Consumer medicine information

Lasix, Lasix M and Lasix High Dose

Furosemide (frusemide)

BRAND INFORMATION

Brand name

Lasix

Active ingredient

Furosemide (frusemide)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Lasix, Lasix M and Lasix High Dose.

What is in this leaflet

This leaflet answers some common questions about Lasix oral medicines (tablets, oral solution) and injections.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking this medicine against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Lasix is used for

Lasix contains furosemide, which belongs to a family of drugs called diuretics. A diuretic helps reduce the amount of excess fluid in the body by increasing the amount of urine produced.

Lasix is used to treat swelling of the ankles, feet, legs or even the brain or lungs. This swelling is called oedema and can occur in some heart, lung, liver or kidney conditions.

Lasix may be used in some patients with more serious kidney problems who may have some fluid retention.

Lasix may also be used to lower high blood pressure (which is also called hypertension).

Everyone has blood pressure. This pressure helps move your blood around your body. Your blood pressure may vary at different times of the day, depending on how busy or worried you are. You have hypertension (high blood pressure) when your blood pressure stays higher than is needed, even when you are calm and relaxed.

If high blood pressure is not treated it can lead to serious health problems, including stroke, heart disease and kidney failure.

Lasix may be taken alone or in combination with other medicines to treat your condition.

Your doctor may have prescribed Lasix for another purpose.

Ask your doctor if you have any questions about why it has been prescribed for you.

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

This medicine is not addictive.

Before you take it

When you must not take it

Do not take Lasix if you have:

  • certain liver and kidney problems
  • no production or no passing of urine
  • low blood pressure (hypotension)
  • low sodium levels in your blood
  • low potassium levels in your blood
  • dehydration
  • jaundice or history of jaundice in newborns or infants
  • hepatic coma or precoma

Do not take Lasix if you are allergic to:

  • this medicine or any of the ingredients listed at the end of this leaflet
  • medicines called sulfonamides (eg. some types of antibiotics which are also referred to as 'sulfur antibiotics') or sulfonylureas which are medicines which can be used to treat diabetes

Some symptoms of an allergic reaction include skin rash, itching, shortness of breath or swelling of the face, lips or tongue, which may cause difficulty in swallowing or breathing.

Do not take Lasix if you are pregnant.

Do not take Lasix if you are breast-feeding or planning to breast-feed. The active drug, furosemide, passes into breast milk and there is a possibility your baby may be affected.

Do not take it after the expiry date (EXP) printed on the pack. If you take it after the expiry date has passed, it may not work as well.

Do not take Lasix if the packaging is torn or shows signs of tampering.

Before you start to take it

Tell your doctor if you have allergies to:

  • any of the ingredients listed at the end of this leaflet
  • any other medicines called sulfonamides or sulfonylureas
  • any other substances, such as foods, preservatives or dyes.

Tell your doctor if you are pregnant or intend to become pregnant. Like most medicines of this kind, Lasix is not recommended to be used during pregnancy. If there is a need to consider Lasix during your pregnancy, your doctor will discuss the risks and benefits of taking it if you are pregnant.

Tell your doctor if you are breast-feeding or planning to breast-feed. Lasix passes into breast milk and there is a possibility your baby may be affected. Your doctor will discuss the risks and benefits of taking it if you are breast-feeding or planning to breast-feed.

Tell your doctor if you have or have had any medical conditions, especially the following:

  • liver problems
  • kidney problems
  • heart problems
  • high cholesterol levels
  • asthma
  • diabetes
  • gout, a disease with painful, swollen joints
  • passing less urine than is normal for you
  • difficulty passing urine
  • no production or no passing of urine
  • prostate problems
  • Systemic Lupus Erythematosus (SLE), a disease affecting the skin, joints and kidneys

Tell your doctor if you are on a salt restricted diet.

If you have not told your doctor about any of the above, tell them before you take Lasix.

Taking other medicines

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

Some medicines should not be taken with Lasix. This includes large amounts of laxatives.

Some medicines may interfere with Lasix. These include:

  • certain other fluid tablets or diuretic medicines
  • medicines used to treat high blood pressure and some other heart conditions, especially ACE inhibitors or angiotensin receptor antagonists
  • digoxin and other medicines used to treat heart failure
  • non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin, medicines used to relieve pain, swelling and other symptoms of inflammation, including arthritis
  • methotrexate, a medicine used to treat arthritis and some types of cancer
  • probenecid, a medicine used to treat gout
  • medicines used to relax muscles before or during surgery
  • lithium, a medicine used to treat mood swings and some types of depression
  • medicines used in emergency situations such as adrenaline (epinephrine) and noradrenaline (norepinephrine)
  • cisplatin, a medicine used to treat cancer
  • theophylline, a medicine used to treat asthma
  • certain antibiotics, especially cephalosporins and aminoglycosides
  • amphotericin B (amphotericin), a medicine used to treat fungal infections
  • barbiturates, medicine used to treat epilepsy, to produce calmness, or to help you sleep
  • narcotic/strong pain killers such as codeine and morphine
  • insulin and tablets used to treat diabetes
  • sucralfate, a medicine used to treat stomach ulcers
  • anticonvulsant medicines such as chloral hydrate or phenytoin
  • corticosteroids such as cortisone, prednisone or dexamethasone
  • medicines used to treat thyroid conditions
  • risperidone, an antipsychotic medication used to schizophrenia
  • medicines used during scans to see the images of your body

These medicines may be affected by Lasix, or may affect how well it works. You may need to use different amounts of your medicine, or take different medicines. Your doctor or pharmacist will advise you.

You should not eat large amounts of liquorice when you are taking Lasix.

Your doctor or pharmacist has more information on medicines to be careful with or to avoid while taking Lasix.

How to take it

How much to take

Follow the directions given to you by your doctor and pharmacist carefully. These directions may differ from the information contained in this leaflet.

Ask your doctor or pharmacist if you are unsure of the correct dose for you. They will tell you exactly how much to take.

Follow the instructions they give you. If you take the wrong dose, Lasix may not work as well and your problem may not improve.

How to take it

Tablets or oral solution:

Take Lasix tablets with a glass of water.

You can take Lasix oral solution with water.

Injections:
Lasix injections are normally administered to you by doctors or nurses in hospital.

When to take it

Tablets or oral solution:

Lasix tablets or oral solution are usually taken once or twice a day.

Take Lasix tablets or oral solution on an empty stomach. For example, one hour before food or two hours after food. Food can interfere with their absorption.

Take Lasix tablets or oral solution at about the same time each day unless your doctor tells you otherwise. Taking your medicine at the same time each day will have the best effect. It will also help you remember when to take the medicine.

If your doctor prescribes Lasix tablets or oral solution to be taken once a day, it is best done in the morning, for example, before breakfast.

