Bumetanide is a type of diuretic that removes excess water from the body. The FDA (Food and Drug Administration)- approved drug treats various edema (fluid retention) conditions associated with or caused by cardiac failure (heart does not pump enough blood), renal, or hepatic disease. It may be used alone or with other antihypertensive agents to treat hypertension.

Bumetanide is a loop diuretic that increases urine production from the kidneys. These drugs are referred to as ‘water pills' and are available only on prescription.

How Does Bumetanide Work?

Bumetanide treats edema by inducing a negative balance of solute and water. The drug increases the urinary excretion of water, sodium, and chloride by blocking sodium and chloride reabsorption in Henle's ascending loop (where absorption takes place), altering electrolyte transfer in the proximal tubule. This results in the excretion of sodium, chloride, and water.

Uses of Bumetanide:

Bumetanide reduces extra bodily fluid caused by conditions such as congestive heart failure, liver disease, and kidney disease. The diuretic helps treat water retention and removes unneeded water and salt from the body into the urine.

This helps to reduce symptoms such as shortness of breath and swelling in the arms, legs, and abdomen. Bumetanide may be used to treat hypertension alone or in combination with other antihypertensive drugs.

Limitations:

Bumetanide can cause excessive water and electrolyte depletion, leading to dehydration. Hence, the drug must be taken under the guidance of a healthcare provider.

Route of Administration

Oral.
Injectable (intravenous or intramuscular).

Dosage Forms and Strengths

Tablets - 0.5 mg, 1 mg, and 2 mg.
Liquid - 0.25 mg / mL.

Typical Dosage

The usual dose for adults to treat heart failure or build-up of bodily fluid (edema) is 1 mg to 10 mg daily. Older adults may be given a lower dose.

Special Considerations:

Allergy - It is advised not to take Bumetanide if the person is allergic to the drug or its ingredients.
Pregnancy and Breastfeeding - Bumetanide is a category C pregnancy drug. The drug is not recommended during pregnancy due to the potential risk of altered uteroplacental blood flow and may affect the baby's development. Bumetanide must be avoided while breastfeeding as it may decrease milk flow.
Geriatrics - Bumetanide must be administered with caution in older adults as there is an increased risk of side effects due to delayed excretion of the drug.
Children - Bumetanide causes dehydration and electrolyte imbalance and should be administered with caution in children. The safety and efficacy of the drug have not been established in neonates, infants, and children.
Mind Alertness - Bumetanide causes side effects like confusion and dizziness and should be avoided while driving or operating machinery.

Warnings and Contraindications

Contraindications:

Hypersensitivity - Bumetanide is contraindicated in patients with hypersensitivity to the drug or components of the formulation. The drug is also contraindicated in patients with hypersensitivity to loop diuretics.
Anuria - Therapy with Bumetanide is contraindicated in patients with anuria (failure of the kidneys to produce urine).

Warnings and Precautions

Renal Dysfunction - Therapy with a loop diuretic, like Bumetanide, must be cautiously administered in patients with severe renal dysfunction, as it may cause delayed excretion of the drug, causing drug accumulation and increased side effects.
Cirrhosis - Therapy with loop diuretics must be initiated under observation in patients with liver cirrhosis and ascites, as there may be sudden fluid and electrolyte imbalance. This may precipitate hepatic encephalopathy and coma in these patients.
Electrolyte loss - Chronic therapy with loop diuretics is associated with the loss of electrolytes such as potassium, sodium, chloride, magnesium, and calcium. Loss of these electrolytes can lead to cardiac arrhythmias, metabolic alkalosis, hyponatremia, dehydration, and hypovolemia. Therapy with loop diuretics must be cautiously administered in patients with predisposed fluid or electrolyte depletion.
Ototoxicity - Therapy with loop diuretics should be administered cautiously in patients with preexisting vestibular and auditory impairments as it may cause irreversible tinnitus and hearing loss.
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Diabetes - Bumetanide should be administered cautiously in patients with diabetes mellitus and glucose intolerance as it may cause hyperglycemia, glycosuria, and alterations in glucose tolerance tests.
Hyperuricemia - Loop diuretics may decrease the rate of uric acid excretion and should be administered with caution in patients with a history of gout or chronic renal failure.

For Patients

What Is Edema?

Swelling is caused by too much fluid trapped in the body’s tissues. It can affect any body part but generally shows up in the legs and feet. It may result from diseases like congestive heart failure, kidney failure, venous insufficiency, or liver cirrhosis. Edema can affect anyone but is generally in pregnant women and adults over 65.

