Furosemide Noridem: detailed information

PACKAGE LEAFLET

Package leaflet: Information for the patient

Furosemide Noridem 10 mg/mL injection solution or for infusion

Generic Medicine
Please read this leaflet carefully before this medicine is administered to you, as
it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult your doctor, pharmacist, or nurse.
Inform your doctor, pharmacist, or nurse if you experience any side effects, including any not listed in this leaflet. See section 4.

Contents of this leaflet

What Furosemide Noridem is and what it is used for
What you need to know before receiving Furosemide Noridem
How Furosemide Noridem is administered
Possible side effects
How to store Furosemide Noridem
Contents of the pack and other information

1. What Furosemide Noridem is and what it is used for

Furosemide belongs to a group of medicines known as loop diuretics (they help produce more urine).
Furosemide Noridem is indicated for the treatment of congestive heart failure, hepatic cirrhosis (irreversible liver fibrosis), or kidney disease associated with fluid retention.
It is indicated for hypertension (high blood pressure) as monotherapy or in combination with other antihypertensive medicines in patients with heart failure or chronic kidney disease, or for sustained hypertension or when first-line medicines are insufficient or not tolerated.
Intravenous administration is recommended when immediate diuresis (rapid removal of excess fluid) is required, such as in the case of pulmonary edema (excess fluid in the lungs).

2. What you need to know before taking Furosemide Noridem

Furosemide Noridem must not be administered
if you are allergic to furosemide or to any of the other ingredients of this medicine
(listed in section 6). Patients who are allergic to sulfonamides (e.g. sulfonamide antibiotics or sulfonylureas) or thiazide diuretics may generally experience cross-sensitivity to Furosemide Noridem,
if you suffer from hypovolemia (low blood volume) or are dehydrated,
if you suffer from anuria due to renal failure, as these patients do not respond to
Furosemide Noridem,
if you have severe hypokalaemia (low levels of potassium (K+) in the blood) (see section 4),
if you have severe hyponatraemia (low levels of sodium in the blood),
if you are in a comatose or pre-comatose state associated with hepatic encephalopathy (a decline in brain function occurring as a result of severe liver failure),
if you suffer from renal failure due to poisoning by medicines that can damage
your kidneys or your liver,
if you are breastfeeding. Regarding pregnancy, see section “Warnings and
precautions”.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Furosemide Noridem.
Free urinary flow must be ensured. In patients with partial urinary tract obstruction
(e.g. patients with bladder emptying problems, enlarged prostate, or urethral stricture), an increase in urine production may cause or worsen symptoms. Therefore, particularly careful monitoring of patients is required, especially during the initial phases of treatment.

Treatment with furosemide requires regular medical check-ups. Particularly careful monitoring is necessary if the patient:

has hypotension (low blood pressure),
is at higher risk of a significant drop in blood pressure (blood vessels in the heart or brain are too narrow),
has diabetes (or may have diabetes),
has gout (inflamed and painful joints due to high levels of uric acid),
has any type of liver or kidney problems,
has low levels of protein in the blood (hypoproteinaemia), for example associated with nephrotic syndrome (a condition in which excessive protein is found in the urine), as this may reduce the medicine’s effects and increase the risk of hearing damage. A dose adjustment may be required.
if a premature newborn is to receive furosemide, kidney function should be monitored and a renal ultrasound performed, as kidney stones may develop. There is also an increased risk of patent ductus arteriosus (PDA) (a condition in which blood flows into the lungs) and neonatal respiratory distress syndrome (causing breathing difficulties in newborns whose lungs are not yet fully developed).
is elderly, is taking other medicines that may cause a drop in blood pressure, or has other conditions that may affect blood pressure. During treatment with Furosemide Noridem, careful monitoring of electrolyte concentrations, especially potassium, calcium, chloride, bicarbonate, and fluid balance is recommended. Frequent monitoring of creatinine and uric acid levels in the blood is also necessary. Carbohydrate metabolism should also be monitored.

Particularly careful monitoring is required for patients at higher risk of developing
electrolyte imbalance or in case of significant additional fluid loss (e.g. due to vomiting, diarrhoea, or excessive sweating). Any hypovolemia (low blood volume) or dehydration, as well as any significant disturbances in acid-base and electrolyte balance,
must be corrected. This may require temporary discontinuation of Furosemide
Noridem.
There is a possibility of worsening or triggering systemic lupus erythematosus (SLE).

Furosemide Noridem in combination with risperidone
Caution should be exercised, and the risk/benefit ratio of this combination or of concomitant treatment with other potent diuretics should be evaluated before initiating therapy. No increase in mortality incidence has been reported in patients taking other diuretics concomitantly with risperidone. Regardless of treatment, dehydration has been a general risk factor for mortality and should therefore be avoided in elderly patients with dementia.

Other medicines and Furosemide Noridem
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicine.

Combinations not recommended
In isolated cases, intravenous administration of furosemide within 24 hours of taking chloral hydrate (used as a sedative) may cause flushing, excessive sweating, restlessness, nausea, increased blood pressure, and tachycardia. The use of Furosemide Noridem together with chloral hydrate is therefore not recommended.

Furosemide should be taken together with aminoglycosides (a class of antibiotics) and other medicines that may damage hearing only for proven medical reasons, as this combination may cause irreversible damage.

Inform your doctor if you are taking:

cisplatin (used as chemotherapy). When taken concomitantly with furosemide, it increases the risk of hearing damage. It may also cause kidney damage if furosemide is not administered at a low dose (e.g. 40 mg in patients with normal renal function) and with a positive fluid balance.
lithium salts (used to treat psychiatric conditions). Furosemide may cause an increase in serum lithium levels. Your doctor may require blood tests to monitor lithium levels.
an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor antagonist (used to lower blood pressure). When administered for the first time or when the dose is increased in patients taking diuretics, significant drops in blood pressure and deterioration of renal function, including cases of renal failure, may occur. Temporary discontinuation or at least reduction of the furosemide dose for 3 days should be considered before starting treatment with, or increasing the dose of, an ACE inhibitor or an angiotensin II receptor antagonist.
risperidone (used to treat certain psychiatric/mood disorders) – caution should be exercised and the risk/benefit ratio of this combination or of concomitant treatment with furosemide or other potent diuretics should be evaluated before initiating therapy.
levothyroxine (a thyroid medicine) – high doses of furosemide may inhibit the binding of thyroid hormones to transport proteins when administered with levothyroxine, thus causing an initial transient increase in free thyroid hormones, followed by an overall decrease in thyroid hormone levels. Your doctor may require blood tests to monitor thyroid hormone levels. Some medicines may interact with Furosemide Noridem and may alter its effects. These include:
non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (used as a painkiller), which may reduce the effects of furosemide. In dehydrated patients or those with hypovolemia, NSAIDs may cause acute renal failure. Salicylate toxicity may be increased by furosemide.
Phenytoin, used to treat epilepsy – may reduce the effect of Furosemide Noridem.
corticosteroids (anti-inflammatory drugs), carbenoxolone, large amounts of liquorice, and prolonged use of laxatives may increase the risk of hypokalaemia (low potassium levels in the blood).
digitalis preparations (used to treat certain heart conditions) and medicines that induce long QT syndrome – their toxicity may be enhanced by changes in electrolyte concentrations (e.g. hypokalaemia, hypomagnesaemia).
antihypertensive agents, diuretics, or other medicines with the potential to lower blood pressure – when administered concomitantly with furosemide, a greater drop in blood pressure may be expected.
probenecid (used to treat gout), methotrexate (used in cancer therapy), and other medicines eliminated by the kidneys may reduce the effects of furosemide. Conversely, furosemide may reduce the renal elimination of these drugs. In case of treatment with high doses (particularly when furosemide is administered concomitantly with other medicines), an increase in serum levels and an increased risk of adverse effects of furosemide or of the drug combination may occur.
medicines for treating diabetes and medicines that increase blood pressure (such as adrenaline, noradrenaline), as their effects may be attenuated.
Furosemide Noridem counteracts the action of curare-like muscle relaxants and potentiates the action of succinylcholine (used during general anaesthesia).
theophylline (used to treat asthma).
medicines that have a harmful effect on the kidneys – their nephrotoxic effect may be enhanced.
cephalosporins (a class of antibiotics) – in patients receiving concomitant therapy with furosemide and high doses of certain cephalosporins, renal failure may develop.
concomitant use of cyclosporine A (used for rheumatoid arthritis, psoriasis, Crohn’s disease, nephrotic syndrome, and in organ transplantation to prevent rejection) together with furosemide – has been associated with an increased risk of developing gouty arthritis secondary to furosemide-induced hyperuricaemia and cyclosporine-induced impairment of urate excretion.
contrast media – patients at high risk for contrast-induced nephropathy (worsening of renal function, typically temporary) treated with furosemide have shown a higher incidence of deterioration in renal function after receiving contrast media compared to high-risk patients who received only intravenous hydration before the contrast agent.
metolazone when taken with furosemide, may cause intense diuresis (increased urine production) in patients who do not respond to furosemide alone.
alcohol, narcotic analgesics, and barbiturates – these may increase the risk of developing a severe drop in blood pressure upon standing.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor
or pharmacist before taking this medicine.

