FUROSEMIDE COMBIX 40 mg TABLETS

2. What you need to know before taking Furosemide Combix

Read carefully the instructions provided in section 3. "How to take Furosemide Combix".

Do not take Furosemide Combix

• If you are allergic to furosemide, to medications of the furosemide type (sulfonamide), or to any of the other components of this medication (listed 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 medication.

• If you have a severely decreased potassium level in your blood (severe hypokalemia).
• If you have a severe deficiency of sodium salts in your 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 the "Pregnancy, breastfeeding, and fertility" section.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Furosemide Combix.

Be particularly careful with this medication:

• If you have problems with urine elimination, especially at the start of treatment.
• If your blood pressure is low (hypotension).
• If you are at high risk of experiencing a significant drop in blood pressure (e.g., in patients with significant coronary or cerebral stenosis).
• If you have latent or manifest diabetes mellitus.
• If you have 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 "Possible side effects" section).
• In premature infants (see "Possible side effects" section).
• If you are an elderly person, if you are being treated with medications 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 this medication, 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 your doctor may require the interruption of treatment.

Elderly patients with dementia who are taking risperidone should be particularly careful when taking this medication. Risperidone is a medication used to treat certain mental illnesses, such as dementia (a disease characterized by several symptoms: memory loss, speech problems, thinking problems).

Using Furosemide Combix with other medications

Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medication.

Inform your doctor if you are being treated with medications for:

• High blood pressure (aliskiren).

Some substances may have increased toxicity in the ear and kidney if administered with this medication. Therefore, if they are administered together, it should be under strict medical control. These substances include:

• Aminoglycoside antibiotics (infection medications) such as gentamicin, kanamycin, and tobramycin.
• Cancer medications (cisplatin).

This medication and sucralfate should not be administered together with an interval of less than 2 hours, as the effect of Furosemide Combix may be reduced.

This medication may weaken the effect of other medications such as:

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

It may also increase the action of other medications such as:

• Asthma medications (theophylline).
• Muscle relaxants such as curare.
• Antidepressant medications (lithium), which may potentiate the harmful effects of lithium on the heart or brain.
• Salicylates (may increase their toxicity)
• Blood pressure-lowering medications (such as diuretics, ACE inhibitors, or angiotensin II receptor antagonists).
• Medications toxic to the kidneys.

Some medications for inflammation and pain, such as indomethacin (non-steroidal anti-inflammatory drugs, including acetylsalicylic acid), and medications for epilepsy (phenytoin) may reduce the effect of Furosemide Combix.

Additionally, medications such as probenecid and methotrexate, or other medications that have significant renal secretion, may reduce the effect of Furosemide Combix or increase its adverse effects (by reducing the renal elimination of these medications).

The following substances may reduce potassium levels in the blood (hypokalemia) if administered with Furosemide Combix:

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

Certain electrolyte disturbances (e.g., decreased potassium (hypokalemia) or magnesium (hypomagnesemia) levels in the blood) may increase the toxicity of some heart medications (e.g., digitalis and medications that induce QT interval prolongation syndrome).

Some patients who receive high doses of cephalosporin antibiotics may experience decreased kidney function.

The concomitant administration of Furosemide Combix and cyclosporin A may produce gouty arthritis.

Patients at high risk of nephropathy (kidney disease) due to contrast who receive Furosemide Combix may experience deterioration of kidney function.

The administration of Furosemide Combix together with risperidone in elderly patients with dementia may increase mortality.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

If you are pregnant, you will only use Furosemide Combix under strict medical indication.

During breastfeeding, Furosemide Combix should not be administered. If its administration is essential, your doctor may require you to interrupt breastfeeding, as Furosemide Combix passes into breast milk.

Driving and using machines

This medication 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.

Furosemide Combix contains lactose

If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

Use in athletes

Patients should be warned that this medication contains furosemide, which may produce a positive result in doping tests.

3. How to take Furosemide Combix

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

Remember to take your medication.

Take Furosemide Combix on an empty stomach, swallowing it whole and with a sufficient amount of liquid.

If you think the action of this medication is too strong or too weak, inform your doctor or pharmacist.

Your doctor will prescribe the lowest sufficient dose to produce the desired effect.

In adults, treatment is recommended to start with half, one, or two tablets (20 to 80 mg of furosemide) daily. The maintenance dose is half to one tablet per day, and the maximum dose will be indicated by your doctor and will depend on your response to treatment.

Use in children

In infants and children, the recommended daily dose is 2 mg/kg of body weight, up to a maximum of 40 mg per day.

Your doctor will indicate the duration of your treatment with this medication. Do not suspend your treatment before.

If you take more Furosemide Combix than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately, go to the emergency department of the nearest hospital with this leaflet, or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication 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, paralysis affecting soft muscles (flaccid paralysis), apathy, and confusion.

No specific antidote is known.