If you are taking Lasix tablets or oral solution more than once a day, take your first dose immediately before breakfast and take your last dose around 2:00 pm (on an empty stomach), unless your doctor tells you otherwise. Lasix may increase the amount of urine you pass, it will also increase the number of times you need to go to the toilet. By taking your last dose around 2:00 pm, there may be less chance that your sleep is disturbed.

Injections:

Lasix Injections are normally given by doctors or nurses in hospital.

If you are not sure when to receive it, ask your doctor or pharmacist.

How long to take it

Oedema:

Continue taking your medicine for as long as your doctor tells you.

The medicine helps control your condition and lowers the fluid build up in your body.

Hypertension:

Continue taking your medicine for as long as your doctor tells you.

The medicine helps control your blood pressure, but it does not cure it. Continue taking the medicine until your doctor tells you to stop.

Ask your doctor or pharmacist if you are not sure how long to take the medicine for.

If you forget to take it

Do not try to make up for missed doses by taking more than one dose at a time. This may increase the chance of getting an unwanted side effect.

If it is almost time for your next dose, skip the dose you missed and take the next dose when you are meant to.

If there is still a long time to go before your next dose, take it as soon as you remember, and then go back to taking it as you would normally.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering when to take your medicine, ask your pharmacist for hints.

If you take too much (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (telephone Australia 13 11 26 or New Zealand 0800 POISON or 0800 764766), or go to Accident and Emergency at your nearest hospital, if you think you or anyone else may have taken too much Lasix.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much Lasix, you may feel confused, dehydrated, dizzy or you may pass excessive urine.

While you are using it

Things you must do

Tell all the doctors, dentists and pharmacists who are treating you that you are taking Lasix.

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

If you plan to have a surgery that needs a general anaesthetic, tell your doctor or dentist that you are taking this medicine. Your blood pressure may drop suddenly.

If you become pregnant while you are taking this medicine, tell your doctor or pharmacist immediately.

Tell your doctor if you have excessive vomiting or diarrhoea while taking Lasix or if you experience any of the following symptoms:

  • dry mouth or thirst
  • fainting
  • weakness, tiredness or drowsiness
  • muscle pain or cramps
  • fast heart beat
  • passing less urine than normal

If you experience these symptoms, you may be dehydrated because you are losing too much water.

Make sure you drink enough water during any exercise and during hot weather when you are taking Lasix, especially if you sweat a lot. If you do not drink enough water while taking Lasix, you may feel faint or light-headed or sick. This is because your blood pressure is dropping suddenly and you are dehydrating. If you continue to feel unwell, tell your doctor.

If you are about to have any blood tests, tell your doctor that you are taking Lasix. There may be some interference with the results of these tests.

If you are taking Lasix to treat high blood pressure, make sure you have your blood pressure checked when your doctor says to make sure Lasix is working properly.

Things you must not do

Do not give this medicine to anyone else, even if they have the same condition as you.

Do not use this medicine to treat any other complaints unless your doctor tells you to.

Do not stop taking Lasix, or change the dosage, without checking with your doctor.

Things to be careful of

If you feel light-headed, dizzy or faint, get up slowly when getting out of bed or standing up. You may feel light-headed or dizzy when you begin to take Lasix. This is because your blood pressure is falling suddenly. Standing up slowly, especially when you get up from beds or chairs, will help your body get used to the change in position and blood pressure. If this problem continues or gets worse, talk to your doctor.

Be careful driving or operating machinery until you know how Lasix affects you. Diuretic medicines may cause dizziness or light-headedness in some people. Make sure you know how you react to your medicine before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or light-headed.

If this occurs do not drive.

If you drink alcohol or take strong painkillers, dizziness or light-headedness may be worse.

The effects of alcohol could be made worse while taking Lasix. It is not recommended that you drink alcohol while taking Lasix.

Lasix oral solution contains ethanol (alcohol) 0.5g per 5ml dose, which is equivalent to 12.7ml of beer or 5.3ml of wine per 5ml dose.

If you are taking Lasix for a long period of time, you should check with your doctor to determine whether or not you should eat more potassium-containing foods or take potassium supplements. However, increasing the amount of potassium in your diet may not be necessary and could be harmful. Check with your doctor.

Lasix may cause your skin to become more sensitive to the sun. If this happens you should take care to wear protective clothing including a hat and sun block when you are outside.

Things that may help your condition

Some self-help measures suggested below may help your condition.

  • Alcohol - your doctor may advise you to limit your alcohol intake
  • diet - eat a healthy diet which includes plenty of fresh vegetables, fruit, bread, cereals and fish. Also eat less fat and sugar
  • exercise - regular exercise helps reduce blood pressure and helps the heart get fitter, but it is important not to overdo it. Walking is a good exercise, but try to find a route that is fairly flat. Before starting any exercise, ask your doctor about the best kind of program for you
  • salt - if you have high blood pressure, your doctor may advise you to watch the amount of salt in your diet. To reduce your salt intake you should avoid using salt in cooking or at the table
  • smoking - your doctor may advise you to stop smoking or at least to cut it down
  • weight - your doctor may suggest that you lose some weight to help lower your blood pressure and help lessen the amount of work your heart has to do. Some people may need a dietician's help to lose weight.

Talk to your doctor or pharmacist about these measures and for more information.

Side effects

All medicines have some unwanted side effects. Sometimes they are serious, but most of the time they are not. Your doctor has weighed the risks of using this medicine against the benefits they expect it will have for you.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Lasix.

Lasix helps most people with high blood pressure or fluid retention, but it may have unwanted side effects in a few people.

Tell your doctor if you notice any of the following and they worry you:

  • very dry mouth or unusual thirst
  • weight loss
  • weakness or tiredness
  • numbness or tingling in the hands and/or feet
  • calf muscle spasms
  • muscle pains or cramps
  • restlessness
  • drowsiness or a lack of energy
  • dizziness or light-headedness
  • headache
  • fever
  • vomiting or nausea
  • diarrhoea
  • blurred or impaired vision
  • unusual bleeding or bruising under the skin
  • ringing or buzzing in the ears
  • confusion

These are more common side effects of Lasix. Mostly they are mild or short-lived.

Tell your doctor as soon as possible if you notice any of the following:

  • irregular or fast heart beat
  • passing less urine than is normal for you
  • severe stomach pain, often with nausea or vomiting
  • severe dizziness or a spinning sensation
  • increased sensitivity to sunlight
  • flaking or peeling of the skin
  • symptoms of anaemia such as tiredness, being short of breath when exercising, dizziness and looking pale
  • frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • bleeding or bruising more easily than normal, nose bleeds
  • loss of control of your bladder or bowels (incontinence)
  • gout, a disease with painful, swollen joints
  • deafness or ringing in the ears

These may be serious side effects of Lasix. You may need urgent medical attention. Serious side effects are uncommon.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • sudden signs of allergy such as rash, itching or hives (pinkish, itchy raised areas) on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing
  • chest pain
  • fainting or having a rapid, weak pulse
  • lockjaw
  • red, often itchy spots similar to the rash seen with measles which starts on the limbs and sometimes on the face and body. The spots may blister and may progress to form raised red, pale-centred marks. Those affected may have fever, sore throat, headache with or without diarrhoea
  • yellowing of the skin and/or eyes (jaundice)

These are serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may occur in some people.

