LASITONE 25 mg/37 mg Hard Capsule

Зміст інструкції

1. What is Lasitone and what is it used for
2. What you need to know before taking Lasitone
3. How to take Lasitone
4. Possible side effects
5. How to store Lasitone
6. Package Contents and Other Information

Lasitone 25 mg + 37 mg hard capsules
furosemide, spironolactone

Read this leaflet carefully before taking this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

• 1. What Lasitone is and what it is used for
• 2. What you need to know before you take Lasitone
• 3. How to take Lasitone
• 4. Possible side effects
• 5. How to store Lasitone
• 6. Contents of the pack and other information

1. What is Lasitone and what is it used for

This medicine contains spironolactone and furosemide, two substances that belong to a group of
drugs called diuretics, which help to produce more urine, thus helping to relieve discomfort caused
by an excessive accumulation of fluids (edema).
Lasitone is used to treat hyperaldosteronism (a disease caused by excessive secretion of the hormone
aldosterone, which manifests with potassium deficiency in the blood and high blood pressure) of a
secondary type (i.e. caused by other diseases such as congestive heart failure, hepatic cirrhosis in
the ascitic phase or nephrotic syndrome) when other therapies have not been effective.

2. What you need to know before taking Lasitone

Do not take Lasitone

• if you are allergic to the active ingredients or to any of the other ingredients of this medicine (listed in section 6) or to sulfonamides (antibiotic medicines) or related derivatives;
• if your kidneys are not functioning properly (acute renal failure, anuria, creatinine levels less than 30 ml/min);
• if you have severe liver disease that causes altered consciousness (hepatic failure with coma or hepatic precoma);
• if your potassium levels in the blood are altered: either high (hyperpotassaemia) or very low (severe hypopotassaemia);
• if your sodium levels in the blood are very low (severe hyponatraemia);
• if you are dehydrated or in case of hypovolaemia (severe decrease in your blood volume), possibly with low blood pressure;
• if you are pregnant or suspect you may be pregnant;
• if you are breastfeeding;
• if you have taken too much (overdose) of digitalis.

Patients allergic to sulfonamide (e.g. sulfonamide-based antibiotics or sulfonylureas) may show
cross-sensitivity to furosemide.

Warnings and precautions
Talk to your doctor or pharmacist before taking Lasitone.
You must take this medicine always under close medical supervision.
Pay particular attention and ask your doctor for advice before taking Lasitone if:

• you suffer from low blood pressure (hypotension), especially if you suffer from severe drops in blood pressure and you are a patient with severe narrowing (stenosis) of the heart (coronary) arteries or blood vessels that irrigate the brain;
• you are elderly, taking other medicines that can cause a decrease in blood pressure and suffer from other diseases that involve risks of low blood pressure;
• speech is important in your life and work activities, as spironolactone can cause voice changes;
• you have diabetes mellitus;
• you have gout;
• you suffer from a chronic autoimmune disease that can affect various organs and tissues of the body called Systemic Lupus erythematosus, because taking this medicine could worsen the condition of your illness, worsening it (after use of the medicine such disease may start in subjects in whom it is not already established).
• if you have an obstruction of the urinary flow (e.g. bladder emptying disorders, enlarged prostate, hydronephrosis, urethral stenosis). In this case, Lasitone can only be used if the outflow of urine is ensured, as increased urine production can lead to excessive bladder distension; you have severe liver (hepatic cirrhosis) and kidney problems; your protein levels in the blood are low and your kidney function is altered (e.g. in kidney diseases with protein loss, lipid metabolism disorders and fluid retention); the drug should therefore be dosed with caution. The effect of the furosemide component may be weakened and its harmful effect on hearing may also be increased.

Your doctor will regularly prescribe tests to check the amount of certain salts, such as potassium and
sodium, as well as sugars and creatinine in the blood. In particular, frequent checks of
potassium in your blood will be necessary if:

• your kidneys are not functioning properly (impaired kidney function);
• you are taking other medicines that cause an increase in potassium.

