Toralis

Patient Information Leaflet

Toralis, 10 mg+5 mg, tablets
Toralis, 10 mg+10 mg, tablets
Toralis, 20 mg+5 mg, tablets
Toralis, 20 mg+10 mg, tablets
Lisinopril + Torasemide
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it to others. This medicine may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents

1. What Toralis is and what it is used for
2. Important information before taking Toralis
3. How to take Toralis
4. Possible side effects
5. How to store Toralis
6. Contents of the pack and other information

1. What Toralis is and what it is used for

Toralis tablets contain two active substances – lisinopril and torasemide – which help control high blood pressure and symptoms of heart failure, such as swelling caused by fluid retention in the body.
Lisinopril belongs to a group of medicines called angiotensin-converting enzyme (ACE) inhibitors. It works by blocking the production of a substance that raises blood pressure, resulting in the widening of blood vessels and making it easier for the heart to pump blood to all parts of the body.
Torasemide belongs to a group of diuretics called loop diuretics, which increase the amount of water excreted in the urine, thereby reducing the volume of fluid in the blood vessels.
Toralis, which contains both lisinopril and torasemide in a single tablet, is intended for patients who have previously been treated with separate tablets containing lisinopril and torasemide at the same doses as those in Toralis. This reduces the number of tablets the patient needs to take.
Toralis may be used in patients:

• with heart disease known as congestive heart failure (a condition in which the heart does not pump enough blood to meet the body's needs),
• with heart disease known as congestive heart failure and high blood pressure.

2. Important information before taking Toralis

When not to take Toralis:

• if the patient is allergic to lisinopril, torasemide, sulfonylurea derivatives, or any of the other ingredients of this medicine (listed in section 6),
• if the patient is pregnant or breastfeeding,
• if the patient has ever experienced allergic reactions with symptoms such as swelling of the face, lips, tongue, throat, legs, and arms, or difficulty swallowing or breathing (angioedema) during treatment with a medicine from the same group as lisinopril,
• if the patient has hereditary angioedema or angioedema of any cause,
• if the patient has diabetes or kidney dysfunction and is being treated with aliskiren,
• if the patient has severe kidney dysfunction and is unable to pass urine,
• if the patient has severe liver dysfunction,
• if the patient has very low blood pressure (hypotension),
• if the patient has low circulating blood volume,
• if the patient has low levels of sodium or potassium in the blood,
• if the patient has significant difficulty passing urine, e.g. due to benign prostatic hyperplasia,
• if the patient has taken or is currently using sacubitril with valsartan, a medicine used to treat certain types of chronic heart failure in adults, because this increases the risk of angioedema (rapid swelling of tissues under the skin, such as in the throat).

Warnings and precautions
Before starting treatment with Toralis, discuss the following with your doctor or pharmacist:

• if the patient has low blood pressure (symptoms may include dizziness or a feeling of "emptiness" in the head, especially when standing up quickly – in such cases, lie down on your back with legs raised); transient hypotension does not constitute a contraindication to continued use of this medicine,
• if the patient is dehydrated due to treatment with diuretics, dialysis, a low-sodium diet, or prolonged and severe vomiting or diarrhoea,
• if the patient has coronary artery disease, cerebrovascular disease, aortic valve stenosis, significant thickening of the heart muscle, or cardiac arrhythmias,
• if the patient has kidney disorders, including those caused by medications, unilateral or bilateral renal artery stenosis, or requiring hemodialysis,
• if the patient has jaundice,
• if the patient has vascular collagenosis,
• if the patient has ever experienced angioedema,
• if the patient has high fever, sore throat, or swollen lymph nodes (these may be signs of infection due to reduced white blood cell count),
• if the patient is undergoing desensitization treatment for allergies (e.g. to bee or wasp venom) or undergoing LDL apheresis (removal of cholesterol from the blood) – the doctor may discontinue Toralis to prevent possible allergic reactions,
• if the patient has abnormal levels of potassium, sodium, uric acid, creatinine, glucose, cholesterol, or triglycerides, or abnormal blood cell counts,
• if the patient has diabetes or gout,
• if the patient has a dry, persistent cough, worsening at night (this may be caused by lisinopril),
• if the patient is taking any of the following medicines: aliskiren, an angiotensin II receptor antagonist (especially if the patient has kidney dysfunction related to diabetes), potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes, lithium, aminoglycoside antibiotics, or cephalosporins,
• if surgery (including dental procedures) is planned – anaesthetic agents used may cause excessive lowering of blood pressure,
• if the patient is taking any of the following medicines, the risk of angioedema may increase:
  • racecadotril, a medicine used to treat diarrhoea;
  • medicines used to prevent organ transplant rejection or to treat cancer (e.g. temsirolimus, sirolimus, everolimus);
  • vildagliptin, a medicine used to treat diabetes.
• if the patient is pregnant, suspects she may be pregnant, or plans to become pregnant.

