Bumex ® (bumetanide) is a loop diuretic available as 0.5 mg (light green), 1 mg (yellow) and 2 mg (peach) tablets for oral administration; each tablet also contains anhydrous lactose, magnesium stearate, microcrystalline cellulose, pregelatinized starch and talc, with the following dye systems: 0.5 mg—D&C Yellow No. 10 aluminum lake and FD&C Blue No. 1 aluminum lake; 1 mg—D&C Yellow No. 10 aluminum lake; 2 mg—red iron oxide. Chemically, bumetanide is 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid. It is a practically white powder having a calculated molecular weight of 364.42, and the following structural formula: FDA-approved impurity specifications differ from the USP. structural formula

Bumex tablets are indicated for the treatment of edema associated with congestive heart failure, hepatic and renal disease, including the nephrotic syndrome. Almost equal diuretic response occurs after oral and parenteral administration of bumetanide. Therefore, if impaired gastrointestinal absorption is suspected or oral administration is not practical, bumetanide should be given by the intramuscular or intravenous route. Successful treatment with Bumex tablets following instances of allergic reactions to furosemide suggests a lack of cross-sensitivity.

Individualize dosage with careful monitoring of patient response. Oral Administration The usual total daily dosage of Bumex tablets 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 tablets 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 tablets are 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, keep the dosage to a minimum. Because cross-sensitivity with furosemide has rarely been observed, bumetanide can be substituted at approximately a 1:40 ratio of bumetanide in proportion to furosemide in patients allergic to furosemide. Parenteral Administration Bumetanide injection may be administered parenterally (intravenously and intramuscularly) to patients in whom gastrointestinal absorption may be impaired or in whom oral administration is not practical. Terminate parenteral treatment and institute oral treatment as soon as possible.

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. 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, i.e., 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. 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. Allergy to Sulfonamides Patients allergic to sulfonamides may show hypersensitivity to Bumex. Thrombocytopenia Since there have been rare spontaneous reports of thrombocytopenia from postmarketing experience, patients should be observed regularly for possible occurrence of thrombocytopenia.

Drug Interactions Drugs with Ototoxic Potential Especially in the presence of impaired renal function, the use of parenterally administered bumetanide in patients to whom aminoglycoside antibiotics are also being given should be avoided, except in life-threatening conditions. Drugs with Nephrotoxic Potential There has been no experience with the concurrent use of Bumex with drugs known to have a nephrotoxic potential. Therefore, the simultaneous administration of these drugs should be avoided. Lithium Lithium should generally not be given with diuretics (such as Bumex) because they reduce its renal clearance and add a high risk of lithium toxicity. Probenecid Pretreatment with probenecid reduces both the natriuresis and hyperreninemia produced by Bumex. This antagonistic effect of probenecid on Bumex natriuresis is not due to a direct action on sodium excretion but is probably secondary to its inhibitory effect on renal tubular secretion of bumetanide. Thus, probenecid should not be administered concurrently with Bumex. Indomethacin Indomethacin blunts the increases in urine volume and sodium excretion seen during Bumex treatment and inhibits the bumetanide-induced increase in plasma renin activity. Concurrent therapy with Bumex is thus not recommended. Antihypertensives Bumex may potentiate the effect of various antihypertensive drugs, necessitating a reduction in the dosage of these drugs. Digoxin Interaction studies in humans have shown no effect on digoxin blood levels. Anticoagulants Interaction studies in humans have shown Bumex to have no effect on warfarin metabolism or on plasma prothrombin activity.