Consumer medicine information

Frusemide Sandoz Tablets

Furosemide (frusemide)

BRAND INFORMATION

Brand name

Frusemide Sandoz Tablets

Active ingredient

Furosemide (frusemide)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Frusemide Sandoz Tablets.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Frusemide Sandoz.

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 risk of you taking this medicine against the benefits it is expected to 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 want to read it again.

WHAT FRUSEMIDE SANDOZ IS USED FOR

This medicine is used to reduce oedema (swelling) by removing the excess fluid from the swollen - of the ankles, feet, legs or even the brain or lungs. It is also used to treat hypertension (high blood pressure) either alone or in combination with other drugs.

It contains the active ingredient frusemide.

Frusemide belongs to a group of medicines called diuretics ("fluid tablets").

It works in your kidneys by increasing the amount of urine produced. This reduces the amount of excess fluid in the body.

Ask your doctor if you have any questions about why Frusemide Sandoz was prescribed for you.

Your doctor may have prescribed Frusemide Sandoz for another reason.

This medicine is not addictive.

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

BEFORE YOU TAKE FRUSEMIDE SANDOZ

When you must not take it

Do not take this medicine if you have an allergy to:

  • frusemide, the active ingredient or any of the inactive ingredients listed at the end of this leaflet under Product Description
  • any other similar medicines, such as diuretics
  • medicines containing sulfonamides, such as sulphur antibiotics or sulfonylureas which are medicines used to treat diabetes.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not take this medicine if you have or have had any of the following medical conditions:

  • kidney problems or have no production or passing of urine
  • liver problems
  • low blood pressure
  • low sodium or 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 breastfeed if you are taking this medicine.

The active ingredient in Frusemide Sandoz passes into breast milk and there is a possibility that your baby may be affected.

Do not give this medicine to children.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

If it has expired or is damaged, return it to your pharmacist for disposal.

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 other medicines, foods, preservatives or dyes.

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

  • a severe imbalance in your electrolytes (the salts in your body)
  • diabetes
  • asthma
  • kidney problems
  • passing less urine than is normal for you
  • difficulty passing urine
  • no production or no passing of urine
  • heart and lung problems
  • liver problems
  • gout, a disease with painful, swollen joints
  • prostate problems
  • systemic lupus erythematosus (SLE), a disease affecting the skin, joints and kidneys
  • high cholesterol levels.

If you have not told your doctor about any of the above, tell him/her before you start taking Frusemide Sandoz.

Taking other medicines

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

Some medicines and Frusemide Sandoz may interfere with each other. These include:

  • digoxin and other medicines used to treat heart failure
  • lithium, used to treat mood disorders and some types of depression
  • non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin, 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 in emergency situations such as adrenaline and noradrenaline
  • medicines used to treat high blood pressure and some other heart conditions, especially ACE inhibitors or angiotensin receptor antagonists
  • certain antibiotics, especially cephalosporin and aminoglycosides
  • medicines used to relax muscle before or during surgery
  • amphotericin, used to treat fungal infections
  • levothyroxine, used to treat hypothyroidism
  • anticonvulsant medicines used to treat epilepsy, e.g. choloral hydrate, or phenytoin
  • sucralfate or carbenoxolone, used to treat stomach ulcers
  • cisplatin, used to treat cancer
  • steroid medicines, such as cortisone, prednisone or dexamethasone
  • insulin and tablet medicines used to treat diabetes, e.g. metformin
  • fluid tablets or diuretic medicines
  • pressor amines, used in emergency situations e.g. adrenaline and noradrenaline
  • barbiturates, medicine used to treat epilepsy, to produce calmness, or to help you sleep
  • narcotics/strong pain killers such as codeine and morphine
  • theophylline, a medicine used to treat asthma
  • risperidone, an antipsychotic medication used to treat schizophrenia
  • medicines used during scans to see the images of your body.

These medicines may be affected by Frusemide Sandoz, or may affect how well it works. You may need to use different amounts of your medicine, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

HOW TO TAKE FRUSEMIDE SANDOZ

Follow all directions given to you by your doctor or pharmacist carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions, ask your doctor or pharmacist for help.