Angioedema occurs more frequently in patients of Black race; in addition, lisinopril may be less effective in lowering blood pressure.
The doctor may recommend regular monitoring of kidney function, blood pressure, blood electrolyte levels (e.g. potassium, sodium), blood counts, and blood glucose and lipid levels.
Use of torasemide may lead to positive results in anti-doping tests.
Children and adolescents
Toralis is not recommended for use in children and adolescents.
Toralis and other medicines
Inform your doctor or pharmacist about all medicines currently taken or recently taken, as well as any medicines the patient plans to take.
The doctor may recommend adjusting the dose and/or taking additional precautions. In some cases, discontinuation of one of the medicines may be necessary.
This particularly applies to the following medicines: aliskiren, angiotensin II receptor antagonists, potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes, and other medicines that may increase blood potassium levels (such as heparin and co-trimoxazole, a combination of trimethoprim and sulfamethoxazole), lithium, aminoglycoside antibiotics, or cephalosporins.
Exercise caution when using concurrently:

• diuretics (thiazides), blood pressure-lowering medicines, or medicines used for chest pain (e.g. glyceryl trinitrate), medicines used in severe psychiatric disorders, morphine, or anaesthetics, as hypotension may occur,
• non-steroidal anti-inflammatory drugs (NSAIDs), as they may reduce the effectiveness of lisinopril and torasemide; their combined use may lead to worsening kidney function and increased blood potassium levels, and when high doses of salicylates are used, torasemide may enhance their toxic effects on the central nervous system,
• acetylsalicylic acid in doses exceeding 3 g per day,
• injectable gold salts, as they may cause sudden flushing (especially of the face), nausea, vomiting, and excessive lowering of blood pressure,
• sympathomimetics such as pseudoephedrine or adrenaline, as they may reduce the effectiveness of lisinopril; torasemide may reduce vasoconstriction caused by these medicines,
• cytotoxic medicines (e.g. methotrexate) or systemic corticosteroids, as reduced white blood cell count (leukopenia) may occur,
• corticosteroids and laxatives, as torasemide may increase potassium loss caused by these medicines,
• oral antidiabetic medicines (e.g. metformin) or insulin, as lisinopril may further lower blood glucose levels, especially during the first weeks of treatment and in patients with kidney dysfunction; torasemide may reduce the effectiveness of these medicines,
• cardiac glycosides,
• probenecid, as it may reduce the effectiveness of torasemide,
• aminoglycosides or cisplatin preparations, as torasemide, especially in high doses, may worsen hearing damage and kidney dysfunction caused by these medicines,
• cephalosporins, as torasemide may enhance their nephrotoxic effects,
• theophylline or muscle relaxants containing curare, as torasemide may enhance the effects of these medicines,
• cholestyramine, as it may reduce absorption and thus the effectiveness of torasemide,
• tissue plasminogen activators (medicines used to dissolve blood clots, usually administered in hospital), as they may increase the risk of angioedema,
• medicines commonly used to prevent organ transplant rejection (sirolimus, everolimus, and other mTOR inhibitors) – see "Warnings and precautions",
• potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that increase blood potassium levels (e.g. trimethoprim and co-trimoxazole, used in bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ transplant rejection; and heparin, a medicine used to thin the blood to prevent clots).

Toralis with food, drink, and alcohol
Toralis may be taken with or without food.
Excessive sodium intake may reduce the effectiveness of the medicine.
If in doubt about the amount of alcohol permissible while taking Toralis, consult your doctor, as blood pressure-lowering medicines and alcohol may mutually enhance their effects.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult her doctor or pharmacist before using this medicine.
The doctor will usually recommend discontinuing Toralis before a planned pregnancy or immediately after pregnancy is confirmed, and will prescribe an alternative medicine. Women of childbearing age who do not plan to become pregnant should use an effective method of contraception.
Inform the doctor if you are breastfeeding or plan to breastfeed. Toralis must not be used during breastfeeding. The doctor will recommend an alternative medicine if the patient wishes to breastfeed.
Driving and operating machinery
This medicine may occasionally cause dizziness, blurred vision, or even fainting, especially at the beginning of treatment, during dose changes, or when combined with alcohol. Do not drive or operate machinery until you know how you personally react to Toralis.

