Bumetanide (Bumex) - for Hypertension & Heart Failure

Bumetanide (Bumex) is a loop diuretic that inhibits the reabsorption of water and solutes (sodium, potassium, calcium, phosphate, and magnesium) from the kidneys. It is used to treat the following conditions:

  • Management of edema due to heart failure, liver or renal disease including the nephrotic syndrome.

  • As an alternative agent for the treatment of hypertension.

Bumetanide Dose in Adults

Note: Bumetanide 1 mg = torsemide 20 mg = furosemide 40 mg = ethacrynic acid 50 mg

Bumetanide for edema and heart failure:

  • 0.5 to 2 mg/dose orally 1 - 2 times a day to a maximum dose of 10 mg/day, OR
  • 0.5 to 1 mg/dose as an intramuscular or intravenous injection.
    • The dose may be repeated in 2 - 3 hours up to a maximum dose of 10 mg/day.
  • Continuous Intravenous infusion:
    • 1 mg Intravenous loading dose then 0.5 - 2 mg/hour as a continuous intravenous infusion.

Off label use as alternative agent in the treatment of Hypertension:

  • 5 to 2 mg/day orally in two divided doses.

Bumetanide Dose in Children

Note: Approximately equivalent dose for adult patients with normal renal function: Furosemide 40 mg, toremide 20 mg, bumetanide 1 mg, and ethacrynic acid 50 mg are the equivalent doses.

Bumetanide use in the treatment of Edema:

Intermittent dosing:

  • Infants and Children:
    • 0.01 to 0.1 mg/kg/dose oral, Intramuscular, or intravenous every 6 - 24 hours to a maximum daily dose of 10 mg/day.
  • Adolescents:
    • 0.5 to 1 mg/dose oral, Intramuscular, or intravenous every 6 - 24 hours to a maximum daily dose of 10 mg/day.

Continuous Intravenous infusion:

  • Infants Children and Adolescents less than 16 years:
    • 1 to 10 mcg/kg/hour to the maximum dose of 50 mcg/kg/hour.

Pregnancy Risk Factor C

  • Animal reproduction research have recorded negative foetal outcomes.

Bumetanide use during breastfeeding:

  • It is not recommended for use during breastfeeding. Furthermore, diuretics suppress lactation.

Bumetanide Dose in Renal Disease:

The manufacturer has not recommended any dose adjustment in patients with renal disease. Patients with anuria should avoid the drug.

Bumetanide Dose in Liver Disease:

  • The manufacturer has not recommended any dose adjustment in patients with liver disease.
  • Patients with hepatic encephalopathy should avoid using it. Those with cirrhosis and ascites should use it with caution as it may precipitate hepatic coma.

Common Side Effects of Bumetanide Include:

  • Endocrine & metabolic:
    • Hyperuricemia
    • Hypochloremia
    • Hypokalemia
  • Genitourinary:
    • Azotemia

Less Common Side Effects Of Bumetanide Include:

  • Central Nervous System:
    • Dizziness
  • Endocrine & Metabolic:
    • Hyponatremia
    • Hyperglycemia
    • Phosphorus Change
    • Variations In Bicarbonate
    • Abnormal Serum Calcium
    • Abnormal Lactate Dehydrogenase
  • Neuromuscular & Skeletal:
    • Muscle Cramps
  • Renal:
    • Increased Serum Creatinine
  • Respiratory:
    • Change in carbon dioxide content.

Contraindication to Bumetanide include:

 

  • Allergy reactions to bumetanide and any component of the formulation
  • Anuria
  • Hepatic Encephalopathy
  • An abnormality in the electrolyte.
  • Allergie to sulfonamide
  • Hepatic Encephalopathy
  • Galactose intolerance
  • Glucose-Galactose malabsorption
  • Lapp Lactose deficiency.

