Tolutris

Leaflet attached to the packaging: patient information

Tolutris, 40 mg + 5 mg + 12.5 mg, tablets

Tolutris, 80 mg + 5 mg + 12.5 mg, tablets

Tolutris, 80 mg + 10 mg + 12.5 mg, tablets

Tolutris, 80 mg + 10 mg + 25 mg, tablets

Telmisartan + Amlodipine + Hydrochlorothiazide

You should carefully read the contents of this leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult your doctor or pharmacist.
• This medicine has been prescribed to you specifically. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What is Tolutris and what is it used for

Tolutris tablets contain three active substances: telmisartan, amlodipine, and hydrochlorothiazide.
All these substances help control high blood pressure.

• Telmisartan belongs to a group of medicines called angiotensin II receptor antagonists. Angiotensin II is a substance produced in the body that causes blood vessels to constrict, thereby increasing blood pressure. Telmisartan blocks the action of angiotensin II, causing blood vessels to dilate and blood pressure to decrease.
• Amlodipine belongs to a group of medicines called calcium antagonists, which work by relaxing and widening blood vessels, making it easier for blood to flow through them.
• Hydrochlorothiazide belongs to a group of substances called thiazide diuretics, which increase urine production, leading to a decrease in blood pressure.

Tolutris is used to treat high blood pressure (essential hypertension) in patients whose blood pressure is adequately controlled with the individual substances at the same doses as in the combination, but in separate tablets.

2. Important information before taking Tolutris

When not to take Tolutris

• If the patient is allergic to telmisartan or any of the other ingredients of this medicine (listed in section 6).
• If the patient is allergic to hydrochlorothiazide or other sulfonamide-derived medicines.
• If the patient is allergic to amlodipine or other calcium antagonists.
• After the third month of pregnancy. (It is also recommended to avoid taking Tolutris during early pregnancy - see "Pregnancy").
• If the patient has severe liver disease, such as cholestasis or biliary obstruction (disorders of bile flow from the liver and gallbladder) or any other severe liver disease.
• If the patient has severe kidney disease.
• If the doctor has found that the patient has low potassium or high calcium levels in the blood that do not improve with treatment.
• If the patient has diabetes or kidney problems and is being treated with a blood pressure-lowering medicine containing aliskiren.
• If the patient has very low blood pressure (severe hypotension).
• If the patient has narrowing of the aortic valve in the heart (aortic stenosis) or cardiogenic shock (a condition in which the heart is unable to supply the body with enough blood).
• If the patient has heart failure after a recent heart attack.

If any of the above situations apply to the patient, they should inform their doctor or pharmacist before taking Tolutris.

Warnings and precautions

Before starting to take Tolutris, the patient should discuss the following with their doctor:

• Low blood pressure (hypotension), which is more likely to occur if the patient is dehydrated (has excessive water loss) or has a low salt level due to the use of diuretics, a low-salt diet, diarrhea, vomiting, or hemodialysis;
• Significant increase in blood pressure (hypertensive crisis);
• Kidney disease or kidney transplant;
• Narrowing of the renal artery (narrowing of the blood vessels of one or both kidneys);
• Liver disease;
• Heart problems, including heart failure and recent heart attack;
• Diabetes;
• Gout;
• High aldosterone levels (water and salt retention in the body, along with electrolyte imbalance);
• Systemic lupus erythematosus (also known as "lupus" or "SLE"), a disease in which the immune system attacks the body;
• If the patient has a history of malignant skin tumors or if an unexpected skin change occurs during treatment. Treatment with hydrochlorothiazide, especially in high doses and for a long time, may increase the risk of certain types of skin cancer and lip cancer (non-melanoma skin cancer). During Tolutris treatment, the patient should protect their skin from sunlight and UV radiation.
• Hydrochlorothiazide may cause rare reactions that lead to vision loss and eye pain. These may be symptoms of fluid accumulation in the vascular layer surrounding the eye (excessive fluid accumulation between the choroid and sclera) or increased pressure in the eyeball, which can occur within a few hours to a few weeks after taking Tolutris. If left untreated, they can lead to permanent vision damage. If the patient has previously been allergic to penicillin or sulfonamides, they may be more prone to developing this disease.
• If the patient has a history of breathing or lung problems (including pneumonia or fluid accumulation in the lungs).
  If the patient experiences severe shortness of breath or difficulty breathing after taking Tolutris, they should seek medical help immediately.

