SEGURIL 20 mg/2ml INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Seguril 20 mg/2 ml Solution for Injection

Furosemide

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet:

1. What is Seguril and what is it used for
2. What you need to know before you use Seguril
3. How to use Seguril
4. Possible side effects
5. Storage of Seguril

1. Contents of the pack and other information

1. What is Seguril and what is it used for

Seguril 20 mg/2 ml Solution for Injection is a diuretic belonging to the group of sulfonamides. It works by increasing urine elimination (diuretic) and reducing blood pressure (antihypertensive).

Always under the prescription of your doctor, this medicine is indicated for the treatment of:

• Edema (swelling due to fluid accumulation) associated with congestive heart failure, liver cirrhosis (ascites), and kidney disease, including nephrotic syndrome (priority is given to the treatment of the underlying disease).

• Pulmonary edema (its administration is performed in conjunction with other therapeutic measures).
• Oliguria (decreased urine production) derived from pregnancy complications (gestosis) after compensation of volemia (total blood volume in a person).
• As a coadjuvant measure in cerebral edema.
• Edema following burns.
• Hypertensive crises, along with other hypotensive measures.
• Maintenance of forced diuresis in intoxications.

2. What you need to know before you use Seguril

Read carefully the instructions provided in section 3. “How to use Seguril”.

Do not use Seguril

• If you are allergic to furosemide, to medicines of the Seguril type (sulfonamides), or to any of the other components of this medicine (included in section 6).
• In case of decreased total blood volume (hypovolemia) or dehydration.
• If you have severe kidney problems, accompanied by a decrease in urine elimination (renal insufficiency with anuria), that do not respond to this medicine.
• If you have a severely decreased potassium level in the blood (severe hypokalemia) (see section 4. “Possible side effects”).
• If you have a severe deficiency of sodium salts in the blood (severe hyponatremia).
• In case of pre-coma and coma associated with hepatic encephalopathy.
• If you are breastfeeding a baby.
• If you are pregnant, see section “Pregnancy, breastfeeding, and fertility”.

Warnings and Precautions

Consult your doctor, pharmacist, or nurse before starting to use Seguril.

Be especially careful with this medicine:

• If you have urine elimination problems, especially at the start of treatment.
• If your blood pressure is low (hypotension).
• If you are at special risk of suffering a pronounced drop in blood pressure (for example, in patients with significant coronary or cerebral stenosis).
• If you have latent or manifest diabetes mellitus.
• If you suffer from gout.
• If you have severe kidney problems associated with severe liver disease (hepato-renal syndrome).
• If your blood protein levels are low (hypoproteinemia), in addition to suffering from, for example, nephrotic syndrome (see section 4. “Possible side effects”).
• In premature children (see section 4. “Possible side effects”).
• There is a possibility of exacerbation or activation of systemic lupus erythematosus.
• If you are an elderly person, if you are being treated with medicines that can cause a decrease in blood pressure or if you have other medical conditions that have associated risk of decreased blood pressure.

During your treatment with Seguril, periodic control of your blood levels of sodium, potassium, and creatinine will generally be required, especially if you suffer from severe fluid loss due to vomiting, diarrhea, or intense sweating. Dehydration or hypovolemia, as well as any significant electrolyte and acid-base balance alterations, must be corrected, as this may require interruption of treatment.

Elderly patients with dementia who are taking risperidone must be especially careful with the concomitant use of risperidone and furosemide. Risperidone is a medicine used to treat certain mental illnesses, such as dementia (a disease characterized by several symptoms: memory loss, speech problems, thinking problems).

Use in Athletes

This medicine contains furosemide, which can produce a positive result in doping tests.

Use of Seguril with Other Medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

The effect of treatment may be affected if Seguril is used at the same time as other medicines.

It is not recommended to administer furosemide intravenously during the 24 hours after chloral hydrate has been administered, as it could lead to flushing, sweating, restlessness, nausea, hypertension, and tachycardia.

Certain substances may have their toxicity increased in the ear or kidneys if administered together with this medicine. Therefore, they should only be administered together if there are medical reasons that require it.

Among these substances are:

• Aminoglycoside antibiotics (infection medicines) such as gentamicin,

kanamycin, and tobramycin.

• Cancer medicines (cisplatin).

The concomitant use of Seguril with other medicines may weaken the effect of these medicines, such as:

• Medicines used for diabetes (antidiabetics).
• Medicines used to increase blood pressure (sympathomimetics with a hypertensive effect, for example, epinephrine and norepinephrine).

In other cases, concomitant use may increase the effects of these medicines, such as:

• Asthma medicines (theophylline).
• Muscle relaxants like curare.
• Medicines for depression (lithium salts): may increase the risk of lithium toxicity, including the risk of harmful effects on the heart or brain.
• Patients undergoing treatment with diuretics may suffer from severe hypotension and deterioration of kidney function, especially when an ACE inhibitor (Angiotensin-Converting Enzyme) or an angiotensin II receptor antagonist is administered for the first time or at a high dose.
• If medicines for treating high blood pressure, diuretics, or other medicines that can decrease blood pressure are administered together with furosemide, a more pronounced drop in blood pressure should be anticipated.
• Nephrotoxic medicines: concomitant administration may potentiate the harmful effect of these medicines on the kidneys.

