Bumex (Tablet)

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Dosage should be individualized with careful monitoring of patient response.<br/>Oral Administration: The usual total daily dosage of Bumex is 0.5 mg to 2 mg and in most patients is given as a single dose. If the diuretic response to an initial dose of Bumex is not adequate, in view of its rapid onset and short duration of action, a second or third dose may be given at 4- to 5-hour intervals up to a maximum daily dose of 10 mg. An intermittent dose schedule, whereby Bumex is given on alternate days or for 3 to 4 days with rest periods of 1 to 2 days in between, is recommended as the safest and most effective method for the continued control of edema. In patients with hepatic failure, the dosage should be kept to a minimum and, if necessary, dosage increased very carefully. Because cross-sensitivity with furosemide has rarely been observed, Bumex can be substituted at approximately a 1:40 ratio of Bumex to furosemide in patients allergic to furosemide.<br/>Parenteral Administration: Bumetanide injection may be administered parenterally (IV or IM) to patients in whom gastrointestinal absorption may be impaired or in whom oral administration is not practical. Parenteral treatment should be terminated and oral treatment instituted as soon as possible.

Bumex is a loop diuretic with a rapid onset and short duration of action. Pharmacological and clinical studies have shown that 1 mg Bumex has a diuretic potency equivalent to approximately 40 mg furosemide. The major site of Bumex action is the ascending limb of the loop of Henle. The mode of action has been determined through various clearance studies in both humans and experimental animals. Bumex inhibits sodium reabsorption in the ascending limb of the loop of Henle, as shown by marked reduction of free-water clearance (CHO) during hydration and tubular free-water reabsorption (THO) during hydropenia. Reabsorption of chloride in the ascending limb is also blocked by Bumex, and Bumex is somewhat more chloruretic than natriuretic. Potassium excretion is also increased by Bumex, in a dose-related fashion. Bumex may have an additional action in the proximal tubule. Since phosphate reabsorption takes place largely in the proximal tubule, phosphaturia during Bumex induced diuresis is indicative of this additional action. This is further supported by the reduction in the renal clearance of Bumex by probenecid, associated with diminution in the natriuretic response. This proximal tubular activity does not seem to be related to an inhibition of carbonic anhydrase. Bumex does not appear to have a noticeable action on the distal tubule. Bumex decreases uric acid excretion and increases serum uric acid. Following oral administration of Bumex the onset of diuresis occurs in 30 to 60 minutes. Peak activity is reached between 1 and 2 hours. At usual doses (1 mg to 2 mg) diuresis is largely complete within 4 hours; with higher doses, the diuretic action lasts for 4 to 6 hours. Diuresis starts within minutes following an intravenous injection and reaches maximum levels within 15 to 30 minutes. Several pharmacokinetic studies have shown that bumetanide, administered orally or parenterally, is eliminated rapidly in humans, with a half-life of between 1 and 1��hours. Plasma protein-binding is in the range of 94% to 96%. Oral administration of carbon-14 labeled Bumex to human volunteers revealed that 81% of the administered radioactivity was excreted in the urine, 45% of it as unchanged drug. Urinary and biliary metabolites identified in this study were formed by oxidation of the N-butyl side chain. Biliary excretion of Bumex amounted to only 2% of the administered dose.<br/>Pediatric Pharmacology: Elimination of bumetanide appears to be considerably slower in neonatal patients compared with adults, possibly because of immature renal and hepatobiliary function in this population. Small pharmacokinetic studies of intravenous bumetanide in preterm and full-term neonates with respiratory disorders have reported an apparent half-life of approximately 6 hours, with a range up to 15 hours and a serum clearance ranging from 0.2 to 1.1 mL/min/kg. In a population of neonates receiving bumetanide for volume overload, mean serum clearance rates were 2.17 mL/min/kg in patients less than 2 months of age and 3.8 mL/min/kg in patients aged 2 to 6 months. Mean serum half-life of bumetanide was 2.5 hours and 1.5 hours in patients aged less than 2 months and those aged 2 to 6 months, respectively. Elimination half-life decreased considerably during the first month of life, from a mean of approximately 6 hours at birth to approximately 2.4 hours at 1 month of age. In preterm neonates, mean serum concentrations following a single 0.05 mg/kg dose ranged from 126 mcg/L at 1 hour to 57 mcg/L at 8 hours. In another study, mean serum concentrations following a single 0.05 mg/kg dose were 338 ng/mL at 30 minutes and 176 ng/mL after 4 hours. A single dose of 0.1 mg/kg produced mean serum levels of 314 ng/mL at 1 hour, and 195 ng/mL at 6 hours. Mean volume of distribution in neonates and infants has been reported to range from 0.26 L/kg to 0.39 L/kg. The degree of protein binding of bumetanide in cord sera from healthy neonates was approximately 97%, suggesting the potential for bilirubin displacement. A study using pooled sera from critically ill neonates found that bumetanide at concentrations of 0.5 to 50 mcg/mL, but not 0.25 mcg/mL, caused a linear increase in unbound bilirubin concentrations. In 56 infants aged 4 days to 6 months, bumetanide doses ranging from 0.005 mg/kg to 0.1 mg/kg were studied for pharmacodynamic effect. Peak bumetanide excretion rates increased linearly with increasing doses of drug. Maximal diuretic effect was observed at a bumetanide excretion rate of about 7 mcg/kg/hr, corresponding to doses of 0.035 to 0.040 mg/kg. Higher doses produced a higher bumetanide excretion rate but no increase in diuretic effect. Urine flow rate peaked during the first hour after drug administration in 80% of patients and by 3 hours in all patients.<br/>Geriatric Pharmacology: In a group of ten geriatric subjects between the ages of 65 and 73 years, total bumetanide clearance was significantly lower (1.8��0.3 mL/min��kg) compared with younger subjects (2.9��0.2 mL/min��kg) after a single oral bumetanide 0.5 mg dose. Maximum plasma concentrations were higher in geriatric subjects (16.9��1.8 ng/mL) compared with younger subjects (10.3��1.5 ng/mL). Urine flow rate and total excretion of sodium and potassium were increased less in the geriatric subjects compared with younger subjects, although potassium excretion and fractional sodium excretion were similar between the two age groups. Nonrenal clearance, bioavailability, and volume of distribution were not significantly different between the two groups.

