Consumer medicine information

Burinex

Bumetanide

BRAND INFORMATION

Brand name

Burinex

Active ingredient

Bumetanide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Burinex.

SUMMARY CMI

BURINEX®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using BURINEX?

BURINEX contains the active ingredient bumetanide. BURINEX is used for people who have swollen feet and ankles due to fluid which has built-up as a result of heart, liver or kidney disease. It is also used when there is too much fluid in the lungs.

For more information, see Section 1. Why am I using BURINEX? in the full CMI.

2. What should I know before I use BURINEX?

Do not use if you have ever had an allergic reaction to BURINEX or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use BURINEX? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with BURINEX and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use BURINEX?

  • Use BURINEX only when prescribed by your doctor. Follow the instructions provided and use BURINEX until your doctor tells you to stop.
  • The usual dose of BURINEX is one tablet (1 mg) every day; however, your doctor may recommend a different dose for you.

More instructions can be found in Section 4. How do I use BURINEX? in the full CMI.

5. What should I know while using BURINEX?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using BURINEX.
  • If you become pregnant while using BURINEX, inform your doctor immediately.
Things you should not do
  • Do not stop using this medicine or change the dose, unless your doctor has told you to.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how BURINEX affects you.
  • BURINEX may cause dizziness in some people, which may affect your ability to drive and use machines.
Participating in sports
  • BURINEX is banned for use in sport at a level subject to anti-doping regulations.
  • It can be detected by routine urine testing and will result in athlete disqualification.
Looking after your medicine
  • Store below 25°C. Keep the blister in the carton to protect it from light.

For more information, see Section 5. What should I know while using BURINEX? in the full CMI.

6. Are there any side effects?

SERIOUS SIDE EFFECTS: related to allergic reaction (sudden onset of swelling of face/lips/tongue causing difficulty to breathe, [itchy] rash, shortness of breath), heart (chest pain, abdominal/irregular heartbeat), gastrointestinal (vomiting, diarrhoea), other (impaired hearing/ear discomfort, unexplained bruising).

Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

COMMON SIDE EFFECTS: related to alertness & orientation (headache, dizziness, fatigue, weakness, light-headedness when standing up quickly), respiratory (cough), kidney (passing less urine/difficulty passing urine, dry mouth/thirst), pain (muscle weakness/pain/cramps, gout – painful swollen joint[s]), circulation (swollen hands/ankles/feet), gastrointestinal (tummy ache/discomfort, nausea, constipation), other (increased breast size [men], blood disorders [low blood cell/platelet count], unusual amount of salts in the body).

Speak to your doctor if you have any of these less serious side effects and they worry you.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

BURINEX® (bue-rin-ex)

Active ingredient: bumetanide


Consumer Medicine Information (CMI)

This leaflet provides important information about using BURINEX. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using BURINEX.

Where to find information in this leaflet:

1. Why am I using BURINEX?
2. What should I know before I use BURINEX?
3. What if I am taking other medicines?
4. How do I use BURINEX?
5. What should I know while using BURINEX?
6. Are there any side effects?
7. Product details

1. Why am I using BURINEX?

BURINEX contains the active ingredient bumetanide. BURINEX belongs to a group of medicines called diuretics. Diuretics are medicines that make the kidneys produce more urine.

BURINEX is effective treatment for people who have swollen feet and ankles due to fluid which has built-up as a result of heart, liver or kidney disease. It is also used when there is too much fluid in the lungs.

2. What should I know before I use BURINEX?

Warnings

Do not use BURINEX if:

  • You are allergic to bumetanide, or any of the ingredients listed at the end of this leaflet
  • Always check the ingredients to make sure you can use this medicine
  • Your body is unable to produce urine
  • You suffer from a severe liver disease which causes a decline in brain function, including coma
  • You suffer from a shortage of salts or chemicals in the blood
  • Symptoms of an allergic reaction may include skin rash, itching, hives, shortness of breath, or swelling of the face, lips of tongue.

Check with your doctor if you:

  • have any other medical conditions such as:
    - an imbalance of salts or chemicals in the blood
    - an imbalance of blood volume
    - low blood pressure
    - lactose intolerance (cannot fully digest the sugar [lactose] in milk after eating or drinking dairy products)
    - diabetes (high blood sugar)
    - kidney problems
    - prostate gland problems
    - difficulty to urinate
    - liver problems, including liver damage
    - a build-up of fluid in your belly
    - allergies to any other medicines, foods, preservatives or dyes
  • Compete in sport at a level subject to anti-doping regulations
  • Take any medicines for any other condition
  • Have been feeling weak, dizzy, tired or confused
  • Suffer from diarrhoea, vomiting or dehydration
  • Are on a low salt diet.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant. Do not use BURINEX if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed. Your doctor will discuss the possible risks and benefits of using BURINEX during breastfeeding and a decision can be made if you should or should not use it.

