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, analdosteroneantagonist 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 electrolyteim balance, hypovolemia, orprerenal 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, orprerenal azotemia, the observed laboratory changes may include hyper-orhypon atremia, hyper -or hypochloremia, 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; torsemide may be restarted at a lower dose. In controlled studies in the United States, torsemide was administered to hypertensive patients at doses o f 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 m Eq/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, orrena l disease treated 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-induced hypokelemia 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, inpatients 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 Values 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 mgJdL (0.02 mmoI/L). Among 426 patients treated with torsemide for an average o f 11 months, hypocalcemia was not reported as an adverse event.
Magnesium Single 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-term hypertension studies, the average 1 year change in serum magnesium was an increase of 0.03 mgJdL (0.01 mmoI/L). Among 426 patients treated with torsemide for an average of 11 months, one case of hypomagnesemia (1.3 m gJdL [0.53 mmol/LJ) was reported as an adverse event. In a tong- 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 mmoI/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 60/0 a nd 9% in the groups receiving 5 mg a nd 10 mg of torsemide, respectively.
Blood Urea Nitrogen (BUN), C reatinin e a nd Uric Acid Torsemide produces small dose-related increases in each of these laboratory values. In hypertensive patients who received 10 mg o f torsemide daily for 6 weeks, the mean increase in blood urea nitrogen was 1.8 mg/dL (0.6 mmoI/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 mmoI/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 m g of daily torsemide experienced a mean increase in serum glucose concentration o f 5.5 mg/dL (0.3 mmol/L) after 6 weeks of therapy, with a further increase of 1.8mg/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 mmoI/L), 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 were associated with mean increases in plasma triglycerides of 16, 13, and 71 mg/dL (0. 15 to 0.8 mmoI/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.
|