Warnings and Precautions

  • Fluid & electrolyte loss: [US Boxed Warning]
    • Bumetanide can be a powerful diuretic, and may cause excessive fluid and electrolyte loss.
    • Hypokalemia, volume loss and hypocalcemia should all be checked.
    • Patients with electrolyte problems may be more susceptible to developing cardiac arrhythmias.
  • Hyperuricemia:
  • Nephrotoxicity:
    • If the patient is given aggressive diuretics, nephrotoxicity can develop.
    • Monitor fluid status, renal function, and serum electrolytes.
  • Ototoxicity:
    • Rapid intravenous administration, those with renal impairment, on high doses, or on other concomitant ototoxic medicines like aminoglycosides may develop ototoxicity.
  • Allergy to sulfonamide
    • Sulfa drugs, which contain a sulfonamide chemical compound group, can cause severe allergic reactions in patients who are allergic to them.
    • You should be cautious as cross-reactivity could occur.
    • Avoid it if you have had severe allergic reactions, such as Steven Johnson syndrome or TEN.
  • Hepatic impairment
    • Patients suffering from cirrhosis must be cautious when taking the drug.
    • With frequent monitoring of electrolytes, a smaller dose should be administered at the beginning.
    • Avoid sudden changes in fluids or electrolytes as they can lead to hepatic-encephalopathy.
  • Renal impairment
    • Higher doses could be necessary for those with reduced renal function to produce the desired effect.

Bumetanide: Drug Interaction

Risk Factor C (Monitor therapy)

Ajmaline

Sulfonamides might make ajmaline more harmful or poisonous. In particular, there may be an elevated risk for cholestasis.

Alfuzosin

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Allopurinol

Loop Diuretics may intensify Allopurinol's harmful or toxic effects. Allopurinol's serum levels may rise in response to loop diuretics. In particular, Oxypurinol, an active metabolite of Allopurinol, may be increased in concentration by Loop Diuretics.

Amikacin (Oral Inhalation)

Loop Diuretics may increase Amikacin's nephrotoxic impact (Oral Inhalation). Loop Diuretics may increase Amikacin's ototoxic effects (Oral Inhalation).

Aminoglycosides

Aminoglycosides may have a worse or more toxic effect when used with loop diuretics. ototoxicity and nephrotoxicity in particular.

Amphetamines

May lessen the effectiveness of antihypertensive agents.

Angiotensin-Converting Enzyme Inhibitors

Angiotensin-Converting Enzyme Inhibitors' hypotensive effects may be strengthened by loop diuretics. Angiotensin-Converting Enzyme Inhibitors' nephrotoxic effects may be increased by loop diuretics.

Antidiabetic Agents

The therapeutic benefit of anti-diabetic agents may be reduced by hyperglycemia-associated agents.

Antipsychotic Agents (Second Generation [Atypical])

Antipsychotic drugs' hypotensive effects may be enhanced by blood pressure-lowering medications (Second Generation [Atypical]).

Barbiturates

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Benperidol

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Beta2-Agonists

May intensify Loop Diuretics' hypokalemic impact.

Bilastine

The QTc-prolonging effects of loop diuretics may be enhanced by bilastine.

Brigatinib

May lessen the effectiveness of antihypertensive agents. Antihypertensive Agents' bradycardic action may be strengthened by brutinib.

Brimonidine (Topical)

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Cardiac Glycosides

Cardiac Glycosides may have a worse or more toxic effect when used with loop diuretics. Particularly, the hypokalemic and hypomagnesemic impact of loop diuretics may worsen cardiac glycoside toxicity.

Cefazedone

May intensify Loop Diuretics' nephrotoxic effects.

Cefotiam

Loop Diuretics may intensify Ceftiam's nephrotoxic effects.

Cefpirome

Loop Diuretics may increase Cefpirome's nephrotoxic effects.

Ceftizoxime

Loop Diuretics may increase Ceftizoxime's nephrotoxic effects.

Cephalothin

Loop Diuretics may increase Cephalothin's nephrotoxic effects.

Cephradine

May intensify Loop Diuretics' nephrotoxic effects.

CISplatin

Loop Diuretics might make CISplatin's nephrotoxic effects worse. The ototoxic impact of CISplatin might be increased by loop diuretics.

Corticosteroids (Orally Inhaled)

May intensify Loop Diuretics' hypokalemic impact.

Corticosteroids (Systemic)

May intensify Loop Diuretics' hypokalemic impact.

CycloSPORINE (Systemic)

May intensify Loop Diuretics' hypokalemic impact.

Dexmethylphenidate

Can lessen an antihypertensive drug's therapeutic impact.

Diacerein

Could make diuretics' therapeutic effects stronger. Particularly, there may be a higher chance of hypokalemia or dehydration.