How much to take

Oedema (swelling)
The usual dose is 20mg to 80mg (a half to two tablets) given as a single dose, once or twice daily. If given twice daily, 8am and 2pm are the suggested times to take Frusemide Sandoz. In some cases, up to 400mg (ten tablets) a day may be taken. Some people may only take Frusemide Sandoz on a few days per week (i.e. two to four consecutive days).

Hypertension (high blood pressure)
The usual starting dose is 40mg (one tablet) twice daily. This will then be increased or decreased depending on the individual response to treatment. Your doctor may reduce or even cease other high blood pressure medication you may be taking.

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, Frusemide Sandoz may not work as well and your problem may not improve.

How to take it

Swallow the tablets with water on an empty stomach.

If you need to break Frusemide Sandoz, hold tablet with both hands and snap along break line.

How long to take Frusemide Sandoz

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

The dosage recommendation and duration of treatment will be determined for your specific condition by your doctor.

Do not take any more than prescribed by your doctor.

If you forget to take it

Take your dose as soon as you remember, and continue to take it as you would normally.

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

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

This may increase the chance of you getting an unwanted side effect.

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 some 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 764 766) or go to Accident and Emergency at your nearest hospital, if you think you or anyone else has taken too much Frusemide Sandoz. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Overdosage of Frusemide Sandoz can result in dehydration. Symptoms of dehydration include dizziness, excessive thirst and dry mouth, headache and visual disturbances, weakness and muscle cramps.

WHILE YOU ARE USING FRUSEMIDE SANDOZ

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Frusemide Sandoz.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine.

It may affect other medicines used during surgery.

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

If you are about to have any blood tests, tell your doctor that you are taking this medicine.

It may interfere with the results of some tests.

Keep all of your doctor's appointments so that your progress can be checked.

Your doctor may do some tests such as check your blood pressure from time to time to make sure the medicine is working and to prevent unwanted side effects.

Tell your doctor if you feel Frusemide Sandoz is not helping your condition.

Tell your doctor if you have severe vomiting or diarrhoea.

Inform your doctor if you are on a low salt diet.

The signs that you are too low in body salts include: dry mouth, thirst, muscle weakness or cramps, fainting, passing less urine than normal, drowsiness, tiredness and a fast or irregular heartbeat.

If you experience these symptoms contact your doctor immediately.

Make sure you drink enough water in hot weather and during exercise while you are taking Frusemide Sandoz, especially if you sweat a lot.

If you do not drink enough water, you may feel faint, light-headed or sick. This is because your blood pressure is dropping suddenly and you are losing too much fluid.

If you continue to feel unwell, contact your doctor.

Things you must not do

Do not take Frusemide Sandoz to treat any other complaints unless your doctor tells you to.

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

Do not stop taking your medicine or lower the dosage without checking with your doctor.

Things to be careful of

Be careful driving or operating machinery until you know how Frusemide Sandoz affects you.

This medicine may cause dizziness or light-headedness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Be careful when drinking alcohol while you are taking this medicine.

If you drink alcohol, dizziness and light-headedness may be worse.

It is not recommended that you drink alcohol while taking Frusemide Sandoz.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly.

Be careful getting up from a sitting or lying position. Dizziness, light-headedness or fainting may occur, especially when you get up quickly. Getting up slowly may help.

Avoid prolonged exposure to direct sunlight.

Frusemide Sandoz may cause your skin to become more sensitive to the sun. If this happens you should wear protective clothing including a hat and sun screen when you are outside.

If you are taking Frusemide Sandoz 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.

SIDE EFFECTS

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

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some side effects.

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

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

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

These are the more common side effects of Frusemide Sandoz. Mostly, these are mild and are short-lived.

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

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

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

If any of the following happen, stop taking Frusemide Sandoz, and 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, 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 a rapid weak pulse
  • red, often itchy spots similar to 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.
  • lockjaw
  • yellowing of the eyes or skin (jaundice).