Allergy to sulphonamides

People who are allergic to sulphonamides may also show allergic reactions when taking BURINEX. Sulphonamides are a type of antibiotic used to treat certain bacterial infections.

Check with your doctor or pharmacist if you are not sure whether you are allergic to sulphonamides.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some commonly used medicines that may interfere with BURINEX include:

  • Lithium (used to treat mood disorders)
  • Probenecid (used to treat gout)
  • Medicines used to treat high or low blood pressure
  • Medicines used to treat heart conditions, including digoxin
  • Medicines which can affect the hearing negatively, e.g. aminoglycoside antibiotics (like gentamicin and tobramycin)
  • Medicines that are toxic to the kidneys
  • Non-steroidal anti-inflammatory drugs (NSAIDs), e.g. ibuprofen and diclofenac (used to treat pain and arthritis)
  • Medicines that affect the amount of potassium in your blood
  • Medicines used to treat abnormal heart rhythms
  • Medicines used to treat gastrointestinal conditions, including ulcers.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect BURINEX.

4. How do I use BURINEX?

How much to take

  • The usual dose of BURINEX is one tablet (1 mg) every day; however, your doctor may recommend a different dose for you
  • Follow the instructions provided and use BURINEX until your doctor tells you to stop.

When to take BURINEX

  • BURINEX should be used either in the morning or early evening.

How to take BURINEX

  • BURINEX tablets should be swallowed with a glass of water
  • The score line is there to help you break the tablet if you have difficulty swallowing it whole.

If you forget to use BURINEX

BURINEX should be used regularly at the same time each day. If you miss your dose at the usual time, take it as soon as you remember.

If your next dose is due in less than 4 hours, or it is near your bedtime, wait and take the next dose at the usual time.

Do not take a double dose to make up for the dose you missed.

If you have any questions, ask your doctor or pharmacist.

If you use too much BURINEX

If you think that you have used too much BURINEX, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

If you take too much BURINEX you may feel thirsty, weak, tired, dizzy and/or confused. You may also have a dry mouth, loss of appetite, experience cramps and/or vomiting.

5. What should I know while using BURINEX?

Things you should do

If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking BURINEX.

Call your doctor straight away if you:

  • Become pregnant while you are taking BURINEX.

Remind any doctor, dentist or pharmacist you visit that you are using BURINEX.

Things you should not do

  • Do not stop using this medicine or change the dose, unless your doctor has told you to
  • Do not give this medicine to anyone else, even if they have the same condition as you
  • Do not take this medicine to treat any other complaints unless your doctor tells you to.

Competing in sports

  • BURINEX is banned for use in sport at a level subject to anti-doping regulations
  • It can be detected by routine urine testing and will result in athlete disqualification.

BURINEX is not addictive.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how BURINEX affects you.

BURINEX may cause dizziness in some people, which may affect your ability to drive and use machines.

Drinking alcohol

Alcohol is not expected to have any effect on the use of BURINEX.

Looking after your medicine

  • Store below 25°C. Keep the blister in the carton to protect it from light.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

When to discard your medicine

If your doctor tells you to stop taking BURINEX, or the tablets have passed their expiry date, ask your pharmacist what to do with the remaining tablets.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Alertness- and orientation-related:
  • Headache
  • Dizziness
  • Fatigue
  • Weakness
  • Feeling light-headed when you stand up quickly
Respiratory-related:
  • Cough
Kidney-related:
  • Passing less urine than what is normal for you
  • Difficulty passing urine
  • Dry mouth and thirst
Pain-related:
  • Muscle weakness, pain or cramps
  • Gout – painful swollen joint(s)
Circulation-related:
  • Swelling of hands, ankles or feet
Gastrointestinal-related:
  • Tummy ache or discomfort
  • Nausea (feeling sick)
  • Constipation
Other:
  • Increased breast size in men
  • Blood disorders e.g. low blood cell or platelet count
  • An unusual amount of salts in the body
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Allergic reaction:
Sudden onset of:
  • Swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • Rash, sometimes itchy
  • Shortness of breath
Heart-related:
  • Chest pain
  • Abnormal or irregular heartbeat
Gastrointestinal-related:
  • Vomiting
  • Diarrhoea
Other:
  • Impaired hearing or ear discomfort
  • Unexplained bruising
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What BURINEX contains

Active ingredient
(main ingredient)
Bumetanide
Other ingredients
(inactive ingredients)
Maize starch
Lactose
Colloidal anhydrous silica
Povidone
Polysorbate 80
Agar
Magnesium stearate
Purified talc

Do not take this medicine if you are allergic to any of these ingredients.