Certain anti-inflammatory and pain medicines (non-steroidal anti-inflammatory drugs, including acetylsalicylic acid) and epilepsy medicines (phenytoin) may reduce the effect of Seguril.

Furosemide may increase the toxicity of salicylates.

Medicines such as probenecid and methotrexate or other medicines that have significant renal elimination may reduce the effect of Seguril. In high-dose treatment, they may increase serum levels and increase the risk of side effects due to furosemide or concomitant administration.

The following substances may increase the risk of reducing potassium levels in the blood (hypokalemia) if administered with Seguril:

• Anti-inflammatory medicines (corticosteroids).
• Carbenoxolone (medicine for the treatment of oral mucosa lesions).
• Large amounts of licorice.
• Prolonged use of laxatives for constipation.

Certain electrolyte disturbances (for example, decreased potassium or magnesium levels in the blood) could increase the toxicity of certain medicines (for example, digitalis medicines and medicines that induce the QT interval prolongation syndrome).

Patients undergoing treatment with Seguril and receiving high doses of certain cephalosporins (antibiotics) may suffer from a decrease in kidney function.

The concomitant administration of Seguril and cyclosporin A (a medicine used to prevent transplant rejection) is associated with an increased risk of gouty arthritis (joint inflammation) secondary to an increase in blood urea levels and kidney urea elimination problems.

Those patients at high risk of suffering from nephropathy (kidney disease) due to contrast media who receive Seguril are more likely to suffer from kidney function deterioration.

The administration of Seguril together with risperidone in elderly patients with dementia could increase mortality.

High doses of furosemide administered with levothyroxine may lead to an initial transient increase in free thyroid hormones, followed by a general decrease in total thyroid hormone levels.

Pregnancy, Breastfeeding, and Fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

If you are pregnant, you will only use Seguril if there are medical reasons that require it.

During breastfeeding, do not administer Seguril. If its administration is essential, your doctor may require you to interrupt breastfeeding, as furosemide passes into breast milk.

Driving and Using Machines

This medicine may cause dizziness or drowsiness. This may occur more frequently at the start of treatment, when your doctor increases the dose, or if you consume alcohol. Do not drive or operate tools or machines if you feel dizzy or drowsy.

Certain side effects (e.g., an undesirable pronounced drop in blood pressure) may impair the ability to concentrate and react, and therefore constitute a risk in situations where these skills are especially important (e.g., operating vehicles or machinery).

Seguril 20 mg/2 ml Solution for Injection Contains Sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 1 ml of solution for injection; that is, it is essentially “sodium-free”.

3. How to Use Seguril

Follow exactly the administration instructions of this medicine indicated by your doctor, pharmacist, or nurse. In case of doubt, consult your doctor, pharmacist, or nurse again.

Seguril 20 mg/2 ml Solution for Injection can be administered by intravenous or intramuscular route.

These routes are indicated when intestinal absorption is altered or rapid fluid elimination is necessary.

Intramuscular administration will be used when oral or intravenous administration is not possible. This route is not recommended in severe situations such as pulmonary edema.

The active substance furosemide by intravenous route should be injected or perfused slowly at a speed not exceeding 4 mg per minute. In patients with severe kidney problems (serum creatinine >5 mg/dl), it is recommended that the perfusion speed does not exceed 2.5 mg per minute.

Furosemide in the form of a solution for injection should not be mixed in the same syringe or perfused together with other medicines.

Your doctor or nurse should take into account that the pH value of the solution to be perfused should be neutral or slightly alkaline, and therefore should not use acidic solutions, as the active ingredient could precipitate. Isotonic saline solution is the suitable diluent. It is recommended that the solution ready for administration be used as soon as possible.

Your doctor will indicate your daily dose and the duration of your treatment. Do not stop your treatment before. The dose is specific for you and may be modified by your doctor based on your response to treatment.

In Adults:the maximum recommended dose of furosemide is 1500 mg per day, although in exceptional cases it may reach 2000 mg.

Use in Children and Adolescents

The maximum recommended daily dose of furosemide in children for parenteral administration is 1 mg of furosemide per kg of body weight up to a maximum of 20 mg of furosemide per day. As soon as possible, the treatment will be switched to oral administration.

In infants and children under 15 years: the administration of furosemide by parenteral route (eventually in slow perfusion) is contraindicated, it will only be performed in cases where it represents a vital risk.

If You Use More Seguril Than You Should

In case of overdose or accidental ingestion, consult your doctor or go to the emergency department of the nearest hospital, accompanied by this leaflet, or call the Toxicology Information Service, telephone 91 562 04 20, indicating the medicine and the amount ingested or administered.

An accidental overdose could lead to a severe decrease in blood pressure (which may evolve into shock), kidney problems (acute renal failure), coagulation problems (thrombosis), delirium, flaccid paralysis affecting soft muscles, apathy, and confusion.

No specific antidote is known.

In case of overdose, treatment will be based on symptoms.