Pregnancy
Furosemide crosses the placental barrier. You should not take this medicine during
pregnancy unless there are compelling medical reasons and only for a short period. Treatment during pregnancy requires monitoring of fetal growth.

Breastfeeding
Furosemide passes into breast milk and inhibits lactation. You must not breastfeed while being treated with Furosemide Noridem.

Driving and using machines
Some adverse effects (such as an undesirable and pronounced drop in blood pressure) may
impair your ability to concentrate and your reactivity. Therefore, you should not drive or
operate machinery if you experience these effects after administration of Furosemide Noridem.
This is particularly important at the beginning of treatment, when changing medication, or when combined with alcohol.

Furosemide Noridem contains sodium

2 ml, 4 ml, 5 ml vials:
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e. it is
essentially "sodium-free".

25 ml vial
This medicine contains up to 93.25 mg of sodium (mainly from table salt) in each vial. This is equivalent to 4.67% of the maximum recommended daily dietary intake of sodium.

3. How to take Furosemide Noridem

This medicine will be administered to you by a doctor or nurse.
To achieve the best possible response and to prevent counter-regulation, continuous infusion of furosemide is generally preferred over repeated bolus injections.
Use the lowest effective dose required to achieve the desired results.

Adults and adolescents over 15 years of age:
In the absence of diseases requiring specific dosing, the recommended initial dose is between 20 mg and 40 mg of Furosemide Noridem. If necessary, a 20 mg dose may be repeated every 2 hours until the desired effect is achieved. This individually calculated dose can then be administered once or twice daily.

Acute pulmonary edema (fluid in the lungs): the initial dose to be administered is 40 mg of Furosemide Noridem given slowly by intravenous injection. If a satisfactory response is not obtained within one hour, the dose should be increased to 80 mg of Furosemide Noridem administered intravenously.

Treatment of congestive heart failure, liver cirrhosis, or renal failure associated with fluid retention when oral administration is not possible: 20–40 mg of Furosemide Noridem administered by intramuscular or intravenous injection. The dose should be increased by 20 mg at two-hour intervals until the desired effect is achieved. Subsequently, this dose should be administered either as a single dose or divided into two daily doses.

High doses should be administered at an infusion rate not exceeding 4 mg/min.

Continuation of treatment depends on fluid elimination and replacement, as well as on electrolyte loss.

In cases of acute acidosis or alkalosis, alkalinization or acidification of urine may increase diuresis.

Neonates, children, and adolescents under 15 years of age:
Furosemide should generally be administered orally.

Parenteral administration (slow intravenous infusion) is permitted only in life-threatening situations.

For slow intravenous infusion of Furosemide Noridem, the dosage is 1 mg/kg body weight up to a maximum of 20 mg. The switch to oral therapy should be made as soon as possible.