Ask your doctor or pharmacist to answer any questions you may have.

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 in Australia or in New Zealand at https://nzphvc.otago.ac.nz/reporting.

By reporting side effects, you can help provide more information on the safety of this medicine.

After using it

If you have any queries about any aspect of your medicine, or any questions regarding the information in this leaflet, discuss them with your doctor or pharmacist.

Storage

Keep your Lasix tablets or oral solution in the bottle until it is time to take them. If you store your Lasix tablets or oral solution out of the container they may not keep well.

Keep your Lasix tablets or oral solution in a cool dry place where the temperature stays below 25°C.

Do not store Lasix or any other medicine in the bathroom, near a sink, or on a windowsill.

Do not leave it in the car. Heat and damp can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Lasix injection is usually stored in the pharmacy or on the ward. The injection is kept in a cool dry place, protected from light, where the temperature stays below 25°C.

Disposal

If your doctor tells you to stop taking Lasix or the medicine has passed its expiry date, ask your pharmacist what to do with any that is left over.

Return any unused medicine to your pharmacist.

Product description

What it looks like

Lasix M 20 mg tablets: white round tablets, marked with "DLF" on one side. These are supplied in bottles of 50 tablets.

Lasix 40 mg tablets: yellow round tablets, marked with "Lasix" and "40" on one side and the Hoechst logo on the other side. These are supplied in bottles of 100 tablets.

Lasix oral solution: a clear, yellow liquid with the odour and taste of orange. It is supplied in a glass, amber-coloured bottle of 30 mL.

Lasix injection is a clear, colourless liquid presented in a glass, amber-coloured ampoule. It is supplied in packs of 5 ampoules of 2 mL or 4 mL solution.

Lasix High Dose injection is a clear, colourless liquid presented in a glass, amber-coloured ampoule. It is supplied in packs of 6 ampoules of 25 mL solution.

Ingredients

Active ingredient:

Lasix M 20 mg tablets contain 20 mg furosemide per tablet.

Lasix 40 mg tablets contain 40 mg furosemide per tablet.

Lasix oral solution contains 10 mg/mL furosemide (300 mg in 30 mL solution).

Lasix and Lasix High Dose injections contain 10 mg/mL furosemide (20 mg in 2 mL, 40 mg in 4 mL, or 250 mg in 25 mL ampoules)

Inactive ingredients:

Lasix M 20 mg tablets also contain maize starch, lactose monohydrate, colloidal anhydrous silica, purified talc, magnesium stearate.

Lasix 40 mg tablets also contain maize starch, lactose monohydrate, colloidal anhydrous silica, purified talc, magnesium stearate, sunset yellow FCF, quinoline yellow aluminium lake.

Lasix oral solution contains ethanol (alcohol) 0.5g per 5ml dose, which is equivalent to 12.7ml of beer or 5.3ml of wine per 5ml dose. It also contains sorbitol solution (70 per cent) (non-crystallising), glycerol, sodium hydroxide, methyl hydroxybenzoate, propyl hydroxybenzoate, quinoline yellow, sunset yellow FCF, Trusil orange flavour 10814413 (P.I. No. 106046), purified water.

Lasix injections also contain sodium chloride, sodium hydroxide and water for injections. Contains 0.16 mmol/mL of sodium.

Lasix High Dose injections also contain mannitol, sodium hydroxide and water for injections. Contains 0.03 mmol/mL of sodium.

Manufacturer/Sponsor

Distributed in Australia by:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113
Freecall: 1800 818 806
Email: [email protected]

Distributed in New Zealand by:

Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics
PO Box 62027
Sylvia Park Auckland 1644
Freecall: 0800 283 684
Email: [email protected]

Australian Register Numbers

The following products are available in Australia:

Lasix M 20 mg tablets*: AUST R 12409

Lasix 40 mg tablets*: AUST R 12406

Lasix oral solution 10 mg/ mL: AUST R 232815

Lasix 20 mg/2 mL injection*: AUST R 12404

Lasix 40 mg/4 mL injection*: AUST R 76767

Lasix High Dose 250 mg/25 mL injection: AUST R 12408

*Not available in New Zealand

The following products are available in New Zealand:

Lasix oral solution 10 mg/ mL

Lasix High Dose 250 mg/25 mL injection

This leaflet was prepared in January 2024

lasix-ccdsv12-cmiv19-09jan24

® Registered Trademark

Published by MIMS March 2024

BRAND INFORMATION

Brand name

Lasix

Active ingredient

Furosemide (frusemide)

Schedule

S4

 

1 Name of Medicine

For oral solution and tablets: furosemide.
For injections: furosemide sodium.

2 Qualitative and Quantitative Composition

Lasix M Tablets contain 20 mg furosemide.
Lasix Tablets contain 40 mg furosemide.
Lasix Oral Solution contains 10 mg/mL furosemide.
Lasix 20 mg/2 mL injection: each 2 mL contains 20 mg furosemide as furosemide sodium. Contains 0.16 mmol/mL of sodium.
Lasix 40 mg/4 mL injection: each 4 mL contains 40 mg furosemide as furosemide sodium. Contains 0.16 mmol/mL of sodium.

Excipients with known effect.

Lasix 20 mg and 40 mg tablets contain sugars as lactose.
Lasix Oral Solution contains benzoates, sorbitol and alcohol.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Lasix M Tablets 20 mg tablets are white, round flat-faced tablets with bevelled edge debossed with "DLF" on one side and plain on the other face.
Lasix 40 mg tablets are yellow, round, flat-faced tablets with bevelled edge debossed with "LASIX" above the score line and "40" below the score line on one side, and the Hoechst logo on the other side.
Lasix Oral Solution is a clear yellow liquid.
Lasix Injections are clear colourless solutions, practically free of visible particles.

4 Clinical Particulars

4.1 Therapeutic Indications

Oedema.

Lasix is indicated in adults, infants and children for the treatment of oedema associated with congestive heart failure, cirrhosis of the liver and renal disease including the nephrotic syndrome. Lasix is particularly useful when an agent with greater diuretic potential than that of those commonly employed is desired. Parenteral therapy should be reserved for patients unable to take oral medication or for patients in emergency clinical situations.
Lasix injection is also indicated as adjunctive therapy in acute pulmonary oedema and cerebral oedema where intense and rapid onset of diuresis is desired. If gastrointestinal absorption is impaired or oral medication is not practical for any reason, Lasix is indicated by the intravenous route. Parenteral use should be replaced with oral Lasix as soon as practical.

