Co-bespres

PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

Co-Bespres, 80 mg + 12.5 mg, film-coated tablets
Co-Bespres, 160 mg + 25 mg, film-coated tablets
Valsartanum + Hydrochlorothiazidum
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not share it with others. This medicine may harm other people, even if their symptoms are the same as yours.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet Contents

1. What Co-Bespres is and what it is used for
2. Important information before taking Co-Bespres
3. How to take Co-Bespres
4. Possible side effects
5. How to store Co-Bespres
6. Contents of the pack and other information

1. What Co-Bespres is and what it is used for

Co-Bespres film-coated tablets contain two active substances called valsartan and hydrochlorothiazide. Both substances help control high blood pressure (hypertension).

• Valsartan belongs to a group of medicines known as "angiotensin II receptor antagonists", which help control high blood pressure. Angiotensin II is a substance produced in the human body that causes blood vessels to constrict, thereby increasing blood pressure. Valsartan works by blocking the action of angiotensin II, resulting in relaxation and widening of blood vessels, thus lowering blood pressure.
• Hydrochlorothiazide belongs to a group of medicines called thiazide diuretics (also referred to as "diuretics"). Hydrochlorothiazide increases urine production, which also helps lower blood pressure.

Co-Bespres is used to treat high blood pressure that cannot be adequately controlled with only one active substance.
High blood pressure increases the workload on the heart and blood vessels. If left untreated, it may damage blood vessels in the brain, heart, and kidneys, potentially leading to stroke, heart failure, or kidney failure. High blood pressure also increases the risk of heart attack. Lowering blood pressure to normal levels reduces the risk of these complications.

2. Important information before using Co-Bespres

When not to use Co-Bespres

• if the patient is allergic to valsartan, hydrochlorothiazide, sulfonamide derivatives (substances with a chemical structure similar to hydrochlorothiazide), or any of the other ingredients of this medicine (listed in section 6).
• if the patient is in the third month of pregnancy or beyond (it is also advisable to avoid using Co-Bespres in early pregnancy – see section 2: Pregnancy and breastfeeding).
• if the patient has severe liver disease, damage to the small bile ducts in the liver (primary biliary cirrhosis), leading to bile accumulation in the liver (cholestasis).
• if the patient has severe kidney disease.
• if the patient is unable to produce urine (anuria).
• if the patient is undergoing dialysis with an artificial kidney.
• if the patient has low blood levels of potassium or sodium, or high blood calcium levels, despite treatment.
• if the patient has gout.
• if the patient has diabetes or kidney dysfunction and is being treated with a blood pressure-lowering medicine containing aliskiren.

If any of the above conditions apply to the patient, Co-Bespres must not be used and
the patient should contact their doctor.
Warnings and precautions
Before starting Co-Bespres, discuss this with your doctor or pharmacist.

• if the patient is taking potassium-sparing medicines, potassium supplements, or potassium-containing salt substitutes, or other medicines that increase blood potassium levels, such as heparin. Your doctor may need to monitor blood potassium levels.
• if the patient has low blood potassium levels.
• if the patient has diarrhoea or severe vomiting.
• if the patient is taking high doses of diuretics (water tablets).
• if the patient has severe heart disease.
• if the patient has heart failure or has had a heart attack. Follow your doctor's advice closely regarding starting treatment – kidney function monitoring may also be necessary.
• if the patient has renal artery stenosis (narrowing of the artery to the kidney).
• if the patient has recently received a kidney transplant.
• if the patient has hyperaldosteronism – a condition in which the adrenal glands produce too much of a hormone called aldosterone. In this case, use of Co-Bespres is not recommended.
• if the patient has liver or kidney disease.
• if the patient has ever experienced swelling of the tongue and face due to an allergic reaction, known as angioedema, after taking another medicine (including ACE inhibitors), inform the doctor. If such symptoms occur while taking Co-Bespres, stop taking it immediately and never use it again. See section 4 "Possible side effects".
• if the patient develops fever, rash, and joint pain, which may be symptoms of systemic lupus erythematosus (SLE, an autoimmune disease).
• if the patient has diabetes, has had gout, or has high cholesterol or triglyceride levels in the blood.
• if the patient has previously experienced allergic reactions after taking other blood pressure-lowering medicines belonging to this group (angiotensin II receptor antagonists), or if the patient has allergies or asthma.
• if the patient experiences vision disturbances or eye pain. These may be symptoms of fluid accumulation in the uvea (the vascular layer surrounding the eye) or increased intraocular pressure, which may occur within hours to weeks after starting Co-Bespres. If left untreated, these conditions can