If You Forget to Use Seguril

Do not use a double dose to make up for forgotten doses.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Adverse effects have been grouped according to their frequency:

Very Common(may affect more than 1 in 10 patients)

• electrolyte alterations (including symptomatic), dehydration, and decrease in total blood volume (hypovolemia), particularly in elderly patients, elevated creatinine, and triglyceride levels in blood.
• with intravenous perfusion: decrease in blood pressure (hypotension, including orthostatic hypotension, problems maintaining an upright position).

Common(may affect up to 1 in 10 patients)

• decrease in sodium (hyponatremia), chloride (hypochloremia), potassium (hypokalemia) levels, increase in cholesterol and uric acid levels in blood, and gout attacks.
• increase in urine volume.
• mental alterations (hepatic encephalopathy) in patients with liver problems (hepatocellular insufficiency).
• increase in blood viscosity (hemoconcentration).

Uncommon(may affect up to 1 in 100 patients)

• alteration of glucose tolerance. Latent diabetes mellitus may manifest.
• nausea.
• hearing disorders, although usually transient, especially in patients with renal insufficiency, decreased protein levels in blood (hypoproteinemia), and/or after too rapid intravenous administration of furosemide. Deafness (sometimes irreversible).
• itching, rash, eruptions, blisters, and other more severe reactions such as erythema multiforme, pemphigoid, exfoliative dermatitis, purpura, and photosensitivity reaction.
• decrease in platelet levels (thrombocytopenia).

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

• allergic inflammation of blood vessels (vasculitis).
• allergic renal reaction (tubulointerstitial nephritis).
• vomiting, diarrhea.
• subjective sensation of ringing (tinnitus).
• severe allergic reactions (anaphylactic or anaphylactoid) (e.g., with shock).
• sensation of tingling in the limbs (paresthesia).
• decrease in white blood cell levels (leukopenia), increase in a type of white blood cell, eosinophils (eosinophilia).
• fever.

Very Rare(may affect up to 1 in 10,000 patients)

• inflammation of the pancreas (acute pancreatitis).
• liver problem (cholestasis), increase in liver enzymes (transaminases).
• decrease in a type of white blood cell, granulocytes (agranulocytosis), decrease in red blood cell count (aplastic anemia or hemolytic anemia).

Frequency Not Known(cannot be estimated from available data)

• decrease in calcium (hypocalcemia), magnesium (hypomagnesemia) levels, increase in urea level in blood, metabolic alkalosis, pseudo-Bartter syndrome in case of misuse and/or prolonged use of furosemide.
• alteration of blood coagulation (thrombosis).
• increase in sodium and chloride levels in urine, urine retention (in patients with partial obstruction of urine flow), formation of kidney stones (nephrocalcinosis/nephrolithiasis) in premature infants, renal failure.

• severe vesicular reactions of the skin and mucous membranes (Stevens-Johnson syndrome), severe skin alteration characterized by blister formation and exfoliative lesions (toxic epidermal necrolysis), acute generalized exanthematous pustulosis (AGEP), and drug hypersensitivity syndrome with eosinophilia and systemic symptoms (DRESS), lichenoid reactions, characterized as small, itchy, reddish-purple lesions, with a polygonal shape, that appear on the skin, genitals, or mouth.

• exacerbation or activation of systemic lupus erythematosus.
• dizziness, fainting, and loss of consciousness, headache.
• cases of rhabdomyolysis have been reported, often in cases with severe hypokalemia (see section "Do not use Seguril").
• increased risk of persistence of the "ductus arteriosus permeable" when furosemide is administered to premature infants during the first weeks of life.
• after intramuscular injection of furosemide, local reactions such as pain at the injection site may appear.

Like other diuretics, after prolonged administration of this medicine, there may be an increase in the elimination of sodium, chloride, water, potassium, calcium, and magnesium. These alterations manifest with intense thirst, headache, confusion, muscle cramps, painful muscle contraction, especially in the limbs (tetany), muscle weakness, alterations in heart rhythm, and gastrointestinal symptoms.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Seguril

Keep this medicine out of sight and reach of children.

Store protected from light.

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Packaging Contents and Additional Information

Composition of Seguril 20 mg/2 ml injectable solution

• The active principle is furosemide. Each 2 ml ampoule contains 21.328 mg of furosemide sodium, equivalent to 20 mg of furosemide, at a concentration of 10 mg of furosemide per ml of injectable solution.
• The other components are: sodium hydroxide, sodium chloride, and water for injectable preparations.

Appearance of the Product and Packaging Contents

It is a transparent and practically colorless solution.

Each packaging contains 5 ampoules of 2 ml of injectable solution.

Marketing Authorization Holder and Manufacturer

Holder

sanofi-aventis, S.A.

C/ Rosselló i Porcel, 21

08016 Barcelona

Spain

Manufacturer

Delpharm Dijon

6, Boulevard de l’Europe

21800 Quetigny

France

or

Chinoin Private Co. Ltd

Csanyikvölgy site, 3510 Miskolc

Csanyikvölgy

Hungary

Date of the Last Revision of this Prospectus: October 2022

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/