Bumetanide

If your doctor prescribes a low-salt or low-sodium diet, or to eat or drink increased amounts of potassium-rich foods (e.g., bananas, prunes, raisins, and orange juice) in your diet, follow these instructions carefully.

Oral/Injectable:

Common side effects include:

• muscle cramps
• dizziness
• low blood pressure
• headache
• nausea

This is not a complete list of bumetanide side effects. Ask your doctor or pharmacist for more information.

Serious side effects can occur. See "Drug Precautions" section.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of bumetanide, there are no specific foods that you must exclude from your diet when receiving this medication.

Before taking bumetanide, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• have liver disease
• have kidney disease
• have diabetes
• have gout
• have electrolyte imbalances
• are allergic to any medications
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Take bumetanide exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The bumetanide dose your doctor recommends will be based on:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication

The recommended total daily dosage of bumetanide is 0.5 mg to 10 mg, depending on the form of the drug.

If you take too much bumetanide call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

Dosing

The dose of bumetanide will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of bumetanide. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For edema:
    • Adults—0.5 to 2 milligrams (mg) once a day. Your doctor may adjust your dose if needed.
    • Children—Use and dose must be determined by your doctor .

Missed Dose

If you miss a dose of bumetanide, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Bumetanide is a loop diuretic, available in 4 mL and 10 mL vials for intravenous or intramuscular injection as a sterile solution. Each mL contains 0.25 mg Bumetanide compounded with 0.85% sodium chloride and 0.4% ammonium acetate as buffers; 0.01% edetate disodium; 1% benzyl alcohol as preservative, and pH adjusted to approximately 7 with sodium hydroxide.

Chemically, Bumetanide is 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid. It is a practically white powder, slightly soluble in water; soluble in alkaline solutions, having a calculated molecular weight of 364.42, and the following structural formula:

Molecular Formula: C17H20N2O5S

Bumetanide Injection, USP is available as:

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature]

PROTECT FROM LIGHT. Retain in carton until ready to use.

Do not use the injection if it is discolored or contains a precipitate.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

LAB-0881-2.0

04/2017

10 mL 10 Multi-dose Vials
Sterile Injection

NDC 0409-1412-10
Rx only

Bumetanide Injection, USP

2.5 mg/10 mL (0.25 mg/mL)

INTRAVENOUS or INTRAMUSCULAR USE

Hospira

• Bumex

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Generic: 0.25 mg/mL (2 mL, 4 mL, 10 mL)

Tablet, Oral:

Bumex: 0.5 mg [contains fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake]

Bumex: 1 mg [contains fd&c yellow #10 (quinoline yellow)]

Bumex: 2 mg

Generic: 0.5 mg, 1 mg, 2 mg

Refer to adult dosing.

Concerns related to adverse effects:

• Fluid/electrolyte loss: [US Boxed Warning]: Loop diuretics are potent diuretics; excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Potassium supplementation and/or use of potassium-sparing diuretics may be necessary to prevent hypokalemia. In contrast to thiazide diuretics, a loop diuretic can also lower serum calcium concentrations. Electrolyte disturbances can predispose a patient to serious cardiac arrhythmias.

• Hyperuricemia: Asymptomatic hyperuricemia has been reported with use.

• Nephrotoxicity: Monitor fluid status and renal function in an attempt to prevent oliguria, azotemia, and reversible increases in BUN and creatinine; close medical supervision of aggressive diuresis required.

• Ototoxicity: Bumetanide-induced ototoxicity (usually transient) may occur with rapid IV administration, renal impairment, excessive doses, and concurrent use of other ototoxins (eg, aminoglycosides).

• Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.

Disease-related concerns:

• Cirrhosis: Use caution in patients with cirrhosis; initiate bumetanide therapy with conservative dosing and close monitoring of electrolytes; avoid sudden changes in fluid and electrolyte balance and acid/base status which may lead to hepatic encephalopathy.

• Renal impairment: Larger doses may be necessary in patients with impaired renal function to obtain the same therapeutic response (Brater 1998).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Neonates: In vitro studies using pooled sera from critically-ill neonates have shown bumetanide to be a potent displacer of bilirubin; avoid use in neonates at risk for kernicterus.

• Surgical patients: If given the morning of surgery, bumetanide may render the patient volume depleted and blood pressure may be labile during general anesthesia.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Other warnings and precautions:

• Diuretic resistance: For some patients, despite higher doses of loop diuretic treatment, an adequate diuretic response cannot be attained. Diuretic resistance can usually be overcome by intravenous administration, the use of two diuretics together (eg, furosemide and chlorothiazide), or the use of a diuretic with a positive inotropic agent. When such combinations are used, serum electrolytes need to be monitored even more closely (ACC/AHA [Yancy, 2013]; HFSA, 2010).

Bumetanide is sometimes used only once, so you may not be on a dosing schedule. If you are using the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Consult your pharmacist.

Commonly reported side effects of bumetanide include: hypokalemia and hyperuricemia. See below for a comprehensive list of adverse effects.

Oral: 0.5 to 2 mg once a day.
IV or IM: 0.5 to 1 mg once.
Continuous IV infusion: 1 mg/hour up to 12 mg/day.

Patients with cirrhosis and ascites should be given smaller doses of bumetanide due to the risk of altered electrolyte balance, which can lead to hepatic encephalopathy.

Summary of Use during Lactation

It is unknown if bumetanide is excreted into breastmilk. It should be avoided while breastfeeding a newborn because it may decrease milk flow or completely suppress lactation. Low doses in mothers whose lactation is well established are unlikely to suppress lactation. In general, alternate drugs are preferred.

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information on bumetanide was not found as of the revision date. Intense diuresis, fluid restriction and breast binding have been used to suppress lactation immediately postpartum.[1][2][3] The added contribution of the diuretic to the other measures, which are effective in suppressing lactation, has not been studied. No data exist on the effects of loop diuretics on established, ongoing lactation.

Alternate Drugs to Consider

Chlorothiazide, Hydrochlorothiazide

References

1. Healy M. Suppressing lactation with oral diuretics. Lancet. 1961;1:1353-4.

2. Stout G. Suppression of lactation. Br Med J. 1962;1:1150. Letter. PMC: PMC1958377

3. Cominos DC, Van Der Walt A, Van Rooyen AJ. Suppression of postpartum lactation with furosemide. S Afr Med J. 1976;50:251-2. PMID: 3858