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

Tell your doctor if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

AFTER USING FRUSEMIDE SANDOZ

Storage

Keep your medicine in the original container.

If you take it out of its original container it may not keep well.

Keep your medicine in a cool dry place where the temperature stays below 25°C. Protect from light.

Do not store Frusemide Sandoz 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 this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

PRODUCT DESCRIPTION

What it looks like

Frusemide Sandoz 40mg - round, white tablets with a score notch on one side.

Available in bottles of 100 tablets.

Ingredients

Active ingredient:

  • Frusemide Sandoz 40mg - 40mg frusemide.

Inactive ingredients:

  • microcrystalline cellulose
  • maize starch
  • sodium starch glycollate
  • lactose monohydrate
  • magnesium stearate.

This medicine does not contain sucrose, gluten, tartrazine or any other azo dyes.

Supplier

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road
Macquarie Park NSW 2113
Australia
Tel: 1800 634 500

Novartis New Zealand Limited
PO Box 99102
Newmarket, Auckland 1149
New Zealand
Tel: 0800 354 335

This leaflet was revised in June 2017

Australian Register Number

40mg tablets: AUST R 64718 (bottles)

BRAND INFORMATION

Brand name

Frusemide Sandoz Tablets

Active ingredient

Furosemide (frusemide)

Schedule

S4

 

Name of the medicine

Frusemide.

Excipients.

Maize starch, lactose monohydrate, sodium starch glycollate, microcrystalline cellulose and magnesium stearate.

Description

Chemical name: 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid. Molecular formula: C12H11ClN2O5S. Molecular weight: 330.75. CAS: 54-31-9.
Frusemide is an anthranilic acid derivative.
Frusemide is a white to off-white odourless crystalline powder. It is practically insoluble in water, sparingly soluble in alcohol, freely soluble in dilute alkali solutions and insoluble in dilute acids.
Frusemide Sandoz tablets also contain the inactive ingredients maize starch, lactose monohydrate, sodium starch glycollate, microcrystalline cellulose and magnesium stearate.

Pharmacology

Site and mode of action.

Frusemide is a potent diuretic. It inhibits sodium and chloride absorption in the ascending limb of the loop of Henle and in both the proximal and the distal tubule. 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.
Frusemide may promote diuresis in cases which have previously proved resistant to other diuretics.
Frusemide has no significant pharmacological effects other than on renal function.

Pharmacokinetics.

Absorption.

Frusemide is rapidly absorbed from the gastrointestinal tract. Absorption rates have been reported to be from 60 to 69% in healthy subjects and from 43 to 46% in patients with end stage renal failure.
The onset of diuresis following oral administration is within one hour. The peak effect occurs within the first or second hour. The duration of diuretic effect is six to eight hours.
In fasted normal men, the mean bioavailability of frusemide tablets is 64% of that from an intravenous injection of the drug. Peak plasma concentrations increase with increasing dose but times to peak do not differ among doses.

Distribution.

Frusemide 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 frusemide glucuronide is the only or at least the major biotransformation product of frusemide in humans.

Excretion.

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.
Frusemide 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.

Indications

Oedema.

Adults.

Treatment of oedema associated with congestive heart failure, cirrhosis of the liver and renal disease, including the nephrotic syndrome. Frusemide Sandoz is particularly useful when an agent with greater diuretic potential than that of those commonly employed is desired.

Hypertension.

Adults.

Frusemide Sandoz tablets 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 Frusemide Sandoz alone.

Contraindications

Known hypersensitivity to frusemide or sulfonamides or any of the inactive ingredients (see Description). Patients allergic to sulfonamides (e.g. sulfonamide antibiotics or sulfonylureas) may show cross sensitivity to frusemide.
Complete renal shutdown, impaired renal function or anuria. If increasing azotaemia and oliguria occur during treatment of severe progressive renal disease, discontinue frusemide. Severe hypokalaemia, 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, frusemide therapy should not be instituted until the underlying conditions have been corrected or ameliorated.
In breastfeeding or pregnant women.

