Volume and Electrolyte Depletion The dose of bumetanide 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 bumetanide 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 bumetanide.
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 (see WARNINGS ) 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 bumetanide 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 bumetanide) 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 bumetanide.
This antagonistic effect of probenecid on bumetanide 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 bumetanide.
Indomethacin Indomethacin blunts the increases in urine volume and sodium excretion seen during bumetanide treatment and inhibits the bumetanide-induced increase in plasma renin activity.
Concurrent therapy with bumetanide is thus not recommended.
Antihypertensives Bumetanide 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 bumetanide to have no effect on warfarin metabolism or on plasma prothrombin activity.
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.
Bumetanide is a loop diuretic, available as scored tablets, 0.5 mg (light green), 1 mg (yellow) and 2 mg (peach) for oral administration; each tablet also contains: anhydrous lactose, magnesium stearate, microcrystalline cellulose, corn starch and talc, with the following colorants: 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 (Ferric oxide red).
Chemically, bumetanide is 3-(butylamino)-4-phenoxy-5-sulfamoyl-benzoic acid.
It is a practically white powder.
It is slightly soluble in water and soluble in alkaline solutions.
It has the following structural formula: Image of Structural Formula
Bumetanide Tablets USP are available as light green, flat, round, bevel-edged tablets, debossed “0.5” on one side and bisected on the other side with company logo on the upper half and “4232” on the lower, containing 0.5 mg bumetanide, USP packaged in bottles of 100 tablets.
Bumetanide Tablets USP are available as yellow, flat, round, bevel-edged tablets, debossed “1” on one side and bisected on the other side with company logo on the upper half and “4233” on the lower, containing 1 mg bumetanide, USP packaged in bottles of 100 and 1000 tablets.
Bumetanide Tablets USP are available as peach, flat, round, bevel-edged tablets, debossed “2” on one side and bisected on the other side with company logo on the upper half and “4234” on the lower, containing 2 mg bumetanide, USP packaged in bottles of 100 and 1000 tablets.
PHARMACIST: Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Manufactured In India By: EMCURE PHARMACEUTICALS LTD.
Hinjwadi, Pune, India Manufactured For: TEVA PHARMACEUTICALS USA Sellersville, PA 18960 Rev.
Geriatric Use Clinical studies of bumetanide did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
INDICATIONS AND USAGE
Bumetanide 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 bumetanide following instances of allergic reactions to furosemide suggests a lack of cross-sensitivity.
Pediatric Use Safety and effectiveness in pediatric patients below the age of 18 have not been established.
In vitro studies using pooled sera from critically ill neonates have shown bumetanide to be a potent displacer of bilirubin (see CLINICAL PHARMACOLOGY , Pediatric Pharmacology ).
The administration of bumetanide could present a particular concern if given to critically ill or jaundiced neonates at risk for kernicterus.
Nursing Mothers It is not known whether this drug is excreted in human milk.
As a general rule, nursing should not be undertaken while the patient is on bumetanide since it may be excreted in human milk.
WARNING Bumetanide is a potent diuretic which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion.
Therefore, careful medical supervision is required, and dose and dosage schedule have to be adjusted to the individual patient’s needs.
(See DOSAGE AND ADMINISTRATION.
DOSAGE AND ADMINISTRATION
Dosage should be individualized with careful monitoring of patient response.
Oral Administration The usual total daily dosage of bumetanide is 0.5 to 2 mg and in most patients is given as a single dose.
If the diuretic response to an initial dose of bumetanide 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 bumetanide 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, bumetanide can be substituted at approximately a 1:40 ratio of bumetanide to furosemide in patients allergic to furosemide.
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.