Lasitone

Patient Information Leaflet: Information for the Patient

Lasitone 25 mg + 37 mg Hard Capsules

furosemide, spironolactone
Please read this leaflet carefully before taking this medicine because 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 give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact 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 taking 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 Lasitone is and what it is used for

This medicinal product contains spironolactone and furosemide, two substances that belong to a group of
medicines called diuretics, which help increase urine production, thereby helping to relieve symptoms caused
by excessive fluid accumulation ( edema ).
Lasitone is used to treat secondary hyperaldosteronism (a condition caused by excessive secretion of the hormone
aldosterone, characterized by low potassium levels in the blood and high blood pressure), when other treatments
have not been effective. Secondary hyperaldosteronism is caused by other diseases such as congestive heart failure,
hepatic cirrhosis with ascites, or nephrotic syndrome.

2. What you should know before taking Lasitone

Do not take Lasitone

• if you are allergic to the active substances or to any of the other ingredients of this medicine (listed in section 6), or to sulfonamides (antibiotic medicines) or their derivatives;
• if your kidneys do not function properly (acute renal failure, anuria, creatinine clearance below 30 ml/min);
• if you have severe liver disease causing disturbances in consciousness (hepatic insufficiency with hepatic coma or precoma);
• if your blood potassium levels are abnormal: either elevated (hyperkalaemia) or very low (severe hypokalaemia);
• if your blood sodium levels are very low (severe hyponatraemia);
• if you are dehydrated or have hypovolemia (a significant decrease in 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 an excessive amount (overdose) of digitalis.

Patients allergic to sulfonamides (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 always take this medicine under close medical supervision.
Pay special attention and consult your doctor before taking Lasitone if:

• you suffer from low blood pressure (hypotension), particularly if you experience significant drops in blood pressure and you are a patient with severe narrowing (stenosis) of the heart (coronary) arteries or blood vessels supplying the brain;
• you are elderly, are taking other medicines that may lower blood pressure, and have other conditions that increase the risk of low blood pressure;
• your voice plays an important role in your life and work, as spironolactone may 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 your condition (the disease may also develop in individuals in whom it was not previously diagnosed following use of the drug);
• you have an obstruction in urinary flow (e.g. bladder emptying disorders, enlarged prostate, hydronephrosis, urethral stenosis). In this case, Lasitone may only be used if urine outflow is ensured, as increased urine production may lead to excessive bladder distension; you have severe liver (hepatic cirrhosis) and kidney problems; your blood protein levels are low and your kidney function is impaired (e.g. in kidney diseases with protein loss, lipid metabolism disorders and fluid retention); therefore, cautious dosing of the medicine is recommended. The effect of the furosemide component may be weakened and its ototoxic (ear-damaging) effect may also be increased.

Your doctor will regularly prescribe tests to monitor levels of certain electrolytes such as potassium and
sodium, as well as glucose and creatinine in the blood. In particular, frequent monitoring of
blood potassium levels will be necessary if:

• your kidneys do not function properly (impaired renal function);
• you are taking other medicines that increase potassium levels.

Premature infants should have kidney function monitored and undergo a kidney ultrasound examination before
using the medicine.
During treatment with Lasitone, it is not recommended to take potassium-sparing diuretics such as spironolactone (antikaliuretics). Concomitant administration of Lasitone with certain medicines, potassium supplements, and potassium-rich foods may lead to severe hyperkalaemia (increased blood potassium levels). Symptoms of severe hyperkalaemia may include muscle cramps, irregular heartbeat, diarrhoea, dizziness, or headache.
Inform your doctor immediately if your blood sodium is low or your blood potassium is high.
In some patients with prostate cancer that has spread to other parts of the body and is resistant to castration, tumour progression has been observed during treatment with spironolactone. Spironolactone may
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 test involving administration of a contrast agent, inform your doctor that you are taking Lasitone, as it is more likely that your kidney function may be impaired.
Lasitone contains lactose: if your doctor has diagnosed you with an intolerance to certain sugars, contact him/her
before taking this medicine.
Lasitone contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially “sodium-free”.
For athletes: using this medicine without therapeutic need constitutes doping and may lead to a positive anti-doping test.
Other medicines and Lasitone
Inform 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:

