Tolutris

Package leaflet: Information for the patient

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
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again later.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

1. What Tolutris is and what it is 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 pack and other information

1. What Tolutris is and what it is used for

Tolutris tablet contains three active substances: telmisartan, amlodipine, and hydrochlorothiazide.
All of 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 narrow, thereby increasing blood pressure. Telmisartan blocks the effect of angiotensin II, causing blood vessels to widen and blood pressure to decrease.
• Amlodipine belongs to a group of medicines called calcium antagonists (calcium channel blockers), which work by relaxing and widening blood vessels, allowing blood to flow more easily.
• Hydrochlorothiazide belongs to a group of substances called thiazide diuretics, which increase urine production, leading to a reduction in blood pressure.

Tolutris is used to treat high blood pressure (essential hypertension) in patients whose blood pressure is adequately controlled with the same doses of the individual active substances given separately as single-component tablets.

2. Important information before using Tolutris

When not to use 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 drugs.
• If the patient is allergic to amlodipine or other calcium channel blockers.
• After the third month of pregnancy. (Tolutris should also be avoided during early pregnancy – see section “Pregnancy”).
• If the patient has severe liver disease, such as biliary obstruction or cholestasis (impaired bile flow from the liver and gallbladder), or any other severe liver disorder.
• If the patient has severe kidney disease or anuria (urine output less than 100 ml per day).
• If the doctor has diagnosed low blood potassium levels or high blood calcium levels that have not improved 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 arterial blood pressure (severe hypotension).
• If the patient has aortic valve stenosis (narrowing of the heart's aortic valve) or cardiogenic shock (a condition in which the heart is unable to deliver sufficient blood to the body).
• If the patient has heart failure following acute myocardial infarction.

If any of the above situations apply, inform your doctor or pharmacist before taking Tolutris.

Warnings and precautions

Before starting Tolutris, discuss with your doctor if the patient has or has had any of the following conditions or diseases:

• Low blood pressure (hypotension), which is more likely if the patient is dehydrated (excessive loss of body water) or has salt deficiency due to diuretics (water tablets), a low-salt diet, diarrhoea, vomiting, or haemodialysis;

• Marked increase in blood pressure (hypertensive crisis);

• Kidney disease or kidney transplant;

• Renal artery stenosis (narrowing of the blood vessels supplying one or both kidneys);

• Liver disease;

• Heart problems, including heart failure and recent myocardial infarction;

• Diabetes;

• Gout;

• Elevated aldosterone levels (water and salt retention in the body, together with electrolyte imbalance);

• Systemic lupus erythematosus (also known as “lupus” or “SLE”), a disease in which the immune system attacks the body itself;

• If the patient has previously had skin cancer or if unexpected skin changes occur during treatment. Treatment with hydrochlorothiazide, especially at high doses over a long period, may increase the risk of certain types of non-melanoma skin cancer and lip cancer. During treatment with Tolutris, protect the skin from sunlight and UV radiation.

• The active substance hydrochlorothiazide may rarely cause reactions leading to vision disturbances and eye pain. These may be symptoms of fluid accumulation in the uvea (excessive fluid buildup between the choroid and sclera) or increased intraocular pressure, which may occur within hours to weeks after taking Tolutris. If untreated, these conditions may lead to permanent vision damage. Patients previously allergic to penicillin or sulfonamides may be at higher risk of developing this condition.

• If the patient has previously experienced breathing problems or lung-related issues (including pneumonia or fluid accumulation in the lungs) after taking hydrochlorothiazide. If the patient develops severe shortness of breath or difficulty breathing after taking Tolutris, seek immediate medical help.

• If the patient is elderly and a dose increase is required.

Before starting Tolutris, inform the doctor if the patient is taking:

• Digoxin,
• Any of the following medicines used to treat high blood pressure:
• Angiotensin-converting enzyme (ACE) inhibitors (e.g. enalapril, lisinopril, ramipril), particularly if the patient has kidney problems related to diabetes.
• Aliskiren.

Treatment with hydrochlorothiazide may lead to electrolyte imbalance in the body. Typical symptoms of fluid or electrolyte imbalance include: dryness of the mucous membranes in the mouth, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, nausea, vomiting, muscle fatigue, and abnormally rapid heartbeat (faster than 100 beats per minute). If any of these symptoms occur, inform your doctor.
If the patient experiences abdominal pain, nausea, vomiting, or diarrhoea after taking Tolutris, discuss this with the doctor. The doctor will decide on further treatment. Do not stop taking Tolutris on your own.
Also inform your doctor if you experience increased skin sensitivity to sunlight, such as sunburn (e.g. redness, itching, swelling, blistering) occurring more quickly than usual.
If undergoing surgery or anaesthesia, inform the doctor that you are taking Tolutris.
Tolutris may be less effective in lowering blood pressure in patients of Black ethnicity.
Your doctor may monitor kidney function, blood pressure, and blood electrolyte levels (e.g. potassium) at regular intervals.
See also information under the heading “When not to use Tolutris”.

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

Tolutris with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. The doctor may decide to adjust the dose of these medicines or take other precautions. In some cases, discontinuation of one of the medicines may be necessary. This particularly applies to concomitant use of the following medicines with Tolutris:

• Lithium preparations, used in the treatment of certain types of depression;
• Medicines associated with low blood potassium levels (hypokalaemia), such as other diuretics (water tablets), laxatives (e.g. castor oil), corticosteroids (e.g. prednisone), ACTH (adrenocorticotropic hormone), amphotericin (an antifungal medicine), carbenoxolone (used to treat oral ulcers), sodium penicillin G (an antibiotic), salicylic acid and its derivatives;
• Medicines that may increase blood potassium levels, e.g. potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, ACE inhibitors, cyclosporine (an immunosuppressant), and other medicinal products such as sodium heparin (an anticoagulant);
• Medicines affected by changes in blood potassium levels, such as cardiac glycosides (e.g. digoxin) or medicines regulating heart rate (e.g. quinidine, disopyramide, amiodarone, sotalol), medicines used to treat psychiatric 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 in diabetes (insulin or oral agents such as metformin);
• Cholestyramine, colestipol, or simvastatin, medicines used to lower blood lipid levels;
• Medicines that raise blood pressure, such as noradrenaline;
• Muscle relaxants, such as tubocurarine;
• Calcium supplements and/or vitamin D;
• Anticholinergic medicines (used to treat various disorders such as gastrointestinal spasms, bladder spasms, asthma, motion sickness, muscle spasms, Parkinson’s disease, and as adjuncts in anaesthesia), such as atropine and biperiden;
• Amantadine (a medicine used in Parkinson’s disease and also for treating or preventing certain viral infections);
• Other medicines used to treat hypertension, corticosteroids, painkillers (e.g. non-steroidal anti-inflammatory drugs, NSAIDs), medicines used to treat cancer, gout, or arthritis;
• Concomitant use of an ACE inhibitor or aliskiren (see also information under the headings “When not to use Tolutris” and “Warnings and precautions”);
• Ketoconazole, itraconazole (antifungal medicines);
• Ritonavir, indinavir, nelfinavir (protease inhibitors used in the treatment of HIV infection);
• Rifampicin, erythromycin, clarithromycin (antibiotics used to treat bacterial infections);
• St. John’s wort (Hypericum perforatum);
• Verapamil, diltiazem (medicines used in heart diseases);
• Dantrolene (an infusion used in 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 hypertension or medicines that may cause low blood pressure (e.g. baclofen, amifostine). Additionally, low blood pressure may be further reduced by: alcohol, barbiturates, opioid painkillers, or antidepressants. Symptoms include dizziness upon standing. If a dose adjustment of another medicine taken during Tolutris treatment is needed, consult your doctor.
The effect of Tolutris may be reduced when taken concomitantly with NSAIDs (non-steroidal anti-inflammatory drugs, e.g. acetylsalicylic acid or ibuprofen).

Tolutris with food and alcohol
Tolutris can be taken with or without food.
Avoid alcohol until you have consulted your doctor. Alcohol may further lower blood pressure and/or increase the risk of dizziness or fainting.
Patients taking Tolutris should not consume grapefruit juice or grapefruit, as they may increase blood levels of the active substance amlodipine, potentially leading to unexpected intensification of Tolutris’s blood pressure-lowering effect.

Pregnancy and breastfeeding
Pregnancy
Inform your doctor if you suspect or are planning pregnancy. Your doctor will usually advise stopping Tolutris before a planned pregnancy or immediately after confirming pregnancy and will recommend an alternative medicine. Tolutris is not recommended during pregnancy and must not be used after the third month of pregnancy, as it may seriously harm the unborn child if used beyond the third month.

Breastfeeding
Inform your doctor if you are breastfeeding or plan to breastfeed. Tolutris is not recommended during breastfeeding. Your doctor may choose an alternative treatment during breastfeeding. Small amounts of amlodipine have been shown to pass into human milk.

Driving and operating machinery
Tolutris may affect the ability to drive and operate machinery. If the medicine causes nausea, dizziness, fatigue, or headache, do not drive or operate machinery; contact your doctor immediately.

Tolutris contains lactose and sodium
This medicine contains lactose. If the patient has been previously diagnosed with intolerance to certain sugars, consult your doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. it is considered “sodium-free”.

3. How to use Tolutris

This medicine should always be taken as directed by your doctor. If in doubt, consult your doctor or pharmacist.
The recommended dose of Tolutris is one tablet per day. Try to take the tablet at the same time each day.
Tolutris may be taken before or after food. Swallow the tablets with water or a non-alcoholic drink. It is important to take Tolutris every day unless otherwise advised by your doctor. Do not take Tolutris with grapefruit juice.

Taking more Tolutris than prescribed
If too many tablets are accidentally taken, symptoms such as low blood pressure and increased heart rate may occur. Cases of slowed heart rate, photophobia, dizziness, vomiting, worsening kidney function, including renal failure, have also been reported. In cases of severe hypotension, shock may occur. The skin then becomes cold and clammy, and the patient may lose consciousness. If an excessive amount of Tolutris has been taken, contact your doctor immediately.
Due to the presence of hydrochlorothiazide, markedly low blood pressure and low blood potassium levels may also occur, which may lead to nausea, drowsiness, muscle cramps, and/or irregular heartbeat, especially when taken concomitantly with drugs such as digitalis glycosides or certain antiarrhythmic medicines. Seek immediate medical advice from your doctor or pharmacist, or go to the nearest hospital emergency department.
Breathlessness caused by fluid accumulation in the lungs (pulmonary oedema) may occur even up to 24–48 hours after taking the medicine.

If you miss a dose of Tolutris
Stay calm. If you forget to take a dose, take it as soon as you remember, on the same day. If a tablet is missed on one day, take your usual dose the next day. Do not take a double dose to make up for a missed dose.

Stopping Tolutris
Your doctor will advise you on the duration of treatment. If you stop taking Tolutris before your doctor advises, your condition may return.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
Some adverse reactions may be serious and require immediate medical attention:
If any of the following symptoms occur, contact your doctor immediately:

• Septicaemia (often referred to as blood poisoning, a severe infection causing systemic inflammatory response, which may be fatal) (may occur in up to 1 in 1,000 patients);
• Severe skin reactions, including severe rash, urticaria, redness of the entire skin surface, intense itching, blistering, peeling and swelling of the skin, mucosal inflammation (Stevens-Johnson syndrome, toxic epidermal necrolysis) (may occur in up to 1 in 10,000 patients);
• Sudden swelling of the skin and mucous membranes (angioedema) (may occur in up to 1 in 1,000 patients);
• Swelling of the eyelids, face or lips (Quincke's oedema) (may occur in up to 1 in 10,000 patients);
• Blistering and peeling of the outer layer of skin (toxic epidermal necrolysis) (frequency cannot be estimated from available data);
• Myocardial infarction (may occur in up to 1 in 10,000 patients);
• Heart rhythm disorders (may occur in up to 1 in 100 patients);
• Pancreatitis, which may cause severe upper abdominal pain radiating to the back, accompanied by a very poor general condition (may occur in up to 1 in 10,000 patients).

Possible adverse reactions of Tolutris:

Very common adverse reactions (may occur in more than 1 in 10 patients):
Decreased potassium blood concentration, increased blood lipid concentration, fluid retention in the body (oedema).

Common adverse reactions (may occur in up to 1 in 10 patients):
Increased blood uric acid concentration, low sodium concentration, low magnesium blood concentration, decreased appetite, dizziness, drowsiness, headache, vision disturbances, palpitations (awareness of heartbeat), sudden drop in blood pressure upon standing, flushing, especially of the face, shortness of breath (dyspnoea), diarrhoea, abdominal pain, constipation, indigestion, vomiting, nausea, changes in bowel habits, rash, urticaria, muscle cramps (leg cramps), ankle swelling, erectile dysfunction (inability to achieve or maintain an erection), weakness, fatigue.

Uncommon adverse reactions (may occur in up to 1 in 100 patients):
Upper respiratory tract infections (e.g. sore throat, sinusitis, common cold), urinary tract infections, deficiency of red blood cells (anaemia), slowed heart rate, increased potassium blood concentration, anxiety, depression, insomnia, fainting, tingling and numbness sensations (paraesthesiae), tremor, taste disturbances, inability to feel pain, vertigo (dizziness), tinnitus, rapid heartbeat (tachycardia), slow heartbeat (bradycardia), low blood pressure, cough, sneezing and/or nasal congestion due to inflammation of the nasal mucosa, dryness of the mucous membranes in the mouth, bloating, itching, increased sweating, hair loss, red skin spots, skin discolouration, widespread rash, back pain, muscle pain, kidney function disorders, including acute renal failure, disturbances in urination, increased need to urinate at night, increased frequency of urination, discomfort or enlargement of the breasts in men, chest pain, pain, malaise, increased blood uric acid concentration, increased blood creatinine concentration, increased or decreased body weight.

Rare adverse reactions (may occur in up to 1 in 1,000 patients):
Pneumonia (bronchitis), throat, and/or sinus inflammation, increased number of white blood cells (eosinophilia), decreased number of platelets (thrombocytopenia), increasing the risk of bleeding or bruising (small purple-red spots on the skin or other tissues caused by haemorrhage), severe allergic reactions (e.g. hypersensitivity, acute anaphylactic reaction/shock, drug eruption), low blood sugar levels (in patients with diabetes), high blood calcium levels, high blood sugar levels (hyperglycaemia), sleep disorders, disorientation, blurred vision, pulmonary oedema, inflammation of the stomach mucosa, stomach irritation, abnormal liver function, jaundice, excess of bile substances in the blood (cholestasis), skin redness (erythema), skin eruption (skin disease), drug rash, toxic skin eruption, photosensitivity reactions, limb pain (leg pain), tendon pain (symptoms mimicking tendonitis), systemic lupus erythematosus (a disease in which the body is attacked by its own immune system), presence of sugars in urine (glucosuria), influenza-like symptoms, increased liver enzyme activity or creatine phosphokinase in blood, decreased haemoglobin concentration (blood protein).

Very rare adverse reactions (may occur in up to 1 in 10,000 patients):
Decreased number of white blood cells (leukopenia, granulocytopenia), abnormal breakdown of red blood cells (haemolytic anaemia), abnormal bone marrow function, allergic reactions, increased pH due to low chloride concentration in blood (acid-base imbalance, hypochloremic alkalosis), increased muscle tone, nerve-related disorders causing muscle weakness, tingling or numbness, inflammation of blood vessels (necrotizing vasculitis), progressive scarring of lung tissue (interstitial lung disease)*, acute respiratory failure (symptom: severe dyspnoea), gum swelling, liver function disorders, lupus-like syndrome (a disease mimicking systemic lupus erythematosus, in which the body is attacked by its own immune system), blistering on lips, eyes or mouth, skin peeling, fever (possible symptoms of erythema multiforme).

* Cases of interstitial lung disease temporally associated with telmisartan use have been reported. However, a causal relationship has not been established.

Adverse reactions with unknown frequency (frequency cannot be estimated from available data):
Malignant skin and lip tumours (non-melanoma skin cancers), decreased blood cell count (aplastic anaemia), tremor, rigidity, facial masking, slowed movements and shuffling gait, unsteady gait, visual field defects and eye pain due to high pressure (possibly symptoms of fluid accumulation in the vascular membrane surrounding the eye, excessive fluid accumulation between choroid and sclera – or acute myopia or acute angle-closure glaucoma), intestinal angioedema – following administration of similar products, intestinal swelling has occurred with symptoms such as abdominal pain, nausea, vomiting and diarrhoea.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of 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 reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Tolutris

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and outer packaging following: EXP. The expiry date refers to the last day of the stated month.
Store in the original packaging to protect from light and moisture.
There are no special storage temperature requirements for this medicinal product.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Tolutris contains

• The active substances in this medicine are telmisartan, amlodipine, and hydrochlorothiazide.
  Tolutris 40 mg + 5 mg + 12.5 mg, tablets: Each tablet contains 40 mg telmisartan, 5 mg amlodipine (as amlodipine besylate) and 12.5 mg hydrochlorothiazide.
  Tolutris 80 mg + 5 mg + 12.5 mg, tablets: Each tablet contains 80 mg telmisartan, 5 mg amlodipine (as amlodipine besylate) and 12.5 mg hydrochlorothiazide.
  Tolutris 80 mg + 10 mg + 12.5 mg, tablets: Each tablet contains 80 mg telmisartan, 10 mg amlodipine (as amlodipine besylate) and 12.5 mg hydrochlorothiazide.
  Tolutris 80 mg + 10 mg + 25 mg, tablets: Each tablet contains 80 mg telmisartan, 10 mg amlodipine (as amlodipine besylate) and 25 mg hydrochlorothiazide.
• The other ingredients (excipients) are: povidone K30, sodium hydroxide, monohydrate lactose, meglumine, crospovidone, microcrystalline cellulose, sodium stearyl fumarate, pregelatinized starch, sodium carboxymethyl starch (type A), magnesium stearate, colloidal anhydrous silica, yellow iron oxide (E 172) (only in tablets 40 mg + 5 mg + 12.5 mg, 80 mg + 10 mg + 12.5 mg and 80 mg + 10 mg + 25 mg) and red iron oxide (E 172) (only in tablets 80 mg + 5 mg + 12.5 mg and 80 mg + 10 mg + 12.5 mg). 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 is brownish-yellow, marbled.
Tablet dimensions: approximately 10 mm in diameter.
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 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 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 is brownish-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 blister packs within a cardboard box.
• 28, 56 or 84 tablets in calendar blister packs within a cardboard box.

Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
KRKA, d.d., Novo mesto,
Šmarješka cesta 6,
8501 Novo mesto,
Slovenia
This medicinal product is authorised in the European Economic Area under the following names:

For more detailed information about the medicinal product, please contact the local representative of the marketing authorization holder:
KRKA-POLSKA Sp. z o.o.
Równoległa 5 Street
02-235 Warsaw
Phone: 22 57 37 500