Before starting to take Tolutris, the patient should tell their doctor if they are taking:

• Digoxin,
• any of the following blood pressure-lowering medicines:
• angiotensin-converting enzyme (ACE) inhibitors (e.g., enalapril, lisinopril, ramipril), especially if the patient has diabetic kidney disease.
• aliskiren.

Treatment with hydrochlorothiazide may lead to electrolyte imbalance in the body.
Typical symptoms of fluid or electrolyte imbalance are: dryness of the mucous membranes in the mouth, weakness, lethargy, drowsiness, restlessness, muscle cramps, nausea (nausea), vomiting, fatigue, and irregular heartbeat (faster than 100 beats per minute). If any of these symptoms occur, the patient should inform their doctor.
If the patient experiences stomach pain, nausea, vomiting, or diarrhea after taking Tolutris, they should discuss this with their doctor. The doctor will decide on further treatment. The patient should not stop taking Tolutris on their own.
The patient should also inform their doctor if they experience increased skin sensitivity to sunlight, such as sunburn (e.g., redness, itching, swelling, blistering) that occurs more quickly than usual.
In the event of planned surgery or anesthesia, the patient should inform their doctor that they are taking Tolutris.
Tolutris may be less effective in lowering blood pressure in black patients.
The treating doctor may monitor kidney function, blood pressure, and electrolyte levels (e.g., potassium) in the blood at regular intervals.
See also the information under the heading "When not to take Tolutris".

Children and adolescents

Tolutris is not recommended for children and adolescents under 18 years of age.

Tolutris and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. The doctor may decide to change the dose of these medicines or take other precautions. In some cases, it may be necessary to discontinue one of the medicines. This is especially true for the following medicines taken concurrently with Tolutris:

• Lithium preparations used to treat certain types of depression;
• medicines that can cause low potassium levels in the blood (hypokalemia), such as other diuretics, laxatives (e.g., castor oil), corticosteroids (e.g., prednisone), adrenocorticotropic hormone (ACTH), amphotericin (an antifungal medicine), carbenoxolone (used to treat mouth ulcers), sodium penicillin G (an antibiotic), salicylic acid, and its derivatives;
• medicines that can increase potassium levels in the blood, such as potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, ACE inhibitors, cyclosporine (an immunosuppressive medicine), and other medicines;
• medicines whose effects are influenced by changes in potassium levels in the blood, such as heart medicines (e.g., digoxin) or medicines that regulate heart rhythm (e.g., quinidine, disopyramide, amiodarone, sotalol), medicines used to treat mental disorders (e.g., thioridazine, chlorpromazine, levomepromazine), and other medicines, such as certain antibiotics (e.g., sparfloxacin, pentamidine) or certain medicines used to treat allergic reactions (e.g., terfenadine);
• medicines used to treat diabetes (insulin or oral medicines, such as metformin);
• cholestyramine, colestipol, or simvastatin, medicines that lower blood lipid levels;
• medicines that increase blood pressure, such as noradrenaline;
• muscle relaxants, such as tubocurarine;
• calcium supplements and/or vitamin D;
• medicines with anticholinergic effects (used to treat various disorders, such as spasms in the digestive tract, bladder spasms, asthma, motion sickness, muscle spasms, Parkinson's disease, and as an adjunct to anesthesia), such as atropine and biperiden;
• amantadine (a medicine used to treat Parkinson's disease and also to treat or prevent certain viral diseases);
• other medicines used to treat high blood pressure, corticosteroids, painkillers (e.g., non-steroidal anti-inflammatory drugs, NSAIDs), medicines used to treat cancer, gout, or arthritis;
• taking an ACE inhibitor or aliskiren (see also the information under the heading "When not to take Tolutris" and "Warnings and precautions");
• ketokonazole, itraconazole (antifungal medicines);
• ritonavir, indinavir, nelfinavir (protease inhibitors used to treat HIV infection);
• rifampicin, erythromycin, clarithromycin (antibiotics used to treat bacterial infections);
• St. John's wort;
• verapamil, diltiazem (medicines used to treat heart diseases);
• dantrolene (an infusion used to treat severe body temperature disorders);
• tacrolimus, sirolimus, temsirolimus, and everolimus (medicines that suppress the patient's immune system).

Tolutris may enhance the blood pressure-lowering effect of other medicines used to treat high blood pressure or medicines that may cause a decrease in blood pressure (e.g., baclofen, amifostine).
Additionally, low blood pressure may be further decreased by: alcohol, barbiturates, opioid painkillers, or antidepressants. The symptom is dizziness when standing up. If necessary, the doctor should be consulted about adjusting the dose of other medicines taken while taking Tolutris.
The effect of Tolutris may be weakened by concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs, e.g., aspirin or ibuprofen).

Tolutris with food and alcohol

Tolutris can be taken with or without food.
The patient should avoid alcohol until they have talked to their doctor. Alcohol may further lower blood pressure and/or increase the risk of dizziness or fainting.
Patient taking Tolutris should not consume grapefruit juice or grapefruits, as they may increase the level of the active substance amlodipine in the blood, which may result in an unexpected increase in the blood pressure-lowering effect of Tolutris.

Pregnancy and breastfeeding

Pregnancy
The patient should inform their doctor if they are pregnant or plan to become pregnant. The doctor will usually recommend stopping Tolutris before planned pregnancy or as soon as pregnancy is detected and will prescribe another medicine instead of Tolutris. Tolutris is not recommended during pregnancy and should not be taken after the third month of pregnancy, as it may seriously harm the unborn baby if taken after the third month of pregnancy.
Breastfeeding
The patient should tell their doctor if they are breastfeeding or plan to breastfeed. Tolutris is not recommended during breastfeeding. The doctor may choose another treatment during breastfeeding. It has been shown that small amounts of amlodipine pass into human milk.

Driving and using machines

Tolutris may affect the ability to drive and use machines. If the medicine causes nausea, dizziness, fatigue, or headache, the patient should not drive or operate machinery; they should contact their doctor immediately.

Tolutris contains lactose and sodium

The medicine contains lactose. If the patient has been diagnosed with intolerance to some sugars, they should consult their doctor before taking the medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means it is essentially "sodium-free".

3. How to take Tolutris

This medicine should always be taken exactly as prescribed by the doctor. If the patient is unsure, they should consult their doctor or pharmacist.
The recommended dose of Tolutris is one tablet per day. The patient should try to take the tablet at the same time every day.
Tolutris can be taken before or after a meal. The tablets should be swallowed with water or a non-alcoholic drink. It is important to take Tolutris every day, unless the doctor tells the patient to stop. The patient should not take Tolutris with grapefruit juice.

Taking a higher dose of Tolutris than recommended

If the patient accidentally takes too many tablets, they may experience symptoms such as low blood pressure and rapid heartbeat. There have also been reports of slow heartbeat, photophobia, dizziness, vomiting, worsening kidney function, including kidney failure. In the event of a significant drop in blood pressure, shock may occur. The skin may become cool and moist, and the patient may lose consciousness. If the patient has taken too many Tolutris tablets, they should contact their doctor immediately.
Due to the presence of hydrochlorothiazide, very low blood pressure and low potassium levels in the blood may also occur, which can lead to nausea, drowsiness, and muscle cramps and/or irregular heartbeat associated with the concurrent use of medicines such as digitalis glycosides and certain anti-arrhythmic medicines. The patient should contact their doctor or pharmacist immediately or go to the nearest hospital emergency department.
Even 24-48 hours after taking the medicine, shortness of breath due to excess fluid accumulation in the lungs (pulmonary edema) may occur.

Missing a dose of Tolutris

The patient should remain calm. If they forget to take a dose, they should take it as soon as they remember, on the same day. If the tablet is not taken on one day, the patient should take the usual dose the next day. The patient should nottake a double dose to make up for the missed dose.

Stopping Tolutris treatment

The doctor will inform the patient about the duration of treatment. If the patient stops taking the medicine before the doctor recommends, the disease may recur.
If the patient has any further doubts about taking this medicine, they should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Tolutris can cause side effects, although not everybody gets them.

Some side effects may be serious and require immediate medical attention:

If the patient experiences any of the following symptoms, they should contact their doctor immediately:

• sepsis (often referred to as blood poisoning, a severe infection with an inflammatory response throughout the body, which can be fatal) (may occur in fewer than 1 in 1000 patients);
• severe skin reactions, including severe rash, hives, redness of the skin all over the body, severe itching, blistering, peeling, and swelling of the skin, Stevens-Johnson syndrome, toxic epidermal necrolysis (may occur in fewer than 1 in 10,000 patients);
• swelling of the eyelids, face, or lips (angioedema) (may occur in fewer than 1 in 10,000 patients);
• blistering and peeling of the outer layer of the skin (toxic epidermal necrolysis) (frequency cannot be estimated from the available data);
• heart attack, arrhythmias (may occur in fewer than 1 in 10,000 patients);
• pancreatitis, which can cause severe abdominal pain radiating to the back, with very poor general condition (may occur in fewer than 1 in 10,000 patients).

Possible side effects of Tolutris:

Very common side effects (may occur in more than 1 in 10 patients):
Fluid retention in the body (edema).
Common side effects (may occur in fewer than 1 in 10 patients):
Dizziness, malaise (nausea), low magnesium levels in the blood, headache, drowsiness (especially at the start of treatment), palpitations (awareness of heartbeat), shortness of breath, flushing, abdominal pain, changes in bowel movements, diarrhea, constipation, indigestion, fatigue, weakness, vision disturbances, double vision, swelling of the ankles.
Uncommon side effects (may occur in fewer than 1 in 100 patients):
Decreased or increased potassium levels in the blood, anxiety, fainting, tingling and numbness (paresthesia), vertigo (dizziness of inner ear origin), rapid heartbeat (tachycardia), arrhythmias, low blood pressure, sudden drop in blood pressure when standing up, dryness of the mucous membranes in the mouth, back pain, muscle pain, erectile dysfunction (inability to achieve or maintain an erection), chest pain, increased uric acid levels in the blood, upper respiratory tract infections (e.g., sore throat, sinusitis, common cold), urinary tract infections, anemia (low red blood cell count), slow heartbeat (bradycardia), kidney problems, including acute kidney failure, cough, mood changes, depression, insomnia, tremors, taste disturbances, loss of pain sensation, tinnitus, sneezing and/or runny nose (due to inflammation of the nasal mucosa), vomiting, hair loss, increased sweating, itching, skin redness, skin discoloration, urinary disorders, increased need to urinate at night, frequent urination, discomfort or enlargement of the breasts in men, pain, malaise, joint pain, weight gain or loss.
Rare side effects (may occur in fewer than 1 in 1000 patients):
Pneumonia (inflammation of the lungs), bronchitis, sinusitis, systemic lupus erythematosus (a disease in which the immune system attacks the body, causing joint pain, skin rashes, and fever), bloating (indigestion), gastritis (inflammation of the stomach lining), abnormal liver function (more common in patients of Japanese origin), skin redness, allergic reactions, such as itching or rash, hives, flu-like symptoms, low sodium levels, increased creatinine levels, increased liver enzyme activity or creatine phosphokinase in the blood, decreased platelet count (thrombocytopenia), increased white blood cell count (eosinophilia), severe allergic reactions (e.g., hypersensitivity, anaphylactic shock), low blood sugar levels (in patients with diabetes), stomach upset, eczema, joint degeneration, tendonitis, decreased hemoglobin levels (anemia), high calcium levels in the blood, disorientation.
Very rare side effects (may occur in fewer than 1 in 10,000 patients):
Progressive scarring of the lung tissue (interstitial lung disease)*, increased pH (disturbed acid-base balance) due to low chloride levels in the blood, acute respiratory failure (symptoms include severe shortness of breath, fever, weakness, and confusion), decreased white blood cell count, high blood sugar levels (hyperglycemia), nerve disorders that can cause weakness, gum hypertrophy, abnormal liver function (hepatitis), jaundice, increased muscle tone, vasculitis (inflammation of blood vessels), often with skin rash, hypersensitivity to light, disorders including stiffness, tremors, and/or difficulty moving.
* Cases of interstitial lung disease have been reported in association with telmisartan. However, a causal relationship has not been established.
Side effects with unknown frequency (frequency cannot be estimated from the available data):
Salivary gland inflammation, malignant skin tumors and lip cancer (non-melanoma skin cancer), decreased or lost appetite, anxiety, dizziness, vision loss and eye pain (possibly symptoms of fluid accumulation in the vascular layer surrounding the eye - excessive fluid accumulation between the choroid and sclera or acute angle-closure glaucoma), systemic lupus erythematosus-like syndrome (a disease that mimics systemic lupus erythematosus, in which the immune system attacks the body), glucose in the urine (glycosuria), fever, electrolyte imbalance, high cholesterol levels in the blood, decreased blood volume, increased blood glucose levels, difficulty controlling blood glucose levels/urine in patients with known diabetes, or blood lipid levels, stiffness, mask-like facial expression, slow movements, and shuffling gait, edema of the intestinal tract - intestinal angioedema has been reported with similar products, with symptoms such as abdominal pain, nausea, vomiting, and diarrhea.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Jerozolimskie Avenue 181C, 02-222 Warsaw
phone: +48 22 49 21 301
fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, it is possible to gather more information on the safety of the medicine.