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

If you forget to take Furosemide Combix

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

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

Side effects have been grouped by frequency according to the following classification:

Very common: may affect more than 1 in 10 patients

Common: may affect up to 1 in 10 patients

Uncommon: may affect up to 1 in 100 patients

Rare: may affect up to 1 in 1,000 patients

Very rare: may affect up to 1 in 10,000 patients

Frequency not known (cannot be estimated from available data).

Metabolic and nutritional disorders

Very common: electrolyte disturbances (including symptomatic ones), dehydration, and decreased total blood volume (hypovolemia), particularly in elderly patients, elevated creatinine and triglyceride levels in the blood.

Common: decreased sodium (hyponatremia), chloride (hypochloremia), potassium (hypokalemia) levels, increased cholesterol and uric acid levels in the blood, gout attacks.

Uncommon: altered glucose tolerance. Latent diabetes mellitus may be revealed.

Frequency not known: decreased calcium (hypocalcemia), magnesium (hypomagnesemia) levels, increased urea level in the blood, metabolic alkalosis, pseudo-Bartter syndrome in case of misuse and/or prolonged use of furosemide.

Vascular disorders

Rare: allergic inflammation of blood vessels (vasculitis).

Frequency not known: alteration of blood coagulation (thrombosis).

Renal and urinary disorders

Common: increased urine volume.

Rare: renal allergic reaction (interstitial nephritis).

Frequency not known: increased sodium and chloride levels in the urine, urine retention (in patients with partial obstruction of urine flow), kidney stone formation (nephrocalcinosis/nephrolithiasis) in premature infants, renal failure.

Gastrointestinal disorders

Uncommon: nausea.

Rare: vomiting, diarrhea.

Very rare: acute pancreatitis.

Hepatobiliary disorders

Very rare: liver problem (cholestasis), increased liver enzymes (transaminases).

Ear and labyrinth disorders

Uncommon: hearing disorders, although transient, especially in patients with renal insufficiency, decreased protein levels in the blood (hypoproteinemia), and/or after too rapid intravenous administration of furosemide, deafness (sometimes irreversible)

Very rare: subjective sensation of ringing (tinnitus).

Skin and subcutaneous tissue disorders

Uncommon: itching, rash, blisters, and other more severe reactions such as erythema multiforme, pemphigoid, exfoliative dermatitis, purpura, and photosensitivity reaction.

Frequency not known: severe skin and mucous membrane reactions (Stevens-Johnson syndrome), severe skin disorder characterized by blistering and exfoliative lesions (toxic epidermal necrolysis), and acute generalized exanthematous pustulosis (AGEP) and drug hypersensitivity syndrome with eosinophilia and systemic symptoms (DRESS).

Immune system disorders

Rare: severe allergic reactions (anaphylactic or anaphylactoid) (e.g., with shock).

Nervous system disorders

Common: mental alterations in patients with liver problems (hepatic encephalopathy)

Rare: sensation of tingling in the limbs (paresthesias).

Frequency not known: dizziness, fainting, and loss of consciousness (caused by symptomatic hypotension).

Blood and lymphatic system disorders

Common: increased blood viscosity (hemoconcentration).

Uncommon: decreased platelet levels (thrombocytopenia).

Rare: decreased white blood cell levels (leukopenia), increased eosinophil levels.

Very rare: decreased granulocyte levels (agranulocytosis), decreased red blood cell count (aplastic anemia, hemolytic anemia).

Congenital, familial, and genetic disorders

Frequency not known: increased risk of persistent ductus arteriosus when furosemide is administered to premature infants during the first weeks of life.

General disorders and administration site conditions

Rare: fever.

As with other diuretics, after prolonged administration of this medication, there may be an increased elimination of sodium, chloride, water, potassium, calcium, and magnesium. These alterations manifest as intense thirst, headache, confusion, muscle cramps, painful muscle contraction (tetany), muscle weakness, cardiac rhythm alterations, and gastrointestinal symptoms.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medications: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Furosemide Combix

Keep this medication out of sight and reach of children.

Store below 25°C.

Keep in the original packaging to protect it from light.

Do not use this medication after the expiration date shown on the packaging after CAD. The expiration date is the last day of the month indicated.

Medications should not be disposed of through wastewater or household waste. Deposit the packaging and medications you no longer need at the SIGRE collection point in the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Packaging Content and Additional Information

Composition of Furosemida Combix

• The active ingredient is furosemide. Each tablet contains 40 mg of furosemide.
• The other components are: lactose monohydrate, pregelatinized corn starch, anhydrous colloidal silica (E551), corn starch, povidone K 30, sodium lauryl sulfate, poloxamer 407, talc (E553b), and magnesium stearate (E470b).

Appearance of the Product and Packaging Content

White or off-white, round, flat tablets with beveled edges, engraved with "40" on one side and scored on the other.

The tablet can be divided into equal doses.

PVC-Aluminum blisters (standard and perforated). Containers containing 10 and 30 tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder

Laboratorios Combix, S.L.U.

C/Badajoz, 2. Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Zydus France

ZAC Les Hautes Patures

Parc d'activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

Date of the Last Revision of this Leaflet: April 2024

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