• mitotane (a medicine used to treat adrenal gland cancer), as spironolactone may reduce its blood levels. Lasitone must not be used together with mitotane;
• potassium salts (used to correct electrolyte imbalances), medicines that reduce potassium excretion, ACE inhibitors (used to treat high blood pressure): these may increase your blood potassium levels (hyperkalaemia);
• non-steroidal anti-inflammatory drugs (NSAIDs): in addition to the risk of increased blood potassium levels, they may reduce the effect of Lasitone; if you are dehydrated or have reduced blood volume (hypovolemia) before starting treatment with Lasitone, taking these medicines concomitantly may cause impairment of kidney function (acute renal failure);
• aminoglycoside antibiotics (e.g. gentamicin, amikacin, neomycin, netilmicin, tobramycin, vancomycin);
• cisplatin (an anticancer medicine): when used concomitantly with furosemide, there is an increased risk of hearing damage. The risk of kidney damage is also increased.
• Therefore, the combination of these medicines should only occur if strictly necessary;
• chloral hydrate (a medicine with sedative properties): taking Lasitone within 24 hours of this medicine may cause a sensation of warmth, sweating episodes, restlessness, nausea, increased blood pressure, and increased heart rate (tachycardia);
• carbenoxolone (used to treat stomach ulcers): may impair the action of spironolactone;
• licorice: taking licorice in high quantities concomitantly may impair the action of Lasitone;
• corticosteroids, carbenoxolone, high quantities of licorice, and laxatives taken for prolonged periods: facilitate reduction of blood potassium (hypokalaemia), increasing the risk of this adverse effect in patients taking Lasitone;
• digitalis medicines, such as digoxin (used to treat heart function disorders): Lasitone increases digoxin blood levels; this may increase the risk of adverse effects;
• medicines that induce long QT syndrome: may increase the risk of adverse effects;
• phenytoin (used to treat 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 lower blood cholesterol levels): concomitant administration of Lasitone may cause hyperchloremic acidosis (increased blood acidity due to excessive loss of sodium bicarbonate) with increased blood potassium (hyperkalaemia);
• antidiabetic medicines (used to maintain normal blood glucose levels) and sympathomimetic medicines (used to treat various conditions): concomitant use of Lasitone may reduce their effectiveness;
• theophylline (used to treat certain respiratory problems) and curare-type muscle relaxants (used in surgical anaesthesia): concomitant use of Lasitone increases the therapeutic effect of these medicines;
• salicylates (belonging to the family of non-steroidal anti-inflammatory drugs) at high doses: the therapeutic action and adverse effects of these medicines may be enhanced;
• cephalosporins (antibiotic medicines): concomitant administration of Lasitone and high doses of certain cephalosporins may lead to impaired kidney function;
• probenecid (used to treat gout), methotrexate (used to treat certain cancers): these may reduce the therapeutic effect of Lasitone, while Lasitone may increase the activity of these medicines. If you take high doses of Lasitone and these medicines, the risk of adverse effects caused by Lasitone increases;
• cyclosporine A (used to prevent transplant rejection): concomitant use with Lasitone increases the risk of developing gouty arthritis (a form of acute inflammatory arthritis);
• nephrotoxic medicines (toxic to the kidneys): Lasitone enhances the kidney-damaging effects already caused by these medicines;
• lithium salts (used to treat mental disorders): Lasitone may enhance the toxic effects of lithium on the heart and brain; your doctor will monitor lithium blood levels during concomitant treatment with Lasitone;
• sucralfate (used to treat stomach ulcers): this medicine reduces the absorption of Lasitone; therefore, Lasitone and sucralfate should not be taken simultaneously or close together;
• ACE inhibitors or angiotensin II receptor antagonists (used to treat high blood pressure): concomitant use of one of these medicines with Lasitone may cause severe drop in blood pressure and impaired kidney function (including renal failure). This is particularly likely at the start of treatment or when increasing the dose of an ACE inhibitor or angiotensin II receptor antagonist; in such cases, your doctor may consider temporarily stopping Lasitone or at least reducing its dose 3 days before starting treatment or increasing the dose;
• risperidone (an antipsychotic medicine used to treat mental disorders): your doctor will consider the risks and benefits before prescribing Lasitone with this medicine due to increased mortality, especially in elderly patients with dementia;
• levotiroxine (a medicine used to stimulate the thyroid gland): high doses of furosemide may lead to an overall decrease in thyroid hormone levels;
• trimethoprim and trimethoprim-sulfamethoxazole.

Your doctor may need to adjust the dose and/or take other precautions if you are taking any of
the following medicines:

• aliskiren (used to treat high blood pressure).

Inform your doctor if you are using abiraterone for prostate cancer treatment.
Lasitone with food and alcohol
Absorption of this medicine is enhanced if taken with a full stomach.
Consumption of alcohol during treatment with Lasitone may impair your ability to drive
vehicles and operate machinery (see section “Driving and use of machines”).
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding,
consult your doctor or pharmacist 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 reduce milk production and because furosemide passes into breast milk.
Driving and use of machinery
This medicine may affect your ability to drive vehicles and operate machinery, as it may reduce
your concentration and slow your reflexes. In particular, be aware that these effects may occur at the beginning of Lasitone treatment or if you consume alcohol during treatment.