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.
Excessive loss of potassium in patients receiving cardiac glycosides may precipitate digitalis toxicity.
In patients with hepatic cirrhosis and ascites, initiation of therapy with frusemide 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 frusemide ototoxicity is associated with severe renal impairment, hypoproteinaemia, doses exceeding several times the usual recommended dose or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid or other ototoxic drugs. In patients with hypoproteinaemia, e.g. associated with nephrotic syndrome, the effect of frusemide 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 frusemide therapy. It is also advisable to discontinue frusemide for one week prior to any elective surgery.
Caution should be exercised and the risks and benefits of combining risperidone with frusemide 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 frusemide 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 frusemide 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 frusemide.
Frusemide 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.
Symptomatic hypotension leading to dizziness, fainting or loss of consciousness can occur in patients treated with frusemide (furosemide), particularly in the elderly, patients on other medications which can cause hypotension and patients with other medical conditions that are risks for hypotension.
As with any effective diuretic, electrolyte depletion may occur during therapy with frusemide, especially in patients receiving higher doses and a restricted salt intake. All patients receiving frusemide 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, e.g. 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 frusemide.
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 or on potassium depleting steroids. Potassium supplementation, diminution in dose or discontinuation of frusemide therapy may be required.
Periodic checks on urine and blood glucose should be made in diabetic patients, and even in those suspected of having latent diabetes, who are receiving frusemide. 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.
Frusemide 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.
Frusemide 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.
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.

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).

Use in pregnancy.

(Category C)

Category C.

Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.
Frusemide 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 thrombocytopenia has been reported with thiazides and related diuretics. Loop diuretics like frusemide 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, frusemide must only be used in patients with a marked reduction in glomerular filtration.

Use in lactation.

Frusemide passes into the breast milk and inhibits lactation. Women must not breastfeed if being treated with frusemide.

Interactions with food.

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

Interactions

Combinations that are not recommended.

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

Precautions for use.

Frusemide should not be used concomitantly with ethacrynic acid or cisplatin because of the possibility of ototoxicity. In addition, nephrotoxicity of cisplatin may be enhanced if frusemide 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.
Frusemide 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.
Frusemide and sucralfate must not be taken within two hours of each other because sucralfate decreases the absorption of frusemide from the intestine and hence, reduces its effect.
The action of other antihypertensive drugs may be potentiated by frusemide, especially in combination with angiotensin converting enzyme (ACE) inhibitors. The administration of ACE inhibitors to patients pretreated with frusemide may lead to a deterioration in renal function including renal failure, or may result in severe hypotension, especially when an ACE inhibitor or angiotensin II receptor antagonist is given for the first time or for the first time in an increased dose. Therefore, consideration must be given to interrupting the administration of frusemide temporarily or at least reducing the dose of frusemide for three 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 frusemide or other potent diuretics should be considered prior to the decision to use. See Precautions regarding increased mortality in elderly patients with dementia concomitantly receiving risperidone.
High doses of frusemide 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.

To be considered.

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 frusemide. 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 Precautions).
Carbenoloxone, 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 frusemide may experience salicylate toxicity at lower doses because of competitive renal excretory sites.
Interactions between frusemide and neuromuscular blocking agents have been reported. These appear to be dependent on the dose of frusemide and the neuromuscular blocking agent involved. Low doses of frusemide (0.1 to 10 microgram/kg) enhance the neuromuscular blockade of tubocurarine and succinylcholine. High doses (1 to 5 mg/kg) of frusemide 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 frusemide and amphotericin may result in an excessive loss of potassium.
Frusemide may decrease arterial responsiveness to noradrenaline. 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 frusemide, a more pronounced fall in blood pressure must be anticipated.
Nonsteroidal anti-inflammatory drugs (NSAIDs) including acetylsalicylic acid may reduce the natriuretic and antihypertensive effects of frusemide in some patients by inhibiting prostaglandin synthesis. In patients with dehydration or pre-existing hypovolaemia, NSAIDs may cause acute renal failure. Salicylate toxicity may be increased by frusemide.
Phenytoin, methotrexate, probenecid and drugs which, like frusemide, undergo significant renal tubular secretion may attenuate the effects of frusemide. Conversely, frusemide may decrease renal elimination of these drugs. In the case of high dose treatment (in particular of both frusemide and the other drugs), this may lead to an increased risk of adverse effects due to frusemide 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 and pressor amines (e.g. adrenaline and noradrenaline) may be attenuated by frusemide (see Precautions).
Impairment of renal function may develop in patients receiving concurrent treatment with frusemide and high doses of certain cephalosporins. The harmful effects of nephrotoxic drugs on the kidney may be increased.
Concomitant use of cyclosporin A and frusemide is associated with increased risk of gouty arthritis secondary to frusemide induced hyperuricaemia and cyclosporin impairment of renal urate excretion.
Patients who were at high risk for radiocontrast nephropathy treated with frusemide 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.