lead to complete loss of vision. Patients who are allergic to penicillin or
sulfonamides have a higher risk of developing such disorders.

• if the patient is taking any of the following medicines for high blood pressure: ACE inhibitors (e.g. enalapril, lisinopril, ramipril), especially if the patient has kidney dysfunction related to diabetes or is taking aliskiren.
• if the patient has previously had skin cancer or develops unexpected skin changes during treatment. Treatment with hydrochlorothiazide, especially at high doses over a prolonged period, may increase the risk of certain types of non-melanoma skin cancer and lip cancer. While taking Co-Bespres, protect the skin from sunlight and UV radiation.
• if the patient has previously experienced breathing or lung problems (including pneumonia or fluid accumulation in the lungs) after taking hydrochlorothiazide. If the patient develops severe shortness of breath or difficulty breathing after taking Co-Bespres, seek immediate medical help.

The treating physician may monitor kidney function, blood pressure, and blood electrolyte levels (e.g.
potassium) at regular intervals.
See also information under the heading "When not to use Co-Bespres".
Co-Bespres may increase skin sensitivity to sunlight.
Inform your doctor if you are pregnant, suspect you may be pregnant, or are planning pregnancy.
Co-Bespres is not recommended during early pregnancy and must not be used after the 3rd
month of pregnancy, as it may seriously harm the unborn child (see section
"Pregnancy and breastfeeding").
If the patient experiences abdominal pain, nausea, vomiting, or diarrhoea after taking Co-Bespres,
discuss this with the doctor. The doctor will decide whether to continue treatment. Do not
independently decide to stop taking Co-Bespres.
Children and adolescents
Co-Bespres is not recommended for use in children and adolescents (under 18 years of age).
Co-Bespres with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Taking Co-Bespres with certain other medicines may affect treatment. Dose adjustments, additional precautions, or in some cases discontinuation of one of the medicines may be necessary. This particularly applies to the following medicines:

• Lithium, a medicine used to treat certain psychiatric disorders.
• Medicines or substances that may increase blood potassium levels, such as potassium supplements, potassium-containing salt substitutes, potassium-sparing medicines, and heparin.
• Medicines that may decrease blood potassium levels, such as diuretics (water tablets), corticosteroids, laxatives, ACTH (adrenocorticotropic hormone), carbenoxolone, amphotericin, penicillin G, salicylic acid and its derivatives.
• Certain antibiotics (rifamycin group), medicines used to prevent rejection of transplanted organs (cyclosporine), or antiretroviral medicines used to treat HIV/AIDS (ritonavir). These medicines may enhance the effect of Co-Bespres.
• Medicines that may cause "torsade de pointes" (a type of heart rhythm disorder), e.g. antiarrhythmics (medicines used to treat heart conditions) and certain antipsychotics.
• Medicines that may reduce blood sodium levels, such as antidepressants, antipsychotics, antiepileptics.
• Medicines used to treat gout, such as allopurinol, probenecid, sulfinpyrazone.
• Vitamin D in therapeutic doses and calcium supplements.
• Medicines used to treat diabetes (oral antidiabetics such as metformin or insulin).
• Other blood pressure-lowering medicines, including methyldopa, angiotensin-converting enzyme (ACE) inhibitors (e.g. enalapril, lisinopril, etc.) or aliskiren (see also information under "When not to use Co-Bespres" and "Warnings and precautions").
• Medicines that may increase blood pressure, such as noradrenaline or adrenaline.
• Digoxin or other cardiac glycosides (medicines used to treat heart conditions).
• Medicines that may increase blood glucose levels, such as diazoxide or beta-blockers.
• Cytotoxic medicines (used in cancer treatment), such as methotrexate or cyclophosphamide.
• Painkillers, such as non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors and acetylsalicylic acid at doses > 3 g.
• Muscle relaxants, such as tubocurarine.
• Anticholinergic medicines (used to treat various disorders such as gastrointestinal spasms, bladder spasms, asthma, motion sickness, muscle spasms, Parkinson's disease, and as an adjunct in anaesthesia), such as atropine or biperiden.
• Amantadine (a medicine used to treat Parkinson's disease and also used in the treatment or prevention of certain viral diseases).
• Cholestyramine and colestipol (medicines mainly used to treat high blood lipid levels).
• Cyclosporine, a medicine used in organ transplant patients to prevent organ rejection.
• Alcohol, hypnotics, and anaesthetics (medicines with sedative or pain-relieving effects, used, for example, during surgery).
• Iodine-containing contrast agents (substances used in imaging procedures).

Co-Bespres with food, drink, and alcohol
Co-Bespres may be taken with or without food.
Avoid consuming alcohol until you have consulted your doctor. Alcohol may
further lower blood pressure and/or increase the risk of dizziness or fainting.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor or pharmacist before using this medicine.
Pregnancy

• If the patient is pregnant, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor before using this medicine. The doctor will usually advise stopping Co-Bespres before planned pregnancy or immediately after pregnancy is confirmed, and will recommend an alternative medicine to Co-Bespres. Co-Bespres is not recommended during early pregnancy and must not be used after the 3rd month of pregnancy, as it may seriously harm the unborn child.

Breastfeeding

• If the patient is breastfeeding or intends to start breastfeeding, she should consult her doctor before using this medicine. Co-Bespres is not recommended during breastfeeding. The doctor may recommend an alternative medicine, especially if breastfeeding a newborn or premature infant.

Driving and operating machinery
Before driving, using tools, operating machinery, or performing other tasks requiring concentration, the patient should become familiar with their individual response to Co-Bespres. Like many other medicines used to treat high blood pressure, Co-Bespres may rarely cause dizziness and affect the ability to concentrate.
Co-Bespres contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per coated tablet, meaning the medicine is considered "sodium-free".
Co-Bespres 80 mg + 12.5 mg contains sunset yellow (E110)
Co-Bespres contains sunset yellow (E110), which may cause allergic reactions.

3. How to use Co-Bespres

This medicine should always be taken exactly as directed by your doctor. Following these instructions will help achieve the best results and reduce the risk of adverse effects. If in doubt, consult your doctor or pharmacist.

People with high blood pressure often do not experience any noticeable symptoms and may feel quite well. For this reason, it is especially important to attend regular check-ups with your doctor, even if you feel well.

Your doctor will inform you how many Co-Bespres tablets you should take. Depending on your response to treatment, your doctor may adjust your dose upwards or downwards.

• The usual recommended dose of Co-Bespres is one tablet daily.
• Do not change the dose or stop treatment without consulting your doctor.
• The medicine should be taken every day at the same time, usually in the morning.
• Co-Bespres may be taken during or independently of meals.
• Swallow the tablet with a glass of water.

Taking more Co-Bespres than recommended
If severe dizziness and/or fainting occur, lie down immediately and contact your doctor without delay.
If an overdose is taken by accident, contact your doctor, pharmacist, or go to the nearest hospital emergency department.

Missing a dose of Co-Bespres
If you miss a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose.
Do not take a double dose to make up for a missed dose.

Stopping Co-Bespres
Stopping treatment with Co-Bespres may cause your high blood pressure to worsen. Do not discontinue the medicine unless instructed by your doctor.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Some adverse reactions may be serious and require immediate medical attention:

• seek immediate medical advice if symptoms of angioedema occur, such as:
• swelling of the face, tongue or throat
• difficulty swallowing
• urticaria and breathing difficulties
• worsening of vision or eye pain due to increased pressure (possible signs of fluid accumulation in the vascular layer surrounding the eye – excessive fluid accumulation between choroid and sclera – or acute angle-closure glaucoma).

The frequency of these adverse reactions is unknown (cannot be estimated from available data).

• severe skin diseases causing rash, redness of the skin, formation of blisters on lips, eyes or oral mucosa, skin peeling, fever (toxic epidermal necrolysis)
• fever, sore throat, frequent infections (agranulocytosis)
• acute respiratory failure (symptoms include severe shortness of breath, fever, weakness and confusion).

These adverse reactions are very rare (may affect fewer than 1 in 10,000 patients).
If any of these symptoms occur, treatment with Co-Bespres must be discontinued and
immediate medical advice sought (see also section 2 "Warnings and precautions").
Other adverse reactions include:
Not common (may affect fewer than 1 in 100 patients)

• cough
• low blood pressure
• sensation of "emptiness" in the head
• dehydration (with thirst, dryness of the oral mucosa and tongue, infrequent urination, dark urine, dry skin)
• muscle pain
• feeling of fatigue
• tingling or numbness
• blurred vision
• tinnitus (e.g. ringing, buzzing in the ears)

Very rare (may affect fewer than 1 in 10,000 patients)

• dizziness
• diarrhoea
• joint pain

Frequency not known (frequency cannot be estimated from available data)

• difficulty breathing
• marked decrease in urine output
• low sodium levels in blood (which may cause fatigue, confusion, muscle twitching and/or seizures in severe cases)
• low potassium levels in blood (sometimes with muscle weakness, cramps, cardiac arrhythmias)
• low white blood cell count (with symptoms such as fever, skin infections, sore throat or oral ulcers due to infection, weakness)
• increased bilirubin levels in blood (which may, in severe cases, cause yellowing of the skin and eyes)
• increased blood urea nitrogen and creatinine levels in blood (which may indicate impaired kidney function)
• increased uric acid levels in blood (which may, in severe cases, trigger gout)
• fainting

The following adverse reactions have been reported after use of walsartan or hydrochlorothiazide alone:
Walsartan
Not common (may affect fewer than 1 in 100 patients)

• sensation of spinning (vertigo)
• abdominal pain

Very rare (may affect fewer than 1 in 10,000 patients)

• intestinal angioedema: intestinal swelling with symptoms such as abdominal pain, nausea, vomiting and diarrhoea

Frequency not known (frequency cannot be estimated from available data)

• blister formation (sign of bullous dermatitis)
• rash with or without itching, occurring with one or more of the following objective or subjective symptoms: fever, joint pain, muscle pain, lymph node swelling and/or flu-like symptoms
• rash, purple-red spots, fever, itching (signs of vasculitis)
• low platelet count (sometimes with unexplained bleeding or bruising)
• high potassium levels in blood (sometimes with muscle cramps, cardiac arrhythmias)
• allergic reactions (with symptoms such as rash, itching, urticaria, difficulty breathing or swallowing, dizziness)
• swelling, mainly of the face and throat; rash; itching
• increased liver enzyme activity
• decreased haemoglobin and haematocrit levels (both parameters may indicate anaemia in severe cases)
• renal failure
• low sodium levels in blood (which may cause fatigue, confusion, muscle twitching and/or seizures in severe cases)

Hydrochlorothiazide
Very common (may affect more than 1 in 10 patients)

• low potassium levels in blood
• increased lipid levels in blood

Common (may affect fewer than 1 in 10 patients)

• low sodium levels in blood
• low magnesium levels in blood
• high uric acid levels in blood
• itchy rash and other types of skin rash
• loss of appetite
• mild nausea and vomiting
• dizziness, fainting upon standing
• inability to achieve or maintain erection

Uncommon (may affect fewer than 1 in 1,000 patients)

• swelling and blistering of the skin (due to increased sensitivity to sunlight)
• high calcium levels in blood
• high blood glucose levels
• presence of glucose in urine
• worsening of metabolic control in diabetes
• constipation, diarrhoea, discomfort in the stomach or intestines, liver disorders which may occur with yellowing of the skin or eyes
• cardiac arrhythmias
• headache
• sleep disturbances
• low mood (depression)
• low platelet count (sometimes with bleeding or bruising under the skin)
• dizziness
• tingling or numbness
• visual disturbances

Very rare (may affect fewer than 1 in 10,000 patients)

• vasculitis with symptoms such as rash, purple-red spots, fever
• rash, itching, urticaria, difficulty breathing or swallowing, dizziness (hypersensitivity reactions)
• facial rash, joint pain, muscle disorders, fever (lupus erythematosus)
• severe upper abdominal pain (pancreatitis)
• breathing difficulties with fever, cough, wheezing, shortness of breath (respiratory failure including pneumonia and pulmonary oedema)
• pale skin, fatigue, shortness of breath, dark urine (haemolytic anaemia)
• fever, sore throat or oral ulcers due to infections (leukopenia)
• confusion, fatigue, tremor and muscle cramps, rapid breathing (hypochloraemic alkalosis)
• absence or low levels of various blood cells

Frequency not known (frequency cannot be estimated from available data)

• weakness, bruising and frequent infections (aplastic anaemia)
• marked decrease in urine output (possible signs of impaired kidney function or renal failure)
• rash, redness of the skin, blistering on lips, eyelids or in the mouth, skin peeling, fever (possible signs of erythema multiforme)
• muscle cramps
• fever
• weakness (asthenia)
• skin and lip cancers (non-melanoma skin cancers).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps provide more information on the safety of this medicine.
Adverse reactions can also be reported to the marketing authorisation holder.

5. How to store Co-Bespres

• Keep out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the packaging and blister after "Expiry date/EXP". The expiry date refers to the last day of that month.
• Do not store above 30°C.
• Do not use Co-Bespres if the packaging is damaged or shows signs of tampering.
• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Co-Bespres contains
The active substances in Co-Bespres are: valsartan and hydrochlorothiazide. Each tablet contains 80 mg/160 mg of valsartan and 12.5 mg/25 mg of hydrochlorothiazide.
Other ingredients in the medicine are: colloidal anhydrous silica, sodium carboxymethyl starch (type A),
crospovidone, microcrystalline cellulose, corn starch, magnesium stearate.
The tablet coating contains:
80 mg + 12.5 mg: hypromellose, polyethylene glycol 8000, talc, titanium dioxide (E171), sunset yellow (E110), iron oxide red (E172).
160 mg + 25 mg: hypromellose, polyethylene glycol 8000, talc, titanium dioxide (E171), iron oxide red (E172), iron oxide black (E172), iron oxide yellow (E172).

What Co-Bespres looks like and contents of the pack
Co-Bespres 80 mg + 12.5 mg, film-coated tablets
Round, pink film-coated tablets, embossed with the number "93" on one side and "7428" on the other side.

Co-Bespres 160 mg + 25 mg, film-coated tablets
Round, brown film-coated tablets, embossed with the number "93" on one side and "7430" on the other side.

The product is available in packs containing: 14, 28, 30, 56, and 60 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Teva Pharmaceuticals Polska Sp. z o.o.
ul. Emilii Plater 53
00-113 Warsaw
tel.: (22) 345 93 00

Manufacturers
Teva Czech Industries s.r.o., Ostravská 29, c.p. 305, 747 70 Opava-Komárov, Czech Republic
Pharmachemie B.V., Swensweg 5, Postbus 552, 2003 RN Haarlem, Netherlands
Teva Pharmaceutical Works Private Limited Company, Pallagi út 13, 4042 Debrecen, Hungary
Teva Pharmaceutical Works Private Limited Company, Táncsics Mihály út 82, 2100 Gödöllő, Hungary
Teva Operations Poland Sp. z o.o., ul. Mogilska 80, 31-546 Kraków, Poland

This medicinal product is authorised in the European Economic Area countries under the following names