FUROSEMIDE 10 MG / ML SOLUTION FOR INJECTION OR INFUSION - patient leaflet, side effects, dosage

1. what furosemide injection is and what it is used for

Furosemide is one of a group of medicines called diuretics. A diuretic helps get rid of excess fluid in the body by causing more urine to be passed. Furosemide Injection is used to remove excess fluid from the body. It may also be used when your kidneys are not functioning properly and not producing normal amounts of urine.

2. what you need to know before you are given furosemide injectionyou should not be given furosemide if: you are allergic to furosemide or any of the other ingredients of this medicine (listed in section 6). signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue

• you are allergic to amiloride, sulfonamides or sulphonamide derivatives, such as sulfadiazine or cotrimoxazole
• you have a low blood volume or are dehydrated (with or without accompanying low blood pressure).
• you have too little potassium or sodium in your blood (shown in blood test)
• you have severe liver problems (cirrhosis)
• you have already taken Furosemide in the past to treat failure to pass urine or kidney failure or if you have kidney failure that is due to medicines or chemicals that are prone to cause kidney or liver damage or if you have kidney failure due to underlying liver disorders
• you are not passing any water (urine) or you have been told by a doctor that you have kidney failure. In some types of kidney failure, it is still okay to have this medicine. Your doctor will be able to decide
• you have an illness called ‘Addison’s Di­sease’. This can make you feel tired and weak or if you are taking digitalis, used to treat heart problems
• you have a disease called porphyria characterized by abdominal pain, vomiting or muscle weakness
• you are breast feeding

Talk to your doctor, pharmacist or nurse before you are given Furosemide Injection:

• if you are elderly, if you are on other medications which can cause a drop in blood pressure and if you have other medical conditions that are risks for a drop in blood pressure
• if you have Low blood pressure or feel dizzy when you stand up
• if you feel dizzy or dehydrated. This can happen if you have lost a lot of water through being sick, having diarrhoea or passing water very often. It can also happen if you are having trouble drinking or eating
• if you have low blood levels of essential minerals like sodium or potassium or you have acid base imbalance in the body identified by blood tests.
• you are planning to undergo procedure that includes the use of radiocontrast (as taking furosemide injection this may increase the risk for kidney damage)
• you cannot tolerate certain sugars like galactose or glucose.
• you are an elderly patient
• you have difficulty in passing water, for example because of an enlarged prostate gland (males only)
• you have diabetes
• you have gout (characterised by painful joints due to elevated uric acid levels)
• you have kidney or liver problems
• you have low blood protein levels (hypoproteinaemia) as this may reduce the effect of the drug and increase the risk of ear damage
• you have raised levels of calcium in the blood; careful monitoring of fluids and electrolyte levels are recommended
• you have a risk of fall in blood pressure; or in case of premature infants as they may be more prone to development of kidney stones
• you are already on medicines like NSAIDs (used for inflammation and pain) or ACE inhibitors

(medicines used to lower blood pressure)

• laboratory monitoring. It is recommended to undergo regular monitoring of blood levels for sodium, potassium, kidney function tests (blood urea nitrogen and creatinine levels), glucose, magnesium, calcium, chloride bicarbonate and uric acid
• regular monitoring is required to check for occurrence of blood dyscrasias (abnormal or imbalance in blood components), liver damage or any symptom that may occur particularly to you
• you are an elderly patient with dementia and are also taking risperidone.

Other medicines and Furosemide Injection

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines

• tell your doctor if you are taking the below medicines as the dose of these may need to be changed to avoid the risk of excessive lowering of blood pressure. Other blood pressure lowering agents (cardiac glycosides e.g. digoxin, other diuretics that help you pass more urine; or other blood pressure lowering agents)
• if you are taking any drugs that can be harmful to your kidneys
• if you have low levels of potassium or magnesium in your blood indicated by the blood counts.

A large number of drugs can interact with Furosemide which can significantly alter their effects. These drugs include:

• medicines such as ramipril, enalapril, perindopril (called ‘ACE inhibitors’) or losartan, candesartan, irbesartan (called ‘angiotensin II receptor antagonists’). Your doctor may need to change the dose of your tablets or ask you to stop taking them
• anti-psychotics (medicines used to treat mental disorders) such as tricyclic antidepressants, hypnotics and anxiolytics

(e.g pimozide, amisulpride, sertindole or phenothiazines) Risperidone used to treat dementia

• medicines for high blood pressure or heart problems (uneven heart beat) such as calcium channel blockers, beta blockers, clonidine, moxonidine, sodium nitroprusside, amiodarone, disopyramide, flecainide, minoxidil, lidocaine, prazosin, diazoxide, methyldopa, sotalol and mexiletine
• cardiac glycosides (drugs used to improve heart function) eg. Digoxin which is used to treat heart failure. Your doctor may need to change the dose of your medicine
• thymoxamine or Hydralazine used to lower blood pressure
• metolazone- medicine used to pass more urine
• nitrates- used to lower blood pressure
• lithium- used for mental illness
• sucralfate- this drug may decrease the absorption of Furosemide
• NSAIDs- drugs used to treat pain and inflammation (eg. Indomethacin, Ketorolac)
• salicylates (eg aspirin)
• antibiotics belonging to class of aminoglycosides, polymixins or vancomycin; as there may be a risk of ear or kidney damage, low sodium levels with trimethoprim, and cephaolsporins e.g. cefalexin and ceftriaxone
• medicines used to treat depression (eg. TCA or MAOIs)
• medicines used to treat diabetics
• medicines used to treat epilepsy (eg Carbamazepine, phenytoin)
• anti-histamines (medicines used to treat allergies)
• anti-fungals e.g. amphotericin (risk of potassium loss or renal damage indicated with Furosemide)
• choral hydrate or Triclorfos (drugs used to treat anxiety)
• drugs used to treat Attention Deficit Hyperactivity Disorder (ADHD) like e.g. atomoxetine, amphetamines
• steroids (used to treat inflammation)
• liquorice; increased risk of loss of potassium with furosemide
• platinum containing compounds like Cisplatin- used to treat cancers (increased risk of kidney damage with Furosemide)
• methotrexate- Increase chance of Furosemide toxicity
• levodopa- Used to treat parkinson’s disease (increased risk of lowering of blood pressure with Furosemide)
• medicines that modify immune system- (eg Aldesleukin or ciclosprorin)
• medicines used as muscle relaxants like baclofen, tizanidine or curare like drugs
• birth control Pills or oestrogen containing drugs may block the effect of Furosemide if taken concurrently
• progesterone containing drugs (drosperidone) may lead to reduced blood potassium levels if taken with Furosemide
• medicines such as alprostadil, used to treat erectile dysfunction (impotency)
• theophylline used for wheezing or difficulty in breathing
• probenecid used for treatment of gout
• medicines used as general anaesthetics to induce unconsciousness. If you are going to have an anaesthetic please ensure that the doctor or nurse knows you are taking furosemide
• laxatives- drugs used to relieve constipation e.g. bisacodyl, senna
• medicines for asthma when given in high doses such as salbutamol, terbutaline sulphate, salmeterol, formoterol or bambuterol
• medicines used to treat blocked noses, such as ephedrine and xylometazoline
• aminoglutethimide used to treat breast cancer.

Furosemide Injection with alcohol

Avoid consumption of alcohol with Furosemide as it may lead to excessive lowering of blood pressure.

Pregnancy and breast-feeding

Pregnancy

If you are pregnant or breast feeding, think you may be pregnant or are planning to have a baby, ask your doctor or nurse for advice before taking this medicine. Furosemide passes through the placenta and hence should not be given during pregnancy unless doctor feels it extremely necessary. If it is given in cases of swelling or water retention, the growth of the baby must be regularly monitored.

Breast-feeding

Furosemide passes into the milk and may inhibit secretion of milk. Hence it should be avoided in breast feeding women.

Driving and using machines

Furosemide may cause some patients to be less alert which could interfere with the ability to drive or to operate machines. If you notice that you are not as alert as usual, do not drive or operate machinery and ask your doctor for advice.

Furosemide Injection contains sodium

Each 2ml ampoule contains 0.26mmol of sodium and each 25ml vial contains 3.25mmol of sodium. This should be taken into consideration

if you are on a controlled sodium diet. 3. How Furosemide Injection should be given

SUMMARY OF PRODUCT CHARACTERISTICS

• 1 NAME OF THE MEDICINAL PRODUCT

Furosemide 10mg/ml Solution for Injection or Infusion

• 2 Qualitative and Quantitative Composition

Each ml contains 10mg of furosemide.

Each 2ml ampoule contains 20mg of furosemide.

Each 25ml vial contains 250mg of furosemide.

For excipients, see section 6.1.

• 3 PHARMACEUTICAL FORM

Solution for injection or infusion

The solution is colourless or almost colourless.

• 4 CLINICAL PARTICULARS

  • 4.1 Therapeutic indications

Furosemide 10mg/ml Injection is a diuretic indicated for use when a prompt and effective diuresis is required. The intravenous formulation is appropriate for use in emergencies or when oral therapy is precluded. Indications include cardiac, pulmonary, hepatic and renal oedema.

• 4.2 Posology and method of administration

Route of administration: intramuscular or intravenous use.

Adults

Intravenous furosemide must be injected or infused slowly; a rate of 4 mg per minute must not be exceeded.

In patients with severe impairment of renal function (serum creatinine>5 mg/dl), it is recommended that an infusion rate of 2.5 mg per minute is not exceeded.

Intramuscular administration must be restricted to exceptional cases where neither oral nor intravenous administration are feasible. It must be noted that intramuscular injection is not suitable for the treatment of acute conditions such as pulmonary oedema.

To achieve optimum efficacy and suppress counter-regulation, a continuous furosemide infusion is generally to be preferred to repeated bolus injections. Where continuous furosemide infusion is not feasible for follow-up treatment after one or several acute bolus doses, a follow-up regimen with low doses given at short intervals (approximately four hours) is to be preferred to a regimen with higher bolus doses at longer intervals.

Doses of 20 to 50 mg intramuscularly or intravenously may be given initially. If larger doses are required, they should be given by 20 mg increments and not given more often than every two hours. If doses greater than 50 mg are required it is recommended that they be given by slow intravenous infusion. The recommended maximum daily dose of furosemide administration is 1,500 mg.

Elderly: The dosage recommendations for adults apply, but in the elderly furosemide is generally eliminated more slowly. Dosage should be titrated until the required response is achieved.

Children: Parenteral doses for children range from 0.5 to 1.5 mg/kg body weight daily up to a maximum total daily dose of 20 mg.

• 4.3 Contraindi­cations

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
• Hypersensitivity to amiloride, sulphonamides or sulphonamide derivatives
• Hypovolaemia and dehydration (with or without accompanying hypotension) (see section 4.4)
• Severe hypokalaemia: severe hyponatraemia (see section 4.4).
• Comatose or pre-comatose states associated with hepatic cirrhosis (see section 4.4)
• Anuria or renal failure with anuria not responding to furosemide, renal failure as a result of poisoning by nephrotoxic or hepatotoxic agents, renal failure associated with hepatic coma
• Impaired renal function with a creatinine clearance below 30ml/min per 1.73 m2 body surface area (see section 4.4)
• Addison’s disease (see section 4.4)
• Digitalis intoxication (see section 4.5)
• Porphyria
• Breast-feeding women (see section 4.6).

• 4.4 Special warnings and precautions for use
  
  Conditions requiring correction before furosemide is started (see also section 4.3)

• Hypotension.
• Hypovolaemia.
• Severe electrolyte disturbances – particularly hypokalaemia, hyponatraemia and acid-base disturbances.

Furosemide is not recommended

• In patients at high risk for radiocontrast nephropathy – it should not be used for diuresis as part of the preventative measures against radiocontrast-induced nephropathy.
• In patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

Particular caution and/or dose reduction required:

Symptomatic hypotension leading to dizziness, fainting or loss of consciousness can occur in patients treated with furosemide, particularly in the elderly, patients on other medications which can cause hypotension and patients with other medical conditions that are risks for hypotension.

• Older people (lower initial dose as particularly susceptible to side-effects – see section 4.2)
• difficulty with micturition including prostatic hypertrophy (increased risk of urinary retention: consider lower dose). Closely monitor patients with partial occlusion of the urinary tract
• diabetes mellitus (latent diabetes may become overt: insulin requirements in established diabetes may increase: stop furosemide before a glucose tolerance test)
• pregnancy (see section 4.6)
• gout (furosemide may raise uric acid levels/precipi­tate gout)
• patients with hepatorenal syndrome
• impaired hepatic function (see section 4.3 and below – monitoring required)
• impaired renal function (see section 4.3 and below – monitoring required)
• adrenal disease (see section 4.3 – contraindication in Addison’s disease)
• hypoproteinaemia e.g. nephritic syndrome (effect of furosemide may be impaired and its ototoxicity potentiated – cautious dose titration required).
• acute hypercalcaemia (dehydration results from vomiting and diuresis – correct before giving furosemide). Treatment of hypercalcaemia with a high dose of furosemide results in fluid and electrolyte depletion – meticulous fluid replacement and correction of electrolyte required.
• Patients who are at risk from a pronounced fall in blood pressure
• premature infants (possible development nephrocalcino­sis/nephrolit­hiasis; renal function must be monitored and renal ultrasonography performed).

Avoidance with other medicines (see also section 4.5 for other interactions)

• concurrent NSAIDs should be avoided – if not possible diuretic effect of furosemide may be attenuated

Laboratory monitoring requirements:

• Serum sodium

Particularly in the older people or in patients liable to electrolyte deficiency

• Serum potassium

The possibility of hypokalaemia should be taken into account, in particular in patients with cirrhosis of the liver, those receiving concomitant treatment with corticosteroids, those with an unbalanced diet and those who abuse laxatives.

Regular monitoring of the potassium, and if necessary treatment with a potassium supplement, is recommended in all cases, but is essential at higher doses and in patients with impaired renal function. It is especially important in the event of concomitant treatment with digoxin, as potassium deficiency can trigger or exacerbate the symptoms of digitalis intoxication (see section 4.5).

A potassium-rich diet is recommended during long-term use.

Frequent checks of the serum potassium are necessary in patients with impaired renal function and creatinine clearance below 60ml/min per 1.73m2 body surface area as well as in cases where furosemide is taken in combination with certain other drugs which may lead to an increase in potassium levels (see section 4.5 & refer to section 4.8 for details of electrolyte and metabolic abnormalities)

• Renal function

Frequent BUN in first few months of treatment, periodically thereafter. Longterm/high-dose BUN should regularly be measured. Marked diuresis can cause reversible impairment of kidney function in patients with renal dysfunction. Adequate fluid intake is necessary in such patients. Serum creatinine and urea levels tend to rise during treatment

• Glucose

Adverse effect on carbohydrate metabolism – exacerbation of existing carbohydrate intolerance or diabetes mellitus. Regular monitoring of blood glucose levels is desirable.

• Other electrolytes

Patients with hepatic failure/alcoholic cirrhosis are particularly at risk of hypomagnesia (as well as hypokalaemia). During long-term therapy (especially at high doses) magnesium, calcium, chloride, bicarbonate and uric acid should be regularly measured.

Clinical monitoring requirements (see also section 4.8):

Regular monitoring for

• blood dyscrasias. If these occur, stop furosemide immediately
• liver damage
• idiosyncratic reactions

Other alterations in lab values

• Serum cholesterol and triglycerides may rise but usually return to normal within 6 months of starting furosemide

Concomitant use with risperidone

In risperidone placebo-controlled trials in older people with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone (7.3%; mean age 89 years, range 75–97 years) when compared to patients treated with risperidone alone (3.1%; mean age 84 years, range 70–96 years) or furosemide alone (4.1%; mean age 80 years, range 67–90 years).

Concomitant use of risperidone with other diuretics (mainly thiazide diuretics used in low dose) was not associated with similar findings.

No pathophysiological mechanism has been identified to explain this finding, and no consistent pattern for cause of death observed. Nevertheless, caution should be exercised and the risks and benefits of this combination or co-treatment with other potent diuretics should be considered prior to the decision to use. There was no increased incidence of mortality among patients taking other diuretics as concomitant treatment with risperidone. Irrespective of treatment, dehydration was an overall risk factor for mortality and should therefore be avoided in older patients with dementia (see section 4.3 Contraindi­cations).

• 4.5 Interaction with other medicinal products and other forms of interaction

General: The dosage of concurrently administered cardiac glycosides, diuretics, anti-hypertensive agents, or other drugs with blood-pressure-lowering potential may require adjustment as a more pronounced fall in blood pressure must be anticipated if given concomitantly with furosemide.

The toxic effects of nephrotoxic drugs may be increased by concomitant administration of potent diuretics such as furosemide.

Some electrolyte disturbances (e.g. hypokalaemia, hypomagnesaemia) may increase the toxicity of certain other drugs (e.g. digitalis preparations and drugs inducing QT interval prolongation syndrome).

Antihypertensi­ves: enhanced hypotensive effect possible with all types. Concurrent use with ACE inhibitors or Angiotensin II receptor antagonists can result in marked falls in blood pressure, furosemide should be stopped or the dose reduced before starting an ACE-inhibitor or Angiotensin II receptor antagonists (see section 4.4) Antipsychotics: furosemide-induced hypokalaemia increases the risk of cardiac toxicity. Avoid concurrent use with pimozide. Increased risk of ventricular arrhythmias with amisulpride or sertindole. Enhanced hypotensive effect with phenothiazines.

When administering risperidone, caution should be exercised and the risks and benefits of the combination or co-treatment with furosemide or with 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

Anti-arrhythmics (including amiodarone, disopyramide, flecanaide and sotalol) : risk of cardiac toxicity (because of furosemide-induced hypokalaemia). The effects of lidocaine, tocainide or mexiletine may be antagonised by furosemide.

Cardiac glycosides: hypokalaemia and electrolyte disturbances (including hypomagnesia) increase the risk of cardiac toxicity.

Drugs that prolong Q-T interval: increased risk of toxicity with furosemide-induced electrolyte disturbances

Vasodilators: enhanced hypotensive effect with moxisylyte (thymoxamine) or hydralazine

Other diuretics: profound diures is possible when furosemide given with metolazone.

Increased risk of hypokalaemia with thiazides.

Renin inhibitors: aliskiren reduces plasma concentrations of furosemide

Nitrates: enhanced hypotensive effect

Lithium: In common with other diuretics, serum lithium levels may be increased when lithium is given concomitantly with furosemide, resulting in increased lithium toxicity, including increased risk of cardiotoxic and neurotoxic effects of lithium. Therefore, it is recommended that lithium levels are carefully monitored and where necessary the lithium dosage is adjusted in patients receiving this combination.

Chelating agents: sucralfate may decrease the gastro-intestinal absorption of furosemide – the 2 drugs should be taken at least 2 hours apart

NSAIDs: increased risk of nephrotoxicity. Indometacin and ketorolac may antagonise the effects of furosemide (avoid if possible see section 4.4). NSAIDs may attenuate the action of furosemide and may cause acute renal failure in cases of pre-existing hypovolaemia or dehydration.

Salicylates: effects may be potentiated by furosemide. Salycylic toxicity may be increased by furosemide

Antibiotics: increased risk of ototoxicity with aminoglycosides, polymixins or vancomycin – only use concurrently if compelling reasons. Increased risk of nephrotoxicity with aminoglycosides or cefaloridine. Furosemide can decrease vancomycin serum levels after cardiac surgery. Increased risk of hyponatraemia with trimethoprim. Impairment of renal function may develop in patients receiving concurrent treatment with furosemide and high doses of certain cephalosporins.

Antidepressants: enhanced hypotensive effect with MAOIs. Increased risk of postural hypotension with TCAs (tricyclic antidepressants). Increased risk of hypokalaemia with reboxetine

Antidiabetics: hypoglycaemic effects antagonised by furosemide

Antiepileptics: increased risk of hyponatraemia with carbamazepine. Diuretic effect reduced by phenytoin.

Antihistamines: hypokalaemia with increased risk of cardiac toxicity

Antifungals: increased risk of hypokalaemia and nephrotoxicity with amphotericin

Anxiolytics and hypnotics: enhanced hypotensive effect. Chloral or triclorfos may displace thyroid hormone from binding site.

CNS stimulants (drugs used for ADHD): hypokalaemia increases the risk of ventricular arrhythmias

Corticosteroids: diuretic effect anatgonised (sodium retention) and increased risk of hypokalaemia

Glychyrrizin: (contained in liquorice) may and increase the risk of developing hypokalaemia.

Cytotoxics: increased risk of nephrotoxicity and ototoxicity with platinum compounds/cis­platin. 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.

Anti-metabolites: effects of furosemide may be reduced by methotrexate and furosemide may reduce renal clearance of methotrexate

Dopaminergics: enhanced hypotensive effect with levodopa.

Immunomodulators: enhanced hypotensive effect with aldesleukin. Increased risk of hyperkalaemia with ciclosprin and tacrolimus. Increased risk of gouty arthritis with ciclosporin

Muscle relaxants: enhanced hypotensive effect with baclofen or tizanidine. Increased effect of curare-like muscle relaxants

Oestrogens: diuretic effect antagonised

Progestogens (drosperidone): increased risk of hyperkalaemia

Prostaglandins: enhanced hypotensive effect with alprostadil

Sympathomimetics: increased risk of hypokalaemia with high doses of beta2 sympathomimetics

Theophylline: enhanced hypotensive effect

Probenecid: effects of furosemide may be reduced by probenecid and furosemide may reduce renal clearance of probenecid.

Anaesthetic agents: general anaesthetic agents may enhance the hypotensive effects of furosemide. The effects of curare may be enhanced by furosemide.

Alcohol: enhanced hypotensive effect

Laxative abuse: increases the risk of potassium loss

Others: Concomitant administration of aminoglutethimide may increase the risk of hyponatraemia.

• 3. How Furosemide Injection should be given

Your injection will be given to you by a doctor or nurse. The solution can be injected directly into a muscle (intramuscularly), be given by a slow injection into a vein (intravenously) over several minutes or diluted with another fluid and given by a drip over a longer period of time.

Adults and the elderly

In adults and the elderly, the usual dose is 20 to 50mg, increasing by 20mg every two hours if necessary.

The maximum daily dose should not be more than 1,500mg.

Use in children

In children the dose will range from 0.5 to 1.5mg/kg of bodyweight daily. The maximum daily dose should not be more than 20mg.

Your doctor will decide the dose which is best for you. If you do not understand, or are in any doubt, ask your doctor or nurse.

If you think you have been given too much Furosemide Injection

Your doctor will decide which dose is best for you. If you think too much medicine has been given to you contact your doctor, nurse, pharmacist or nearest hospital.

If you think you have missed a dose of Furosemide Injection

If you think you have missed a dose of Furosemide Injection, inform your doctor or nurse.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If any of the below mentioned side effects are observed please inform your doctor immediately

• allergic reactions such as itching, skin rash with severe itching and nettle rash, fever, allergic to light, severe allergic reaction with (high) fever, red patches on the skin, joint pain and/or inflammation of the eyes,“acute generalised exanthematous pustulosis (AGEP)”, DRESS, (acute febrile drug eruption) characterized by severe acute (allergic) reaction accompanied by fever and blisters on the skin/peeling skin and tiny spots from bleeding in the skin
• sudden inflammation of the pancreas accompanied by severe pain in the upper abdomen, shifting towards the back
• abnormal blood counts, severe changes in blood count- and signs e.g. sore throat, mouth ulcers, fever, unexplained bruising or bleeding
• signs of kidney inflammation e.g. blood in the urine, pain in the lower back
• signs of metabolic acidosis: chest pain, irregular heartbeat, nausea, vomiting, weakness.

The other possible side effects are listed under headings of frequency, using the following categories:

Uncommon (may affect up to 1 in 100 people)

• blurred vision
• lowering of blood pressure, resulting in impaired concentration and reactions, light-headedness,
• a feeling of pressure in the head, headache, dizziness, drowsiness, a feeling of weakness, visual disturbances, dry mouth and an inability to stand upright
• sensitivity to light (photosensitivity)
• feeling of tiredness
• dry mouth, thirst, disturbances of bowel like diarrhoea, constipation or vomiting
• raised blood levels of creatinine and urea
• deafness (sometimes irreversible).

Rare (may affect up to 1 in 1,000 people)

• abnormal blood count (white blood cell deficiency) accompanied by a increased susceptibility to infection
• increase in certain substances (eosinophilic cells) in the blood
• a crawling sensation on the skin, itching or tingling without any reason
• a life-threatening form of unconsciousness
• acute kidney failure
• inflammation of a blood vessel
• shock (severe drop in blood pressure, extreme paleness , restlessness, weak fast pulse, clammy skin, impaired consciousness) as a result of a sudden severe dilatation of the blood vessels due to allergy to certain substances
• fever
• muscle aches
• inability to control urination
• if you have a urinary tract obstruction, increased urine production may occur or worsen
• if you have a bladder disorder, enlarged prostate or narrowing of the ureters, urine production can stop suddenly
• minor mental disturbances.

Very rare (may affect up to 1 in 10,000 people)

• anaemia (a condition characterised by shortage of red blood cells)
• very severe blood abnormality (white blood cell deficiency) accompanied by a sudden high fever, severe throat pain and ulcers in the mouth.

Not known (frequency cannot be estimated from the available data)

• certain liver function disorders or increase in certain liver enzymes
• Furosemide can cause an excessive depletion of bodily fluids (e.g. passing urine more often than normal) and minerals (sodium, potassium, magnesium, calcium). Symptoms that can occur are thirst, headache, confusion, muscle cramps, increased irritability of the muscles, muscular weakness, heart rhythm disturbances and gastrointestinal problems such as sensation of unease and discomfort in stomach with an urge to vomit, or diarrhoea
• reduced concentration, light-headedness, sensations of pressure in the head, headache, dizziness, drowsiness, weakness, confusion
• if you have a shortage of sodium (sodium deficiency):

• – cramp in the calf muscles

• – loss of appetite

• – listlessness

• – feeling of weakness

• – dizziness

• – drowsiness

• – confusion

• If you have a shortage of potassium (potassium deficiency):

• – muscular weakness and the inability to contract one or more muscles (paralysis)

• – increased excretion of urine

• – heart problems

• in the case of severe potassium deficiency: interference with the function of the intestine or confusion which can result in coma
• if you have a shortage of magnesium and calcium (magnesium and calcium deficiency):

• – increased irritability of the muscles

• – heart rhythm disturbances

• deposits of calcium salts in the kidneys or heart defects like patent ductus arteriosus have been reported in premature babies following treatment with furosemide
• during treatment with furosemide, the blood levels of some fats (cholesterol and triglyceride) may rise, but usually return to normal within

• 6 months

• in the elderly, this can lead to a low blood volume, fluid depletion and thickening of the blood.

This can cause clots to form in the blood

• dizziness, fainting and loss of consciousness (caused by symptomatic hypotension).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can

also report side effects directly via the national reporting systems listed below:

United Kingdom

Yellow card scheme

or search for MHRA Yellow Card in the Google Play or Apple App Store.

Malta

ADR Reporting

Website:

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

5. how to store furosemide injectionkeep this medicine out of the sight and reach of children. this medicine should not be used after the expiry date shown on the label. the expiry date refers to the last day of the month.

• Furosemide injection should not be given if it shows signs of deterioration such as discoloration.
• Store in the original packaging in order to protect the product from light.
• For single use. Discard any unused product immediately after use.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6. contents of the pack and other informationwhat furosemide injection containsthe active substance in the injection is furosemide.

Other ingredients are sodium chloride, sodium hydroxide and water for injections.

What Furosemide Injection looks like and contents of the pack

Furosemide Injection is a colourless or almost colourless solution for injection or infusion. It is available in two presentations: a 2ml amber glass ampoule containing 20mg of furosemide and a 25ml amber glass vial containing 250mg of furosemide.

Both presentations are available in packs of 1, 5 or 10. Not all pack sizes may be marketed.

Marketing Authorisation Holder

Marketing Authorisation Holder in UK: Wockhardt UK Ltd, Ash Road North, Wrexham, LL13 9UF, UK.

Marketing Authorisation Holder in Malta:

Pinewood Laboratories Ltd., Ballymacarbry, Clonmel, Co. Tipperary, Ireland.

Manufacturer

Laboratorio Reig Jofre, Gran Capitan, no 10, 08970 Sant Joan Despi, Barcelona, Spain.

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Product Name	Reference Number
Furosemide 10mg/ml Solution for Injection or Infusion (20mg in 2ml)	29831/0098
Furosemide 10mg/ml Solution for Injection or Infusion (250mg in 25ml)	29831/0201

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This leaflet was last revised in 02/2020

103380/8 B10248–04

• 4.6 Pregnancy and lactation
  
  Pregnancy

  Furosemide crosses the placental barrier and should not be given during pregnancy unless there are compelling medical reasons. It should only be used for the pathological causes of oedema which are not directly or indirectly linked to the pregnancy. The treatment with diuretics of oedema and hypertension caused by pregnancy is undesirable because placental perfusion can be reduced, so, if used, monitoring of fetal growth is required. However, furosemide has been given after the first trimester of pregnancy for oedema, hypertension and toxaemia of pregnancy without causing fetal or newborn adverse effects.

Breast-feeding (see section 4.3)

Furosemide is contraindicated as it passes into breast milk and may inhibit lactation.

• 4.7 Effects on ability to drive and use machines

Reduced mental alertness, dizziness and blurred vision have been reported, particularly at the start of treatment, with dose changes and in combination with alcohol. Patients should be advised that if affected, they should not drive, operate machinery or take part in activities where these effects could put themselves or others at risk.

• 4.8 Undesirable effects

Undesirable effects can occur with the following frequencies: Very common (>1/10), Common (>1/100 to <1/10), Uncommon (>1/1,000 to <1/100), Rare (>1/10,000 to <1/1,000), Very rare (<1/10,000, including isolated reports), not known (cannot be estimated from the available data)

Blood and lymphatic system disorders:

Uncommon: thrombocytopenia

Rare: Eosinophilia, leukopenia, bone marrow depression (necessitates withdrawal of treatment). The haemopoietic status should be therefore be regularly monitored.

Very Rare: Aplastic anaemia or haemolytic anaemia, agranulocytosis

Nervous system disorders:

Rare: Paraesthesia, hyperosmolar coma

Not known: Dizziness, fainting and loss of consciousness (caused by symptomatic hypotension).

Endocrine disorder:

Glucose tolerance may decrease with furosemide. In patients with diabetes mellitus this may lead to a deterioration of metabolic control; latent diabetes mellitus may become manifest. Insulin requirements of diabetic patients may increase.

Eye disorders:

Uncommon: visual disturbance

Ear and labyrinth disorders:

Hearing disorders and tinnitus, although usually transitory, may occur in rare cases, particularly in patients with renal failure, hypoproteinaemia (e.g. in nephritic syndrome) and/or when intravenous furosemide has been given too rapidly.

Uncommon: Deafness (sometimes irreversible)

Cardiac disorders:

Uncommon: Cardiac arrhythmias

Furosemide may cause a reduction in blood pressure which, if pronounced may cause signs and symptoms such as impairment of concentration and reactions, light headedness, sensations of pressure in the head, headache, dizziness, drowsiness, weakness, disorders of vision, dry mouth, orthostatic intolerance. The diuretic effect of furosemide can result in hypovolaemia and dehydration, especially in the elderly. There is an increased risk of thrombosis.

Hepatobiliary disorders:

In isolated cases, intrahepatic cholestasis, an increase in liver transaminases or acute pancreatitis may develop.

Hepatic encephalopathy in patients with hepatocellular insufficiency may occur (see Section 4.3).

Vascular Disorder:

Rare: Vasculitis

Skin and subcutaneous tissue disorders:

Uncommon: Photosensitivity

Rare: Skin and mucous membrane reactions may occasionally occur, e.g. itching, urticaria, other rashes or bullous lesions, fever, hypersensitivity to light, exsudative erythema multiforme (Lyell’s syndrome and Stevens-Johnson syndrome), bullous exanthema, exfoliative dermatitis, purpura, and DRESS (Drug rash with eosinophilia and systemic symptoms).

Not known: Acute generalised exanthematous pustulosis (AGEP)

Metabolism and nutrition disorders:

As with other diuretics, electrolytes and water balance may be disturbed as a result of diuresis after prolonged therapy. Furosemide leads to increased excretion of sodium and chloride and consequently increase excretion of water. In addition, excretion of other electrolytes (in particular potassium, calcium and magnesium) is increased.

Metabolic acidosis can also occur. The risk of this abnormality increases at higher dosages and is influenced by the underlying disorder (e.g. cirrhosis of the liver, heart failure), concomitant medication (see section 4.5) and diet.

Symptomatic electrolyte disturbances and metabolic alkalosis may develop in the form of a gradually increasing electrolyte deficit or e.g. where higher furosemide doses are administered to patients with normal renal function, acute severe electrolyte losses

Symptoms of electrolyte imbalance depend on the type of disturbance:

Sodium deficiency can occur; this can manifest itself in the form of confusion, muscle cramps, muscle weakness, loss of appetite, dizziness, drowsiness and vomiting.

Potassium deficiency manifests itself in neuromuscular symptoms (muscular weakness, paralysis), intestinal symptoms (vomiting, constipation, meterorism), renal symptoms (polyuria) or cardiac symptoms. Severe potassium depletion can result in paralytic ileus or confusion, which can result in coma.

Magnesium and calcium deficiency result very rarely in tetany and heart rhythm disturbances.

Serum calcium levels may be reduced; in very rare cases tetany has been observed.

Nephrocalcino­sis/Nephrolit­hiasis has been reported in premature infants.

Serum cholesterol (reduction of serum HDL-cholesterol, elevation of serum LDL-cholesterol) and triglyceride levels may rise during furosemide treatment. During long term therapy they will usually return to normal within six months.

As with other diuretics, treatment with furosemide may lead to transitory increase in blood creatinine and urea levels. Serum levels of uric acid may increase and attacks of gout may occur.

The diuretic action of furosemide may lead to or contribute to hypovolaemia and dehydration, especially in elderly patients. Severe fluid depletion may lead to haemoconcentration with a tendency for thrombosis to develop.

Increased production of urine may provoke or aggravate complaints in patients with an obstruction of urinary outflow. Thus, acute retention of urine with possible secondary complications may occur. For example, in patients with bladder-emptying disorders, prostatic hyperplasia or narrowing of the urethra.

Congenital, familial and genetic disorders:

If furosemide is administered to premature infants during the first weeks of life, it may increase the risk of persistence of patent ductus arteriosus.

General disorders and administration site conditions:

Uncommon: Fatigue

Rare: Severe anaphylactic or anaphylactoid reactions (e.g. with shock) occurs rarely, fever, malaise

Gastrointestinal disorders:

Uncommon: Dry mouth, thirst, nausea, bowel motility disturbances, vomiting, diarrhea, constipation

Rare: Acute Pancreatitis

Gastro-intestinal disorders such as nausea, malaise or gastric upset (vomiting or diarrhoea) and constipation may occur but not usually severe enough to necessitate withdrawal of treatment.

Renal and urinary disorders:

Uncommon: Serum creatinine and urea levels can be temporarily elevated during treatment with furosemide.

Rare: interstitial nephritis, acute renal failure.

Increased urine production, urinary incontinence, can be caused or symptoms can be exacerbated in patients with urinary tract obstruction. Acute urine retention, possibly accompanied by complications, can occur for example in patients with bladder disorders, prostatic hyperplasia or narrowing of the urethra.

Pregnancy, puerperium and perinatal conditions:

In premature infants with respiratory distress syndrome, administration of Furosemide in the initial weeks after birth entails an increased risk of a persistent patent ductus arteriosus.

In premature infants, furosemide can be precipitated as nephrocalcino­sis/kidney stones.

Rare complications may include minor psychiatric disturbances.

Special population:

Patients with hepatic impairment

Pre-existing metabolic alkalosis (e.g. in decompensated cirrhosis of the liver) may be aggravated by furosemide treatment.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the national reporting systems listed below:

United Kingdom

Yellow Card Scheme

or search for MHRA Yellow Card in the Google Play or Apple App Store.

Malta

ADR Reporting

Website:

• 4.9 Overdose
  
  Symptoms:

  The clinical picture in acute or chronic overdose depends primarily on the extent and consequences of electrolyte and fluid loss, e.g. hypovolaemia, dehydration, haemoconcentration, cardiac arrhythmias due to excessive diuresis. Symptoms of these disturbances include severe hypotension (progressing to shock), acute renal failure, thrombosis, delirious states, flaccid paralysis, apathy and confusion.

Treatment:

Treatment should therefore be aimed at fluid replacement and correction of the electrolyte imbalance. Together with the prevention and treatment of serious complications resulting from such disturbances and of other effects on the body, this corrective action may necessitate general and specific intensive medical monitoring and therapeutic measures.

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 those designed to reduce absorption (e.g. activated charcoal).

• 5 PHARMACOLOGICAL PROPERTIES

  • 5.1 Pharmacody­namic properties

The evidence from many experimental studies suggests that furosemide acts along the entire nephron with the exception of the distal exchange site. The main effect is on the ascending limb of the loop of Henle with a complex effect on renal circulation. Blood-flow is diverted from the juxta-medullary region to the outer cortex.

The principle renal action of furosemide is to inhibit active chloride transport in the thick ascending limb. Re-absorption of sodium chloride from the nephron is reduced and a hypotonic or isotonic urine produced. It has been established that prostaglandin (PG) biosynthesis and the renin-angiotensin system are affected by furosemide administration and that furosemide alters the renal permeability of the glomerulus to serum proteins.

• 5.2 Pharmacoki­netic properties

Furosemide is a weak carboxylic acid which exists mainly in the dissociated form in the gastrointestinal tract. Furosemide is rapidly but incompletely absorbed (60–70%) on oral administration and its effect is largely over within 4 hours. The optimal absorption site is the upper duodenum at pH 5.0. Regardless of route of administration, 69–97% of activity from a radio-labelled dose is excreted in the first 4 hours after the drug is given. Furosemide is bound to plasma albumin and little biotransformation takes place. Furosemide is mainly eliminated via the kidneys (80–90%); a small fraction of the dose undergoes biliary elimination and 10–15% of the activity can be recovered from the faeces.

In renal/ hepatic impairment

Where liver disease is present, biliary elimination is reduced up to 50%. Renal impairment has little effect on the elimination rate of furosemide, but less than 20% residual renal function increases the elimination time.

The elderly

The elimination of furosemide is delayed in the elderly where a certain degree of renal impairment is present.

New born

A sustained diuretic effect is seen in the newborn, possibly due to immature tubular function.

• 5.3 Preclinical safety data

Not applicable.

• 6 PHARMACEUTICAL PARTICULARS

  • 6.1 List of excipients

Sodium chloride

Sodium hydroxide

Water for injections

• 6.2 Incompati­bilities

Furosemide may precipitate out of solution in fluids of low pH (e.g. dextrose solutions).

• 6.3 Shelf life

Three years

• 6.4 Special precautions for storage

Store in the original package

• 6.5 Nature and contents of container

Furosemide 20mg in 2ml

Type I amber coloured glass ampoule (3ml capacity). Each pack contains 1,5 or 10 ampoules*.

Furosemide 250mg in 25ml

Type I amber coloured glass vial (25ml capacity) sealed with a bromobutyl stopper, aluminium overseal and polypropylene flip-off cap. Each pack contains 1, 5 or 10 vials*. *Not all pack sizes may be marketed

6.6 instructions for use and handling

From a microbiological point of view, unless the method of dilution precludes the risk of microbial contamination, the product should be used immediately.

For single use only.

Furosemide 10mg/ml Injection solution should not be mixed with any other drugs in the injection bottle.

Intravenous furosemide must be injected or infused slowly; a rate of 4 mg per minute must not be exceeded. In patients with severe impairment of renal function (serum creatinine>5 mg/dl), it is recommended that an infusion rate of 2.5 mg per minute is not exceeded.

• 7 MARKETING AUTHORISATION HOLDER

Marketing Authorisation Holder in UK:

Wockhardt UK Limited

Ash Road North

Wrexham

LL13 9UF

UK

Marketing Authorisation Holder in Malta:

Pinewood Laboratories Ltd.,

Ballaymacarbry,

Clonmel,

Co. Tipperary, Ireland

• 8 MARKETING AUTHORISATION NUMBER

Furosemide 10mg/ml Injection (20mg in 2ml) – PL 29831/0098 MA 143/03103

Furosemide 10mg/ml Injection (250mg in 25ml) – PL 29831/0201 MA 143/03102

• 9 DATE OF FIRST AUTHORISATION/RE­NEWAL OF THE AUTHORISATION

01/05/2007 (UK) 12/03/2015 (MT)

• 10 DATE OF REVISION OF THE TEXT