Patient Information Leaflet

Tolucombi 40 mg/12.5 mg tablets, 80 mg/12.5 mg tablets, 80 mg/25 mg tablets

telmisartan/hydrochlorothiazide
Please read this entire leaflet carefully before taking this medicine, as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.
Contents of this leaflet:
1. What Tolucombi is and what it is used for
2. What you need to know before taking Tolucombi
3. How to take Tolucombi
4. Possible side effects
5. How to store Tolucombi
6. Contents of the pack and other information

1. What Tolucombi is and what it is used for

Tolucombi is a combination of two active substances, telmisartan and hydrochlorothiazide, in a single tablet. Each of these components helps control high blood pressure.

Telmisartan belongs to a group of medicines 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. Telmisartan blocks this effect of angiotensin II, causing blood vessels to relax and thus reducing blood pressure.
Hydrochlorothiazide belongs to a group of medicines known as thiazide diuretics, which increase urine flow, thereby contributing to lowering blood pressure.

If left untreated, high blood pressure (hypertension) can damage blood vessels in various organs and may eventually lead to heart attack, heart or kidney failure, stroke, or blindness. Hypertension usually does not produce symptoms until such damage has occurred. Therefore, it is important to have regular blood pressure checks to ensure it remains within the normal range.
Tolucombi (40 mg/12.5 mg, 80 mg/12.5 mg) is used to treat high blood pressure (essential hypertension) in adults whose blood pressure is not adequately controlled by telmisartan alone.
Tolucombi (80 mg/25 mg) is used to treat high blood pressure (essential hypertension) in adults whose blood pressure is not adequately controlled by Tolucombi 80 mg/12.5 mg, or in patients who have previously been stabilized on telmisartan and hydrochlorothiazide given separately.

2. What you need to know before taking Tolucombi

Do not take Tolucombi

if you are allergic to telmisartan or to any of the other ingredients of this medicine (listed in section 6).
if you are allergic to hydrochlorothiazide or to any other sulfonamide-derived medicine.
if you are more than 3 months pregnant (it is better to avoid taking Tolucombi even in the early stages of pregnancy – see section on pregnancy).
if you have severe liver problems such as cholestasis or biliary obstruction (problems with bile drainage from the liver and gallbladder) or other serious liver diseases.
if you have severe kidney disease.
if your doctor determines that your blood potassium levels are low or your calcium levels are high and do not improve with treatment.
if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren. If you are in any of these conditions, inform your doctor or pharmacist before taking Tolucombi.

Warnings and precautions

Talk to your doctor before taking Tolucombi if you have or have had any of the following conditions or diseases:

Low blood pressure (hypotension), which is more likely if you are dehydrated (excessive loss of body water) or have salt deficiency due to diuretic therapy (diuretics), a low-salt diet, diarrhoea, vomiting, or haemodialysis.
Kidney disease or kidney transplant.
Renal artery stenosis (narrowing of the blood vessels to one or both kidneys).
Liver disease.
Heart problems.
Diabetes.
Gout.
Elevated levels of aldosterone (water and salt retention in the body with imbalance of various minerals in the blood).
Systemic lupus erythematosus (also called "lupus" or "SLE"), a disease in which the body's immune system attacks the body itself.
The active substance hydrochlorothiazide may cause an unusual reaction, leading to vision loss and eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in the eye and may occur from hours to weeks after taking Tolucombi. If left untreated, this may lead to permanent vision loss.
If you have previously had skin cancer or are developing unexpected skin lesions during treatment. Treatment with hydrochlorothiazide, particularly long-term use with high doses, may increase the risk of certain types of non-melanoma skin cancer and lip cancer. Protect your skin from exposure to sunlight and UV rays while taking Tolucombi.
If you have previously experienced breathing or lung problems (including inflammation or fluid in the lungs) after taking hydrochlorothiazide. If you develop shortness of breath or severe breathing difficulties after taking Tolucombi, consult a doctor immediately.

Talk to your doctor before taking Tolucombi if you are taking:

digoxin.
one of the following medicines used to treat high blood pressure:
- an "ACE inhibitor" (e.g. enalapril, lisinopril, ramipril), particularly if you have kidney problems related to diabetes.
- aliskiren.

You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Tolucombi is not recommended during early pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to the baby if taken during this period (see section on pregnancy).

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

You should also inform your doctor if you have developed increased skin sensitivity to sunlight, manifesting as faster-than-normal onset of sunburn symptoms (such as redness, itching, swelling, blisters).

If you are undergoing surgery or receiving anaesthetics, inform the doctor that you are taking Tolucombi.

Tolucombi may be less effective in lowering blood pressure in patients of African origin.

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

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

Children and adolescents

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

Other medicines and Tolucombi

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Your doctor may decide to adjust the dose of these other medicines or take other precautions. In some cases, it may be necessary to stop taking one of these medicines. This particularly applies to the following medicines when taken concurrently with Tolucombi:

Medicines containing lithium used to treat certain types of depression.
Medicines associated with low blood potassium levels (hypokalaemia), 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 may increase blood potassium levels, such as potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, ACE inhibitors, cyclosporine (an immunosuppressant), and other medicines such as sodium heparin (an anticoagulant).
Medicines that are affected by changes in blood potassium levels, 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. sparfloxacin, pentamidine) or certain medicines for treating allergic reactions (e.g. terfenadine).
Medicines for the treatment of diabetes (insulin or oral agents such as metformin).
Cholestyramine and colestipol, medicines used to lower blood fat levels.
Medicines to increase blood pressure, such as noradrenaline.
Muscle relaxants, such as tubocurarine.
Calcium and/or vitamin D supplements.
Anticholinergic medicines (drugs used to treat various disorders such as gastrointestinal cramps, bladder spasms, asthma, motion sickness, muscle spasms, Parkinson's disease, and as an aid in anaesthesia), such as atropine and biperiden.
Amantadine (a medicine used to treat Parkinson's disease and also used to treat or prevent virus-related illnesses).
Other substances used to treat high blood pressure, corticosteroids, painkillers (such as non-steroidal anti-inflammatory drugs [NSAIDs]), cancer treatments, gout or arthritis medicines.
If you are taking an ACE inhibitor or aliskiren (see also the sections "Do not take Tolucombi" and "Warnings and precautions").
Digoxin.

Tolucombi may enhance the effect of other medicines used to lower blood pressure or medicines that may potentially reduce blood pressure (e.g. baclofen, amifostine). Additionally, blood pressure reduction may be worsened by alcohol, barbiturates, narcotics, or antidepressants. You may experience this drop in blood pressure as dizziness when standing up.

Consult your doctor if you need to adjust the dose of other medicines while taking Tolucombi.

The effect of Tolucombi may be reduced when taking NSAIDs (non-steroidal anti-inflammatory drugs, e.g. acetylsalicylic acid or ibuprofen).

Tolucombi with food and alcohol

You may take Tolucombi with or without food.

Avoid consuming alcohol before discussing it with your doctor. Alcohol may further lower blood pressure and/or increase the risk of dizziness or fainting.

Pregnancy and breastfeeding

Pregnancy

Inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking Tolucombi before becoming pregnant or as soon as you learn you are pregnant and will recommend an alternative medicine instead of Tolucombi.

Tolucombi is not recommended during pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to the baby if taken after the third month of pregnancy.

Breastfeeding

Inform your doctor if you are breastfeeding or planning to breastfeed. Tolucombi is not recommended for women who are breastfeeding, and your doctor may choose another treatment if you wish to breastfeed.

Driving and using machines

Some patients may experience dizziness or drowsiness when taking Tolucombi. If you experience these effects, do not drive or operate machinery.

Tolucombi contains lactose, sorbitol and sodium

If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

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

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

Patients weighing 58.8 kg or less should consider 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 if you have been diagnosed with hereditary fructose intolerance, a rare genetic condition in which patients cannot metabolize fructose, speak with your doctor before you (or your child) take this medicine.

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially "sodium-free".

3. How to take Tolucombi

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
The recommended dose is one tablet daily. Try to take the tablet at the same time each day. You may take Tolucombi with or without food. Swallow the tablets with a little water or another non-alcoholic drink. It is important to take Tolucombi every day until your doctor tells you otherwise.
If your liver function is impaired, the usual dose of 40 mg/12.5 mg per day must not be exceeded.
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 heartbeat. Slow heartbeat, dizziness, vomiting, and reduced kidney function including kidney failure have also been reported. Due to the presence of hydrochlorothiazide, markedly low blood pressure and low blood potassium levels may also occur, which can cause nausea, drowsiness, and muscle cramps and/or irregular heartbeat, particularly when used concomitantly with medications such as digoxin or certain antiarrhythmic treatments.
Contact your doctor, pharmacist, or the nearest hospital emergency department immediately.
If you forget to take Tolucombi
If you forget to take your dose, do not worry. Take it as soon as you remember, then continue as before. If you miss a day's dose, take your normal dose the next day. Do not take a double dose to make up for a missed dose.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Some side effects may be serious and require immediate medical treatment:
You must contact your doctor immediately if you experience any of the following symptoms:
Sepsis* (often called "blood infection") is a severe infection with an inflammatory response throughout the entire body, rapid swelling of the skin and mucous membranes (angioedema), development of blisters and shedding of the outer layer of the skin (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 serious, and patients must stop taking the medicine and consult a doctor immediately. If these effects are not treated, they may be fatal.
An increased incidence of sepsis has been observed with telmisartan alone; however, this cannot be excluded for Tolucombi.
Possible side effects of Tolucombi:
Common side effects (may affect up to 1 in 10 people):
Dizziness.
Uncommon side effects (may affect up to 1 in 100 people):
Low blood potassium levels, anxiety, fainting (syncope), numbness sensation, tingling sensation (paraesthesia), sensation of spinning (vertigo), rapid heartbeat (tachycardia), heart rhythm disorders, low blood pressure, sudden drop in blood pressure upon standing, shortness of breath (dyspnoea), diarrhoea, dry mouth, flatulence, back pain, muscle spasm, muscle pain, erectile dysfunction (inability to achieve or maintain an erection), chest pain, increased blood uric acid levels.
Rare side effects (may affect up to 1 in 1,000 people):
Lung inflammation (bronchitis), activation or worsening of systemic lupus erythematosus (a disease in which the immune system attacks the body itself, causing joint pain, skin rash, and fever), sore throat, sinusitis, feeling of sadness (depression), difficulty falling asleep (insomnia), altered vision, breathing difficulties, abdominal pain, constipation, swelling (dyspepsia), feeling unwell (nausea), stomach inflammation (gastritis), abnormal liver function (this side effect is more likely in Japanese patients), skin redness (erythema), allergic reactions such as itching or skin rash, increased sweating, urticaria, joint pain (arthralgia) and pain in the extremities, muscle cramps, flu-like illness, pain, low sodium levels, increased blood levels of creatinine, liver enzymes, or creatine phosphokinase.
Adverse reactions reported with one of the individual components may also be potential adverse reactions with Tolucombi, even if not observed in clinical studies with this product.
Telmisartan
In patients treated with telmisartan alone, the following additional side effects have been observed:
Uncommon side effects (may affect up to 1 in 100 people):
Upper respiratory tract infection (e.g. sore throat, sinusitis, common cold), urinary tract infections, reduced red blood cells (anaemia), high potassium levels, slow heart rate (bradycardia), kidney impairment including acute renal failure, feeling of weakness, cough.
Rare side effects (may affect up to 1 in 1,000 people):
Low platelet count (thrombocytopenia), increase in certain white blood cells (eosinophilia), severe allergic reaction (e.g. hypersensitivity, anaphylactic reaction, drug rash), low blood sugar levels (in diabetic patients), stomach disorder, eczema (skin disorder), osteoarthritis, tendon inflammation, decrease in haemoglobin (a blood protein), drowsiness.
Very rare side effects (may affect up to 1 in 10,000 people):
Progressive scarring of lung tissue (interstitial lung disease)**.
*The event may have occurred by chance or could be related to a currently unknown mechanism.
**Cases of progressive scarring of lung tissue have been reported during treatment with telmisartan. However, it is not known whether telmisartan was the cause.
Hydrochlorothiazide
In patients treated with hydrochlorothiazide alone, the following additional side effects have been observed:
Common side effects (may affect up to 1 in 10 people):
Malaise (nausea), low blood magnesium levels.
Rare side effects (may affect up to 1 in 1,000 people):
Reduced platelet count, increasing the risk of bleeding or bruising (small purple-red spots on the skin or other tissues due to bleeding), high blood calcium levels, headache.
Very rare side effects (may affect up to 1 in 10,000 people):
Increased pH (altered acid-base balance) due to low blood chloride levels, acute respiratory distress (signs include severe shortness of breath, fever, weakness, and confusion).
Side effects of unknown frequency (frequency cannot be determined from available data):
Inflammation of the salivary glands, skin and lip cancer (non-melanoma skin cancer), decreased number (or even absence) of blood cells, including reduced red and white blood cell counts, severe allergic reactions (e.g. hypersensitivity, anaphylactic reaction), decreased or loss of appetite, restlessness, dizziness, blurred or yellowish vision, reduced vision and eye pain (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or of acute myopia or closed-angle glaucoma), inflammation of blood vessels (necrotizing vasculitis), pancreatitis, stomach disorder, yellowing of the skin or eyes (jaundice), lupus-like syndrome (a condition mimicking a disease called systemic lupus erythematosus, in which the immune system attacks the body itself); skin disorders such as inflammation of blood vessels in the skin, increased sensitivity to sunlight, skin rash, redness of the skin, blistering on lips, eyes or mouth, skin peeling, fever (possible signs of erythema multiforme), feeling of weakness, kidney inflammation or altered kidney function, glucose in urine (glucosuria), fever, electrolyte imbalance, elevated blood cholesterol levels, reduced blood volume, increased glucose levels, difficulty controlling blood/urine glucose levels in patients diagnosed with diabetes mellitus, or elevated blood fat levels.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Tolucombi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and on the blister after
EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature.
Store in the original packaging to protect the medicine from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Tolucombi contains

The active substances 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 excipients are: hydroxypropyl cellulose, monohydrate lactose, magnesium stearate, mannitol, meglumine, povidone (K30), red iron oxide (E172) – only in tablets of 40 mg/12.5 mg and 80 mg/12.5 mg, anhydrous colloidal silica, sodium hydroxide (E524), sodium stearil fumarate, sorbitol (E420) and yellow iron oxide (E172) – only in tablets of 80 mg/25 mg. See paragraph 2.

“Tolucombi contains lactose, sorbitol and sodium”.

Description of the appearance of Tolucombi and contents of the pack
Tablets 40 mg/12.5 mg: white, whitish or pinkish on one side and marbled pink on the opposite side of a two-layer, biconvex, oval tablet; tablet size 15 mm x 7 mm.
Tablets 80 mg/12.5 mg: white, whitish or pinkish on one side and marbled pink on the opposite side of a two-layer, biconvex, oval tablet; tablet size 18 mm x 9 mm.
Tablets 80 mg/25 mg: white tending to yellow on one side and marbled yellow on the opposite side of a two-layer, biconvex, oval tablet; tablet size 18 mm x 9 mm.
Blister (OPA/Al/PVC sheet//Al sheet): 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 (OPA/Al/PE foil with desiccant//Al sheet): 14 x 1 and 98 x 1 tablet in a box.
Not all pack sizes may be marketed.

Marketing Authorization Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
KRKA-POLSKA Sp. z o.o., ul. Równoległa 5, 02-235 Warszawa, Poland
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
KRKA Belgium, SA. UAB KRKA Lietuva
Tél/Tel: +32 (0) 487 50 73 62 Tel: +370 5 236 27 40

България Luxembourg/Luxemburg
КРКА България ЕООД KRKA Belgium, SA.
Teл.: +359 (02) 962 34 50 Tél/Tel: +32 (0) 487 50 73 62 (BE)

Česká republika Magyarország
KRKA ČR, s.r.o. KRKA Magyarország Kereskedelmi Kft.
Tel: +420 (0) 221 115 150 Tel.: +36 (1) 355 8490

Danmark Malta
KRKA Sverige AB E. J. Busuttil Ltd.
Tlf: +46 (0)8 643 67 66 (SE) Tel: +356 21 445 885

Deutschland Nederland
TAD Pharma GmbH KRKA Belgium, SA.
Tel: +49 (0) 4721 606-0 Tel: +32 (0) 487 50 73 62 (BE)

Eesti Norge
KRKA, d.d., Novo mesto Eesti filiaal KRKA Sverige AB
Tel: +372 (0) 6 671 658 Tlf: +46 (0)8 643 67 66 (SE)

Ελλάδα Österreich
KRKA ΕΛΛΑΣ ΕΠΕ KRKA Pharma GmbH, Wien
Τηλ: +30 2100101613 Tel: +43 (0)1 66 24 300

España Polska
KRKA Farmacéutica, S.L. KRKA-POLSKA Sp. z o.o.
Tel: +34 911 61 03 80 Tel.: +48 (0)22 573 7500

France Portugal
KRKA France Eurl KRKA Farmacêutica, Sociedade Unipessoal Lda.
Tél: +33 (0)1 57 40 82 25 Tel: +351 (0)21 46 43 650

Hrvatska România
KRKA - FARMA d.o.o. KRKA Romania S.R.L., Bucharest
Tel: +385 1 6312 100 Tel: +4 021 310 66 05

Ireland Slovenija
KRKA Pharma Dublin, Ltd. KRKA, d.d., Novo mesto
Tel: +353 1 413 3710 Tel: +386 (0) 1 47 51 100

Ísland Slovenská republika
LYFIS ehf. KRKA Slovensko, s.r.o.
Sími: +354 5343500 Tel: +421 (0) 2 571 04 501

Italia Suomi/Finland
KRKA Farmaceutici Milano S.r.l. KRKA Finland Oy
Tel: +39 02 3300 8841 Puh/Tel: +358 20 754 5330

Κύπρος Sverige
KI.PA. (PHARMACAL) LIMITED KRKA Sverige AB
Τηλ: +357 24 651 882 Tel: +46 (0)8 643 67 66 (SE)

Latvija United Kingdom (Northern Ireland)
KRKA Latvija SIA KRKA Pharma Dublin, Ltd.
Tel: +371 6 733 86 10 Tel: +353 1 413 3710

More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.