Consumer medicine information

Uremide

Furosemide (frusemide)

BRAND INFORMATION

Brand name

Uremide

Active ingredient

Furosemide (frusemide)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Uremide.

What is in this leaflet

This leaflet answers some common questions about UREMIDE.

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

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

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

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

What UREMIDE is used for

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

UREMIDE 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

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

UREMIDE 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 be different 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.

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

Your doctor may have prescribed UREMIDE for another purpose.

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

UREMIDE is only available with a doctor's prescription.

This medicine is not addictive.

Before you take UREMIDE

When you must not take it

Do not take UREMIDE if you are allergic to:

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

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 UREMIDE 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 this medicine if you are pregnant. It may affect your developing baby if you take it during pregnancy.

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

Do not take this medicine 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 UREMIDE if the packaging is torn or shows signs of tampering.

If you are not sure whether you should start taking this medicine, talk to your doctor.

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, UREMIDE is not recommended to be used during pregnancy. If there is a need to consider UREMIDE 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 breastfeed. UREMIDE 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.

Restricting your salt intake may lead to increased side effects. If you have not told your doctor about any of the above, tell them before you start taking UREMIDE.

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 UREMIDE. This includes large amounts of laxatives.

Some medicines may interfere with UREMIDE. 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 medicines 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 UREMIDE, 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 UREMIDE.

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

How to take UREMIDE

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.

Your doctor will tell you how many tablets you need to take each day and when to take them. This depends on your condition and how you respond to this medicine.

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, UREMIDE may not work as well and your problem may not improve.

How to take it

Swallow the tablets with a glass of water.

When to take it

UREMIDE is usually taken once or twice a day.

Take UREMIDE on an empty stomach. For example, 1 hour before food or 2 hours after food. Food can interfere with the absorption of UREMIDE.

Take UREMIDE 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 UREMIDE to be taken once a day, it is best done in the morning, for example, before breakfast.

If you are taking UREMIDE 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. UREMIDE 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.

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 the missed dose 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 take too much (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have taken too much UREMIDE.

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

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

While you are taking UREMIDE

Things you must do

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

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

If you plan to have a surgery that needs a general anaesthetic, tell your doctor or dentist that you are taking UREMIDE. 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 UREMIDE or if you experience any of the following symptoms:

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

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 UREMIDE, especially if you sweat a lot. If you do not drink enough water while taking UREMIDE, you may feel faint or lightheaded or sick. This is because your blood pressure is dropping suddenly and you are becoming dehydrated. 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 UREMIDE. There may be some interference with the results of these tests.

If you are taking UREMIDE to treat high blood pressure, make sure you have your blood pressure checked when your doctor says to make sure UREMIDE 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 your medicine, 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 UREMIDE. 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 UREMIDE 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 lightheaded.

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 UREMIDE. It is not recommended that you drink alcohol while taking UREMIDE.

If you are taking UREMIDE 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.

UREMIDE 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 UREMIDE.

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

These may be serious side effects of UREMIDE. 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 taking UREMIDE

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 tablets in the pack until it is time to take them. If you take the tablets out of the pack they may not keep well.

Keep your tablets in a cool dry place where the temperature stays below 30°C.

Do not store UREMIDE or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness 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.

Disposal

If your doctor tells you to stop taking UREMIDE, 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

UREMIDE is a 8 mm flat bevelled edged white tablet marked FE/40 on one side, alpha symbol on the reverse.

Each pack contains 30 or 100 tablets.

Ingredients

The active ingredient in UREMIDE is furosemide. Each UREMIDE tablet contains 40 mg of furosemide.

The tablets also contain:

  • lactose monohydrate
  • maize starch
  • pregelatinised maize starch
  • magnesium stearate.

UREMIDE tablets contain sugars as lactose and trace quantities of sulfites.

Manufacturer

UREMIDE is made in Australia by:

Alphapharm Pty Ltd trading as Viatris
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

This leaflet was prepared in September 2023.

Australian registration numbers:

AUST R 17704

UREMIDE® is a Viatris company trade mark

UREMIDE_cmi\Sep23/00

Published by MIMS October 2023

BRAND INFORMATION

Brand name

Uremide

Active ingredient

Furosemide (frusemide)

Schedule

S4

 

1 Name of Medicine

Furosemide.

2 Qualitative and Quantitative Composition

Each Uremide tablet contains 40 mg of furosemide as the active ingredient.

Excipients with known effect.

Sugars as lactose and trace quantities of sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Uremide 40 mg tablet: 8 mm flat bevelled edged white tablet marked FE/40 on one side, alpha symbol on the reverse.

4 Clinical Particulars

4.1 Therapeutic Indications

Oedema.

Furosemide 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. Furosemide is particularly useful when an agent with greater diuretic potential than that of those commonly employed is desired.

Hypertension.

Furosemide 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 furosemide alone.

4.2 Dose and Method of 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 furosemide 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 furosemide 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 furosemide 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 furosemide 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 furosemide 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 furosemide is added to the regimen. As the blood pressure falls under the potentiating effect of furosemide, a further reduction in dosage or even discontinuation of other antihypertensive drugs may be necessary.