Premature infants should monitor kidney function and undergo a renal ultrasound before
using the drug.
During therapy with Lasitone, it is not recommended to take diuretics that act by reducing
potassium losses in the urine such as spironolactone (potassium-sparing diuretics). The concomitant administration of
Lasitone with certain medicines, potassium supplements and potassium-rich foods can lead to severe
hyperpotassaemia (increased potassium levels in the blood). Symptoms of severe hyperpotassaemia may
include muscle cramps, irregular heartbeat, diarrhoea, dizziness or headache.
Tell your doctor immediately if your sodium levels in the blood are low or your potassium levels in the blood are high.
In some patients with prostate cancer that has spread to other parts of the body, resistant to castration,
progression of the tumor has been observed during treatment with spironolactone. Spironolactone can
increase levels of prostate-specific antigen (PSA), a protein produced by the prostate.
Radiological examinations
If you are at risk of developing kidney disease (nephropathy) and need to undergo a diagnostic examination
involving the administration of a contrast agent, you must inform your doctor that you are taking Lasitone,
because your kidney function is more likely to be altered.

Lasitone contains lactose:if your doctor has diagnosed you with intolerance to certain sugars, contact him
before taking this medicine.

For athletes: the use of the drug without therapeutic need constitutes doping and may
still result in positive doping tests.

Other medicines and Lasitone
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicine.
In particular, it is not recommended to take Lasitone with:

• potassium salts(used to restore an alteration of mineral salts), medicines that reducepotassium excretion, ACE inhibitors(used in the treatment of high blood pressure): may increase potassium levels in your blood (hyperpotassaemia);
• non-steroidal anti-inflammatory drugs (NSAIDs): in addition to the risk of increased potassium levels in your blood, they may reduce the effect of Lasitone; if you are dehydrated or your blood volume is already reduced (you suffer from hypovolaemia) before starting treatment with Lasitone, the simultaneous assumption with this category of medicines can cause an alteration of your kidney function (acute renal failure);
• aminoglycoside antibiotics(for example gentamicin, amikacin, neomycin, netilmicin, tobramycin, vancomycin);
• cisplatin(anticancer drug): if used in conjunction with furosemide, the possibility of hearing damage is expected. It also increases the risk of kidney damage.
• The association of these drugs should therefore only occur if absolutely necessary;
• chloral hydrate (medicine with sedative properties):taking Lasitone within 24 hours of taking this medicine can cause a feeling of warmth, sweating, agitation, nausea, increased blood pressure and increased heart rate (tachycardia);
• carbenoxolone(used for the treatment of stomach ulcers): may compromise the action of spironolactone;
• licorice: simultaneous intake of licorice in large quantities may compromise the action of Lasitone;
• corticosteroids, carbenoxolone, large amounts of licorice and laxatives for prolonged periods:facilitate the reduction of potassium in the blood (hypopotassaemia), increasing the risk of this adverse effect in patients taking Lasitone;
• digitals, such as digoxin (used in the treatment of cardiac dysfunction): Lasitone increases levels of digoxin in the blood; may increase the risk of adverse effects;
• medicines that induce QT prolongation syndrome:may increase the risk of adverse effects;
• phenytoin (used for the treatment of epilepsy):may reduce the effect of Lasitone;
• medicines used to lower blood pressure or other diuretics:may lead to an excessive drop in blood pressure;
• cholestyramine(used to reduce cholesterol levels in the blood): simultaneous intake of Lasitone may induce hyperchloremic acidosis (increased amount of acid in your blood due to excessive loss of sodium bicarbonate) with increased potassium in the blood (hyperpotassaemia);
• antidiabetic drugs (used to maintain glucose levels in the blood normal)and sympathomimetic drugs (used to treat various diseases): simultaneous intake of Lasitone may reduce their effectiveness;
• theophylline (used to treat some respiratory problems) and curariform muscle relaxants (used foranesthesia in surgery):simultaneous intake of Lasitone increases the therapeutic action of this category of medicines;
• salicylates (belonging to the family of non-steroidal anti-inflammatory drugs)at high doses :the therapeutic action and adverse effects of this category of medicines may be potentiated;
• cephalosporins (antibiotic drugs):simultaneous administration of Lasitone and high doses of some cephalosporins may lead to an alteration of your kidney function;
• probenecid (used for the treatment of gout), methotrexate( used in the treatment of some cancers): may reduce the therapeutic action of Lasitone, whose action may instead increase the activity of these medicines. If you take high doses of Lasitone and these categories of drugs, the risk of adverse effects caused by Lasitone increases;
• cyclosporine A (used to prevent transplant rejection): simultaneous intake with Lasitone increases the risk of developing gouty arthritis (an acute inflammatory form of arthritis);
• drugs toxic to the kidney (nephrotoxic): Lasitone potentiates the harmful effects already exerted on the kidneys by this category of medicines;
• lithium salts (used for the treatment of mental disorders):Lasitone may potentiate the onset of toxic effects of lithium on the heart and brain; the doctor will check the amounts of this drug in your blood during concomitant treatment with Lasitone;
• sucralfate (used for the treatment of stomach ulcers):this medicine reduces the absorption of Lasitone; therefore Lasitone and sucralfate should not be taken at the same time or shortly after each other;
• ACE inhibitors or angiotensin II receptor blockers (used for the treatment of highblood pressure): simultaneous intake of one of these medicines and Lasitone can cause severe decrease in blood pressure and impairment of kidney function (including acute renal failure). This happens in particular in conjunction with the first administration or the first time you increase the doses of an ACE inhibitor or an angiotensin II receptor blocker; the doctor in these cases will consider the possibility of temporarily suspending the administration of Lasitone or, at least, reducing its dose 3 days before starting treatment or before increasing the doses;
• risperidone (antipsychotic drug, for treating mental disorders):the doctor will consider the risks and benefits before having you take Lasitone together with this medicine for the increased deaths that may occur, especially in elderly patients with dementia;
• levothyroxine (a medicine used to stimulate the thyroid):high doses of furosemide may lead to an overall decrease in thyroid hormone;
• trimethoprim and trimethoprim- sulfamethoxazole;
• aliskiren (used for the treatment of high blood pressure).Tell your doctor if you are using abiraterone for the treatment of prostate cancer.

