Package leaflet: Information for the user

FUROSEMIDE S.A.L.F. 20 mg/2 ml injectable solution, 250 mg/25 ml solution for infusion

Furosemide
Generic medicine
Please read this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What FUROSEMIDE S.A.L.F. is and what it is used for
What you need to know before using FUROSEMIDE S.A.L.F.
How to use FUROSEMIDE S.A.L.F.
Possible side effects
How to store FUROSEMIDE S.A.L.F.
Contents of the pack and other information

1. What FUROSEMIDE S.A.L.F. is and what it is used for

FUROSEMIDE S.A.L.F. contains the active substance furosemide, which belongs to a group of
medicines called diuretics, used to promote the elimination of excess fluid.
FUROSEMIDE S.A.L.F. 20 mg/2 ml injectable solution is indicated for the treatment of:

all forms of oedema, i.e. swelling due to fluid accumulation, caused by heart problems (e.g. due to heart failure);
ascites, i.e. swelling due to fluid accumulation in the peritoneum, the membrane covering the abdominal organs, which may be caused by liver problems (hepatic cirrhosis), organ or blood vessel obstruction, or heart failure;
oedema caused by kidney problems (such as nephrotic syndrome, in which it may be used together with other medicines such as ACTH or corticosteroids) or by obstruction of an organ or blood vessels;
swelling due to fluid accumulation in the extremities (peripheral oedema);
mild to moderate high blood pressure.

FUROSEMIDE S.A.L.F. 250 mg/25 ml infusion solution is indicated only if one of the following
conditions applies to you:

if you suffer from severe kidney function problems such as:
severely impaired glomerular filtration,
acute renal failure, chronic renal failure (especially in cases of chronic pulmonary oedema),
nephrotic syndrome (e.g. in chronic glomerulonephritis, systemic lupus erythematosus, or Kimmelstiel-Wilson syndrome, a renal complication of diabetes), when anti-inflammatory medicines called corticosteroids are not sufficient to control oedema or are contraindicated,
chronic renal failure without fluid retention. In the latter case, if daily urine output is less than 2.5 litres, you will need blood filtration procedures (dialysis), or if you are in shock characterised by severe circulatory problems. Before starting treatment in this case, your doctor must first administer therapy to correct all imbalances caused by shock (hypotension, hypovolaemia, electrolyte imbalances, acid-base disturbances).

2. What you need to know before using FUROSEMIDE S.A.L.F.

Do not use FUROSEMIDE S.A.L.F.:

if you are allergic to furosemide or to any of the other ingredients of this medicine (listed in section 6)
if you are allergic to medicines called sulfonamides used for infections
if you have a significantly reduced blood volume (hypovolemia) or are dehydrated
if you are not producing urine (anuria) due to severe kidney problems (renal failure)
if you have low levels of potassium (hypokalaemia) or sodium (hyponatraemia) in the blood
if you are in a pre-coma or coma state associated with hepatic encephalopathy, a condition involving impaired brain function due to inadequate liver function
if you have taken high doses of a heart medicine called digitalis
if you are in the first three months of pregnancy (see section “Pregnancy and breastfeeding”)
if you are breastfeeding (see section “Pregnancy and breastfeeding”)

In addition to the above contraindications, FUROSEMIDE S.A.L.F. 250 mg/25 ml solution
for infusion is also contraindicated:

if you suffer from very low blood pressure (severe hypotension)
if you are pregnant, or think you may be pregnant (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using FUROSEMIDE S.A.L.F.
Use this medicine under direct medical supervision.
FUROSEMIDE S.A.L.F. should be administered with caution in the following cases:

if you are elderly, if you are taking other medicines that may lower blood pressure, or if you have other conditions that increase the risk of low blood pressure;
if you have difficulty emptying your bladder or suffer from conditions causing difficulty in urine elimination (prostatic hyperplasia or urethral stenosis). In patients with obstructed urinary flow, careful monitoring is required, especially at the beginning of treatment;
if you suffer from low blood pressure or are at risk of excessive drop in arterial blood pressure due to circulatory problems (significant narrowing of coronary arteries or blood vessels supplying the brain);
if you have diabetes (latent or overt diabetes mellitus). During treatment, your doctor will need to monitor your blood and urine glucose levels;
if you suffer from gout, a condition caused by uric acid accumulation. During treatment, your doctor will need to monitor your blood uric acid levels;
if you have severe liver or kidney problems (hepatorenal syndrome, functional renal failure associated with severe hepatopathy);
if you have low levels of protein in the blood (hypoproteinaemia);
if you are at risk of electrolyte imbalances in the blood or have lost large amounts of fluids (e.g. due to vomiting, diarrhoea, or excessive sweating). In such cases, your doctor will monitor your blood levels of sodium, potassium, and creatinine and, if necessary, may