Diazoxide

The hypotensive effects of blood pressure-lowering medications may be strengthened.

DULoxetine

The hypotensive impact of DULoxetine may be enhanced by blood pressure lowering medications.

Empagliflozin

May strengthen Loop Diuretics' hypotensive effects.

Fosphenytoin

May lessen Loop Diuretics' diuretic effects.

Herbs (Hypertensive Properties)

May lessen the effectiveness of antihypertensive agents.

Herbs (Hypotensive Properties)

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Hypotension-Associated Agents

The hypotensive action of hypotension-associated agents may be strengthened by blood pressure lowering medications.

Ipragliflozin

May intensify Loop Diuretics' harmful or hazardous effects. In particular, there may be an elevated risk for intravascular volume depletion.

Ivabradine

Ivabradine's ability to induce arrhythmias may be enhanced by loop diuretics.

Levodopa-Containing Products

Levodopa-Containing Products' hypotensive effects may be strengthened by blood pressure-lowering medications.

Licorice

May intensify Loop Diuretics' hypokalemic impact.

Lithium

Loop Diuretics may lower the level of lithium in the blood. Loop Diuretics may raise the level of lithium in the blood.

Lormetazepam

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Methylphenidate

May lessen the effectiveness of antihypertensive agents.

Molsidomine

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Naftopidil

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Neuromuscular-Blocking Agents

The neuromuscular-blocking effects of neuromuscular-blocking agents may be lessened by loop diuretics. Neuromuscular-Blocking Agents' ability to block neuromuscular activity may be enhanced by loop diuretics.

Nicergoline

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Nicorandil

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Nitroprusside

Nitroprusside's hypotensive impact may be strengthened by blood pressure-lowering medications.

Opioid Agonists

Could make diuretics' harmful or toxic effects worse. Opioid antagonists may reduce diuretics' therapeutic benefit.

Pentoxifylline

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Phenytoin

May lessen Loop Diuretics' diuretic effects.

Pholcodine

Pholcodine's hypotensive impact may be strengthened by blood pressure lowering medications.

Phosphodiesterase 5 Inhibitors

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Probenecid

May intensify Loop Diuretics' harmful or hazardous effects. The diuretic action of loop diuretics may be reduced by probenecid. Loop Diuretics' serum levels may rise in response to probenecid. Monitoring for diminished diuretic effects or increased side effects of loop diuretics while probenecid is also being used concurrently. The prescribing advice for bumetanide cautions against using probenecid at the same time.

Prostacyclin Analogues

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Quinagolide

The hypotensive effects of blood pressure-lowering medications may be strengthened.

Reboxetine

May intensify Loop Diuretics' hypokalemic impact.

RisperiDONE

Loop Diuretics may intensify RisperiDONE's harmful or hazardous effects.

Salicylates

May lessen Loop Diuretics' diuretic effects. The content of salicylates in the serum may rise when using loop diuretics.

Tobramycin (Oral Inhalation)

Loop Diuretics may increase Tobramycin's nephrotoxic effects (Oral Inhalation). Loop Diuretics may increase Tobramycin's ototoxic effects (Oral Inhalation).

Topiramate

Topiramate's effect on hypokalemia may be enhanced by loop diuretics.

Xipamide

May intensify Loop Diuretics' harmful or hazardous effects. Particularly, there may be a higher chance of hypovolemia, electrolyte imbalances, and prerenal azotemia.

Yohimbine

May lessen the effectiveness of antihypertensive agents.

Risk Factor D (Consider therapy modification)

Amifostine

Amifostine's hypotensive impact may be strengthened by blood pressure lowering medications. Treatment: Blood pressure-lowering drugs need to be avoided for 24 hours before amifostine is administered when used at chemotherapeutic doses. Amifostine should not be given if blood pressure lowering treatment cannot be stopped.

Bile Acid Sequestrants

Loop Diuretics' ability to absorb water may be reduced.

Canagliflozin

May strengthen Loop Diuretics' hypotensive effects. Management: If canagliflozin is taken with a loop diuretic, watch for signs of hypotension and intravascular volume depletion. Canagliflozin and loop diuretics should not be taken together, according to Canadian product labelling.