3. How to take Lasitone

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts,
consult your doctor or pharmacist.
The recommended dose is 1–3 capsules per day, according to your doctor's instructions.
Method of administration
It is advisable to take the medicine with a full stomach, in the morning during breakfast or lunch.
The capsules should be swallowed whole, without chewing, with a sufficient amount of liquid (approximately 1 glass).
Taking the medicine in the evening is not recommended due to increased urine production.
If you take more Lasitone than you should
If you take more than the prescribed dose, contact your doctor immediately or go to the nearest hospital.
Symptoms of overdose depend on excessive fluid loss through urine, leading to dehydration,
reduced blood volume, excessive blood concentration, heart rhythm disturbances (A-V block and ventricular fibrillation),
severe drop in blood pressure (severe hypotension up to shock), kidney problems (acute renal failure),
formation of blood clots in blood vessels (thrombosis), delirium, muscle paralysis, apathy, and confusion.
If you forget to take Lasitone
Do not take a double dose to make up for the missed dose.
If you stop taking Lasitone
Consult your doctor if you intend to discontinue treatment.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking this medicine and contact your doctor immediately if you experience any of 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 occurs rarely.

The possible side effects are listed below:

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

• electrolyte imbalance (also symptomatic), reduction in blood volume and dehydration (particularly in elderly patients), increased creatinine in the blood, increased blood lipids (triglycerides). The possible development of electrolyte disturbances may be influenced by pre-existing conditions (e.g. hepatic cirrhosis, weakened heart muscle), other medications and nutritional status. Electrolyte imbalances should be corrected, especially if pronounced. In severe cases, vital parameters must be monitored under intensive medical care, and repeated checks of fluid and electrolyte balance, acid-base balance, blood glucose, and diuretic substances must be performed, with correction of any abnormalities as necessary.
• drop in blood pressure and circulatory disturbances; dehydration, especially in elderly patients; reduction in blood volume (hypovolemia), especially in elderly patients; increase in certain blood tests (creatinine and triglycerides);

Common (may affect up to 1 in 10 people)

• increase in blood concentration (haemoconcentration);
• reduction in sodium in the blood (hyponatraemia);
• reduction in chloride in the blood (hypochloraemia);
• reduction in potassium in the blood (hypokalaemia);
• increase in cholesterol;
• increase in uric acid levels in the blood (hyperuricaemia);
• gout (joint inflammation causing pain and swelling);
• brain disturbances as a consequence of liver disorders (hepatic encephalopathy);
• production of a large amount of urine associated with increased frequency of need to urinate (polyuria).

Uncommon (may affect up to 1 in 100 people)

• reduction in the number of blood cells called platelets (thrombocytopenia);
• diabetes and worsening of pre-existing diabetes (impaired glucose tolerance, clinical manifestation of latent diabetes mellitus);
• drowsiness;
• headache;
• dizziness;
• confusion;
• visual disturbances;
• hearing disturbances up to deafness, usually transient, especially in patients with kidney problems (renal insufficiency);
• reduction in blood proteins (hypoproteinaemia) in case of kidney problems (nephrotic syndrome);
• change in heart rhythm (cardiac arrhythmias);
• dry mouth;
• nausea;
• intestinal motility disorders;
• itching, urticaria, skin irritation, formation of blisters on the skin and mucous membranes (symptoms of skin diseases such as bullous dermatitis, exfoliative dermatitis, erythema multiforme, pemphigoid);
• small red or purple spots spread over the skin, with or without joint pain, muscle pain, weakness and fever (may be symptoms of inflammation of blood vessel walls, known as purpura);
• allergic reaction to sunlight manifesting as skin irritation accompanied by itching (photosensitivity reaction);
• sudden, severe muscle pain caused by involuntary contraction of one or more muscles (cramps);
• muscle weakness (myasthenia);
• cramps, muscle spasms, involuntary muscle contractions and tremors (symptoms of a condition known as tetany);
• fatigue.

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

• reduction in white blood cells in the blood (leucopenia);
• increase in white blood cells in the blood (eosinophilia);
• altered sensation in limbs or other body parts (paraesthesia);
• inflammation of blood vessels (vasculitis);
• lowering of the voice (hoarseness);
• change in voice tone (lowering of pitch in women, raising of pitch in men);
• vomiting;
• diarrhoea;
• abnormal hair growth (hirsutism);
• alteration in kidney function (interstitial nephritis);
• alteration of the menstrual cycle;
• inability to achieve or maintain erection (impotence);
• fever.

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

• inadequate production in the bone marrow of all types of blood cells (aplastic anaemia);
• severe reduction in the number of white blood cells called granulocytes (agranulocytosis);
• excessive reduction in haemoglobin concentration in the blood due to abnormal destruction of red blood cells (haemolytic anaemia);
• ringing in the ears (tinnitus);
• alteration in pancreatic function (acute pancreatitis);
• stomach ulcer, even with bleeding;
• impairment of normal bile flow (cholestasis);
• increase in certain liver enzyme levels in the blood (transaminases).