advise you to temporarily discontinue furosemide treatment and follow
an appropriate therapy to restore normal electrolyte levels;

if you are taking a medicine called risperidone (see section “Other medicines and FUROSEMIDE S.A.L.F.”);
if you suffer from high blood pressure, as you may need to take additional antihypertensive medicines alongside furosemide.

To reduce the risk of low potassium levels in the blood during treatment with
FUROSEMIDE S.A.L.F., follow a potassium-rich diet (potatoes, bananas, oranges, tomatoes, spinach,
and dried fruit). Your doctor may also recommend potassium supplements if needed
to restore normal potassium levels in the blood.
You are at risk of low potassium levels:

if you have liver problems (hepatic cirrhosis);
if you suffer from chronic diarrhoea;
if you use laxatives for prolonged periods;
if you follow a diet low in potassium;
if you are taking medicines called mineralocorticoids that regulate water and salt levels in the blood.

In case of ascites due to liver problems (hepatic cirrhosis), FUROSEMIDE S.A.L.F.
should only be administered in hospital.
Furosemide S.A.L.F. does not alter blood pressure values in normotensive individuals, but has a hypotensive effect in hypertensive patients; in severe forms of hypertension, combination therapy with other agents is recommended.
Attention for those engaged in sports: the medicinal product contains substances prohibited in
doping. Any use differing from the recommended dosage regimen or route of administration is prohibited.
Children
This medicine may cause kidney problems (nephrocalcinosis/nephrolithiasis) in premature infants.
Therefore, during treatment with FUROSEMIDE S.A.L.F., your doctor must closely monitor your child’s kidney function.
Other medicines and FUROSEMIDE S.A.L.F.
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
In general, treatment with high doses of other medicines or of FUROSEMIDE S.A.L.F. increases the
risk of adverse effects due to FUROSEMIDE S.A.L.F. or to concomitant therapies.
FUROSEMIDE S.A.L.F. is not recommended if you are taking any of the following medicines:

chloral hydrate, a sedative medicine. If furosemide is administered intravenously within 24 hours of chloral hydrate intake, it may cause skin flushing, sudden sweating, restlessness, nausea, increased blood pressure, and tachycardia;
aminoglycosides, antibiotics used for bacterial infections and other medicines that may cause ear damage. FUROSEMIDE S.A.L.F. may increase ototoxic effects in such cases.

FUROSEMIDE S.A.L.F. should be administered with caution if you are taking any of the following
medicines:

cisplatin, a medicine used in certain cancers. When taken together with furosemide, it may cause damage to the ears and kidneys;
lithium salts, medicines used for depression. Furosemide may increase lithium toxicity; therefore, if both medicines are taken together, your doctor must closely monitor your blood lithium levels;
ACE inhibitors or angiotensin II receptor antagonists, medicines used to lower blood pressure. Your doctor will need to determine the appropriate furosemide dose and may advise temporarily stopping its administration;
risperidone, a medicine used for mental disorders (see section “Warnings and precautions”). Cases of death in elderly patients with dementia taking risperidone together with furosemide have been reported (see section “Warnings and precautions”).

The concomitant use of the following medicines with furosemide should be carefully evaluated by
your doctor, as they may reduce the effect of furosemide:

non-steroidal anti-inflammatory drugs (NSAIDs), such as acetylsalicylic acid, medicines used for inflammation that may also increase toxic effects. If you are dehydrated or have low blood volume, you may also develop kidney problems;
phenytoin, a medicine used for epilepsy;
probenecid, a medicine used for gout, and methotrexate, a medicine used to treat certain cancers, as they may reduce the effect of furosemide.

