 mg/day, respectively, there was no fetotoxicity or teratogenicity. However, in pregnant rats and rabbits administered 50 and 6.8 times the human dose, respectively, decreases in body weight, decreased fetal resorption and delayed fetal ossification was observed.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major malformations and miscarriage in clinically recognized pregnancies is 2-4%, and 15-20%, respectively.

Data

There was no fetotoxicity or teratogenicity in rats treated with up to 5 mg/kg/day of torsemide (on a mg/kg basis, this is 15 times a human dose of 20 mg/day; on a mg/m² basis, the animal dose is 10 times the human dose), or in rabbits, treated with 1.6 mg/kg/day (on a mg/kg basis, 5 times the human dose of 20 mg/kg/day; on a mg/m² basis, 1.7 times this dose). Fetal and maternal toxicity (decrease in average body weight, increase in fetal resorption and delayed fetal ossification) occurred in rabbits and rats given doses 4 (rabbits) and 5 (rats) times larger.

Lactation

Risk Summary

There are no data regarding the presence of DEMADEX in human milk or the effects of DEMADEX on the breastfed child. Diuretics can suppress lactation.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Administration of another loop diuretic to premature infants has been associated with the precipitation of nephrocalcinosis/nephrolithiasis. Nephrocalcinosis/nephrolithiasis has also been observed in children under 4 years of age with no history of prematurity who have been treated chronically with the other loop diuretic. The other loop diuretic, when administered during the first weeks of life, has also been reported to increase the risk of persistent patent ductus arteriosus. The use of DEMADEX in such patients has not been studied.

Geriatric Use

Of the total number of patients who received DEMADEX in United States clinical studies, 24% were 65 or older while about 4% were 75 or older. No specific age-related differences in effectiveness or safety were observed between younger patients and elderly patients.

Use In Renal Impairment

In single-dose studies in patients with non-anuric renal failure, high doses of DEMADEX (20 mg to 200 mg) caused marked increases in water and sodium excretion. In patients with non-anuric renal failure, severe enough to require hemodialysis, chronic treatment with up to 200 mg of daily DEMADEX 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 DEMADEX, 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.

Use In Hepatic Impairment

DEMADEX can cause sudden alterations of fluid and electrolyte balance which may precipitate hepatic coma in patients with hepatic disease with cirrhosis and ascites. In these patients, diuresis with DEMADEX is best initiated in the hospital.

Diuretic treatment can cause or contribute to the development of hypovolemia, hypokalemia, metabolic alkalosis, hyponatremia or azotemia which can lead to new or worsening hepatic encephalopathy. Consider suspending or discontinuing DEMADEX [see CONTRAINDICATIONS].

To prevent hypokalemia and metabolic alkalosis, use an aldosterone antagonist or potassium-sparing drug with DEMADEX in patients with hepatic disease.

When given with aldosterone antagonists, DEMADEX 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 DEMADEX 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 DEMADEX 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.

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 3/17/2017

Warnings
Precautions

Demadex - User Reviews

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