Symptoms of Edema:

Puffiness of the tissue right under the skin, especially in the legs or arms.
Increase in the stomach area.
Stretched and shiny skin.
Heaviness in the leg.
Pitting (a dimple in the skin after it has been pressed for a few seconds).
Trouble breathing.
Sore feeling in the affected area.
Visual anomalies.

Why Is Bumetanide Prescribed to Treat Edema?

Bumetanide is more efficiently absorbed in the body. It is found to have high bioavailability (the ability of the drug to be absorbed and used by the body) of 80 percent. They are potent diuretics that increase the elimination of sodium and chloride by preventing their reabsorption.

Facts One Should Know About Bumetanide:

Bumetanide is a strong diuretic. When taken in high doses, it can make one urinate more, leading to severe water and electrolyte loss.
Bumetanide is usually taken once a day or maybe taken twice a day, preferably in the morning and afternoon.
The drug makes one want to urinate within 30 minutes of taking Bumetanide.
Do not take Bumetanide after 4 pm as one may have to wake up at night to use the toilet.
During the therapy with Bumetanide, the doctor may regularly check potassium and other electrolyte levels, blood pressure, weight, and kidney function.

How Should One Take Bumetanide?

Bumetanide is available as a tablet and is usually taken once a day.
When used to treat edema, a second or third dose may be given every four to five hours.
The dosage of Bumetanide is based on the medical condition and the response to the treatment. It is recommended to take the medication at the same time each day.
Bumetanide may be taken with or without food. It is advised not to take the medication after 4 pm, or it may be required to wake up at night to pass urine.
Do not share the medication with others.

Information Be Given to the Doctor Before Taking Bumetanide:

Medical History - Tell the doctor if one has kidney disease, diabetes, heart, or liver disease.
Drug History - It is advised to inform the doctor of one’s prescription and nonprescription medications, vitamins, supplements, and herbal products that one may be taking.
Allergy - Inform the doctor if one has had an allergic reaction to Bumetanide or its ingredients. Check the drug composition for the ingredients.
Pregnancy and Breastfeeding - Inform the doctor if one plans a pregnancy, pregnancy, or breastfeeding. It is advised to avoid getting pregnant while taking Bumetanide as it can harm the fetus.
Surgery - Inform the doctor if one has had or is planning a surgery, including dental surgery, before taking Bumetanide.
Laboratory Tests - Inform the doctor about taking Bumetanide before having any tests.

Safety of Bumetanide:

Bumetanide is a strong diuretic and may cause dehydration and electrolyte imbalance. Hence, the drug must be taken exactly as prescribed by the doctor. Bumetanide is safe to be taken for a long time but requires regular monitoring of the electrolyte levels.

Effectiveness of Bumetanide:

The high efficacy of loop diuretics, like Bumetanide, is due to the unique site of action involving the loop of Henle (a portion of the renal tubule) in the kidneys.

Side Effects Expected With Bumetanide:

The common side effects of Bumetanide include

Muscle cramps.
Dizziness.
Low blood pressure.
Headache.
Nausea.

Serious side effects and their symptoms may include

Skin reactions such as Stevens-Johnson syndrome with symptoms.
Rash.
Fever.
Burning eyes.
Blistering.
Bruising.
Sores.
Swelling.

Severe electrolyte loss can cause symptoms that may include

Weakness.
Confusion.
Loss of energy.
Dizziness.
Vomiting.

Can One Stop Taking Bumetanide Suddenly Without the Doctor's Approval?

It is advised not to stop taking Bumetanide suddenly or without discussing it with the doctor, as it may cause fluid to build up in the body and worsen the swelling. Abrupt cessation of Bumetanide can also worsen the symptoms of heart failure and other conditions.

Dietary Restrictions to Consider When Taking Bumetanide:

Alcohol - Bumetanide and ethanol may have additive effects in lowering blood pressure and cause headaches, lightheadedness, dizziness, or changes in the heart rate.
High-Sodium Foods - It is advised to avoid high-sodium foods such as processed foods or ready meals.

Storage of Bumetanide:

Keep the medicine in their original packaging and a tightly closed container.
Store at room temperature between 15 to 30 degrees.
Direct contact with heat, air, and light may damage the medicines. Therefore, keep the medicines away from direct light and heat.
Keep all medicines out of reach of children and pets. Always lock the safety caps of the medication to protect small children from poisoning themselves.

Disposal of Bumetanide:

Do not keep outdated medicines or medicines that are no longer needed.
If the medicine passes its expiry date or the doctor stops the treatment, return the medicines to the pharmacist. Do not flush them down the toilet or throw them away in the trash.
Dispose of the medicine through the local medicine take-back program, which can be accessed or learned more about through the local pharmacist.

Overdose:

Extensive or too frequent dosage can lead to acute electrolyte depletion.

In case of an overdose, call the poison control helpline.
Call the emergency services if the person has collapsed or has trouble breathing.
Symptoms of overdose include weakness, dizziness, confusion, extreme tiredness, loss of appetite, vomiting, and stomach cramps.
Adequate replacement of fluids and electrolytes, such as potassium supplements or potassium-sparing diuretics.

For Doctors

Indications:

Bumetanide manages various edematous conditions secondary to cardiac failure (with or without ascites) and hepatic or renal disease, including the nephrotic syndrome. The drug may also be prescribed for refractory edema resistant to other loop diuretics. Bumetanide is often prescribed off-label to treat hypertension in conjunction with other antihypertensives.

Pharmacology of Bumetanide

Description - Bumetanide is a potent sulfamoyl-anthranilic acid derivative belonging to the class of loop diuretics.

Components

Active Ingredients - Bumetanide.

Inactive Ingredients

Microcrystalline cellulose.
Povidone.
Lactose.
Maize starch.
Pregelatinized starch.
Colloidal silicon dioxide.
Magnesium stearate.
Talc.

Clinical Pharmacology

Mechanism of Action

Bumetanide inhibits the reabsorption of sodium and chloride in an ascending loop of Henle, thereby causing the excretion of water and sodium, chloride, calcium, magnesium, potassium, and hydrogen ions.

Pharmacodynamics

Bumetanide is a loop diuretic of the sulfanyl category. These loop diuretics increase the fractional excretion of volume, sodium, potassium, chloride, and calcium in all stages of renal failure.

Pharmacokinetics

The Mean Cmax- 148.60 ng/ml.
Median Tmax- Intravenous - 5 minutes, intramuscular - 30 minutes, and oral - one to two hours.

[Cmax- Maximum concentration achieved by a drug in the blood, cerebrospinal fluid, or target organ after administration of a dose].

[Tmax- Time taken for a drug to reach maximum concentration after administration of a dose].

Pharmacokinetic Changes

A. Distribution

Bioavailability - 80 percent to 100 percent.
Mean Half-Life - 1.0 to 1.5 hours.
Protein Bound - 95 percent.
Plasma Clearance - 225 to 228 ml/minute.
Mean Volume of Distribution - 25 liters.

B. Metabolism

Metabolic Processes - Bumetanide is completely absorbed with food and has complete bioavailability. Forty five percent of Bumetanide is excreted unchanged. Urinary and biliary metabolites are formed by oxidation of the N-butyl side chain.

C. Elimination - 81 percent of the administered radioactivity was excreted in the urine, and 45 percent was an unchanged drug. Biliary excretion amounts to only two percent of the administered dose.

Half-Life - 60 to 90 minutes.

Drug Interactions:

Bumetanide can interact with other medications, vitamins, herbs, or supplements.

Lithium - The drug must not be combined with diuretics, such as Bumetanide, as it can reduce renal clearance and increase the risk of lithium toxicity.
Captopril or Enalapril - Bumetanide may potentiate the effect of various antihypertensives, like Captopril or Enalapril. It may be required to reduce the dosage of these drugs.
Metoprolol - Using Bumetanide and beta-blockers, like Metoprolol and Atenolol, may lower blood pressure and slow the heart rate.
Probenecid - Using gout medicines, like Probenecid, with Bumetanide can reduce the effects of the drug and may also increase the risk of side effects of Bumetanide.
Indomethacin - Certain pain medicines, like Diclofenac, Indomethacin, and Ketorolac, may reduce the effects of Bumetanide. When combined with Bumetanide, these drugs may reduce the effect of decreasing swelling.

What Have Clinical Trials Shown About Bumetanide?

Trial 1:

Objective - To study the efficacy and safety of Bumetanide in patients with amyotrophic lateral sclerosis (a neurodegenerative disease).

A double-blind, placebo-controlled trial in which amyotrophic lateral sclerosis (ALS) patients were randomized 1:1 to receive Bumetanide 2 mg or a matching placebo group for up to four months.
Eighteen patients were allocated Bumetanide, while 18 were allocated to the placebo group.
Primary Endpoint - Motor unit number index (MUNIX), motor unit size index (MUSIX).
Secondary Endpoint - Functional rating scale (ALSFRS-R) was assessed before and after treatment.
Results - Patients in the placebo group showed a significant decrease in MUNIX value after treatment, while the MUNIX value in the Bumetanide group increased significantly. ALSFRS-S score decreased significantly in the placebo group after treatment and improved in the Bumetanide group. Bumetanide treatment is effective in the treatment of ALS symptoms.