Lasitone with food and alcohol
The absorption of this medicine is favored if you are on a full stomach.
Taking alcohol during treatment with Lasitone may compromise your ability to drive
vehicles and use machinery (see section “Driving and operating machinery”).

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant or are planning a pregnancy, or if you are breastfeeding
ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Do not take Lasitone during pregnancy.
Breastfeeding
Do not take this medicine if you are breastfeeding, as the two diuretics (furosemide and spironolactone)
contained in the medicine may decrease milk production and because furosemide passes into breast
milk.

Driving and operating machinery
This medicine may impair your ability to drive vehicles and operate machinery, as it may reduce
your level of concentration and decrease the promptness of your reflexes. In particular, be aware that these
disorders may occur at the beginning of therapy with Lasitone or if you take alcohol during treatment.

3. How to take Lasitone

Take this medicine following exactly the instructions of your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended dose is 1-3 capsules per day, as directed by your doctor.

Method of administration
It is recommended to take the medicine on a full stomach in the morning during breakfast or during lunch. The
capsules must be swallowed whole without being chewed, with a sufficient amount of liquid (about 1
glass).
It is not recommended to take the medicine in the evening, due to the increased production of urine.

If you take more Lasitone than you should
In case of taking a dose higher than that prescribed, immediately inform your doctor or go to the
nearest hospital.
The disorders of overdose depend on the excessive loss of fluids with the urine such as dehydration,
decrease in blood volume, excessive concentration of the blood, heart rhythm disturbances
(A-V block and ventricular fibrillation), decrease in blood pressure even severe (severe hypotension
up to shock), kidney disorders (acute renal failure), formation of blood clots in blood vessels
(thrombosis), states of delirium, paralysis of muscles, apathy and confusion.

If you forget to take Lasitone
Do not take a double dose to make up for a missed dose.

If you stop taking Lasitone
Ask your doctor for advice if you intend to stop treatment.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Stop treatment with this medicine and contact your doctor immediatelyif you experience the following symptoms:
difficulty breathing or swallowing, swelling of the face, eyes, lips and/or tongue, skin irritation;
these may be symptoms of a severe allergic reaction (anaphylactic shock), which is rare.
The side effects that may occur are as follows:

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

• electrolyte imbalance (also symptomatic), decreased blood volume and dehydration (especially in elderly patients), increased creatinine in the blood, increased lipids

in the blood (triglycerides). The possible development of electrolyte disorders is influenced by pre-existing conditions
(e.g. cirrhosis of the liver, weakened heart muscle), other medications and nutrition. Electrolyte disorders
must be corrected, especially if they are pronounced. In the most severe cases, vital signs must be
monitored under intensive medical conditions and repeated checks on water and electrolyte balance, acid-base
balance, blood sugar and diuretics must be performed, and deviations corrected if necessary.