What BURINEX looks like

BURINEX® tablets are white, flat and round (with a diameter of 8 mm). One side is market with a score line and the number 133.

BURINEX® tablets are supplied in PVC/aluminium blisters and are packed in cartons containing 100 tablets.

(AUST R 51734)

Who distributes BURINEX

AFT Pharmaceuticals Pty Ltd
113 Wicks Road
North Ryde
NSW 2113
Email:[email protected]
Freephone (AU): 1800 AFTPHARM (1800 238 74276)

This leaflet was prepared in January 2021.

Published by MIMS May 2021

BRAND INFORMATION

Brand name

Burinex

Active ingredient

Bumetanide

Schedule

S4

 

1 Name of Medicine

Bumetanide.

2 Qualitative and Quantitative Composition

Each Burinex tablet contains 1 mg bumetanide.

Excipients with known effect.

Lactose monohydrate (see Section 4.4 Special Warnings and Precautions for Use).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Burinex 1 mg tablets are white, flat, circular (diameter 8 mm) and uncoated, with a bevelled edge, and are marked on one face with a score line and the number 133.

4 Clinical Particulars

4.1 Therapeutic Indications

Burinex is indicated for the treatment of oedema, particularly that associated with congestive heart failure, hepatic and renal diseases including the nephrotic syndrome and acute pulmonary oedema.

4.2 Dose and Method of Administration

Oral administration.

Most patients will respond to 1 mg daily, administered as a single dose, either in the morning or early evening.
If the diuretic response to an initial dose of Burinex is not adequate, and 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 in refractory patients. An intermittent dose schedule, whereby Burinex is given on alternate days or for 3 - 4 days with rest periods of 1 - 2 days in between, is recommended as the safest and most effective method for the continued control of oedema.

4.3 Contraindications

Anuria.

Although Burinex can be used to induce diuresis in renal insufficiency, any marked increase in blood urea nitrogen or creatinine or the development of oliguria during therapy of patients with progressive renal disease is an indication for discontinuation of treatment with Burinex.
Hepatic encephalopathy including coma.
Severe electrolyte depletion.
Hypersensitivity to the active substance (bumetanide) or to any of the excipients (see Section 6.1 List of Excipients). Reports of successful treatment with Burinex following instances of allergic reactions to frusemide suggests a lack of cross sensitivity between the two substances.

4.4 Special Warnings and Precautions for Use

Volume and electrolyte imbalance.

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. Replacement therapy should be instituted where indicated.
Serum potassium should be measured regularly and potassium supplements or potassium sparing diuretics added if necessary. Prevention of hypokalaemia is of particular importance in patients receiving digitalis and diuretics for congestive heart failure, hepatic cirrhosis or ascites, states of aldosterone excess with normal renal function, potassium losing nephropathy, certain diarrhoeal states, or other states where hypokalemia is thought to represent particular added risks to the patient, i.e. history of ventricular arrhythmias.
Periodic determinations of other electrolytes (in particular, sodium, potassium, chloride, calcium and bicarbonate) are advised in patients treated with high doses or for prolonged periods, particularly in those on low salt diets.
Symptoms of electrolyte depletion are weakness, dizziness, lethargy, leg cramps, anorexia, vomiting or mental confusion.
As with other diuretics, bumetanide may cause an increase in blood uric acid.
Reversible elevations of blood urea nitrogen (BUN) and creatinine may also occur, especially in association with dehydration and in patients with renal failure.
Administration of proton pump inhibitors has been associated with development of hypomagnesaemia. Hypomagnesaemia may be exacerbated with co-administration of Burinex and particular attention to magnesium levels should be given when this combination is used.

Hypotension.

Caution should be exercised when bumetanide is used in patients with hypotension.

Allergy to sulphonamides.

Patients allergic to sulphonamides may also exhibit hypersensitivity to bumetanide.

Lactose intolerance.