Hypertension.

Oral Lasix may be used in adults for the treatment of hypertension alone or in combination with other antihypertensive agents. Hypertensive patients who cannot be adequately controlled with thiazides will probably also not be adequately controlled with Lasix alone.

4.2 Dose and Method of Administration

Oral administration.

Oedema. Therapy should be individualised according to patient's response. This therapy should be titrated to gain maximal therapeutic response with the minimum dose possible to maintain that diuretic response.

Adults.

The usual initial daily dose is 20 to 80 mg given as a single dose. If the diuretic response to a single dose of 20 to 80 mg is not satisfactory, increase this dose by increments of 20 to 40 mg, not sooner than 6 to 8 hours after the previous dose, until the desired diuretic effect is obtained. This individually determined dose should be given once or twice (e.g. at 8 am and 2 pm) daily. The dose of Lasix may be carefully titrated up to 400 mg/day (except in advanced renal failure) in those patients with severe clinical oedematous states. The mobilisation of oedema may be most efficiently and safely accomplished by giving Lasix on 2 to 4 consecutive days each week.
When doses exceeding 80 mg/day are given for prolonged periods, careful clinical laboratory observations are particularly advisable.

Infants and children.

The usual initial dose of oral Lasix for infants and children is 2 mg/kg bodyweight given as a single dose. If the diuretic response is not satisfactory, the dose may be increased by 1 to 2 mg/kg no sooner than 6 to 8 hours after the previous dose. Doses of greater than 6 mg/kg bodyweight are not recommended.
For maintenance therapy in infants and children, the dose should be adjusted to the minimum effective level.
Hypertension. Therapy should be individualised according to the patient's response. This therapy should be titrated to gain maximal therapeutic response with the minimum dose possible to maintain that therapeutic response.

Adults.

The usual initial daily dose of Lasix for hypertension is 80 mg, usually divided into 40 mg twice a day. Dosage should then be adjusted according to response. If response is not satisfactory, add other antihypertensive agents.
Changes in blood pressure must be carefully monitored when Lasix is used with other antihypertensive drugs, especially during initial therapy.
To prevent an excessive drop in blood pressure, the dosage of other agents should be reduced by at least 50% when Lasix is added to the regimen. As the blood pressure falls under the potentiating effect of Lasix, a further reduction in dosage or even discontinuation of other antihypertensive drugs may be necessary.

Parenteral administration.

Adults. Parenteral therapy with Lasix injection should be used only in patients unable to take oral medication or in emergency situations and should be replaced with oral therapy as soon as practical. To achieve optimum efficacy and suppress counter regulation, a continuous furosemide infusion is generally preferred to repeat bolus injections.
Intramuscular administration must be restricted to exceptional cases where neither oral nor intravenous administration are feasible. It must be noted that intramuscular injection is not suitable for the treatment of acute conditions such as pulmonary oedema.

Oedema.

The usual initial dose of Lasix is 20 to 40 mg given as a single dose, injected intramuscularly or intravenously. The intravenous dose should be given slowly (see Section 4.4 Special Warnings and Precautions for Use). Ordinarily a prompt diuresis ensues. If needed, another dose may be administered in the same manner 2 hours later, or the dose may be increased. The dose may be raised by 20 mg and given not sooner than 2 hours after the previous dose, until the desired diuretic effect has been obtained. This individually determined single dose should then be given once or twice daily.
Therapy should be individualised according to patient response to gain maximal therapeutic response and to determine the minimal dose needed to maintain that response. Close medical supervision is necessary. If the physician elects to use high dose parenteral therapy, add the Lasix to either sodium chloride injection or Lactated Ringer's injection, and administer as a controlled intravenous infusion at a rate not greater than 4 mg/min. Lasix injection is a buffered alkaline solution.

Acute pulmonary oedema.

The usual initial dose of Lasix is 40 mg injected slowly intravenously (see Section 4.4 Special Warnings and Precautions for Use). If a satisfactory response does not occur within 1 hour, the dose may be increased to 80 mg injected slowly intravenously. If necessary, additional therapy (e.g. digitalis, oxygen) may be administered concomitantly.

Cerebral oedema.

The following procedure is recommended, pending further experience:
Intravenous injection of 20 to 40 mg three times daily. A more uniform diuretic action is obtained if the same doses are infused. The rate of infusion must be determined individually in accordance with the diuretic action and the neurological findings.
Infants and children. Parenteral therapy should be used only in patients unable to take oral medication or in emergency situations and should be replaced with oral therapy as soon as practical.
The recommended dose of Lasix injection (intravenously or intramuscularly) in infants and children is 1 mg/kg bodyweight and should be given slowly under close medical supervision. If the diuretic response to the initial dose is not satisfactory, dosage may be increased by 1 mg/kg not sooner than 2 hours after the previous dose, until the desired effect has been obtained. Doses of greater than 6 mg/kg bodyweight are not recommended.
Lasix injection should be inspected visually for particulate matter and discolouration before administration. Do not use if solution is discoloured.
Although the chemical stability of diluted Lasix injection has been demonstrated for storage at 25°C for 24 hours, the diluted solution should be used as soon as practicable to reduce risk of microbiological hazard. If storage is necessary, hold the diluted solution at 2-8°C for not more than 24 hours.

4.3 Contraindications

Known hypersensitivity to furosemide or sulfonamides or any of the inactive ingredients (see Section 6.1 List of Excipients). Patients allergic to sulfonamides (e.g. sulfonamide antibiotics or sulfonylureas) may show cross sensitivity to Lasix.
Complete renal shutdown; impaired renal function or anuria. If increasing azotaemia and oliguria occur during treatment of severe progressive renal disease, discontinue furosemide.
Severe hypokalaemia (see Section 4.8 Adverse Effects (Undesirable Effects)), hyponatraemia, hypovolaemia, dehydration or hypotension must be regarded as contraindications until serum electrolytes, fluid balance and blood pressure have been restored to normal levels.
In hepatic coma or precoma and conditions producing electrolyte depletion, furosemide therapy should not be instituted until the underlying conditions have been corrected or ameliorated.
In breastfeeding or pregnant women.
Do not administer furosemide to newborns presenting jaundice or to infants with conditions which might induce hyperbilirubinaemia or kernicterus (e.g. Rhesus incompatibility, familial nonhaemolytic jaundice, etc.) because of furosemide's 'in vitro' potential to displace bilirubin from albumin.
Lasix 250 mg injection must not be used as a bolus injection. It must only be infused using volume or rate controlled infusion pumps to reduce the risk of accidental overdose.

4.4 Special Warnings and Precautions for Use

Identified precautions.