• low blood pressure and circulatory disorders; dehydration, especially in elderly patients; decreased blood volume (hypovolemia), especially in elderly patients; increased levels of some blood tests (creatinine and triglycerides);

Common (may affect up to 1 in 10 people)

• increased blood concentration (hemoconcentration);
• decreased sodium in the blood (hyponatremia);
• decreased chlorine in the blood (hypochloremia);
• decreased potassium in the blood (hypokalemia);
• increased cholesterol;
• increased uric acid levels in the blood (hyperuricemia);
• gout (inflammation of the joints causing pain and swelling);
• brain changes as a result of liver disorders (hepatic encephalopathy);
• production of a large amount of urine associated with an increased frequency of the need to urinate (polyuria).

Uncommon (may affect up to 1 in 100 people)

• decreased number of blood cells called platelets (thrombocytopenia);
• diabetes and worsening of initial diabetes (impaired glucose tolerance, clinical manifestation of latent diabetes mellitus);
• drowsiness;
• headache;
• dizziness;
• confusional state;
• vision impairment;
• hearing disorders up to deafness, usually transient, especially in patients with kidney problems (renal insufficiency);
• decreased blood proteins (hypoproteinemia) in case of kidney problems (nephrotic syndrome);
• irregular heartbeat (cardiac arrhythmias);
• dry mouth;
• nausea;
• motility disorders of the intestine;
• itching, hives, skin irritation, formation of blisters on the skin and mucous membranes (these are the symptoms of skin diseases such as bullous dermatitis, exfoliative dermatitis, erythema multiforme, pemphigoid);
• small red or purple spots spread over the skin, associated or not with joint, muscle pain, weakness and fever (these may be symptoms of inflammation of the blood vessel walls, called purpura);
• allergic reaction to sunlight which manifests as skin irritation accompanied by itching (photosensitivity reaction);
• severe sudden muscle pain, caused by involuntary contraction of one or more muscles (cramps);
• muscle weakness (myasthenia);
• cramps, muscle spasms, involuntary muscle contraction and tremors (these are the symptoms of a disease known as tetany);
• fatigue.

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

• decreased white blood cells in the blood (leukopenia);
• increased white blood cells in the blood (eosinophilia);
• alteration of the sensitivity of the limbs or other parts of the body (paresthesia);
• inflammation of the blood vessels (vasculitis);
• lowering of the voice (hoarseness);
• alteration of the tone of the voice (lowering of the tone in women, increase of the tone in men);
• vomiting;
• diarrhea;
• abnormal hair growth (hirsutism);
• alteration of the function of your kidneys (interstitial nephritis);
• alteration of the menstrual cycle;
• inability to achieve and maintain an erection (impotence);
• fever.

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

• insufficient production in the bone marrow of all types of blood cells (aplastic anemia);
• severe reduction in the number of white blood cells called granulocytes (agranulocytosis);
• excessive reduction in hemoglobin concentration in the blood caused by abnormal destruction of red blood cells (hemolytic anemia);
• ringing in the ears (tinnitus);
• alteration of the function of the pancreas (acute pancreatitis);
• stomach ulcer also with bleeding;
• impaired flow of bile (cholestasis);
• increased levels of some liver enzymes in the blood (transaminases).

Not known (frequency cannot be estimated on the basis of available data)