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 furosemide.
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 non-haemolytic jaundice etc.) because of furosemide's in vitro potential to displace bilirubin from albumin.

4.4 Special Warnings and Precautions for Use

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.
Excessive loss of potassium in patients receiving cardiac glycosides may precipitate digitalis toxicity.
In patients with hepatic cirrhosis and ascites, initiation of therapy with furosemide 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.
Cases of reversible or irreversible tinnitus or hearing impairment have been reported. Usually, reports indicate that furosemide 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 furosemide may be weakened and its ototoxicity potentiated. Cautious dose titration is required.
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 furosemide 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.
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.
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. 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.
As with any effective diuretic, electrolyte depletion may occur during treatment with furosemide, especially in patients receiving higher doses and a restricted salt intake. All patients receiving furosemide 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 furosemide.
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.
Periodic checks on urine and blood glucose should be made in diabetics and even those suspected of latent diabetes when receiving furosemide. Increases in blood glucose and alterations in glucose tolerance tests with abnormalities of the fasting and 2 hour post prandial sugar have been observed, and rare cases of precipitation of diabetes mellitus have been reported.
Furosemide 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.
As with many other drugs, patients should be observed regularly for the possible occurrence of blood dyscrasias, liver damage, or other idiosyncratic reactions.
Renal calcifications (from barely visible on X-ray to staghorn) have occurred in some severely premature infants treated with intravenous furosemide 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.
The possibility exists of exacerbation or activation of systemic lupus erythematosus.
Asymptomatic hyperuricaemia can occur and rarely, gout may be precipitated.

Driving a vehicle or performing other potentially hazardous tasks.

See Section 4.7 Effects on Ability to Drive and Use Machines.

Interactions with food.

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

Use in the elderly.

No data available.

Paediatric use.

In children, urge to defecate, complaints of abdominal pain and cramping have been reported after intravenous furosemide. An association of these symptoms with a low serum calcium and/or a low calcium/ protein ratio is possible.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Combinations that are not recommended.

Furosemide 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 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.

Precautions for use.

Furosemide 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 furosemide 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.
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.
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.
The action of other antihypertensive drugs may be potentiated by furosemide, especially in combination with ACE inhibitors. The administration of ACE inhibitors to patients pre-treated 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 furosemide temporarily or at least reducing the dose of furosemide for 3 days before starting treatment with or increasing the dose of an ACE inhibitor or angiotensin II receptor antagonist.
Caution should be exercised and the risks and benefits of treating a patient on risperidone with furosemide 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.
High doses of furosemide may inhibit binding of thyroid hormones to carrier proteins when administered with levothyroxine, 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.

Take into account.

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.
Patients receiving high doses of salicylates, as in rheumatic disease, in conjunction with furosemide, may experience salicylate toxicity at lower doses because of competitive renal excretory sites.
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 to 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.
The combination of furosemide and amphotericin B (amphotericin) may result in an excessive loss of potassium.
Furosemide 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 furosemide, a more pronounced fall in blood pressure must be anticipated.
Nonsteroidal anti-inflammatory drugs including acetylsalicylic acid may reduce the natriuretic and antihypertensive effects of furosemide in some patients by inhibiting prostaglandin synthesis. In patients with dehydration or pre-existing hypovolaemia, nonsteroidal anti-inflammatory drugs may cause acute renal failure. Salicylate toxicity may be increased by furosemide.
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.
The effects of curare-type muscle relaxants or of theophylline may be increased.
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).
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.
Concomitant use of ciclosporine A and furosemide is associated with increased risk of gouty arthritis secondary to furosemide-induced hyperuricemia and ciclosporine impairment of renal urate excretion.
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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.
Furosemide 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 (hyponatraemia), 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 (hypocalcaemia) 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 furosemide 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 hepatobiliary disorders.

Reactions with normal doses are uncommon with furosemide. 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 furosemide 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. 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 generalised exanthematous pustulosis), lichenoid reactions and DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) have 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 uretostenosis 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 furosemide 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 furosemide in biological fluids associated with toxicity or death is not known.
No specific antidote to furosemide 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.

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 on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Furosemide is an anthranilic acid derivative. Furosemide 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 gastrointestinal tract. Absorption rates in healthy subjects have been reported from 60 to 69%, and from 43 to 46% in patients with end stage 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. Peak plasma concentrations of furosemide 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.
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

Lactose monohydrate, maize starch, pregelatinised maize starch and magnesium stearate.

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 30°C.

6.5 Nature and Contents of Container

Container type: HDPE bottle with child resistant cap.
Pack sizes: 30, 50*, 60*, 90*, 100, 1000*.
*Some strengths, pack sizes and/or pack types may not be marketed.

Australian register of therapeutic goods (ARTG).

AUST R 17704 - Uremide 40 furosemide (frusemide) 40 mg tablet bottle.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

Chemical name: 4-chloro-N-furfuryl-5-sulfamoylanthranilic.
Structural formula:
Molecular formula: C12H11ClN2O5S. Molecular weight: 330.74.

CAS number.

54-31-9.
Furosemide is a white or almost white, odourless crystalline powder. It is practically insoluble in water, sparingly soluble in ethanol (96%), freely soluble in dilute aqueous solutions of the alkali hydroxides.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes