Leaflet: information for the user

Tolucombi 40 mg/12.5 mg EFG tablets

Tolucombi 80 mg/12.5 mg EFG tablets

Tolucombi 80 mg/25 mg EFG tablets

telmisartán/hidroclorotiazida

Read this leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Tolucombi is an association of two active principles, telmisartán and hydrochlorothiazide in a tablet. Both active principles help control high blood pressure.

• Telmisartán belongs to a group of medications known as angiotensin II receptor antagonists. Angiotensin II is a substance produced in the body that causes blood vessels to constrict, thereby increasing blood pressure. Telmisartán blocks the effect of angiotensin II, causing blood vessels to relax and reducing blood pressure.

• Hydrochlorothiazide belongs to a group of medications known as thiazide diuretics, which increase urine production, resulting in a decrease in blood pressure.

High blood pressure, if left untreated, can damage blood vessels in various organs, which in some cases can cause a heart attack, heart failure, kidney failure, stroke, or blindness.

There are usually no symptoms of high blood pressure before damage occurs. Therefore, it is essential to monitor blood pressure periodically to ensure it is within the normal range.

Tolucombi (40 mg/12.5 mg, 80 mg/12.5 mg) is used forthe treatment of high blood pressure (essential hypertension) in adults whose blood pressure is not controlled sufficiently when using telmisartán alone.

Tolucombi (80 mg/25 mg) is used forthe treatment of high blood pressure (essential hypertension) in adults whose blood pressure is not adequately controlled with Tolucombi 80 mg/12.5 mg or in patients who have previously been stabilized with telmisartán and hydrochlorothiazide separately.

Do not take Tolucombi

• if you are allergic to telmisartan or any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to hydrochlorothiazide or other sulfonamide-derived medicines;
• if you are more than 3 months pregnant. (In any case, it is better to avoid taking Tolucombi at the beginning of your pregnancy - see Pregnancy section);
• if you have severe liver problems such as, for example, cholestasis or biliary obstruction (problems with bile drainage from the liver and gallbladder) or any other serious liver disease;
• if you have severe kidney disease;
• if your doctor determines that you have low levels of potassium or high levels of calcium in your blood, which do not improve with treatment;
• if you have diabetes or kidney insufficiency and are being treated with a blood pressure-lowering medicine that contains aliskiren.

Inform your doctor or pharmacist about any of the above before taking Tolucombi.

Warnings and precautions

Consult your doctor before starting to take Tolucombi if you have or have had any of the following conditions or diseases:

• Low blood pressure (hypotension), which may occur if you are dehydrated (excessive loss of body water) or have a deficiency of salts due to diuretic treatment, low-sodium diet, diarrhea, vomiting, or hemodialysis;
• Kidney disease or kidney transplant;
• Renal artery stenosis (narrowing of the blood vessels of one or both kidneys);
• Liver disease;
• Heart problems;
• Diabetes;
• Gout;
• Elevated aldosterone levels (retention of water and salt in the body along with imbalance of several minerals in the blood);
• SLE (systemic lupus erythematosus), a disease in which the body's immune system attacks the body itself;
• The active ingredient hydrochlorothiazide may cause a rare reaction, leading to a decrease in vision and eye pain. These symptoms may be indicative of fluid accumulation in the vascular layer of the eye (choroidal effusion) or an increase in pressure in your eye and may appear between hours and weeks after taking Tolucombi. If left untreated, it may lead to permanent vision loss.
• If you have had skin cancer or if you develop an unexpected skin lesion during treatment. The treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of skin cancer and lip cancer (non-melanoma skin cancer). Protect your skin from sun exposure and UV rays while taking Tolucombi.
• If you have had respiratory or pulmonary problems (such as inflammation or fluid in the lungs) after taking hydrochlorothiazide in the past. If you experience severe shortness of breath or difficulty breathing after taking Tolucombi, seek medical attention immediately.

Consult your doctor before starting to take Tolucombi if you are taking:

• digoxin;
• any of the following blood pressure-lowering medicines (hypertension):

• an angiotensin-converting enzyme inhibitor (ACE inhibitor) (e.g. enalapril, lisinopril, ramipril), particularly if you have kidney problems related to diabetes;
• aliskiren.

If you are pregnant, if you suspect you may be pregnant, or if you plan to become pregnant, inform your doctor. Tolucombi is not recommended for use at the beginning of pregnancy (first 3 months) and should not be administered after the third month of pregnancy because it may cause serious harm to your baby, see Pregnancy section.

Treatment with hydrochlorothiazide may cause an electrolyte imbalance in your body. Typical symptoms of a fluid or electrolyte imbalance include dry mouth, weakness, drowsiness, restlessness, muscle pain or cramps, nausea, vomiting, muscle fatigue, and an abnormally fast heart rate (more than 100 beats per minute). If you experience any of these symptoms, inform your doctor.

You should also inform your doctor if you experience increased skin sensitivity to the sun with symptoms of sunburn (such as redness, itching, swelling, and blistering) that appear more quickly than usual.

If you are to undergo surgery (surgery) or anesthesia, inform your doctor that you are taking Tolucombi.

Tolucombi may be less effective in reducing blood pressure in black patients.

Your doctor may monitor your kidney function, blood pressure, and electrolyte levels in your blood (e.g. potassium) at regular intervals.

See also the information under the heading "Do not take Tolucombi".

Children and adolescents

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

Other medicines and Tolucombi

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine. Your doctor may need to change the dose of those other medicines or take other precautions. In some cases, you may need to stop using one of these medicines, especially if you are using it with Tolucombi one of the following medicines:

• Medicines containing lithium for the treatment of certain types of depression;
• Medicines associated with low levels of potassium in the blood (hypokalemia) such as other diuretics, laxatives (e.g. castor oil), corticosteroids (e.g. prednisone), ACTH (adrenocorticotropic hormone), amphotericin (an antifungal medicine), carbenoxolone (used in the treatment of mouth ulcers), penicillin G sodium (an antibiotic), and aspirin and its derivatives;
• Medicines that may increase potassium levels in the blood such as potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, ACE inhibitors, cyclosporine (an immunosuppressant), and other medicines such as heparin sodium (an anticoagulant).
• Medicines that are affected by changes in potassium levels in the blood such as heart medicines (e.g. digoxin) or medicines to control heart rhythm (e.g. quinidine, disopyramide, amiodarone, sotalol), medicines used for mental disorders (e.g. thioridazine, chlorpromazine, levomepromazine), and other medicines such as certain antibiotics (e.g. ciprofloxacin, pentamidine) or certain medicines for allergic reactions (e.g. terfenadine).
• Medicines for the treatment of diabetes (insulins or oral agents such as metformin).
• Colestiramine and colestipol, medicines to reduce cholesterol levels in the blood;
• Medicines to increase blood pressure, such as noradrenaline;
• Relaxants, such as tubocurarine;
• Calcium and/or vitamin D supplements;
• Anticholinergic medicines (medicines used to treat a variety of disorders such as gastrointestinal spasms, urinary spasms, asthma, motion sickness, muscle spasms, Parkinson's disease, and as an aid to anesthesia) such as atropine and biperiden;
• Amantadine (a medicine used to treat Parkinson's disease and also to treat or prevent certain diseases caused by viruses).
• Other medicines used to treat high blood pressure, corticosteroids, analgesics (such as non-steroidal anti-inflammatory drugs [NSAIDs]), medicines for cancer treatment, gout, or arthritis;
• If you are taking an ACE inhibitor or aliskiren (see also the information under the headings "Do not take Tolucombi" and "Warnings and precautions").
• Digoxin.

Tolucombi may increase the effect of other medicines to lower blood pressure or of medicines that may potentially lower blood pressure (e.g. baclofen, amifostine). Additionally, the decrease in blood pressure may be exacerbated by alcohol, barbiturates, narcotics, or antidepressants. You may notice this effect as dizziness when standing up. Inform your doctor about the need to adjust the dose of your other medicines while taking Tolucombi.

The effect of Tolucombi may decrease when using NSAIDs (non-steroidal anti-inflammatory drugs, e.g. aspirin or ibuprofen).

Taking Tolucombi with food and alcohol

You can take Tolucombi with or without food.

Avoid drinking alcohol until you have spoken with your doctor. Alcohol may reduce your blood pressure even further and/or increase the risk of feeling dizzy or weak.

Pregnancy and breastfeeding

Pregnancy

Inform your doctor if you are pregnant, if you suspect you may be pregnant, or if you plan to become pregnant. Your doctor will usually advise you to stop taking Tolucombi before becoming pregnant or as soon as you become pregnant, and recommend taking another blood pressure-lowering medicine instead. Tolucombi is not recommended for use during pregnancy and should not be administered after the third month of pregnancy because it may cause serious harm to your baby, see Pregnancy section.

Breastfeeding

Inform your doctor if you plan to start or are breastfeeding because Tolucombi is not recommended for use during this period. Your doctor may decide to administer a more suitable treatment if you want to breastfeed.

Driving and operating machinery

Some patients may feel dizzy or tired when taking Tolucombi. If you feel dizzy or tired, do not drive or operate machinery.

Tolucombi contains lactose, sorbitol, and sodium

If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medicine.

Tolucombi 40 mg/12.5 mg contains 147.04 mg of sorbitol in each tablet equivalent to 5/mg/kg/day, if the body weight is 29.8 kg.

Tolucombi 80 mg/12.5 mg and Tolucombi 80 mg/25 mg contain 294.08 mg of sorbitol in each tablet equivalent to 5/mg/kg/day, if the body weight is 58.8 kg.

Patients weighing 58.8 kg or less should note that sorbitol is a source of fructose. If your doctor has told you that you (or your child) have an intolerance to certain sugars, or have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which the patient cannot break down fructose, consult with your doctor (or your child) before taking this medicine.

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; it is essentially "sodium-free".

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

The recommended dose is one tablet per day. Try to take one tablet every day at the same time. You can take Tolucombi with or without food. The tablets should be swallowed with a little water or other non-alcoholic beverage. It is essential to take Tolucombi every day until your doctor tells you otherwise.

If your liver does not function correctly, the usual dose should not exceed 40 mg/12.5 mg once a day.

If you take more Tolucombi than you should

If you accidentally take too many tablets, you may experience symptoms such as low blood pressure and rapid heartbeats. Slow heartbeats, dizziness, vomiting, and reduced kidney function, including kidney failure, have also been described. Due to the hydrochlorothiazide component, you may also experience notably low blood pressure and low potassium levels in the blood, which can lead to nausea, drowsiness, and muscle cramps and/or irregular heartbeats associated with the concomitant use of medications such as digitalis or certain antiarrhythmic treatments. Contact your doctor or pharmacist immediately or the nearest hospital emergency service.

If you forgot to take Tolucombi

If you forget to take the medication, do not worry. Take the dose as soon as you remember and continue as before. If you miss a dose, take your normal dose the next day. Do not take a double dose to compensate for the missed doses.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

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

Some side effects can be severe and require immediate medical attention:

If you experience any of the following symptoms, you should visit your doctor immediately:

Sepsis* (also known as "blood infection"), is a severe infection that involves a systemic inflammatory reaction, rapid skin and mucous membrane swelling (angioedema); formation of blisters and peeling on the skin's surface (toxic epidermal necrolysis); these side effects are rare (may affect up to 1 in 1,000 people) or of unknown frequency (toxic epidermal necrolysis) but are extremely severe and patients should stop taking the medicine and visit their doctor immediately.

If these side effects are not treated, they can be fatal. An increased incidence of sepsis with telmisartan alone has been observed; however, it cannot be ruled out for Tolucombi.

Possible side effects of Tolucombi:

Frequent side effects(may affect up to 1 in 10 people):

Dizziness.

Rare side effects(may affect up to 1 in 100 people):

Decreased potassium levels in the blood, anxiety, fainting (syncope), tingling sensation, numbness (paresthesia), dizziness (vertigo), rapid heart rate (tachycardia), heart rhythm disturbances, low blood pressure, sudden drop in blood pressure upon standing, shortness of breath (dyspnea), diarrhea, dry mouth, flatulence, back pain, muscle spasms, muscle pain, erectile dysfunction (inability to achieve or maintain an erection), chest pain, and increased uric acid levels in the blood.

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

Pneumonia (bronchitis), activation or worsening of systemic lupus erythematosus (a disease in which the body's immune system attacks the body, causing joint pain, skin rashes, and fever), sore throat, sinusitis, feeling of sadness (depression), difficulty falling asleep (insomnia), vision disturbances, difficulty breathing, abdominal pain, constipation, abdominal distension (dyspepsia), general discomfort (vomiting), stomach inflammation (gastritis), liver function disturbances (Japanese patients are more prone to experiencing this side effect), skin redness (erythema), allergic reactions such as itching or rashes, increased sweating, hives (urticaria), joint pain (arthralgia), and limb pain, muscle cramps, pseudogripal disease, pain, low sodium levels, increased creatinine levels, liver enzymes or creatine phosphokinase in the blood.

Notified adverse reactions for one of the individual components may be potential adverse reactions of Tolucombi, although they have not been observed in clinical trials with this product.

Telmisartan

The following additional side effects have been described in patients taking telmisartan alone:

Rare side effects(may affect up to 1 in 100 people):

Upper respiratory tract infection (e.g., sore throat, sinusitis, common cold), urinary tract infections, anemia, high potassium levels, slow heart rate (bradycardia), acute kidney failure, weakness, and cough.

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

Low platelet count (thrombocytopenia), increased levels of certain white blood cells (eosinophilia), severe allergic reactions (e.g., hypersensitivity, anaphylactic reactions, skin rash), low blood sugar levels (in diabetic patients), stomach discomfort, eczema (a skin disorder), arthritis, tendon inflammation, decreased hemoglobin (a blood protein), drowsiness.

