Side Effects of Bumex (bumetanide)

Bumex (bumetanide) is a potent diuretic (water pill) that causes a profound increase in urine output (diuresis) by preventing the kidney from retaining fluid in people with congestive heart failure, liver disease or kidney disorder. Specifically, it blocks the reabsorption of sodium and fluid from the kidney's tubules. 

It is in a class of diuretics called "loop" diuretics which also includes furosemide (Lasix) and torsemide (Demadex). One mg of bumetanide is approximately equivalent to 10-20 mg of torsemide and 40 mg of furosemide. 

The potent diuretic effect of Bumex can cause the loss of large amounts of body water leading to dehydration as well as the loss of electrolytes (for example, sodium, potassium, magnesium, and calcium). Careful medical supervision is necessary during treatment.

Common side effects of Bumex include

• low blood levels of potassium,
• magnesium,
• sodium and
• calcium.

Serious side effects of Bumex include

• fluid losses that can lead to dehydration (symptoms of dehydration may include dry mouth, thirst, weakness, drowsiness, reduced kidney function, heart arrhythmias, muscle aches and pains, nausea, and vomiting),
• toxicity to the inner ear in the form of ringing in the ear (tinnitus) and hearing loss, and
• high uric acid concentrations in the blood leading to attacks of gouty arthritis.

Drug interactions of Bumex include other diuretics such as metolazone, hydrochlorothiazide, or chlorthalidone, which can exaggerate the losses of potassium and magnesium.

• The body's ability to eliminate lithium may decrease in patients receiving Bumex. Careful monitoring of lithium levels in blood is recommended when Bumex and lithium are taken together in order to prevent increases in lithium levels and lithium toxicity.
• Indomethacin can reduce the diuretic and blood pressure-lowering effects of other loop diuretics (for example furosemide) and it probably can do the same with Bumex.
• Other nonsteroidal anti-inflammatory drugs (NSAIDs), for example, ibuprofen and naproxen, may interact similarly. Concomitant use of Bumex and aminoglycosides may increase the risk of hearing impairment since both agents can affect hearing. 

There have been no adequate studies on the effects of Bumex on the fetus. The physician must carefully weigh the potential but unknown risks and benefits of Bumex before prescribing it for pregnant women. 

It is unknown if Bumex is excreted into breast milk. It should be used in women who are breastfeeding only if its potential benefits outweigh the unknown risks.

Potent diuretics like bumetanide can cause low blood levels of potassium, magnesium, sodium and calcium. Additionally, fluid losses can occur leading to dehydration.

The symptoms of dehydration may include:

• dry mouth,
• thirst,
• weakness,
• drowsiness,
• reduced kidney function,
• heart arrhythmias,
• muscle aches and pains,
• nausea, and
• vomiting.

Toxicity to the inner ear in the form of tinnitus (ringing in the ear) and hearing loss have been associated with loop diuretics. High plasma levels of bumetanide are toxic to the inner ear of animals. These effects on the inner ear are far more common with intravenous use of the drugs. High uric acid concentrations in the blood leading to attacks of gouty arthritis may occur during diuretic therapy.

The most frequent clinical adverse reactions considered probably or possibly related to Bumex are

• muscle cramps (seen in 1.1% of treated patients),
• dizziness (1.1%),
• hypotension (0.8%),
• headache (0.6%),
• nausea (0.6%) and
• encephalopathy (in patients with preexisting liver disease) (0.6%).

One or more of these adverse reactions have been reported in approximately 4.1% of patients treated with Bumex.

Serious skin reactions (i.e., Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported in association with bumetanide use.

Less frequent clinical adverse reactions to Bumex are

• impaired hearing (0.5%),
• pruritus (0.4%),
• electrocardiogram changes (0.4%),
• weakness (0.2%),
• hives (0.2%),
• abdominal pain (0.2%),
• arthritic pain (0.2%),
• musculoskeletal pain (0.2%),
•  rash (0.2%) and
• vomiting (0.2%).

One or more of these adverse reactions have been reported in approximately 2.9% of patients treated with Bumex.

Other clinical adverse reactions, which have each occurred in approximately 0.1% of patients, are

• vertigo,
• chest pain,
• ear discomfort,
•  fatigue,
• dehydration,
• sweating,
• hyperventilation,
• dry mouth,
• upset stomach,
• renal failure,
• asterixis,
• itching,
• nipple tenderness,
• diarrhea,
• premature ejaculation and
• difficulty maintaining an erection.

Laboratory abnormalities reported have included

• hyperuricemia (in 18.4% of patients tested),
• hypochloremia (14.9%),
• hypokalemia (14.7%),
• azotemia (10.6%),
• hyponatremia (9.2%),
• increased serum creatinine (7.4%),
• hyperglycemia (6.6%), and
• variations in
  • phosphorus (4.5%),
  • CO content (4.3%),
  • bicarbonate (3.1%) and
  • calcium (2.4%).

Although manifestations of the pharmacologic action of Bumex, these conditions may become more pronounced by intensive therapy.

Also reported have been thrombocytopenia (0.2%) and deviations in hemoglobin (0.8%), prothrombin time (0.8%), hematocrit (0.6%), WBC (0.3%) and differential counts (0.1%).

There have been rare spontaneous reports of thrombocytopenia from postmarketing experience.

Diuresis induced by Bumex may also rarely be accompanied by changes in LDH (1.0%), total serum bilirubin (0.8%), serum proteins (0.7%), SGOT (0.6%), SGPT (0.5%), alkaline phosphatase (0.4%), cholesterol (0.4%) and creatinine clearance (0.3%). Increases in urinary glucose (0.7%) and urinary protein (0.3%) have also been seen.

To report SUSPECTED ADVERSE REACTIONS, contact Validus Pharmaceuticals, LLC at 1-866-982-5438 (1-866-9VALIDUS) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.