3. How to take Toralis

This medicine should always be taken as directed by the physician. In case of doubt, consult your doctor.
Following these instructions ensures optimal treatment results and reduces the risk of adverse effects.
The recommended dose is one tablet per day.

• It is recommended to take the tablet at the same time each day, for example in the morning.
• Swallow the tablet whole with water.
• Toralis may be taken during meals or independently of meals.

The physician will determine the dose individually, depending on the patient's clinical condition and other medications being taken. The response to treatment will be monitored based on blood pressure measurements and certain blood test results. Depending on these results, the physician may recommend a higher or lower dose.
If you feel that the effect of Toralis is too strong or too weak, contact your doctor immediately.

Patients with renal impairment
In patients with impaired kidney function, the physician may adjust the dose depending on blood pressure values and the degree of renal impairment. If the patient is undergoing dialysis, modification of the daily dose of Toralis may be necessary.

Patients with hepatic impairment
In patients with impaired liver function, the physician may adjust the dose depending on blood pressure values and the degree of liver impairment.

Use in children and adolescents
The use of Toralis is not recommended in children and adolescents.

Taking more than the recommended dose of Toralis
Do not take more than the recommended dose. If an excessive number of Toralis tablets has been taken, contact a doctor immediately. Medical assistance may be required.
The following symptoms may occur: dizziness due to excessive lowering of blood pressure, shortness of breath, rapid or slow heartbeat, palpitations, anxiety, cough, gastrointestinal disturbances. The patient may produce excessive urine, feel drowsy or confused.

Missed dose of Toralis
If a patient forgets to take a dose, it should be taken as soon as possible, and the next dose should be taken at the usual time. However, if it is almost time for the next dose, the missed dose should be skipped. Do not take a double dose to make up for a missed tablet.

Stopping treatment with Toralis
Discontinuing treatment with Toralis may lead to worsening of the disease. The medicine should be taken regularly and medical check-ups should continue even if the patient feels well. Do not stop treatment unless advised by a physician.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Toralis contains two active substances – lisinopril and torasemide – which the patient previously took as separate tablets. Adverse effects associated with each active substance may occur. Your doctor may periodically recommend blood and/or urine tests to monitor whether treatment with Toralis is causing any adverse effects.

The adverse effects reported for lisinopril and torasemide are listed below and may occur during treatment with Toralis.

The adverse effects listed below may be serious; therefore, if any of them occur,
seek immediate medical advice:

Common (may occur in less than 1 in 10 patients): dizziness (may be due to low blood pressure), worsening of metabolic alkalosis (symptoms include apathy, confusion, heart rhythm disturbances, seizures, breathing difficulties), reduction in circulating blood volume (symptoms include dizziness, excessive thirst, marked dryness of the oral mucosa, reduced urine output, dark urine colour, or constipation).

Uncommon (may occur in less than 1 in 100 patients): chest pain, inability to pass urine in patients with urinary disorders, disturbances in blood circulation in fingers and toes with colour change and pain (Raynaud's phenomenon).

Rare (may occur in less than 1 in 1,000 patients): excessive drop in blood pressure, fainting, angioedema, blistering rash, marked reduction in urine output, syndrome of inappropriate antidiuretic hormone secretion (symptoms include weakness, muscle cramps, headache, dark urine colour or changes in urine volume, reduced appetite, excessive thirst, diarrhoea or constipation, nausea or vomiting, low mood, confusion, stupor, or coma).

Very rare (may occur in less than 1 in 10,000 patients): severe skin reactions (toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pseudolymphoma of the skin), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) (a combination of several or all of the following symptoms: fever, muscle and joint pain, arthritis, rash, skin changes, including after exposure to light), myocardial infarction or stroke, pancreatitis (symptoms include severe upper abdominal pain radiating to the back, accompanied by marked malaise), acute abdominal pain with cramps, nausea and vomiting (symptoms of intestinal angioedema), liver function disturbances, bronchospasm, bone marrow dysfunction, very low number of red blood cells (symptoms include pale skin, dizziness, feeling of fatigue, shortness of breath, rapid heartbeat, yellowing of the skin and eyes, dark urine), very low platelet count (symptoms include easy bruising, spontaneous bleeding, small red spots on the skin), very low white blood cell count (symptoms include weakness, fever, frequent infections).