Dofetilide

Loop Diuretics may increase Dofetilide's ability to extend QTc. Management: When dofetilide is taken with loop diuretics, serum potassium and magnesium levels should be continuously monitored. The need for therapy change may arise.

Foscarnet

Loop Diuretics may raise the level of foscarnet in the blood.

Methotrexate

May reduce Loop Diuretics' therapeutic efficacy. Loop diuretics may raise the level of methotrexate in the serum. Loop Diuretics' serum levels may be raised by methotrexate. Management involves monitoring for elevated methotrexate and/or loop diuretic levels/toxicity with concurrent use of these drugs as well as for diminished loop diuretic therapeutic effects. It could be essential to reduce the dosage of loop diuretics or methotrexate.

Nonsteroidal Anti-Inflammatory Agents

May lessen Loop Diuretics' diuretic effects. Nonsteroidal Anti-Inflammatory Drugs may have a greater nephrotoxic effect when used with loop diuretics. Management: When using an NSAID at the same time as loop diuretics, watch out for signs of kidney damage or diminished therapeutic efficacy. Avoid using concurrently if you have cirrhosis or CHF. Bumetanide and indomethacin should not be used concurrently.

Obinutuzumab

The hypotensive effects of blood pressure-lowering medications may be strengthened. Management: Take into account temporarily stopping blood pressure-lowering drugs 12 hours before the start of the obinutuzumab infusion and keeping them off until 1 hour after the infusion is finished.

Sodium Phosphates

The nephrotoxic effects of sodium phosphates may be increased by diuretics. In particular, there may be an increased risk of acute phosphate nephropathy. Treatment: You might want to temporarily stop taking diuretics or look for an alternative to the oral sodium phosphate bowel preparation in order to prevent this combo. If the combination cannot be avoided, drink well and keep an eye on your kidney and fluid levels.

Risk Factor X (Avoid combination)

Bromperidol

The hypotensive impact of bromperidol may be enhanced by blood pressure lowering medications. Blood Pressure Lowering Agents' hypotensive effects may be lessened by bromperidol.

Desmopressin

Desmopressin's hyponatremic impact may be increased by loop diuretics.

Levosulpiride

Levosulpiride's harmful or toxic effects may be exacerbated by loop diuretics.

Mecamylamine

Sulfonamides may intensify Mecamylamine's harmful or hazardous effects.

Promazine

Loop Diuretics may increase Promazine's ability to extend QTc.

Monitor:

  • Blood pressure
  • Serum electrolytes
  • Renal function
  • Fluid status

How to administer Bumetanide?

  • Intravenous administration:
    • Administer as a slow intravenous injection over 1 - 2 minutes.
  • Intramuscular administration:
    • It may be administered as an Intramuscular injection.
  • Oral administration:

Mechanism of action of Bumetanide:

  • It increases water excretion because it inhibits the reabsorption sodium and chloride from the proximal renal tubules.
  • It not only increases water excretion but also causes sodium, magnesium, phosphate and calcium excretion through interfering in the chloride binding cotransport system.
  • It doesn't affect the distal tubules in the kidneys.

The Onset of action after intramuscular injection is 0.5 to 1 hour, 2 - 3 minutes after intravenous administration.

One to two hours after oral administration and 15 to thirty minutes after intravenous administration, respectively, the maximal impact is observed.

4 to 6 hours after oral treatment and 2 to 3 hours after intravenous administration pass before the effects start to take effect. The medication is protein-bound to an extent of 94–96%.

Its bioavailability ranges from 59 to 89% and the liver partially metabolises it.

Elimination has a half-life of 6 hours in neonates, 2.5 hours in infants younger than 2 months, 1.5 hours in children between 2 and 6 months, and 1 to 1.5 hours in adults. Most of it is excreted.

International Brands of Bumetanide:

  • Biulan
  • Brinex
  • Budema
  • Bumecard
  • Bumelex
  • Bumet
  • Bumetanid
  • Burinex
  • Butinat
  • Conart
  • Diunide
  • Drenural
  • Edemex
  • Exametanide
  • Fontego
  • Fordiuran
  • Huiyuan
  • Miccil
  • Urenide
  • Urinide

Bumetanide brands in Pakistan:

Bumetanide [Tabs 0.5 mg]

Xurin- K

Pacific Pharmaceuticals Ltd.