Very rare side effects(may affect up to 1 in 10,000 people): Progressive fibrosis of lung tissue (interstitial lung disease) **

* This may have been a chance finding or related to an unknown mechanism.

** Cases of progressive fibrosis of lung tissue have been reported during telmisartan treatment. However, it is unknown whether telmisartan was the cause.

Hidroclorotiazida

The following additional side effects have been described in patients taking hydrochlorothiazide alone:

Frequent side effects(may affect up to 1 in 10 people):

Nausea, decreased magnesium levels in the blood.

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

Decreased platelet count, which increases the risk of bleeding and hematoma formation (small purple-red marks on the skin or other tissues caused by bleeding), elevated calcium levels in the blood, headache.

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

Increased pH (alteration of acid-base balance) due to low chloride levels in the blood, acute respiratory distress (symptoms include severe difficulty breathing, fever, weakness, and confusion).

Side effects of unknown frequency(cannot be estimated from available data):

Salivary gland inflammation, skin cancer and lip cancer (non-melanoma skin cancer), decreased number (or even absence) of blood cells, including low red and white blood cell counts; severe allergic reactions (e.g., hypersensitivity, anaphylactic reactions), decreased or loss of appetite; restlessness, dizziness, blurred or yellowish vision, decreased vision, and eye pain (possible signs of fluid accumulation in the eye's vascular layer (choroidal hemorrhage) or acute myopia or acute angle-closure glaucoma), necrotizing vasculitis, pancreatitis, stomach discomfort, yellowing of the skin or eyes (jaundice), pseudolupus syndrome (a condition that mimics a disease called systemic lupus erythematosus in which the body's immune system attacks the body), skin disorders such as inflammation of blood vessels in the skin, increased sensitivity to sunlight, skin rash, redness of the skin, formation of blisters on the lips, eyes, or mouth, skin peeling, fever (possible signs of erythema multiforme), weakness, kidney inflammation or function disturbances, glucose in the urine (glucosuria), fever, electrolyte imbalance, high cholesterol levels in the blood, decreased blood volume, increased glucose levels in the blood, difficulty controlling blood glucose levels/orine in patients with diabetes mellitus, or blood fat.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box and on the blister pack after CAD. The expiration date is the last day of the month indicated.

This medication does not require any special storage temperature.

Store in the original packaging to protect it from light.

Medications should not be disposed of through drains or trash. Ask your pharmacist how to dispose of the containers and medications you no longer need. This will help protect the environment.

Composition of Tolucombi

• The active principles are telmisartan and hydrochlorothiazide.

Each tablet contains 40 mg of telmisartan and 12.5 mg of hydrochlorothiazide.

Each tablet contains 80 mg of telmisartan and 12.5 mg of hydrochlorothiazide.

Each tablet contains 80 mg of telmisartan and 25 mg of hydrochlorothiazide.

• The other components are hydroxypropylcellulose, lactose monohydrate, magnesium stearate, mannitol, meglumine, povidone (K30), iron oxide red (E172) only in 40 mg/12.5 mg and 80 mg/12.5 mg tablets, and anhydrous colloidal silica, sodium hydroxide (E524), stearoyl sodium fumarate, sorbitol (E420), and iron oxide yellow (E172) in 80 mg/25 mg tablets. See section 2 “Tolucombi contains lactose, sorbitol, and sodium”.

Appearance of the product and contents of the pack

40 mg/12.5 mg tablets: biconvex, oval-shaped, two-layered, white to almost white or pale pink on one face and rose-speckled on the opposite face, dimensions 15 mm x 7 mm.

80 mg/12.5 mg tablets: biconvex, oval-shaped, two-layered, white to almost white or pale pink on one face and rose-speckled on the opposite face, dimensions 18 mm x 9 mm.

80 mg/25 mg tablets: biconvex, oval-shaped, two-layered, white to pale yellow on one face and yellow-speckled on the opposite face, dimensions 18 mm x 9 mm.

Blister packs (OPA/Al/PVC//Al foil): 14 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, 84 x 1, 90 x 1, 98 x 1, and 100 x 1 tablet in a box.

Blister packs (OPA/Al/PE with desiccant//Al foil): 14 x 1 and 98 x 1 tablet in a box.

Only some pack sizes may be marketed.

Marketing Authorization Holder

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

Responsible Person

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

Slovenia KRKA-POLSKA Sp.z o.o., ul. Równolegla 5, 02-235 Warszawa, Poland

TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

The detailed information on this medicinal product is available on the website of the European Medicines Agencyhttp://www.ema.europa.eu.