Burinex tablets contain lactose as an excipient. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Glucose metabolism.

Studies in normal subjects receiving Burinex revealed no adverse effects on glucose tolerance, plasma insulin, glucagon and growth hormone levels, but the possibility of an effect on glucose metabolism exists. Periodic determinations of urine and blood glucose should be made, particularly in patients with diabetes or suspected latent diabetes.

Genito-urinary conditions.

Bumetanide should be used with caution in patients with potential obstruction of the urinary tract. Bumetanide should be used with care in patients with prostatic hypertrophy or impairment of micturition.

Use by athletes.

Bumetanide found in urine by doping test is cause for disqualification of athletes.

Use in hepatic impairment.

Caution is advised if bumetanide is to be administered to patients with severe hepatic impairment. Special caution should be used in patients with hepatic cirrhosis and ascites since sudden changes in electrolyte balance may precipitate hepatic encephalopathy and coma.

Use in renal impairment.

Caution is advised if bumetanide is to be administered to patients with severe or progressive renal impairment or with elevated urea/BUN or creatinine (see Section 4.3 Contraindications).

Use in the elderly.

No data available.

Paediatric use.

Safety and efficacy in children below the age of 18 years has not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Lithium.

Burinex should not be administered concurrently with lithium salts since diuretics can reduce lithium clearance, resulting in high serum levels of lithium.

Probenecid.

The diuretic and natriuretic effects of bumetanide are inhibited by probenecid.

Antihypertensives and medicinal products inducing postural hypotension.

Bumetanide may potentiate the effect of antihypertensive drugs including diuretics and drugs inducing postural hypotension (e.g. tricyclic antidepressants). First-dose hypotension may occur. A reduction in the dosage of the antihypertensive may be necessitated.

Digitalis glycosides.

Hypokalaemia increases the sensitivity to digitalis glycosides which may result in digitalis toxicity (nausea, vomiting and arrhythmias). Hypokalaemia may also increase the sensitivity of the myocardium to the toxic effects of digitalis preparations. Potassium level and signs of digitalis toxicity should be monitored. Potassium supplementation and lower digitalis glycoside dose should be considered.

Drugs with ototoxic potential.

Animal studies have shown bumetanide may produce ototoxicity.
The possibility of ototoxic potentiation in humans cannot be excluded.
Concomitant administration of bumetanide and ototoxic drugs such as aminoglycosides may increase ototoxic effects and should be avoided. This is of particular importance when renal function is impaired. It has been suggested that bumetanide may cause significantly less ototoxicity than frusemide.

Drugs with nephrotoxic potential.

There has been no experience on the concurrent use of Burinex with drugs known to have a nephrotoxic potential. Therefore, the simultaneous administration of these drugs should be avoided.

Anticoagulants.

Interaction studies in humans have shown Burinex to have no effect on warfarin metabolism or on plasma prothrombin activity.

Non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs inhibit the effect of bumetanide. The effects of concurrent use should be monitored (e.g. blood pressure, signs of renal failure). Diuretics, such as bumetanide, may enhance the nephrotoxicity of NSAIDs.

Non-depolarising neuromuscular blocking agents.

Hypokalaemia increases sensitivity to non-depolarising neuromuscular blocking agents.

Antiarrhythmics.

Concomitant use of bumetanide and class III antiarrhythmic drugs may increase the risk of electrolyte imbalance and subsequent cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest). Monitor electrolyte levels and arrhythmia symptoms.

Potassium depleting agents.

The potassium depleting effect of bumetanide may be increased by other potassium depleting agents.

Proton pump inhibitors.

Administration of proton pump inhibitors has been associated with development of hypomagnesaemia. Hypomagnesaemia may be exacerbated with co-administration of Burinex and particular attention to magnesium levels should be given when this combination is used (see Section 4.4 Special Warnings and Precautions for Use).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no clinical studies with bumetanide regarding fertility.
(Category C)
Bumetanide may cause harmful pharmacological effects during pregnancy, to the foetus or to the newborn child.
Thiazides, related diuretics and loop diuretics enter the foetal circulation and may cause electrolyte disturbances. Neonatal thrombocytopenia has been reported with thiazides and related diuretics. Loop diuretics like frusemide and bumetanide are also associated with this risk.
Burinex should not be used during pregnancy unless the expected benefits outweigh the potential risks.
It is not known whether bumetanide is excreted in breast milk, therefore the drug should not be used during lactation unless the expected benefits outweigh the potential risks.