The concomitant use of the following medicines with furosemide should be carefully evaluated by
your doctor, as they may increase the toxic effects of these medicines or alter their efficacy:

nephrotoxic medicines (nephrotoxic agents), such as cephalosporins (antibiotics used for bacterial infections);
corticosteroids, medicines for inflammation, carbenoxolone, a medicine for ulcers, and laxatives used over long periods, as they may increase the risk of low potassium levels in the blood;
digitalis-based medicines, used for heart conditions. Furosemide may increase their toxic effects by altering magnesium and potassium levels in the blood;
antihypertensives, medicines for high blood pressure, and diuretics, medicines that promote urine elimination, as a pronounced drop in blood pressure may occur;
antidiabetics, medicines used to treat diabetes;
sympathomimetics such as adrenaline and noradrenaline;
curare-like muscle relaxants, used in anaesthesia;
theophylline;
cephalosporins, medicines used against bacteria, as kidney damage may occur;
cyclosporine A, a medicine used after organ transplantation, as it may increase the risk of uric acid accumulation;
contrast media, medicines used in certain diagnostic procedures, as kidney damage may occur.

FUROSEMIDE S.A.L.F. and food
If you consume large amounts of liquorice during treatment with this medicine, you may
experience a decrease in blood potassium levels.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, or are planning a pregnancy, consult your
doctor or pharmacist before using this medicine.
FUROSEMIDE S.A.L.F. 20 mg/2 ml injectable solution is contraindicated during the first three
months of pregnancy. During the second and third trimesters, it may be administered only if strictly necessary and under direct medical supervision.
FUROSEMIDE S.A.L.F. 250 mg/25 ml solution for infusion is contraindicated throughout
pregnancy.
Breastfeeding
FUROSEMIDE S.A.L.F. is contraindicated during breastfeeding. You must interrupt breastfeeding during treatment with
FUROSEMIDE S.A.L.F. because the medicine passes into breast milk.
Driving and using machines
This medicine may impair your concentration and reaction time. Therefore, if this occurs, avoid driving vehicles or operating machinery.
FUROSEMIDE S.A.L.F. contains sodium
1 vial of Furosemide S.A.L.F. 20 mg/2 ml contains approximately 0.06 mmol (1.4 mg) of sodium, i.e.
practically sodium-free.
1 vial of Furosemide S.A.L.F. 250 mg/25 ml contains approximately 0.75 mmol (17.3 mg) of sodium, i.e.
practically sodium-free.

3. How to use FUROSEMIDE S.A.L.F.

You must use this medicine exactly as instructed by your doctor, pharmacist, or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.
The doctor will determine the dose, duration of treatment, method, and rate of injection according to the disease being treated and your individual health condition.
The medicine must be injected intravenously or administered by infusion through a suitable device very slowly.
Intramuscular administration should be limited to exceptional cases, when administration via other routes is not possible.

If you use more FUROSEMIDE S.A.L.F. than you should
In case of overdose, possible effects include reduced blood volume (hypovolemia), dehydration, blood abnormalities (hemoconcentration), heart problems (arrhythmias, including A-V block and ventricular fibrillation). Symptoms may include a severe drop in blood pressure (up to shock), serious kidney problems (acute renal failure), circulatory problems (thrombosis), muscle paralysis (flaccid paralysis), delirium, apathy, or confusion.
Depending on your condition, the doctor will decide on appropriate treatment.
If you have taken an excessive dose of this medicine, contact your doctor immediately or go to the nearest hospital.

If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur:

Very common (may affect more than 1 in 10 people):

dehydration, changes in levels of certain salts in the blood (electrolyte disturbances)
dehydration
decrease in blood volume in the body (hypovolemia)
increased levels of creatinine and triglycerides in the blood, including when standing up (orthostatic hypotension)
decrease in blood pressure (also occurring later)

Common (may affect up to 1 in 10 people):

decreased levels of sodium, chloride, and potassium in the blood (hyponatremia, hypochloremia, hypokalemia) and increased levels of other substances in the blood (cholesterol, urea)
alteration of blood (hemoconcentration)
impairment of brain function due to inadequate liver function (hepatic encephalopathy in patients with hepatocellular insufficiency)
increased urine production (polyuria)

Uncommon (may affect up to 1 in 100 people):

deafness (sometimes irreversible)
heart rhythm problems (arrhythmias)
drowsiness, headache, dizziness, confusion
visual disturbances
dry mouth, nausea, vomiting, diarrhea, intestinal problems (intestinal motility disorders)
reduced glucose tolerance and manifestation of latent diabetes
muscle problems (cramps, tetany, myasthenia)
fatigue
transient hearing disturbances, reversible or irreversible hearing loss, especially following too rapid intravenous administration of furosemide or in patients with renal impairment and hypoalbuminemia
decreased number of platelets in the blood (thrombocytopenia)