The duration of treatment is determined by the physician according to the type and severity of the disease.

If you take more Furosemide Noridem than you should
The clinical picture in cases of acute or chronic overdose primarily depends on the extent and consequences of fluid and electrolyte loss, such as dehydration and cardiac arrhythmias. Symptoms of overdose include a severe drop in blood pressure (up to shock), acute renal failure, thrombosis (blood clot formation), delirium, weakness or paralysis with loss of muscle tone, apathy (lack of emotion), and confusion.

There is no known specific antidote for furosemide.

The aim of treatment is to replace fluids and correct disturbances in acid-base and electrolyte balance, with regular and frequent monitoring of electrolytes and blood pressure. In addition to preventing and treating serious complications arising from such imbalances and other systemic effects, this corrective action may require both intensive general and specific medical monitoring and therapeutic measures. Hemodialysis does not accelerate the removal of furosemide.

If you forget to take Furosemide Noridem
Your doctor or nurse will have instructions on when to administer this medicine to you. It is unlikely that you will receive this medicine differently than prescribed. However, if you think a dose has been missed, inform your doctor or nurse.

If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Very Common (may affect more than 1 in 10 people):

electrolyte imbalance (also symptomatic), dehydration and hypovolemia, especially in elderly patients, increased blood creatinine and increased triglyceride levels.
For intravenous infusions: low blood pressure, including orthostatic hypotension (see section 2 “Warnings and precautions”). Common (may affect up to 1 in 10 people):
hyponatremia (low sodium concentration in the blood), hypochloremia (low chloride concentration in the blood), hypokalemia (low potassium concentration), increased blood cholesterol, increased serum uric acid levels and gout attacks.
increased urine production.
hepatic encephalopathy (decline in brain function due to severe liver damage) in patients with hepatic insufficiency. (See section 2 “Warnings and precautions”). Therefore, regular monitoring of urine output and electrolytes is necessary, as well as appropriate correction of any imbalances.
haemoconcentration (increase in red blood cells in the blood due to reduced plasma volume)

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

reduced glucose tolerance. Manifestation of latent diabetes mellitus. See section 2 “Warnings and precautions”.
nausea (feeling unwell)
hearing disturbances, although typically transient, especially in patients with renal insufficiency, low blood protein levels (e.g. nephrotic syndrome) and/or when furosemide is administered intravenously very rapidly. Cases of deafness, sometimes irreversible, have been reported following oral or intravenous administration of furosemide.
pruritus, urticaria, skin rashes, bullous dermatitis, erythema multiforme, pemphigoid, exfoliative dermatitis, purpura, photosensitivity reactions.
thrombocytopenia (low platelet count, which may cause bleeding).

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

inflammation of blood vessels
tinnitus (ringing in the ears)
inflammation of the renal tubules
vomiting, diarrhoea
severe anaphylactic or anaphylactoid reactions (e.g. with shock)
leucopenia (low white blood cell count), eosinophilia
paraesthesia (abnormal sensations such as pins and needles)
fever

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

inflammation of the pancreas
cholestasis, elevated transaminase levels (enzymes)
blood disorders (agranulocytosis, aplastic anaemia, haemolytic anaemia)

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

hypocalcemia (low blood calcium levels), hypomagnesemia (low blood magnesium levels), increased blood urea, metabolic alkalosis (a condition occurring when blood becomes too alkaline), pseudo-Bartter syndrome in cases of inappropriate and/or prolonged use of furosemide.
Thrombosis (blood clots).
increased sodium levels in urine, increased chloride levels in urine, urinary retention (in patients with partial obstruction of the urinary tract, see section 2 “Warnings and precautions”)
kidney stones in premature infants (see section 2 “Warnings and precautions”)
renal failure (see section 2 “Other medicines and Furosemide Noridem”)
severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis (AGEP), and drug rash with eosinophilia and systemic symptoms (DRESS)
Dizziness, fainting or loss of consciousness, headache
cases of rhabdomyolysis have been reported, often in clinical settings of severe hypokalemia (see section 2).
Increased risk of persistent patent ductus arteriosus when furosemide is administered to a premature neonate within the first weeks.
following intramuscular injection, local reactions such as pain.
xanthopsia (altered colour vision), thrombophlebitis (inflammation of a vein causing blood clot formation), abnormally high levels of uric acid in the blood, azotemia (accumulation of creatinine and urea). Dehydration is common, especially in the elderly and during summer months.
worsening or activation of systemic lupus erythematosus (SLE)