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

• decrease in calcium levels in the blood (hypocalcaemia);
• decrease in magnesium levels in the blood (hypomagnesaemia);
• alteration in blood acidity (metabolic alkalosis);
• increase in urea in the blood;
• increase in potassium in the blood (hyperkalaemia), especially with prolonged therapy; markedly increased potassium levels in the blood which may lead to muscle paralysis and cardiac arrhythmias, as well as dizziness and leg cramps.
• Bartter syndrome (a rare kidney disease) in case of abuse or prolonged use of Lasitone;
• sensation of a "full head";
• formation of blood clots within blood vessels (thrombosis);
• skin disorders such as urticaria, development of red papules or widespread blisters and peeling, particularly 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 generalised exanthematous pustulosis (AGEP), or DRESS syndrome;
• lichenoid reactions, characterised by small itchy, reddish-purple, polygonal lesions on the skin, genitals or in the mouth;
• increase in sodium in the urine;
• increase in chloride in the urine;
• difficulty emptying the bladder (urinary retention, in patients with prostatic hypertrophy, urethral stenosis or other bladder emptying difficulties);
• alteration in kidney function (renal failure), especially if you suffer from reduced blood circulation to the kidneys;
• increased nipple sensitivity to touch;
• breast pain (mastodynia);
• increase in breast volume (dose-dependent effect);
• development of breast tissue in men (reversible effect dependent on dose and duration of therapy);
• progression of castration-resistant prostate cancer;
• onset or worsening of a chronic autoimmune disease affecting various organs and tissues of the body, known as systemic lupus erythematosus;
• inflammation of the liver (hepatitis);
• headache (cephalalgia);
• difficulty in performing movements (ataxia);
• loss of sensitivity and reflex responsiveness (numbness);
• mental confusion and drowsiness (lethargy);
• menstrual cycle irregularities, dose-dependent, including absence of menstruation (amenorrhoea);
• 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 muscles (rhabdomyolysis), generally in the context of severe potassium deficiency in the blood.

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

• kidney stones (nephrolithiasis) or calcifications in the kidneys (nephrocalcinosis) in preterm neonates;
• increased risk of heart abnormalities (patent ductus arteriosus) in premature neonates treated with Lasitone during the first weeks of life.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via 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 below 30°C.
Keep in the original packaging to protect the medicine from light.
Do not use this medicine after the expiry date stated on the carton after “Exp.”. The expiry date refers to the last day of that month.
Do not dispose of any medicine 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 Lasitone contains

• The active substances are: furosemide and spironolactone. Each hard capsule contains 25 mg of furosemide and 37 mg of spironolactone.
• The other components are: Capsule contents: microcrystalline cellulose, monohydrate lactose, talc, sodium carboxymethylstarch (type C) and magnesium stearate. Capsule shell: gelatin and titanium dioxide (E171).

Description of the appearance of Lasitone and contents of the pack
Lasitone 25 mg + 37 mg hard capsules are supplied in a box containing a blister of 20 capsules.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Sanofi S.r.l. - Viale L. Bodio, 37/B - Milan
Manufacturer
Opella Healthcare Poland Sp. z o.o. - Rzeszów Branch - Ul. Lubelska 52 - 35-233 Rzeszów - Poland
Sanofi S.r.l. - S.S. 17 km 22 - 67019 Scoppito (L’Aquila)

The following information is intended exclusively for healthcare professionals:

Laboratory tests
Treatment with Lasitone requires regular monitoring of serum levels of sodium, potassium, creatinine, and glucose.
Frequent monitoring of serum potassium is necessary in patients with impaired renal function and creatinine clearance below 60 mL/min per 1.73 m² of body surface area, as well as in patients receiving Lasitone concomitantly with other drugs that may increase serum potassium levels.
Therefore, during Lasitone therapy, administration of potassium supplements or other potassium-sparing agents is not recommended, except in highly specific circumstances. In any case, treatment must be discontinued if serum sodium falls below 126 mEq/L or serum potassium exceeds 5 mEq/L.

Concomitant use with risperidone
In placebo-controlled studies on risperidone 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 those 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).
Concomitant use of risperidone with other diuretics (mainly low-dose thiazide diuretics) did not result in a similar outcome.
No physiopathological mechanism has been identified to explain these findings, and no pattern related to cause of death has been observed. However, caution must be exercised before deciding to use this combination, and the risks and benefits of this combination or co-administration with other potent diuretics should be carefully considered. No increase in mortality incidence has been reported in patients taking risperidone concomitantly with other diuretics. Regardless of treatment, dehydration has been identified as a general risk factor for mortality and should therefore be avoided in elderly patients with dementia (see Other medicines and Lasitone).