Tolucombi 80 mg/12.5 mg tablets

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 all of this 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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Tolucombi and what is it used for
2. What you need to know before you take Tolucombi
3. How to take Tolucombi
4. Possible side effects
5. Storage of Tolucombi
6. Contents of the pack and other information

1. What is Tolucombi and what is it used for

Tolucombi is a combination of two active substances, telmisartan and hydrochlorothiazide, in one tablet. Both active substances help to 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, thus increasing your blood pressure. Telmisartan blocks the effect of angiotensin II, so that your blood vessels relax and your blood pressure is reduced.

• Hydrochlorothiazide belongs to a group of medicines known as thiazide diuretics, which increase the amount of urine you produce, leading to a reduction in your blood pressure.

High blood pressure, if left untreated, can damage the blood vessels of various organs, which can sometimes lead to a heart attack, heart failure, or kidney failure, stroke, or blindness.

Usually, there are no symptoms of high blood pressure before damage occurs. Therefore, it is important to regularly check your blood pressure 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 adequately controlled with telmisartan 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 telmisartan and hydrochlorothiazide separately.

2. What you need to know before you take Tolucombi

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 also at the beginning of your pregnancy - see section Pregnancy);
• if you have severe liver problems, such as cholestasis or biliary obstruction (problems with bile drainage from the liver and gallbladder) or any other severe liver disease;
• if you have severe kidney disease;
• if your doctor determines that you have low potassium or high calcium levels 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 that contains aliskiren.

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

Warnings and precautions

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

• Low blood pressure (hypotension), which can occur if you are dehydrated (excessive loss of body water) or have an electrolyte deficiency due to treatment with diuretics, 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.
• High aldosterone levels (water and salt retention in the body along with an 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 itself.
• The active ingredient hydrochlorothiazide may cause a rare reaction, leading to decreased vision and eye pain. These symptoms can 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 within hours to weeks after taking Tolucombi. If left untreated, it can lead to permanent vision loss.
• 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 skin 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 shortness of breath or severe 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 medicines used to treat high blood pressure:

• 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, think you may be pregnant, or are planning to become pregnant, inform your doctor. Tolucombi is not recommended during the first trimester of pregnancy (the first 3 months) and should not be used after the third month of pregnancy, as it may cause serious harm to your baby (see section Pregnancy).

Treatment with hydrochlorothiazide may cause an electrolyte imbalance in your body. Typical symptoms of fluid or electrolyte imbalance include dry mouth, weakness, lethargy, somnolence, 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, blistering) that appear more quickly than usual.

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

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

Your doctor may check your kidney function, blood pressure, and blood electrolyte levels (such as 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 recently taken, or might take any other medicines. Your doctor may need to change the dose of those other medicines or take other precautions. In some cases, it may be necessary to stop using one of these medicines, especially if you are using any of the following medicines with Tolucombi:

• Medicines containing lithium for the treatment of certain types of depression.
• Medicines associated with low potassium levels in the blood (hypokalemia), such as other diuretics, laxatives (e.g., castor oil), corticosteroids (e.g., prednisone), adrenocorticotropic hormone (ACTH), amphotericin (an antifungal medicine), carbenoxolone (used to treat mouth ulcers), sodium penicillin G (an antibiotic), and acetylsalicylic acid and derivatives.
• Medicines that can increase potassium levels in the blood, such as potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, ACE inhibitors, cyclosporine (an immunosuppressive medicine), and other medicines like heparin sodium (an anticoagulant).
• Medicines whose effects are influenced by changes in potassium levels in the blood, such as heart medicines (e.g., digoxin) or medicines to control your heart rate (e.g., quinidine, disopyramide, amiodarone, sotalol), medicines used for mental disorders (e.g., thioridazine, chlorpromazine, levomepromazine), and other medicines like certain antibiotics (e.g., sparfloxacin, pentamidine) or certain medicines for treating allergic reactions (e.g., terfenadine).
• Medicines for the treatment of diabetes (insulins or oral agents like metformin).
• Colestyramine and colestipol, medicines 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 (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) like 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 treating cancer, 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 medicines that can potentially lower blood pressure (e.g., baclofen, amifostine). Additionally, the decrease in blood pressure may be enhanced by alcohol, barbiturates, narcotics, or antidepressants. You may notice this effect as dizziness when standing up. You should inform your doctor about the need to adjust the dose of your other medicines while using Tolucombi.

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

Taking Tolucombi with food and alcohol

You can take Tolucombi with or without food.

Avoid drinking alcohol until you have talked to your doctor. Alcohol can 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 normally advise you to stop taking Tolucombi before you become pregnant or as soon as you find out you are pregnant, and will recommend that you take a different blood pressure-lowering medicine instead. Tolucombi is not recommended during pregnancy and should not be used after the third month of pregnancy, as it may cause serious harm to your baby.

Breastfeeding

Inform your doctor if you are about to start or are breastfeeding, as Tolucombi is not recommended for use in women during this period. Your doctor may decide to give you a treatment that is more suitable if you want 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 use machinery.

Tolucombi contains lactose, sorbitol, and sodium

If your doctor has told you that you have an intolerance to some sugars, consult your doctor 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 who weigh 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 before taking this medicine.

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

3. How to take Tolucombi

Follow exactly the instructions for administration of this medicine given by your doctor. If you are unsure, consult your doctor or pharmacist again.

The recommended dose is one tablet per day. Try to take one tablet each 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 drink. It is important that you take Tolucombi every day until your doctor tells you to stop.

If your liver is not working properly, 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 a fast heart rate. Slow heart rate, dizziness, vomiting, and reduced kidney function, including kidney failure, have also been reported. Due to the hydrochlorothiazide component, you may also experience very low blood pressure and low potassium levels in the blood, which can lead to nausea, somnolence, and muscle cramps and/or irregular heartbeats associated with concomitant use of medicines like digitalis or certain antiarrhythmic treatments. Contact your doctor or pharmacist or the nearest hospital emergency department immediately.

If you forget to take Tolucombi

If you forget to take your medicine, do not worry. Take the dose as soon as you remember and continue as before. If you miss a dose one day, take your normal dose the next day. Do not take a double dose to make up for forgotten doses.

If you have any further questions on 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 all people suffer from them.

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

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

Sepsis* (frequently called "blood infection"), is a serious infection that involves an inflammatory reaction of the entire body, rapid swelling of the skin and mucous membranes (angioedema); blistering and peeling of the outer layer of the 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 serious and patients should stop taking the medicine and visit their doctor immediately.

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

Possible Adverse Effects of Tolucombi:

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

Dizziness.

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

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

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

Bronchitis (inflammation of the lungs), activation or worsening of systemic lupus erythematosus (a disease in which the body's immune system attacks the body itself, causing joint pain, skin rashes, and fever), sore throat, sinusitis, feeling of sadness (depression), difficulty falling asleep (insomnia), vision disturbances, breathing difficulties, abdominal pain, constipation, abdominal distension (dyspepsia), general malaise (vomiting), gastritis (inflammation of the stomach), liver function disorders (Japanese patients show a greater tendency to experience this adverse effect), skin redness (erythema), allergic reactions such as itching or rash, increased sweating, hives (urticaria), joint pain (arthralgia), and pain in the limbs, muscle cramps, pseudogrippal illness, pain, low sodium levels, increased creatinine, liver enzymes, or creatine phosphokinase levels in the blood.

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

Telmisartan

The following adverse effects have been additionally described in patients taking telmisartan alone:

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

Upper respiratory tract infection (e.g., sore throat, sinusitis, common cold), urinary tract infections, anemia (low red blood cell count), high potassium levels, slow heart rate (bradycardia), kidney function disorders including acute kidney failure, weakness, cough.

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

Low platelet count (thrombocytopenia), increased white blood cell count (eosinophilia), severe allergic reactions (e.g., hypersensitivity, anaphylactic reactions, drug rash), low blood sugar levels (in diabetic patients), stomach discomfort, eczema (a skin disorder), arthrosis, tendonitis, decreased hemoglobin (a blood protein), somnolence.

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

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

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

Hydrochlorothiazide

The following adverse effects have been additionally described in patients taking hydrochlorothiazide alone:

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

Nausea, decreased magnesium levels in the blood.

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

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

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

Increased pH (acid-base imbalance) due to low chloride levels in the blood, acute respiratory distress (signs include severe respiratory distress, 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 blood cell count, including low red and white blood cell count; severe allergic reactions (e.g., hypersensitivity, anaphylactic reactions), decreased or lost appetite; restlessness, dizziness, blurred or yellowish vision, decreased vision, and eye pain (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma), vasculitis (inflammation of blood vessels), pancreatitis, stomach discomfort, yellowing of the skin or eyes (jaundice), pseudolupus syndrome (a condition that mimics systemic lupus erythematosus), skin disorders such as vasculitis, increased sensitivity to sunlight, skin rash, skin redness, blistering of the lips, eyes, or mouth, skin peeling, fever (possible signs of erythema multiforme), weakness, kidney inflammation or dysfunction, glucose in the urine (glucosuria), fever, electrolyte imbalance, high cholesterol levels in the blood, decreased blood volume, increased blood glucose levels, difficulty controlling blood glucose levels in patients with diabetes mellitus, or fat in the blood.

Reporting Adverse Effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing 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 expiration date stated on the carton and blister after EXP. The expiration date is the last day of the month indicated.

This medicine does not require any special storage temperature.

Store in the original packaging to protect from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Tolucombi Composition

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

Product Appearance and Packaging Contents

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

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

80 mg/25 mg tablets: biconvex, oval, white to yellowish-white on one side and yellow-mottled on the other 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 tablets per carton.

Blister packs (OPA/Al/PE with desiccant//Al foil): 14 x 1 and 98 x 1 tablets per carton.

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. Równolegla 5, 02-235 Warszawa, Poland

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

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

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