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse.
You can also report side effects directly via the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Furosemide Noridem

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the vial after “EXP”. The expiry date refers to the last day of that month.
Store the vials in their original packaging to protect them from light.
This medicine does not require any special storage conditions.
After first opening, the product should be used immediately.
After dilution (only the PP infusion bags may be used for dilution):
Chemical and physical in-use stability has been demonstrated for:

24 hours at 2 - 8°C and 23 - 27°C when protected from light.
24 hours at 23 - 27°C under artificial light.

From a microbiological point of view, the product should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and normally should not exceed 24 hours at a temperature of 2 °C to 8 °C, unless reconstitution/dilution has taken place under controlled and validated aseptic conditions. Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Furosemide Noridem contains

The active substance is furosemide. Each 2 ml solution contains 20 mg of furosemide. Each 4 ml solution contains 40 mg of furosemide. Each 5 ml solution contains 50 mg of furosemide. Each 25 ml solution contains 250 mg of furosemide.
The other ingredients are sodium chloride, sodium hydroxide 5N, water for injections.

Description of the appearance of Furosemide Noridem and package contents
Polypropylene vials containing 2 ml of solution, in packs of 5 or 10 vials with aluminum pouch.
Polypropylene vials containing 4 ml of solution, in packs of 5 or 10 vials with or without aluminum pouch.
Polypropylene vials containing 5 ml of solution, in packs of 5 or 10 vials with or without aluminum pouch.
For heat-sealed vials: each pouch contains 5 vials.
Amber Type I glass bottles containing 25 ml of solution, in cartons of 5 or 10 bottles, closed with 20 mm bromobutyl rubber stoppers and sealed with an aluminum cap, with a tamper-evident plastic flip-off cap.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
Noridem Enterprises Limited
Evagorou & Makariou, Mitsi Building 3, Office 115,
1065 Nicosia, Cyprus
Manufacturer:
DEMO S.A. PHARMACEUTICAL INDUSTRY,
21st Km Athinon Lamias National Rd
14568 Krioneri, Attiki, Greece,
T: +30 210 8161802, F: +30 210 8161587.

This medicinal product is authorized in the European Economic Area countries and in the United Kingdom (Northern Ireland) under the following names:
Italy: Furosemide Noridem
Greece: DEMEFUR 10 mg/ml Solution for injection/infusion
Poland: Furosemid Noridem
Hungary: Furosemid Noridem 10 mg/ml oldatos injekció/infúzió

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The following information is intended exclusively for physicians or healthcare professionals:

Method of administration
Parenteral administration of Furosemide Noridem is indicated in cases of reduced intestinal absorption or when a rapid fluid excretion is required.
Furosemide Noridem for intravenous use must be injected slowly, not exceeding a rate of 4 mg per minute. In patients with significant renal function impairment (serum creatinine > 5 mg/dl), a maximum infusion rate of 2.5 mg of furosemide per minute is recommended.
Intramuscular administration should be reserved for exceptional cases where neither oral nor intravenous routes are feasible. It should be emphasized that intramuscular injections are not suitable for the treatment of acute conditions such as pulmonary edema.
The duration of therapy is determined by the physician according to the type and severity of the disease.
This medicinal product should not be infused together with other medicinal products or mixed in the same syringe with other medicinal products.
Furosemide is a solution with a pH ranging between 8.0 – 9.3, without buffering properties. Therefore, the active substance may precipitate at a pH below 7. Consequently, if this solution is diluted, care must be taken to maintain the pH of the solution from slightly alkaline to neutral. Saline solution and Ringer's lactate are suitable diluents. It is recommended to administer the diluted solution as soon as possible.