5. How to store Tolutris

The medicine should be stored out of sight and reach of children.
The patient should not use this medicine after the expiry date stated on the blister pack and carton after: EXP. The expiry date refers to the last day of the month stated.
The medicine should be stored in its original packaging to protect it from light and moisture.
There are no special storage temperature requirements for the medicinal product.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Tolutris contains

• The active substances of Tolutris are telmisartan, amlodipine, and hydrochlorothiazide. Tolutris, 40 mg + 5 mg + 12.5 mg, tablets:Each tablet contains 40 mg of telmisartan, 5 mg of amlodipine (as amlodipine besylate) and 12.5 mg of hydrochlorothiazide. Tolutris, 80 mg + 5 mg + 12.5 mg, tablets:Each tablet contains 80 mg of telmisartan, 5 mg of amlodipine (as amlodipine besylate) and 12.5 mg of hydrochlorothiazide. Tolutris, 80 mg + 10 mg + 12.5 mg, tablets:Each tablet contains 80 mg of telmisartan, 10 mg of amlodipine (as amlodipine besylate) and 12.5 mg of hydrochlorothiazide. Tolutris, 80 mg + 10 mg + 25 mg, tablets:Each tablet contains 80 mg of telmisartan, 10 mg of amlodipine (as amlodipine besylate) and 25 mg of hydrochlorothiazide.
• The other ingredients (excipients) are: povidone K30, sodium hydroxide, lactose monohydrate, meglumine, crospovidone, microcrystalline cellulose, sodium stearyl fumarate, starch maize, sodium carboxymethyl starch (type A), magnesium stearate, colloidal anhydrous silica, yellow iron oxide (E 172) (only in 40 mg + 5 mg + 12.5 mg, 80 mg + 10 mg + 12.5 mg, and 80 mg + 10 mg + 25 mg tablets) and red iron oxide (E 172) (only in 80 mg + 5 mg + 12.5 mg and 80 mg + 10 mg + 12.5 mg tablets). See section 2 "Tolutris contains lactose and sodium".

What Tolutris looks like and contents of the pack

Tolutris, 40 mg + 5 mg + 12.5 mg, tablets:
round, biconvex, two-layer tablets. One layer of the tablet is white or almost white, marked with the symbol "L1". The other layer of the tablet is brown-yellow, marbled.
Tablet dimensions: diameter approximately 10 mm.
Tolutris, 80 mg + 5 mg + 12.5 mg, tablets:
oval, biconvex, two-layer tablets. One layer of the tablet is white or almost white, marked with the symbol "L2". The other layer of the tablet is pink, marbled.
Tablet dimensions: approximately 18 mm x 9 mm.
Tolutris, 80 mg + 10 mg + 12.5 mg, tablets:
oval, biconvex, two-layer tablets. One layer of the tablet is white or almost white, marked with the symbol "L3". The other layer of the tablet is orange, marbled.
Tablet dimensions: approximately 18 mm x 9 mm.
Tolutris, 80 mg + 10 mg + 25 mg, tablets:
oval, biconvex, two-layer tablets. One layer of the tablet is white or almost white, marked with the symbol "L4". The other layer of the tablet is brown-yellow, marbled.
Tablet dimensions: approximately 18 mm x 9 mm.
Tolutris is available in packs containing:

• 28, 30, 56, 60, 84, or 90 tablets, in blisters in a cardboard box.
• 28, 56, or 84 tablets, in blister calendars in a cardboard box.

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

KRKA, d.d., Novo mesto,
Šmarješka cesta 6,
8501 Novo mesto,
Slovenia

This medicine is authorized in the Member States of the European Economic Area under the following names:

To obtain more detailed information on the medicine, the patient should contact their local representative of the marketing authorization holder:
KRKA-POLSKA Sp. z o.o.
Równoległa 5
02-235 Warsaw
phone: 22 57 37 500
Date of last revision of the leaflet:17.05.2025