Other possible adverse effects of Toralis:

Common (may occur in less than 1 in 10 patients): headache, feeling of fatigue, weakness, cough, diarrhoea, stomach pain, nausea, vomiting, constipation, loss of appetite, muscle cramps, low blood potassium levels (due to torasemide), low blood sodium levels, increased blood uric acid, glucose, triglycerides and cholesterol levels, or increased activity of certain liver enzymes in blood.

Uncommon (may occur in less than 1 in 100 patients): high blood potassium levels (due to lisinopril), vertigo, rapid or irregular heartbeat, hallucinations, tingling sensation, nasal congestion, dryness of the oral mucosa, impotence, increased blood urea or creatinine levels.

Rare (may occur in less than 1 in 1,000 patients): urinary tract infection; high blood urea levels; abnormal blood test results (reduced haemoglobin concentration or haematocrit value); low blood sugar levels in diabetic patients treated with oral antidiabetic drugs or insulin, increased blood bilirubin levels, mood changes, confusion, reduced libido, depression, insomnia, excessive drowsiness, loss of appetite, taste disturbances, indigestion, bloating, smell disturbances, blurred vision, skin redness, rash, urticaria, itching, excessive sweating, hair loss, photosensitivity, psoriasis, shortness of breath, pulmonary infiltrates, laryngitis, bronchitis, nasal obstruction, sore throat, back pain, joint pain, shoulder pain, gout, breast enlargement in men.

Very rare (may occur in less than 1 in 10,000 patients): reduced or absent urine output, tinnitus, hearing loss, sinusitis, lung infection or pneumonia due to hypersensitivity, swollen lymph nodes, autoimmune disease; reduced platelet, red blood cell, or white blood cell (leukocyte) counts.

Lisinopril increases blood potassium levels and therefore may reduce potassium loss caused by torasemide.

Reporting of adverse effects

If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl

Adverse effects can also be reported to the marketing authorisation holder.

Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store Toralis

Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister pack. The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Toralis contains

• The active substances in this medicine are lisinopril and torasemide. Each Toralis, 10 mg + 5 mg tablet contains 10 mg of lisinopril (as lisinopril dihydrate) and 5 mg of torasemide.
  Toralis, 10 mg + 10 mg, tablets: Each tablet contains 10 mg of lisinopril (as lisinopril dihydrate) and 10 mg of torasemide.
  Toralis, 20 mg + 5 mg, tablets:
  Each tablet contains 20 mg of lisinopril (as lisinopril dihydrate) and 5 mg of torasemide.
  Toralis, 20 mg + 10 mg, tablets:
  Each tablet contains 20 mg of lisinopril (as lisinopril dihydrate) and 10 mg of torasemide.

• Other ingredients are: mannitol E421, maize starch, pregelatinised maize starch, microcrystalline cellulose, magnesium stearate.

What Toralis looks like and contents of the pack
Toralis, 10 mg + 5 mg, tablets:
White or almost white, round, biconvex tablets, smooth on both sides, with a diameter of 8.2 mm.
Toralis, 10 mg + 10 mg, tablets:
White or almost white, round, biconvex tablets with the imprint “L10T10” on one side and smooth on the other side, with a diameter of 11.0 mm.
Toralis, 20 mg + 5 mg, tablets:
White or almost white, round, biconvex tablets with a score line and double imprint “LT” on one side and smooth on the other side, with a diameter of 11.0 mm.
Toralis, 20 mg + 10 mg, tablets:
White or almost white, round, biconvex tablets with the imprint “L20T10” on one side and smooth on the other side, with a diameter of 11.0 mm.
Toralis, 10 mg + 5 mg, tablets:
The medicine is available in packs containing 30, 60 or 90 tablets. One blister contains 15 tablets.
Toralis, 10 mg + 10 mg, 20 mg + 5 mg, 20 mg + 10 mg, tablets:
The medicine is available in packs containing 30, 60 or 90 tablets. One blister contains 10 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Aflofarm Farmacja Polska Sp. z o.o.
ul. Partyzancka 133/151
95-200 Pabianice
tel.: (42) 22-53-100

Manufacturer
Aflofarm Farmacja Polska Sp. z o.o.
ul. Szkolna 31
95-054 Ksawerów

This medicinal product is authorised in the European Economic Area under the following names:
Czech Republic: Tolirasim
Lithuania: Tolirasim, 10mg/5mg, tabletės, Tolirasim, 10mg/10mg, tabletės, Tolirasim, 20mg/5mg, tabletės, Tolirasim, 20mg/10mg, tabletės
Poland: Toralis
Slovakia: Lisemid 10 mg/5 mg, Lisemid 10 mg/10 mg, Lisemid 20 mg/5 mg, Lisemid 20 mg/10 mg