4.7 Effects on Ability to Drive and Use Machines

Dizziness may occur during treatment which may impact on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

Clinical trial adverse effects.

The frequency of adverse effects is based on pool data from LEO Pharma clinical studies in the approved indication, and include 369 patients who had received bumetanide.
AEs ≥ 1% from LEO Pharma clinical studies in approved indication. See Table 1.
AEs ≥ 0.5% and < 1% from LEO Pharma clinical studies in approved indication.

Metabolism and nutrition disorders.

Gout.

Ear and labyrinth disorders.

Hearing impairment.

Respiratory, thoracic and mediastinal disorders.

Cough.

Gastrointestinal disorders.

Vomiting, diarrhoea, constipation.

Skin and subcutaneous tissue disorders.

Pruritus, urticaria (hives), rash.

Musculoskeletal and connective tissue disorders.

Arthralgia, musculoskeletal pain, pain in extremity.

General disorders and administration site conditions.

Chest pain, malaise/weakness, thirst.

Investigations.

Electrocardiogram changes.
Manifestations of the pharmacologic activity, such as increased serum creatinine and BUN, hyperuricaemia and azotemia may occur, particularly during intensive or prolonged therapy.
Blood dyscrasias (including leucopenia and thrombocytopenia), liver damage, idiosyncratic reactions and gynaecomastia have been reported.
In one study, increased serum amylase values were observed in 4 out of 11 patients. The cause of this is unknown, but could be due to subclinical pancreatitis with some extrahepatic cholestasis.
Other clinical adverse reactions, which have each occurred in approximately 0.1% of patients, are vertigo, ear discomfort, fatigue, dehydration, sweating, hyperventilation, dry mouth, upset stomach, renal failure, asterixis, itching, nipple tenderness, premature ejaculation and difficulty maintaining an erection.

Abnormal laboratory findings: hematologic, clinical chemistry and other quantitative data.

Laboratory abnormalities reported have included hyperuricaemia (in 18.4% of patients tested), hypochloremia (14.9%), hypokalaemia (14.7%), azotemia (10.6%), hyponatraemia (9.2%), increased serum creatinine (7.4%), hyperglycaemia (6.6%) and variations in phosphorus (4.5%), CO2 content (4.3%), bicarbonate (3.1%) and calcium (2.4%). Although manifestations of the pharmacologic action of bumetanide, these conditions may become more pronounced by intensive therapy.
Diuresis induced by bumetanide may also rarely be accompanied by changes in LDH (1.0%), total serum bilirubin (0.8%), serum proteins (0.7%), AST (0.6%), ALT (0.5%), alkaline phosphatase (0.4%), cholesterol (0.4%) and creatinine clearance (0.3%). Also reported have been deviations in haemoglobin (0.8%), prothrombin time (0.8%), haematocrit (0.6%), WBC (0.3%), platelet counts (0.2%) and differential counts (0.1%). Increases in urinary glucose (0.7%) and urinary protein (0.3%) have also been seen.

Post-marketing adverse effects.

The following lists the types of adverse effects that have been reported from post-marketing experience. Because these ADRs are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency.

Blood and lymphatic system disorders.

Bone marrow failure and pancytopenia, thrombocytopenia, leukopenia including neutropenia, anaemia.

Metabolism and nutrition disorders.

Electrolyte imbalance (including hypokalaemia, hyponatraemia, hypochloraemia and hyperkalaemia), dehydration, glucose metabolism disorder, hyperuricaemia and gout.

Nervous system disorders.

Dizziness (including orthostatic hypotension and vertigo), fatigue (including lethargy, somnolence, asthenia and malaise), headache, syncope.

Ear and labyrinth disorders.

Hearing disturbances.

Cardiac disorders.

Chest pain and discomfort.

Vascular disorders.

Hypotension.

Respiratory, thoracic and mediastinal disorders.

Dyspnoea, cough.

Gastrointestinal disorders.

Abdominal pain, nausea, vomiting, diarrhoea, constipation, dry mouth and thirst.

Skin and subcutaneous tissue disorders.

Rash (various types of rash reactions such as erythematous, maculo-papular and pustular have been reported), dermatitis and eczema, urticarial, pruritus, photosensitivity.

Musculoskeletal and connective tissue disorders.

Muscle spasms, pain and myalgia.

Renal and urinary disorders.

Micturition disorder, renal impairment (including renal failure).

General disorders and administration site conditions.