Excessive diuresis may result in dehydration and reduction in blood volume with circulatory collapse and with the possibility of vascular thrombosis and embolism, particularly in elderly patients.
Particularly careful monitoring is required in patients with gout, patients with partial obstruction of urinary outflow, in patients with hypotension or who are at particular risk from a pronounced fall in blood pressure (e.g. patients with significant stenoses of the coronary arteries or of the blood vessels supplying the brain), in patients with latent or manifest diabetes mellitus, in patients with hepatorenal syndrome or in patients with hypoproteinaemia (e.g. associated with nephrotic syndrome). Dose titration, especially in this latter case, is required.
Cases of reversible or irreversible tinnitus or hearing impairment have been reported. Usually, reports indicate that Lasix ototoxicity is associated with rapid injection or infusion, severe renal impairment, hypoproteinaemia, doses exceeding several times the usual recommended dose, or concomitant therapy with aminoglycoside antibiotics, etacrynic acid, or other ototoxic drugs. In patients with hypoproteinaemia, e.g. associated with nephrotic syndrome, the effect of Lasix may be weakened, and its ototoxicity potentiated. Cautious dose titration is required. If the physician elects to use high dose parenteral therapy, controlled intravenous infusion is advisable (for adults with normal renal function, an infusion rate not exceeding 4 mg Lasix per minute must be used; for adults with impaired renal function [creatinine > 5 mg/dL], an infusion rate of no greater than 2.5 mg per minute must be used).
Caution should be exercised when administering curare or its derivatives to patients undergoing furosemide therapy. It is also advisable to discontinue furosemide for one week prior to any elective surgery.
Caution should be exercised and the risks and benefits of combining risperidone with Lasix or other potent diuretics should be considered prior to the decision to treat. In the risperidone placebo controlled trials in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone (7.3%; mean age 89 years, range 75 to 97) compared to treatment with risperidone alone (3.1%; mean age 84 years, range 70 to 96) or furosemide alone (4.1%; mean age 80 years, range 67 to 90). Concomitant use of risperidone with other diuretics (mainly thiazide diuretics used in low doses) was not associated with similar mortality findings. No pathophysiological mechanism has been identified to explain this finding and no consistent pattern for cause of death was observed. Nevertheless, caution is advised. Irrespective of treatment, dehydration was an overall risk factor for mortality and should, therefore, be carefully avoided in elderly patients with dementia.
Rigid sodium restriction is conducive to both hyponatraemia and hypokalaemia, thus strict restriction of sodium intake is not advisable in patients receiving furosemide.
Excessive loss of potassium in patients receiving cardiac glycosides may precipitate digitalis toxicity.
During long-term therapy, a high potassium diet is recommended. Potassium supplements may be required, especially when high doses are used for prolonged periods. Particular caution with potassium is necessary when the patient is on digitalis glycosides, potassium depleting steroids or in the case of infants and children. Potassium supplementation, diminution in dose, or discontinuation of furosemide therapy may be required.
As with many other drugs, patients should be observed regularly for the possible occurrence of blood dyscrasias, liver damage, or other idiosyncratic reactions.
The possibility exists of exacerbation or activation of systemic lupus erythematosus.

Excipient warning.

Ethanol (alcohol) - Lasix oral solution contains 12.7% v/v ethanol (alcohol). The safety of ethanol at a concentration of 12.7% v/v in a medicine intended for use in children has not been established. This should be taken into consideration when deciding whether to prescribe Lasix oral solution in this age group.
The ethanol content of this formulation (0.5 g per 5 mL dose) is harmful to those suffering from alcoholism. This should also be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease, or epilepsy.
The sorbitol present in the vehicle may cause diarrhoea (especially in children) when higher doses of Lasix oral solution are given.
When Lasix is administered parenterally, a maximum injection rate of 4 mg/minute should be used to minimise the risk of ototoxicity.
Intramuscular administration of Lasix must be limited to exceptional cases where neither oral nor intravenous administration are feasible. Intramuscular administration is not suitable for acute conditions such as pulmonary oedema.

Use in hepatic impairment.

In patients with hepatic cirrhosis and ascites, initiation of therapy with Lasix is best carried out in hospital. Sudden alterations of fluid and electrolyte balance in patients with cirrhosis may precipitate hepatic coma, therefore, strict observation is necessary during the period of diuresis.

Use in renal impairment.

Furosemide should be used with care, especially in the initial stages, in patients with impairment of micturition (e.g. prostatic hypertrophy). Urinary outflow must be secured. In patients with a partial obstruction of urinary outflow (e.g. in patients with bladder emptying disorders, prostatic hyperplasia or narrowing of the urethra), increased production of urine may provoke or aggravate complaints. Thus, these patients require careful monitoring.
Patients who were at high risk for radiocontrast nephropathy treated with furosemide experienced a higher incidence of deterioration in renal function after receiving radiocontrast compared to high-risk patients who received only intravenous hydration prior to receiving radiocontrast.

Use in the elderly.

See "Identified precautions"; see Section 4.8 Adverse Effects (Undesirable Effects), Metabolism and nutritional disorders, Renal and urinary disorders, Vascular disorders.

Paediatric use.

In premature infants, there is the possible development of nephrocalcinosis/nephrolithiasis and therefore renal function must be monitored and renal ultrasonography performed. In premature infants, furosemide administered during the first weeks of life may increase the risk of persistence of Botallo's duct.
In children, urge to defecate, complaints of abdominal pain and cramping have been reported after IV furosemide. An association of these symptoms with a low serum calcium and/or a low calcium/protein ratio is possible.
Renal calcifications (from barely visible on X-ray to staghorn) have occurred in some severely premature infants treated with intravenous Lasix for oedema due to patent ductus arteriosus and hyaline membrane disease. The concurrent use of chlorothiazides has been reported to decrease hypercalciuria and to dissolve some calculi.

Effects on laboratory tests.

As with any effective diuretic, electrolyte depletion may occur during therapy, especially in patients receiving higher doses and a restricted salt intake. All patients receiving Lasix therapy should be observed for signs of fluid or electrolyte imbalance; namely hyponatraemia, hypochloraemic alkalosis, and hypokalaemia. Periodic determinations of serum electrolytes to detect a possible imbalance should be performed at appropriate intervals, as well as creatinine, blood urea and CO2 content determinations. This is particularly important when the patient is at high risk of developing electrolyte imbalances (e.g. receiving parenteral fluids) or in case of significant additional fluid loss such as vomiting, diarrhoea and intense sweating. Warning signs of an imbalance, irrespective of cause include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia, and gastrointestinal disturbances such as nausea and vomiting. Hypovolaemia or dehydration as well as any significant electrolyte and acid-base disturbances must be corrected. This may require temporary discontinuation of Lasix.
Periodic checks on urine and blood glucose should be made in diabetics and even those suspected of latent diabetes when receiving Lasix. Increases in blood glucose and alterations in glucose tolerance tests with abnormalities of the fasting and 2-hour postprandial sugar have been observed, and rare cases of precipitation of diabetes mellitus have been reported.
Lasix may lower calcium levels, and rare cases of tetany have been reported. Accordingly, periodic serum calcium levels should be obtained.
Reversible elevations of blood urea may be seen. These have been observed in association with dehydration, which should be avoided, particularly in patients with renal insufficiency.
Furosemide increases cholesterol and triglycerides short-term. It is not clear whether this effect persists long-term, however, the current evidence does not indicate this.
Asymptomatic hyperuricaemia can occur and rarely, gout may be precipitated.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Interactions with food.