• decreased levels of calcium in the blood (hypocalcemia);
• decreased levels of magnesium in the blood (hypomagnesemia);
• alteration of the acidity of the blood (metabolic alkalosis);
• increased urea in the blood;
• increased potassium in the blood (hyperkalemia), especially in case of prolonged therapy; significantly increased potassium levels in the blood that can lead to muscle paralysis and cardiac arrhythmias, as well as dizziness and leg cramps.
• Bartter's syndrome (a rare disease affecting the kidneys) in case of abuse or prolonged use of Lasitone;
• feeling of fullness in the head;
• formation of blood clots inside the blood vessels (thrombosis);
• skin disorders, such as hives, formation of red or blistered papules spread and scaling especially on legs, arms, hands and feet, which may extend to the face and lips, occasionally accompanied by fever. These may be symptoms of severe skin diseases such as Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis (AGEP) or DRESS syndrome;
• lichenoid reactions, characterized by small, itchy, reddish-purple, polygonal lesions on the skin, genitals or in the mouth;
• increased sodium in the urine;
• increased chlorine in the urine;
• difficulty emptying the bladder (urinary retention, in patients with prostatic hypertrophy, urethral stenosis or other difficulty emptying the bladder);
• alteration of the function of your kidneys (renal insufficiency), especially if you suffer from reduced blood flow to the kidneys;
• increased sensitivity of the nipples to the touch;
• breast pain (mastodynia);
• increased breast volume (dose-dependent effect);
• development of the breast in men (reversible effect that depends on the dose and duration of therapy);
• progression of prostate cancer, resistant to castration;
• onset or worsening of a chronic autoimmune disease, which can affect various organs and tissues of the body called Systemic Lupus Erythematosus;
• inflammation of the liver (hepatitis);
• headache;
• difficulty performing movements (ataxia);
• loss of sensitivity and promptness of reflexes (numbness);
• mental confusion and drowsiness (lethargy);
• irregularities of the menstrual cycle, depending on the dose, including absence of the menstrual cycle (amenorrhea);
• dizziness, fainting and loss of consciousness (due to symptomatic hypotension or other causes);
• severe damage to skeletal muscle and release into the blood of substances contained in the muscles (rhabdomyolysis), generally in the context of a severe potassium deficiency in the blood.

Additional side effects in children
Not known (frequency cannot be estimated on the basis of available data)

• kidney stones (nephrolithiasis) or calcifications at the level of the kidneys (nephrocalcinosis) in preterm infants;
• increased risk of heart changes (patent ductus arteriosus) in premature infants to whom Lasitone is administered during the first weeks of life.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please tell your
doctor or pharmacist. You can also report side effects directly through the national reporting system at:
http://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 Lasitone

Keep this medicine out of the sight and reach of children.
Store at a temperature below 30°C.
Store in the original package to protect the medicine from light.
Do not use this medicine after the expiry date that is stated on the pack after “Exp.”. The expiry date
refers to the last day of that month.
Do not dispose of any medicine in 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 Lasitone contains

• The active ingredients are: furosemide and spironolactone. Each hard capsule contains 25 mg of furosemide and 37 mg of spironolactone.
• The other ingredients are: Capsule content:microcrystalline cellulose, lactose monohydrate, talc, sodium carboxymethylcellulose (type C) and magnesium stearate.

Capsule shell:gelatin and titanium dioxide (E171).

Description of the appearance of Lasitone and package contents
Lasitone 25 mg + 37 mg hard capsules are presented in a box containing a blister pack of 20 capsules.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Sanofi S.r.l. - Viale L. Bodio, 37/B - Milan

Manufacturer
Opella Healthcare Poland Sp. z o.o. - Oddział w Rzeszowie - Ul. Lubelska 52 - 35-233 Rzsezow - Poland
Sanofi S.r.l. - S.S. 17 km 22 - 67019 Scoppito (L’Aquila)
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The following information is intended exclusively for healthcare professionals:
Laboratory tests
Therapy with Lasitone requires regular monitoring of serum sodium, potassium, creatinine and glucose levels.
Frequent monitoring of potassium levels is necessary in patients with impaired renal function and
creatinine clearance less than 60 mL/min per 1.73 m of body surface area, as well as in patients in
whom Lasitone is administered with other drugs that may lead to increased potassium levels.
During therapy with Lasitone, the administration of potassium supplements or
other antikaliuretic drugs is not indicated unless in extremely special cases. In any case, treatment should be
discontinued when sodium levels fall below 126 mEq/l and potassium levels exceed 5 mEq/l.
Concomitant use with risperidone
In studies on risperidone, controlled with placebo, in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone (7.3%; mean age 89 years,
range 75 - 97 years) compared to patients treated with risperidone alone (3.1%; mean age 80 years, range 70 - 96
years) or furosemide alone (4.1%; mean age 80 years, range 67 - 90 years). The concomitant use of risperidone
with other diuretics (mainly low-dose thiazide diuretics) was not associated with a similar
event. No pathophysiological mechanism has been identified to explain this data, and no pattern correlated with the cause of death has been observed. However, before deciding to use this combination, caution must be exercised and the risks and benefits of this combination or
co-administration with other potent diuretics must be considered. There was no increase in mortality incidence in
patients taking other diuretics in conjunction with risperidone. Regardless of treatment,
dehydration was a global risk factor for mortality and therefore must be avoided in
elderly patients with dementia (see Other medicines and Lasitone).