Bumex is contraindicated in anuria. Although Bumex can be used to induce diuresis in renal insufficiency, any marked increase in blood urea nitrogen or creatinine, or the development of oliguria during therapy of patients with progressive renal disease, is an indication for discontinuation of treatment with Bumex. Bumex is also contraindicated in patients in hepatic coma or in states of severe electrolyte depletion until the condition is improved or corrected. Bumex is contraindicated in patients hypersensitive to this drug.

http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00887

dailymed-ingredient:bumetanide

diseasome-diseases:1110, diseasome-diseases:1227, diseasome-diseases:139, diseasome-diseases:1571, diseasome-diseases:1968, diseasome-diseases:2053, diseasome-diseases:2715, diseasome-diseases:297, diseasome-diseases:3523, diseasome-diseases:4001, diseasome-diseases:565, diseasome-diseases:894

Overdosage can lead to acute profound water loss, volume and electrolyte depletion, dehydration, reduction of blood volume and circulatory collapse with a possibility of vascular thrombosis and embolism. Electrolyte depletion may be manifested by weakness, dizziness, mental confusion, anorexia, lethargy, vomiting and cramps. Treatment consists of replacement of fluid and electrolyte losses by careful monitoring of the urine and electrolyte output and serum electrolyte levels.

Bumex (Tablet)

Volume and Electrolyte Depletion: The dose of Bumex should be adjusted to the patient's need. Excessive doses or too frequent administration can lead to profound water loss, electrolyte depletion, dehydration, reduction in blood volume and circulatory collapse with the possibility of vascular thrombosis and embolism, particularly in elderly patients.<br/>Hypokalemia: Hypokalemia can occur as a consequence of Bumex administration. Prevention of hypokalemia requires particular attention in the following conditions: patients receiving digitalis and diuretics for congestive heart failure, hepatic cirrhosis and ascites, states of aldosterone excess with normal renal function, potassium-losing nephropathy, certain diarrheal states, or other states where hypokalemia is thought to represent particular added risks to the patient, ie, history of ventricular arrhythmias. In patients with hepatic cirrhosis and ascites, sudden alterations of electrolyte balance may precipitate hepatic encephalopathy and coma. Treatment in such patients is best initiated in the hospital with small doses and careful monitoring of the patient's clinical status and electrolyte balance. Supplemental potassium and/or spironolactone may prevent hypokalemia and metabolic alkalosis in these patients.<br/>Ototoxicity: In cats, dogs and guinea pigs, bumetanide has been shown to produce ototoxicity. In these test animals bumetanide was 5 to 6 times more potent than furosemide and, since the diuretic potency of bumetanide is about 40 to 60 times furosemide, it is anticipated that blood levels necessary to produce ototoxicity will rarely be achieved. The potential exists, however, and must be considered a risk of intravenous therapy, especially at high doses, repeated frequently in the face of renal excretory function impairment. Potentiation of aminoglycoside ototoxicity has not been tested for bumetanide. Like other members of this class of diuretics, bumetanide probably shares this risk.<br/>Allergy to Sulfonamides: Patients allergic to sulfonamides may show hypersensitivity to Bumex.<br/>Thrombocytopenia: Since there have been rare spontaneous reports of thrombocytopenia from postmarketing experience, patients should be observed regularly for possible occurrence of thrombocytopenia.

http://www4.wiwiss.fu-berlin.de/dailymed/resource/organization/Roche_Pharmaceuticals

Bumex