Whether and to what extent the absorption of Lasix is affected by taking it with food seems to depend on the pharmaceutical formulation of Lasix. It is recommended that oral formulations of Lasix be taken on an empty stomach.

Combinations that are not recommended.

Antibiotics.

Lasix may increase the ototoxic and nephrotoxic potential of certain antibiotics (e.g. aminoglycosides and certain cephalosporins (e.g. cephaloridine)) and other ototoxic drugs, especially in the presence of impaired renal function, therefore, the simultaneous administration of these drugs is not advisable.

Anticonvulsants.

Anticonvulsants may decrease the response to furosemide. In isolated cases intravenous administration of furosemide within 24 hours of taking chloral hydrate may lead to flushing, sweating attacks, restlessness, nausea, increase in blood pressure and tachycardia. Use of furosemide concomitantly with chloral hydrate is, therefore, not recommended.

Combinations that require precautions.

Etacrynic acid or cisplatin.

Lasix should not be used concomitantly with etacrynic acid or cisplatin because of the possibility of ototoxicity. In addition, nephrotoxicity of cisplatin may be enhanced if Lasix is not given in low doses (e.g. 40 mg in patients with normal renal function) and with positive fluid balance when used to achieve forced diuresis during cisplatin treatment.

Lithium salts.

Furosemide decreases the excretion of lithium salts and may cause increased serum lithium levels, resulting in increased risk of lithium toxicity, including increased risk of cardiotoxic and neurotoxic effects of lithium. Therefore, it is recommended that lithium levels are carefully monitored in patients receiving this combination.

Sucralfate.

Oral furosemide and sucralfate must not be taken within two hours of each other because sucralfate decreases the absorption of furosemide from the intestine and, hence, reduces its effect.

Antihypertensives.

The action of other antihypertensive drugs may be potentiated by Lasix, especially in combination with ACE inhibitors. The administration of ACE inhibitors to patients pretreated with furosemide may lead to a deterioration in renal function, including renal failure, or may result in severe hypotension, especially when an angiotensin converting enzyme inhibitor (ACE inhibitor) or angiotensin II receptor antagonist is given for the first time or for the first time in an increased dose. Consideration must be given to interrupting the administration of Lasix temporarily or at least reducing the dose of Lasix for 3 days before starting treatment with, or increasing the dose of an ACE inhibitor or angiotensin II receptor antagonist.

Risperidone.

Caution should be exercised and the risks and benefits of treating a patient on risperidone with Lasix or other potent diuretics should be considered prior to the decision to use. See Section 4.4 Special Warnings and Precautions for Use, regarding increased mortality in elderly patients with dementia concomitantly receiving risperidone.

Levothyroxine sodium.

High doses of furosemide may inhibit binding of thyroid hormones to carrier proteins when administered with levothyroxine sodium, and thereby lead to an initial transient increase in free thyroid hormones, followed by an overall decrease in total thyroid hormone levels. It is recommended that thyroid hormones be monitored.

Other combination to consider.

Drugs inducing QT interval prolongation.

The effects of digitalis preparations and drugs inducing QT interval prolongation syndrome may be potentiated by changes in electrolyte concentrations (e.g. hypokalaemia, hypomagnesaemia) due to furosemide. When a cardiac glycoside is administered concurrently, it should be remembered that potassium or magnesium deficiency increases the sensitivity of the myocardium to digitalis, and may increase the toxicity of drugs which induce QT interval prolongation syndrome. When a glucocorticoid is administered during diuretic treatment, the potassium lowering effect of the steroid should be borne in mind (see Section 4.4 Special Warnings and Precautions for Use). Carbenoxolone, corticosteroids, prolonged use of laxatives or ingestion of liquorice in large amounts may also predispose a patient to hypokalaemia.

Salicylates.

Patients receiving high doses of salicylates, as in rheumatic disease, in conjunction with Lasix may experience salicylate toxicity at lower doses because of competitive renal excretory sites.

Neuromuscular blockers.

Interactions between furosemide and neuromuscular blocking agents have been reported. These appear to be dependent on the dose of furosemide and the neuromuscular blocking agent involved. Low doses of furosemide (0.1-10 microgram/kg) enhance the neuromuscular blockade of tubocurarine and succinylcholine. High doses (1-5 mg/kg) of furosemide have a tendency to antagonise the skeletal muscle relaxing effect of tubocurarine but may potentiate the action of succinylcholine. The clinical relevance of these findings is uncertain.

Amphotericin B (amphotericin).

The combination of furosemide and amphotericin B (amphotericin) may result in an excessive loss of potassium.

Noradrenaline (norepinephrine).

Lasix may decrease arterial responsiveness to noradrenaline (norepinephrine). This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.
If antihypertensive agents, diuretics or other drugs with blood pressure lowering potential are given concomitantly with Lasix, a more pronounced fall in blood pressure must be anticipated.

Non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs including acetylsalicylic acid may reduce the natriuretic and antihypertensive effects of Lasix in some patients by inhibiting prostaglandin synthesis. In patients with dehydration or pre-existing hypovolaemia, non-steroidal anti-inflammatory drugs may cause acute renal failure. Salicylate toxicity may be increased by furosemide.

Drugs eliminated by renal tubular secretion.

Phenytoin, methotrexate, probenecid and other drugs which, like furosemide, undergo significant renal tubular secretion may reduce the effect of furosemide. Conversely, furosemide may decrease renal elimination of these drugs. In the case of high dose treatment (in particular of both furosemide and the other drugs), this may lead to an increased risk of adverse effects due to furosemide or the concomitant medication.

Theophylline.

IV furosemide was shown to increase the steady-state concentration of theophylline by 20% in a small number of asthmatic patients; hence it is appropriate to measure serum theophylline levels when both drugs are given together.

Muscle relaxants.

The effects of curare type muscle relaxants or of theophylline may be increased.

Antidiabetic agents and adrenaline (epinephrine).

It should be borne in mind that the effect of antidiabetics or of pressor amines (e.g. adrenaline (epinephrine), noradrenaline (norepinephrine)) may be attenuated by furosemide (see Section 4.4 Special Warnings and Precautions for Use).

Cephalosporins.

Impairment of renal function may develop in patients receiving concurrent treatment with furosemide and high doses of certain cephalosporins. The harmful effects of nephrotoxic drugs on the kidney may be increased.

Ciclosporin.