Oedema peripheral.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at: https://www.tga.gov.au/reporting-problems.

4.9 Overdose

In high doses and during long term treatment loop diuretics may cause electrolyte imbalance, polyuria and dehydration. Further overdose can lead to reduction of blood volume and circulatory collapse with a possibility of vascular thrombosis and embolism.

Symptoms of electrolyte imbalance.

Dry mouth, thirst, weakness, lethargy, drowsiness, confusion, gastrointestinal disturbances, restlessness, muscle pain, cramps, seizures, anorexia and vomiting.

Symptoms of dehydration.

Dizziness, postural hypotension, postural tachycardia. With large and acute fluid losses hypovolemic shock may occur, manifest as hypotension, tachycardia, peripheral vasoconstriction, and hypoperfusion with cyanosis, cold and clammy extremities, oliguria, and altered mental status.

Treatment.

Symptomatic treatment.

Adjustment of the fluid and electrolyte imbalance by careful monitoring of urine and electrolyte output and serum electrolyte levels should be carried out. General measures should be taken to restore blood volume, maintain blood pressure and correct electrolyte disturbances.
For information on the management of overdose, contact the Poison Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Burinex is a loop diuretic with a rapid onset and short duration of action. Pharmacological and clinical studies have shown that 1 mg bumetanide has a diuretic efficacy equivalent to approximately 40 mg frusemide. The major site of action is the ascending limb of the loop of Henle where it inhibits sodium reabsorption.
Reabsorption of chloride in the ascending loop is also blocked by bumetanide. The excretion of chloride is greater than that of sodium and bumetanide also increases potassium excretion in a dose related fashion. Bumetanide decreases uric acid excretion and increases serum uric acid. Bumetanide may have an additional action on the proximal tubule. This proximal tubular activity does not seem to be related to an inhibition of carbonic anhydrase.
Bumetanide does not exert an observable effect on the distal tubule. The diuretic effect of bumetanide is dose related so that patients who fail to respond to a low initial dose usually respond as the dose is increased.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

After oral administration, diuresis begins within 30 minutes with a peak effect between 1 and 2 hours. At usual doses (1-2 mg) the diuretic effect is virtually complete in 3-4 hours. After higher doses (3-5 mg) the diuretic action lasts for 4-6 hours. This short and rapid action minimises disturbance of the patient's daily routine.
Maximum plasma concentrations range between 30 nanogram/mL (80 nanomoles/L) after administration of 1 mg, to 420 nanogram/mL (1,150 nanomoles/L) after 5 mg.

Absorption.

Bumetanide is rapidly and almost completely absorbed when given orally.

Distribution.

The apparent volume of distribution is approximately 25 L indicating that the drug is not distributed into tissues to any great extent. The degree of plasma protein binding is approximately 95%.

Metabolism.

Metabolism occurs by oxidation of the N-butyl side chain to form alcohol metabolites. These are excreted in the urine and bile mainly as glucuronides.
The similar fate of bumetanide following intravenous and oral administration excludes the possibility of any significant first pass effect or degradation in the gastro-intestinal tract.

Excretion.

Approximately 75 - 80% of an administered dose is excreted in the urine within 48 hours, approximately 50% of the dose as the unchanged drug. Approximately 10% of the dose is excreted in the faeces. Bumetanide is eliminated rapidly with a plasma half-life of 60 - 90 minutes.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Maize starch, lactose monohydrate, colloidal anhydrous silica, povidone, polysorbate 80, agar, magnesium stearate, purified talc.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Keep the blister in the carton in order to protect from light.

6.5 Nature and Contents of Container

Burinex 1 mg tablets are packed in PVC/aluminium blisters.
Burinex 1 mg tablets are presented in blister packs of 100.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Bumetanide is a derivative of metanilamide, and is therefore structurally different to frusemide and the thiazides which are derivatives of sulphanilamide. It is a white odourless crystalline powder with a slightly bitter taste. It melts at approximately 230°C and at 22°C is soluble in ethanol and acetone; slightly soluble in ether and chloroform, very slightly soluble in water and practically insoluble in hydrochloric acid. It should be protected from light.
The chemical name for bumetanide is 3-n-(butylamino)-4-phenoxy-5-sulphamoyl-benzoic acid. The molecular weight is 364.41.

Chemical structure.


CAS number.

The CAS registry number is 28395-03-1.

7 Medicine Schedule (Poisons Standard)

Schedule 4. Prescription Only Medicine (S4).