Adverse Effects

Whenever adverse reactions are moderate or severe, frusemide 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 frusemide, 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 frusemide).
Excessive diuresis may give rise, especially in elderly patients and children, to circulatory disturbances, e.g. 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 Interactions with Other Medicines) or nutritional inadequacies (excessive restriction of salt intake), may lead to sodium (hyponatraemia), chloride (hypochloraemia), 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.
Frusemide may lower the serum calcium level (hypocalcaemia), which may trigger a state of increased neuromuscular irritability. Frusemide 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 frusemide 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 frusemide treatment. Metabolic alkalosis has been reported with frusemide use.
Treatment with frusemide 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 frusemide has been reported.
Very common: electrolyte disturbances (including symptomatic), dehydration and hypovolaemia especially in elderly patients, increased blood creatinine, increased blood triglycerides.
Common: hyponatraemia, hypochloraemia, 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 frusemide. 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. Frusemide 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 frusemide-induced diuresis.

Ear and labyrinth disorders.

Reversible tinnitus and hearing impairment 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 in patients who are also receiving drugs known to be ototoxic.
Cases of deafness, sometimes irreversible, have been reported after oral administration of frusemide.

Skin and subcutaneous tissue disorders.

Allergic reactions may occur in the form of dermatitis including rash, itching, urticaria, pruritus and rare cases of exfoliative dermatitis, necrotising angitis, bullous lesions or eruptions, pemphigoid, Steven-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme and purpura. Also, photosensitivity reactions have been reported. AGEP (acute generalized exanthematous pustulosis) and DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) have been reported with frusemide 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.

Renal and urinary disorders.

Excessive diuresis and dehydration could cause transient elevation of creatinine and BUN and reduction of glomerular filtration rate (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 frusemide use. 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 frusemide use.

Vascular disorders.

Very common, orthostatic hypotension may occur and may be aggravated by alcohol, narcotics and barbiturates. Due to the possibility of side effects such as hypotension, the patient's 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.
Rare: vasculitis.
Cases of thrombosis have been reported.

Immune system disorders.

Severe anaphylactic or anaphylactoid reactions (e.g. with shock) are rare, but are 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 Contraindications).

General disorders.

Rarely, fever may occur. Restlessness has also been reported.

Dosage and 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 six to eight 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 Frusemide Sandoz 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 Frusemide Sandoz on two to four consecutive days each week.
When doses exceeding 80 mg/day are given for prolonged periods, careful clinical laboratory observations are particularly advisable.

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

Overdosage

Contact the Poisons Information Centre on 131 126 for advice on management of overdose.

Symptoms.

The clinical picture in acute or chronic overdose depends 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 frusemide has been determined in mice, rats and dogs. In all three, the oral LD50 exceeded 1,000 mg/kg bodyweight. The acute intragastric toxicity in neonatal rats is seven to ten times that of adult rats. The concentration of frusemide in biological fluids associated with toxicity or death is not known.

Treatment.

No specific antidote to frusemide 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 gastric lavage or those designed to reduce absorption (e.g. 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 frusemide elimination.

Presentation

Tablets, 40 mg (white, round, scored on one side): 100's (bottle).

Storage

Store below 25°C. Protect from light.

Poison Schedule

S4.