Concomitant use of ciclosporin A and furosemide is associated with increased risk of gouty arthritis secondary to furosemide induced hyperuricemia and ciclosporin impairment of renal urate excretion.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Lasix must not be given during pregnancy unless there are compelling medical reasons. Treatment during pregnancy requires monitoring of foetal growth.
Thiazides, related diuretics and loop diuretics enter the foetal circulation and may cause electrolyte disturbances. Neonatal thrombocytopaenia has been reported with thiazides and related diuretics. Loop diuretics, like furosemide and bumetanide, are probably also associated with this risk. During the latter part of pregnancy, products of this type should only be given on sound indications, and then in the lowest effective dose. In pregnancy, furosemide must only be used in patients with a marked reduction in glomerular filtration.
 Furosemide passes into the breast milk and inhibits lactation. Women must not breastfeed if being treated with furosemide.

4.7 Effects on Ability to Drive and Use Machines

Some adverse effects (e.g. an undesirable pronounced fall in blood pressure) may impair the patient's ability to concentrate and react and therefore constitute a risk in situations where these abilities are of special importance (e.g. operating a vehicle or machinery).

4.8 Adverse Effects (Undesirable Effects)

Whenever adverse reactions are moderate or severe, furosemide dose should be reduced or therapy withdrawn.

Metabolism and nutritional disorders.

As with other diuretics, electrolytes and water balance may be disturbed during therapy with furosemide, especially in patients receiving high doses for a prolonged period. The serum potassium concentration may decrease, especially at the commencement of treatment (owing to the earlier onset of action of furosemide).
Excessive diuresis may give rise, especially in elderly patients and children, to circulatory disturbances such as headache, dizziness, dry mouth or visual impairment, as symptoms of hypovolaemia. In extreme cases, hypovolaemia and dehydration may lead to hypotension, circulatory collapse and in elderly patients in particular, thrombophilia. However, with individualised dosage, acute haemodynamic reactions are generally not to be expected, although diuresis sets in rapidly.
All saluretics may cause hypokalaemia, mainly in cases of low potassium diet, vomiting or chronic diarrhoea.
Factors such as underlying diseases (liver cirrhosis, cardiac failure), concomitant medication (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions) or nutritional inadequacies (excessive restriction of salt intake), may lead to sodium (hyponatremia), chloride (hypochloremia), or other electrolyte or fluid deficiencies which may produce a fall in orthostatic blood pressure, calf muscle spasms, anorexia, weakness, dizziness, drowsiness, apathy, vomiting and confusion.
Furosemide may lower the serum calcium level (hypocalcemia) which may trigger a state of increased neuromuscular irritability. Furosemide may cause a rise in serum cholesterol and triglyceride.
Hypomagnesaemia and, in rare cases, tetany or cardiac arrhythmias have been observed as a consequence of increased renal magnesium loss.
Treatment with Lasix may lead to transitory increases in urine volume, blood creatinine and urea levels. Serum levels of uric acid (hyperuricaemia) may increase and attacks of gout may occur.
Pre-existing metabolic alkalosis (e.g. due to decompensated liver cirrhosis) may be aggravated during furosemide treatment. Metabolic alkalosis has been reported with furosemide use.
Treatment with furosemide has occasionally caused reduced glucose tolerance and deterioration in cases of manifest diabetes, or made latent diabetes manifest.
Pseudo-Bartter syndrome in the context of misuse and/or long-term use of furosemide has been reported.
Very common: electrolyte disturbances (including symptomatic), dehydration and hypovolaemia especially in elderly patients, increased blood creatinine, increased blood triglycerides.
Common: hyponatremia, hypochloremia, hypokalaemia, blood cholesterol increased, blood uric acid increased and attacks of gout, urine volume increased.
Uncommon: impaired glucose tolerance. Latent diabetes mellitus may manifest.

Gastrointestinal disorders and hepato-biliary disorders.

Reactions with normal doses are uncommon with Lasix. They include anorexia, oral and gastric irritation, nausea, vomiting, cramping, diarrhoea and constipation.
In isolated cases, acute pancreatitis and increases in transaminases have been observed. Additionally, cholestasis and jaundice have been reported. Furosemide may increase the bile flow and distend the biliary tree which is already obstructed.

Central nervous system disorders.

Reactions such as dizziness, vertigo, paraesthesia, headache and blurred vision occasionally accompany Lasix induced diuresis.

Ear and labyrinth disorders.

Reversible hearing impairment and tinnitus and, rarely, permanent tinnitus and impairment of hearing have been observed, especially in patients with markedly reduced renal function or hypoproteinaemia (e.g. in nephrotic syndrome). This occurs particularly when the recommended rate of injection or infusion of 4 mg per minute (normal renal function) or 2.5 mg per minute (impaired renal function) is exceeded, or in patients who are also receiving drugs known to be ototoxic.
Cases of deafness, sometimes irreversible have been reported after oral or IV administration of furosemide.

Skin and subcutaneous tissue disorders.

Uncommon allergic reactions include dermatitis, dermatitis bullous, rashes, urticaria, pruritus, photosensitivity reactions, pemphigoid, erythema multiforme, purpura and exfoliative dermatitis. Itching may occur and rare cases of necrotising angiitis, Stevens-Johnson syndrome, toxic epidermal necrolysis. AGEP (acute generalized exanthematous pustulosis), lichenoid reactions and DRESS (drug rash with eosinophilia and systemic symptoms) has been reported with furosemide use.

Blood and the lymphatic system disorders.

Common: haemoconcentration.
Uncommon: thrombocytopenia.
The following rare adverse reactions have been reported: eosinophilia, thrombophlebitis, haemolytic or aplastic anaemia, leukopaenia and agranulocytosis.

Congenital and familial/genetic disorders.

The persistence of patent ductus arteriosus when furosemide has been administered to a premature infant during the first weeks of life has been reported.

Renal and urinary disorders.

Excessive diuresis and dehydration could cause transient elevation of creatinine and BUN and reduction of GFR. Rare cases of tubulointerstitial nephritis have been reported. In elderly men with prostatic hypertrophy, acute urinary retention with overflow incontinence may occur. Symptoms of existing conditions of obstructed micturition, such as ureterostenosis or hydronephrosis, may be triggered or aggravated by pronounced diuresis. Interstitial nephritis has also been reported with furosemide use. In premature infants, calcium salts may be deposited in the renal tissue (nephrocalcinosis/ nephrolithiasis). In patients with a partial obstruction of urinary outflow, acute retention of urine may occur. Increases in sodium and/or chloride urine levels, and renal failure has been reported with furosemide use.

Vascular disorders.

Very common (especially for intravenous infusion), orthostatic hypotension may occur and may be aggravated by alcohol, narcotics and barbiturates. Due to the possibility of side effects such as hypotension, patients' ability to drive or operate machinery may be impaired, especially at the commencement of therapy. Ischaemic complications have also been reported in elderly patients. A tendency for thromboses has been reported. If furosemide is administered to premature infants during the first weeks of life, it may increase the risk of persistence of patent ductus arteriosus.
Rare: vasculitis.
Cases of thrombosis have been reported.

