SEGURIL 250 mg/25 ml INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Seguril 250 mg/25 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 further information

1. What is Seguril and what is it used for

Seguril 250 mg/25 ml Solution for Injection for infusion is a diuretic belonging to the group of sulfonamides. It acts by increasing urine elimination (diuretic) and reducing blood pressure (antihypertensive).

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

• Kidney filtration problems (through the kidneys).
• Acute renal failure, in order to maintain fluid elimination and to facilitate parenteral nutrition, as long as some filtration capacity remains.
• Chronic renal failure in the pre-dialysis stage, with fluid retention and hypertension.
• Terminal renal failure, to maintain functional renal capacity.
• Nephrotic syndrome in patients in whom a dose of furosemide of 120 mg per day orally is not sufficient; priority is given to the treatment of the underlying disease.

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 suffer from serious kidney problems, accompanied by a decrease in urine elimination (renal failure with anuria), that do not respond to this medicine.

• If your blood potassium level is severely decreased (severe hypokalemia) (see section 4. “Possible side effects”).

• If you suffer from 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”.

Seguril 250 mg/25 ml Solution for Injection should not be administered as an intravenous bolus. It should only be infused using infusion pumps that control the volume or speed to avoid the risk of accidental overdose.

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 serious 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 an associated risk of decreased blood pressure.

During your treatment with Seguril, periodic monitoring 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 or acid-base imbalance, should be corrected, as this may require interruption of treatment.

Elderly patients with dementia who are taking risperidone should be especially careful when using risperidone and furosemide concomitantly. 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.

These substances include:

• 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 such as 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 who are being treated with diuretics may suffer from severe hypotension and deterioration of renal 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 high blood pressure, diuretics, or other medicines that can decrease blood pressure are administered together with furosemide, a more pronounced decrease in blood pressure should be expected.
• 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. At high doses, they may increase serum levels and increase the risk of adverse effects due to furosemide or concomitant administration.

The following substances may increase the risk of reducing blood potassium levels (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 blood potassium levels (hypokalemia) or magnesium levels (hypomagnesemia)) may increase the toxicity of certain medicines (for example, digitalis medicines and medicines that induce the QT interval prolongation syndrome).

Patients treated with Seguril who receive high doses of certain cephalosporins (antibiotics) may suffer from decreased renal 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 deterioration of renal function.

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, pharmacist, or nurse 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, Seguril should not be administered. 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 happen more frequently at the start of treatment, when your doctor increases the dose, or if you consume alcohol. Do not drive or use tools or machines if you feel dizzy or drowsy.

Certain side effects (e.g., a pronounced undesirable 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 250 mg/25 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, as indicated by your doctor, pharmacist, or nurse. In case of doubt, consult your doctor, pharmacist, or nurse again.

Seguril 250 mg/25 mg Solution should not be administered as an intravenous bolus.

It should be used exclusively by intravenous infusion.

It should only be infused using infusion pumps that control the volume or speed to avoid the risk of accidental overdose.

The active substance furosemide should be injected or infused slowly, at a rate not exceeding 4 mg per minute. In patients with serious kidney problems (serum creatinine >5 mg/dl), it is recommended that the infusion rate 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 infused together with other medicines.

Your doctor or nurse should take into account that the pH value of the solution to be infused 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

In children, the maximum recommended daily dose of furosemide 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, treatment will be switched to oral administration.

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

In these cases, the presentation of Seguril 20 mg/2 ml Solution for Injection may be used.

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.

Your doctor or nurse will ensure that you receive the correct dose.

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 of 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 disturbances (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, i.e., 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 disturbances (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 be manifested.
• nausea.
• hearing disorders, usually of a transient nature, 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 kidney 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 or hemolytic anemia).

Frequency Not Known(cannot be estimated from the 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, kidney failure.

• severe vesicular reactions of the skin and mucous membranes (Stevens-Johnson syndrome), severe skin disorder characterized by blistering 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, red-purple lesions, polygonal in shape, appearing 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 where there is a severe decrease in potassium levels in the blood (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.

As with 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 contraction of the muscles, 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 the 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. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Seguril 250 mg/25 ml injectable solution

• The active ingredient is furosemide. Each 25 ml ampoule contains 266.6 mg of furosemide sodium, equivalent to 250 mg of furosemide, at a concentration of 10 mg of furosemide per ml of injectable solution.
• The other components are: sodium hydroxide, mannitol, and water for injectable preparations.

Appearance of the Product and Package Contents

It is a transparent and practically colorless solution.

Each package contains 6 ampoules of 25 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 on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/