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

decreased number of certain blood cells (leukopenia, eosinophilia)
severe kidney problems (interstitial nephritis)
skin reactions (urticaria, pruritus, rash, purpura, bullous dermatitis, erythema multiforme, pemphigoid, exfoliative dermatitis, photosensitivity reactions)
inflammation of blood vessels (vasculitis)
fever, allergic reactions including severe ones (anaphylactic or anaphylactoid reactions)
loss of sensation (paresthesia)

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

blood disorders (aplastic anemia, agranulocytosis, hemolytic anemia)
ringing in the ears (tinnitus)
inflammation of the pancreas (acute pancreatitis)
liver problems (intrahepatic cholestasis, increased hepatic transaminases)

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

severe liver problems (hepatic encephalopathy in patients with hepatocellular insufficiency)
severe skin reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP) (acute febrile drug eruption)
dizziness, fainting, and loss of consciousness (due to symptomatic hypotension)
decreased number of certain blood cells (leukopenia, aplastic anemia, agranulocytosis, thrombocytopenia, hemolytic anemia, eosinophilia)
decreased levels of calcium and magnesium in the blood (hypocalcemia, hypomagnesemia), increased blood pH (metabolic alkalosis), increased blood urea levels
decreased blood volume, formation of blood clots in blood vessels (thrombosis)
increased excretion of sodium and chloride in urine, problems with urination (urinary retention in patients with prostatic hypertrophy, urethral stenosis, or bladder emptying difficulties), severe kidney problems (renal failure, nephrocalcinosis/nephrolithiasis in preterm neonates treated with furosemide), pseudo-Bartter syndrome (a condition characterized by disturbances in levels of certain salts in the body)
local-type reactions
Increased risk of persistent patent ductus arteriosus when furosemide is administered to premature neonates during the first weeks of life.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at
www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store FUROSEMIDE S.A.L.F.

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.".
The expiry date refers to the last day of that month.
Store in the original container, tightly closed, to protect the medicine from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What FUROSEMIDE S.A.L.F. contains
FUROSEMIDE S.A.L.F. 20 mg / 2 ml injection solution

The active substance is furosemide. Each vial contains 20 mg of furosemide.
The other components are: sodium hydroxide, water for injections.

FUROSEMIDE S.A.L.F. 250 mg / 25 ml infusion solution

The active substance is furosemide. Each bottle contains 250 mg of furosemide.
The other components are: sodium hydroxide, water for injections.

Description of the appearance of FUROSEMIDE S.A.L.F. and contents of the pack
FUROSEMIDE S.A.L.F. 20 mg / 2 ml: 5 vials of 2 ml.
FUROSEMIDE S.A.L.F. 250 mg / 25 ml: 5 bottles of 25 ml.
Marketing Authorisation Holder and Manufacturer
S.A.L.F. S.p.A. Laboratorio Farmacologico – Via Marconi, 2 - Cenate Sotto (BG) - Tel. 035 – 940097 –
Italy.

The following information is intended exclusively for physicians or healthcare professionals

Dosage and administration
The solution must be clear, colourless or almost colourless, and free from visible particles.

Furosemide S.A.L.F. 20 mg/2 ml injectable solution:
In the presence of intestinal malabsorption disorders or when rapid removal of oedematous fluid is required, parenteral administration of Furosemide S.A.L.F. is indicated at a dose of 20 mg (1 vial) 1–2 times daily, depending on need.

Administration
Injection/infusion: intravenous furosemide must be injected or infused slowly, without exceeding a rate of 4 mg/min. In patients with severe renal impairment (serum creatinine > 5 mg/dL), a maximum infusion rate of 2.5 mg per minute is recommended.
Intramuscular injection: intramuscular administration should be limited to exceptional circumstances, when neither intravenous nor oral administration is possible. It should be emphasized that intramuscular injection is unsuitable for the treatment of acute conditions, such as pulmonary oedema.

Dosage in renal impairment: Dose adjustment is necessary when glomerular filtration rate falls below 10 ml/min.

Dosage in hepatic impairment: Dose adjustment may be necessary in patients with liver cirrhosis and in those with concomitant renal and hepatic insufficiency. Response to furosemide is reduced in patients with liver cirrhosis.

Furosemide S.A.L.F. 250 mg/25 ml infusion solution
The infusion rate must always be adjusted so that no more than 4 mg of furosemide are administered per minute. The pH of the ready-to-use infusion solution must not be lower than 7, as furosemide may precipitate in acidic solutions. The furosemide solution must not be infused together with other drugs and should be used immediately after preparation.

If a test dose of 40–80 mg of furosemide, administered by slow i.v. injection (over approximately 2–5 minutes), does not produce a significant increase in diuresis within 30 minutes, infusion treatment with Furosemide S.A.L.F. 250 mg/25 ml infusion solution may be initiated. The contents of one vial of Furosemide S.A.L.F. 250 mg/25 ml infusion solution should be diluted in 250 ml of neutral or alkaline isotonic solution (e.g., Ringer's lactate, glucose solution).
Considering the prescribed infusion rate, in this case (250 mg in 275 ml), the infusion duration is approximately 1 hour. If the patient responds to this dose, an increase in diuresis should already be observed during the infusion. Therapeutically, the aim is to achieve an increase in diuresis of at least 40–50 ml/hour.

In patients with severe renal impairment (serum creatinine > 5 mg/dL), a maximum infusion rate of 2.5 mg/minute is recommended.

If a satisfactory increase in diuresis is not achieved with the first dose of Furosemide S.A.L.F. 250 mg/25 ml, one hour after completion of the first infusion, a second infusion should be administered using two vials of Furosemide S.A.L.F. 250 mg/25 ml infusion solution (corresponding to 500 mg), diluted in an appropriate infusion solution, adjusting the infusion volume according to the patient's hydration status. The duration of the infusion must always be adjusted to ensure that no more than 4 mg/min of active substance are infused.

If the desired diuretic response is still not achieved after this dose, one hour after completion of the second infusion, a third infusion may be administered using four vials of Furosemide S.A.L.F. 250 mg/25 ml infusion solution (corresponding to 1000 mg). For total infusion volume and infusion rate, the previously indicated guidelines apply. If no satisfactory diuretic effect is obtained even with this dose, consideration should be given to switching to dialysis.

In hypervolaemic patients, if the test dose of 40–80 mg i.v. proves ineffective, it is preferable to administer Furosemide S.A.L.F. 250 mg/25 ml infusion solution undiluted or added to a volume of compatible infusion solution appropriate to the patient's hydration status, in order to avoid hyperhydration. Direct infusion of the vial contents may only be performed if administration rate is guaranteed not to exceed 4 mg of furosemide/min (= 0.4 ml/min).

Administration
Furosemide S.A.L.F. 250 mg/25 ml infusion solution must not be used for intravenous bolus injection, but only for slow intravenous infusion using volumetric or rate-controlled infusion pumps, in order to reduce the risk of accidental overdose.
Infusion: intravenous furosemide must be infused slowly, without exceeding a rate of 4 mg/min.

Overdose
The clinical picture following acute or chronic overdose primarily depends on the extent and consequences of water and electrolyte loss, e.g., hypovolaemia, dehydration, haemoconcentration, cardiac arrhythmias (including A-V block and ventricular fibrillation). Symptoms of these disturbances include severe hypotension (up to shock), acute renal failure, thrombosis, delirium, flaccid paralysis, apathy, and confusion.

No specific antidote for furosemide is known. If drug intake has just occurred, attempts may be made to limit systemic absorption of the active substance by measures such as gastric lavage or those aimed at reducing absorption (e.g., activated charcoal). Clinically significant water and electrolyte imbalances must be corrected.
In addition to preventing and treating serious complications arising from such imbalances and other effects on the body, corrective action may require intensive monitoring of clinical status and appropriate therapeutic measures.

In patients with urinary voiding disorders, such as prostatic hypertrophy or unconsciousness, it is necessary to ensure restoration of free urinary flow.

Incompatibilities
Furosemide, as an anthranilic acid derivative, is soluble in alkaline environments. The solution has a pH of approximately 9 and has no buffering effect; below pH 7, the active substance may precipitate. Therefore, it should be noted that Furosemide S.A.L.F. may be mixed with alkaline, neutral, or weakly acidic solutions with modest buffering capacity, such as Ringer's lactate and glucose solution. Acidic solutions, particularly those with high buffering capacity, must not be mixed with Furosemide S.A.L.F. Injectable or infusion solutions of Furosemide S.A.L.F. must not be mixed with other drugs in the same syringe.

Once diluted, the solution should be used as soon as possible.

For further information, consult the Summary of Product Characteristics.