Immune system disorders.

Severe anaphylactic or anaphylactoid reactions (e.g. with shock) is rare, but is acutely life-threatening if it does occur.
Cases of exacerbation or activation of systemic lupus erythematosus have been reported.

Nervous system disorders.

Common: hepatic encephalopathy in patients with hepatocellular insufficiency.
Rare: paraesthesia.
Headache, dizziness, fainting or loss of consciousness have been reported.

Musculoskeletal and connective tissue disorders.

Cases of rhabdomyolysis have been reported, often in the context of severe hypokalaemia (see Section 4.3 Contraindications).

General disorders and administration site conditions.

Rarely, fever may occur. Following intramuscular injection, local reactions such as pain may occur. Restlessness has also been reported.

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 www.tga.gov.au/reporting-problems.

4.9 Overdose

The clinical picture in acute or chronic overdose depends primarily on the extent and consequences of electrolyte and fluid loss, e.g. dehydration, blood volume reduction, hypotension, electrolyte imbalance, cardiac arrhythmias (including A-V block and ventricular fibrillation), hypokalaemia and hypochloraemic alkalosis, and extensions of its diuretic action. Symptoms of these disturbances include severe hypotension (progressing to shock), acute renal failure, thrombosis, delirious states, flaccid paralysis, apathy and confusion.
The acute toxicity of Lasix has been determined in mice, rats and dogs. In all three, the oral LD50 exceeded 1000 mg/kg bodyweight, while the intravenous LD50 ranged from 300 to 680 mg/kg. The acute intragastric toxicity in neonatal rats is 7 to 10 times that of adult rats. The concentration of Lasix in biological fluids associated with toxicity or death is not known.
No specific antidote to Lasix is known. If ingestion has only just taken place, attempts may be made to limit further systemic absorption of the active ingredient by measures such as activated charcoal.
Treatment of overdosage is supportive and consists of replacement of excessive fluid and electrolyte losses. Serum electrolytes, carbon dioxide level and blood pressure should be determined frequently. Adequate drainage must be assured in patients with urinary bladder outlet obstruction (such as prostatic hypertrophy). Haemodialysis does not accelerate furosemide elimination.
For information of the management of overdose, contact the Poisons information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Lasix is a potent diuretic. It inhibits sodium and chloride absorption in the ascending limb of Henle's loop and in both the proximal and distal tubules. The high degree of efficacy is due to this unique site of action. The action on the distal tubule is independent of any inhibitory effect on carbonic anhydrase or aldosterone.
Furosemide may promote diuresis in cases which have previously proved resistant to other diuretics.
Furosemide has no significant pharmacological effects other than on renal function.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Furosemide is rapidly absorbed from the GIT. Absorption rates in healthy subjects have been reported from 60-69% and from 43-46% in patients with endstage renal failure.
The onset of diuresis following oral administration is within 1 hour. The peak effect occurs within the first or second hour. The duration of diuretic effect is 6 to 8 hours.
The onset of diuresis following intravenous administration is within 5 minutes and somewhat later after intramuscular administration. The peak effect occurs within the first half hour. The duration of diuretic effect is approximately 2 hours.
In fasted normal men, the mean bioavailability of furosemide from Lasix tablets and Lasix oral solution is 64% and 60% respectively of that from an intravenous injection of the drug. Although furosemide is more rapidly absorbed from the oral solution (50 minutes) than from the tablet (87 minutes), peak plasma levels and area under the plasma concentration time curves do not differ significantly. Peak plasma concentrations increase with increasing dose, but times to peak do not differ among doses.

Distribution.

Furosemide is extensively bound to plasma proteins, mainly to albumin. Plasma concentrations ranging from 1 to 400 microgram/mL are 91 to 99% bound in healthy individuals. The unbound fraction averages 2.3 to 4.1% at therapeutic concentrations.

Metabolism.

Recent evidence suggests that furosemide glucuronide is the only, or at least the major, biotransformation product of furosemide in man.

Excretion.

In patients with normal renal function, approximately 80% of an intravenous or intramuscular dose is excreted in the urine within 24 hours. Urinary excretion is accomplished both by glomerular filtration and proximal tubular secretion, which accounts for roughly 66% of the ingested dose, the remainder being excreted in the faeces. A small fraction is metabolised by cleavage of the side chain.
Significantly, more furosemide is excreted in urine following the IV injection than after the tablet or oral solution. There are no significant differences between the two oral formulations in the amount of unchanged drug excreted in urine.
Furosemide has a biphasic half-life in the plasma with t1/2 ranging up to 100 minutes; t1/2 is prolonged by renal and hepatic insufficiency and in newborn infants.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Lasix M Tablets 20 mg inactive ingredients are lactose monohydrate, maize starch, colloidal anhydrous silica, purified talc and magnesium stearate.
Lasix Tablets 40 mg inactive ingredients are lactose monohydrate, maize starch, colloidal anhydrous silica, purified talc, magnesium stearate, sunset yellow FCF and quinoline yellow aluminium lake.
Lasix Oral Solution inactive ingredients are sorbitol solution (70 per cent) (non-crystallising), glycerol, sodium hydroxide, methyl hydroxybenzoate, propyl hydroxybenzoate, ethanol, quinoline yellow, sunset yellow FCF, Trusil Orange Flavour 10814413 (ARTG PI No: 106046), purified water.
Lasix 20 mg/2 mL and 40 mg/4 mL injections inactive ingredients are sodium chloride, sodium hydroxide and water for injections.

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

Tablets and oral solution.

Store below 25°C. Protect from light. Use within 8 weeks of opening.

Injections.

Store below 25°C. Protect from light. Occasionally, crystal deposits may be seen when ampoules are stored at low temperatures which dissolve on warming up to 40°C. Use within 8 weeks of opening.

6.5 Nature and Contents of Container

Lasix M Tablets 20 mg.

50s in HDPE bottles with a polypropylene closure.

Lasix Tablets 40 mg.

100s in HDPE bottles with a polypropylene closure.

Lasix Oral Solution.

30 mL glass Type III coloured bottles with a child resistant polypropylene closure.

Lasix Injections.

Amber Type I glass ampoules in packs of 5.

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

Furosemide and furosemide sodium are anthranilic acid derivatives.
Chemically, they are 4-chloro-N-furfuryl-5 sulfamoylanthranilic acid and sodium; 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid.
Furosemide and furosemide sodium are white to off-white odourless crystalline powders. They are practically insoluble in water, sparingly soluble in alcohol, freely soluble in dilute alkali solutions and insoluble in dilute acids.

Chemical structure.


CAS number.

54-31-9 furosemide.
41733-55-5 furosemide sodium.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes