Tolucombi 40 mg/12.5 mg tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Tolucombi 40 mg/12.5 mg tablets EFG

Tolucombi 80 mg/12.5 mg tablets EFG

Tolucombi 80 mg/25 mg tablets EFG

telmisartan/hydrochlorothiazide

Read the entire leaflet carefully before you start taking this medicine, because 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

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. Both active substances help control high blood pressure.

• Telmisartan belongs to a group of medicines known as angiotensin II receptor antagonists. Angiotensin II is a substance produced in your body that causes your blood vessels to narrow, thereby increasing your blood pressure. Telmisartan blocks the effect of angiotensin II, allowing your blood vessels to relax and your blood pressure to decrease.

• Hydrochlorothiazide belongs to a group of medicines known as thiazide diuretics, which increase your urine output, resulting in a reduction of your blood pressure.

If left untreated, high blood pressure can damage blood vessels in various organs, sometimes leading to heart attack, heart or kidney failure, stroke, or blindness.

Usually, there are no symptoms of high blood pressure before such damage occurs. Therefore, it is important to have your blood pressure checked regularly to ensure it remains within the normal range.

Tolucombi (40 mg/12.5 mg, 80 mg/12.5 mg) is used for the treatment of high blood pressure (essential hypertension) in adults whose blood pressure is not adequately controlled with telmisartan alone.

Tolucombi (80 mg/25 mg) is used for the 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 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 components of this medicine (listed in section 6);
• if you are allergic to hydrochlorothiazide or to other sulfonamide-derived medicines;
• if you are more than 3 months pregnant. (In any case, it is better to avoid taking Tolucombi also during early pregnancy – see Pregnancy section);
• if you have severe liver problems such as 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 has found that you have low levels of potassium or high levels of calcium in your blood that do not improve with treatment;
• if you have diabetes or kidney failure and are being treated with a blood pressure-lowering medicine containing aliskiren.

If any of the above apply to you, tell your doctor or pharmacist before taking Tolucombi.

Warnings and precautions

Talk to your doctor before starting 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 salt deficiency due to treatment with diuretics, a low-sodium 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;
• High levels of aldosterone (retention of water and salt in the body together with imbalance of several blood minerals);
• 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 a rare reaction leading to vision loss and eye pain. These symptoms may indicate fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased eye pressure and may appear from hours to weeks after taking Tolucombi. If not treated, this may lead to permanent vision damage.
• If you have had skin cancer or if you develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, particularly long-term use at 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 had breathing or lung problems (such as inflammation or fluid in the lungs) after taking hydrochlorothiazide in the past. If you develop shortness of breath or severe difficulty breathing after taking Tolucombi, seek medical help immediately.

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

• digoxin;

• any of the following medicines used to treat high blood pressure (hypertension):

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

If you are pregnant, think you might be pregnant, or are planning to become pregnant, you must inform your doctor. Use of Tolucombi is not recommended during early pregnancy (first 3 months), and it must not be used from the third month of pregnancy onwards, as it may cause severe harm to your baby – see Pregnancy section.

Treatment with hydrochlorothiazide may cause an electrolyte imbalance in your body. Typical symptoms of fluid or electrolyte imbalance include dry mouth, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, nausea, vomiting, muscle fatigue, and abnormally rapid 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 develop increased sensitivity of the skin to sunlight, with symptoms of sunburn (such as redness, itching, swelling, blistering) appearing more quickly than usual.

If you are scheduled for surgery or anaesthesia, you must inform your doctor that you are taking Tolucombi.

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

Your doctor may regularly monitor your kidney function, blood pressure, and blood electrolyte levels (e.g. potassium).

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

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. Your doctor may need to adjust the dose of these other medicines or take other precautions. In some cases, you may need to stop taking one of these medicines, especially if you are using any of the following together 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), ACTH (adrenocorticotropic hormone), amphotericin (an antifungal medicine), carbenoxolone (used to treat mouth ulcers), sodium penicillin G (an antibiotic), and acetylsalicylic 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 affected by changes in blood potassium levels, such as heart medicines (e.g. digoxin) or medicines to control your 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 used to treat allergic reactions (e.g. terfenadine);
• Medicines for the treatment of diabetes (insulins or oral agents such as metformin);
• Cholestyramine and colestipol, medicines used to reduce blood fat levels;
• Medicines to increase blood pressure, such as noradrenaline;
• Muscle relaxants, such as tubocurarine;
• Calcium and/or vitamin D supplements;
• Anticholinergic 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 anaesthesia), 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 (such as non-steroidal anti-inflammatory drugs [NSAIDs]), medicines for cancer, gout, or arthritis;
• If you are taking an angiotensin-converting enzyme (ACE) inhibitor or aliskiren (see also information under the headings “Do not take Tolucombi” and “Warnings and precautions”);
• Digoxin.

Tolucombi may enhance the blood pressure-lowering effect of other medicines or medicines that may potentially lower blood pressure (e.g. baclofen, amifostine). In addition, blood pressure reduction may be worsened by alcohol, barbiturates, narcotics, or antidepressants. You may notice this effect as dizziness when standing up. Inform your doctor, as dose adjustments of your other medicines may be needed while using Tolucombi.

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

Taking Tolucombi with food and alcohol

You may take Tolucombi with or without food.

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

Pregnancy and breastfeeding

Pregnancy

Inform your doctor if you are pregnant, think you may be pregnant, or are planning to become pregnant. Your doctor will usually advise you to stop taking Tolucombi before becoming pregnant or as soon as pregnancy is confirmed, and will recommend another antihypertensive medicine instead. Tolucombi is not recommended during pregnancy, and must not be used from the third month of pregnancy onwards, as it may cause severe harm to your baby when used from that time.

Breastfeeding

Inform your doctor if you are planning to start or are currently breastfeeding, as Tolucombi is not recommended for women during this period. Your doctor may decide to prescribe a treatment more suitable if you wish to breastfeed.

Driving and using machines

Some patients 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 him 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 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 body weight is 58.8 kg.

Patients weighing 58.8 kg or less should be aware 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 your doctor (or your child’s doctor) before taking this medicine.

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

3. How to take Tolucombi

Follow exactly the instructions for use of this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

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

If your liver is not functioning properly, the usual dose should not exceed 40 mg/12.5 mg once daily.

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 hydrochlorothiazide component, markedly low blood pressure and low blood potassium levels may also occur, which could lead to nausea, drowsiness, muscle cramps, and/or irregular heartbeat, particularly when used concomitantly with medications such as digitalis 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, and then continue as before. If you miss a day, take your normal dose the next day. Do not take a double dose to make up for missed doses.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

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

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

Sepsis* (commonly called "blood infection") is a serious infection involving a systemic inflammatory response, rapid swelling of the skin and mucous membranes (angioedema), and blistering and peeling of the outer layer of skin (toxic epidermal necrolysis). These adverse effects are rare (may affect up to 1 in 1,000 people) or of unknown frequency (toxic epidermal necrolysis), but are extremely severe. Patients must stop taking the medicine and see their doctor immediately.

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

Possible adverse effects of Tolucombi:

Common adverse effects (may affect up to 1 in 10 people):

Dizziness.

Uncommon adverse effects (may affect up to 1 in 100 people):

Decreased blood potassium levels, anxiety, fainting (syncope), tingling sensation, pins and needles (paresthesia), dizziness (vertigo), rapid heartbeat (tachycardia), irregular heart rhythm, 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 blood uric acid levels.

Rare adverse 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 body's immune system attacks its own tissues, causing joint pain, skin rashes, and fever), sore throat, sinus inflammation, feeling of sadness (depression), difficulty sleeping (insomnia), vision disturbances, difficulty breathing, abdominal pain, constipation, abdominal bloating (dyspepsia), general malaise (vomiting), stomach inflammation (gastritis), liver function abnormalities (Japanese patients show a higher tendency to experience this adverse effect), skin redness (erythema), allergic reactions such as itching or rash, increased sweating, hives (urticaria), joint pain (arthralgia), limb pain, muscle cramps, flu-like illness, pain, low sodium levels, increased levels of creatinine, liver enzymes, or creatine phosphokinase in blood.

Adverse reactions reported for one of the individual components may also be potential adverse reactions of Tolucombi, even if they have not been observed in clinical trials with this product.

Telmisartan

The following additional adverse effects have been reported in patients taking telmisartan alone:

Uncommon adverse effects (may affect up to 1 in 100 people):

Upper respiratory tract infection (e.g. sore throat, sinus inflammation, common cold), urinary tract infections, deficiency of red blood cells (anemia), high potassium levels, slow heart rate (bradycardia), kidney function impairment including acute renal failure, weakness, cough.

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

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

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

• This may have been a coincidental finding or related to a currently unknown mechanism.

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

Hydrochlorothiazide

The following additional adverse effects have been reported in patients taking hydrochlorothiazide alone:

Common adverse effects (may affect up to 1 in 10 people):

Nausea, decreased blood magnesium levels.

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

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

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

Increased pH (acid-base imbalance) due to low blood chloride levels, acute breathing difficulty (signs include severe shortness of breath, fever, weakness, and confusion).

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

Salivary gland inflammation, skin and lip cancer (non-melanoma skin cancer), decreased number (or even absence) of blood cells, including low counts of red and white blood cells; severe allergic reactions (e.g. hypersensitivity, anaphylactic reactions), 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 acute myopia or acute angle-closure glaucoma), inflammation of blood vessels (necrotizing vasculitis), pancreatitis, stomach discomfort, yellowing of the skin or eyes (jaundice), pseudolupus syndrome (a condition mimicking systemic lupus erythematosus, in which the body's immune system attacks its own tissues), skin disorders such as inflammation of skin blood vessels, increased sensitivity to sunlight, skin rash, skin redness, blistering of lips, eyes or mouth, skin peeling, fever (possible signs of erythema multiforme), weakness, kidney inflammation or impaired function, glucose in urine (glucosuria), fever, electrolyte imbalance, high blood cholesterol levels, reduced blood volume, increased blood glucose levels, difficulty controlling blood/urine glucose levels in patients diagnosed with diabetes mellitus, or fat in the blood.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Tolucombi

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

Do not use this medicine after the expiry date stated on the carton and blister after EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage temperature conditions.

Store in the original packaging to protect from light.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Tolucombi

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

Appearance of the product and contents of the pack

Tablets 40 mg/12.5 mg: two-layer, biconvex, oval tablets, white to almost white or pinkish white on one side and mottled pink on the opposite side, tablet dimensions 15 mm x 7 mm.

Tablets 80 mg/12.5 mg: two-layer, biconvex, oval tablets, white to almost white or pinkish white on one side and mottled pink on the opposite side, tablet dimensions 18 mm x 9 mm.

Tablets 80 mg/25 mg: two-layer, biconvex, oval tablets, white to yellowish white on one side and mottled yellow on the opposite side, tablet 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 certain 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. 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:

Date of the most recent review of this leaflet:

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.