Cotareg

Patient Information Leaflet

Cotareg 80 mg/12.5 mg film-coated tablets, 160 mg/12.5 mg film-coated tablets, 160 mg/25 mg film-coated tablets, 320 mg/12.5 mg film-coated tablets, 320 mg/25 mg film-coated tablets

Valsartan/hydrochlorothiazide
Please read all of this leaflet carefully before you start 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 other people, even if they have the same symptoms as you, because it may be harmful to them.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Cotareg is and what it is used for

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

• Valsartan belongs to a class of medicines known as "angiotensin II receptor antagonists", which help control high blood pressure. Angiotensin II is a substance in the body that causes blood vessels to narrow, thereby increasing blood pressure. Valsartan works by blocking the effect of angiotensin II. As a result, blood vessels relax and blood pressure decreases.
• Hydrochlorothiazide belongs to a group of medicines called thiazide diuretics. Hydrochlorothiazide increases the amount of urine produced and, in this way, reduces blood pressure.

Cotareg is used to treat high blood pressure when it is not adequately controlled by a single medicine.
When blood pressure is high, the workload on the heart and arteries increases. If left untreated, it can damage blood vessels in the brain, heart, and kidneys, 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 developing these conditions.

2. What you should know before taking Cotareg

Do not take Cotareg:

• if you are allergic (hypersensitive) to valsartan, hydrochlorothiazide, sulphonamide derivatives (chemically related substances to hydrochlorothiazide), or to any of the excipients of this medicine (listed in section 6)
• if you are more than 3 months pregnant (it is better to avoid taking Cotareg even in the early stages of pregnancy – see section Pregnancy)
• if you have severe liver disorders, destruction of the small bile ducts within the liver (biliary cirrhosis) leading to bile accumulation in the liver (cholestasis)
• if you have severe kidney disorders
• if you are unable to urinate (anuria)
• if you are undergoing treatment with an artificial kidney
• if your blood potassium or sodium levels are lower than normal, or if your blood calcium levels are higher than normal despite treatment
• if you have gout
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.

If any of the above conditions apply to you, do not take this medicine and consult your doctor.
Warnings and precautions
Consult your doctor

• if you are taking potassium-sparing medicines, potassium supplements, potassium-containing salt substitutes, or other medicines that increase blood potassium levels, such as heparin. Your doctor may need to regularly monitor your blood potassium levels
• if your blood potassium levels are low
• if you have diarrhoea or severe vomiting
• if you are taking high doses of medicines that increase fluid elimination (diuretics)
• if you have serious heart problems
• if you suffer from heart failure or have had a heart attack. Follow your doctor’s instructions carefully regarding the starting dose of therapy. Your doctor will also monitor your kidney function
• if you have renal artery stenosis (narrowing of the artery to the kidney)
• if you have recently received a kidney transplant
• if you suffer from hyperaldosteronism, a condition in which the adrenal glands produce too much aldosterone hormone. If this applies to you, use of Cotareg is not recommended
• if you have liver or kidney diseases
• if you have previously experienced swelling of the tongue and face due to an allergic reaction called angioedema when taking other medicines (including ACE inhibitors), inform your doctor. If these symptoms occur while taking Cotareg, stop taking Cotareg immediately and never take it again. See section 4, “Possible side effects”
• if you have fever, skin rashes, and joint pain, which may be signs of systemic lupus erythematosus (SLE, an autoimmune disease)
• if you have diabetes, gout, or elevated cholesterol or triglyceride levels in the blood
• if you have previously had allergic reactions to other blood pressure-lowering medicines belonging to the same class (angiotensin II receptor antagonists) or if you suffer from allergies or asthma
• if you experience a decrease in vision or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased intraocular pressure and may occur from a few hours to weeks after taking Cotareg. If left untreated, this may lead to permanent vision loss. If you have previously been allergic to penicillins or sulphonamides, you may have a higher risk of developing this condition.
• if you are taking any 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
• if you have previously had skin cancer or if you develop unexpected skin lesions

during treatment. Treatment with hydrochlorothiazide, particularly long-term use with high doses, may increase the risk of certain types of skin and lip cancer (non-melanoma skin cancer). Protect your skin from exposure to sunlight and UV rays while taking Cotareg.

• if you have previously experienced respiratory or lung problems (including inflammation or fluid in the lungs) after taking hydrochlorothiazide. If shortness of breath or severe breathing difficulties occur after taking Cotareg, consult a doctor immediately.

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 Cotareg”.
Cotareg may increase skin sensitivity to sunlight.
The use of Cotareg is not recommended in children and adolescents (under 18 years of age).
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Cotareg 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 unborn child if taken during this period (see section Pregnancy).
Taking other medicines and Cotareg
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The effect of treatment may be affected if Cotareg is taken with certain other medicines. It may be necessary to adjust the dose, take additional precautions, or in some cases, stop taking one of the medicines. This particularly applies to the following medicines:

• lithium, a medicine used in the treatment of certain psychiatric disorders
• medicines or substances that can increase blood potassium levels. These include potassium supplements or potassium-containing salt substitutes, potassium-sparing medicines, and heparin
• medicines that can decrease blood potassium levels, such as diuretics (medicines that increase fluid elimination), corticosteroids, laxatives, carbenoxolone, amphotericin, or penicillin G
• certain antibiotics (rifampicin group), a drug used to prevent transplant rejection (cyclosporine), and an antiretroviral drug used to treat HIV/AIDS infections (ritonavir). These medicines may increase the effect of Cotareg
• medicines that may induce torsades de pointes (irregular heartbeat), such as antiarrhythmics (medicines used to treat heart problems) and certain antipsychotics
• medicines that may reduce blood sodium levels, such as antidepressants, antipsychotics, antiepileptics
• medicines for the treatment of gout, such as allopurinol, probenecid, sulfinpyrazone
• therapeutic supplements of vitamin D and calcium
• medicines used to treat diabetes (oral such as metformin or insulin)
• other blood pressure-lowering medicines, including methyldopa, ACE inhibitors (such as enalapril, lisinopril, etc.) or aliskiren (see also information under “Do not take Cotareg” and “Warnings and precautions”)
• medicines that may increase blood pressure, such as noradrenaline or adrenaline
• digoxin or other digitalis glycosides (medicines used to treat heart problems)
• medicines that may increase blood sugar 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 > 3 g
• muscle relaxants, such as tubocurarine
• anticholinergic medicines (used to treat various disorders such as gastrointestinal cramps, bladder spasms, asthma, motion sickness, muscle spasms, Parkinson’s disease, and to facilitate anaesthesia)
• amantadine (a medicine used to treat Parkinson’s disease and also to treat or prevent certain viral diseases)
• cholestyramine and colestipol (medicines mainly used in the treatment of high blood lipid levels)
• cyclosporine, a medicine used in organ transplantation to prevent organ rejection
• alcohol, hypnotics, and anaesthetics (medicines with narcotic or pain-relieving effects, used, for example, during surgical procedures)
• iodinated contrast agents (used in radiological examinations)

Taking Cotareg with food and drink
Avoid consuming alcohol unless you have discussed it with your doctor. Alcohol may further lower blood pressure and/or increase the risk of dizziness or fainting.
Pregnancy and breastfeeding

• You must 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 Cotareg before becoming pregnant or as soon as you find out you are pregnant, and will recommend another medicine instead of Cotareg. Cotareg 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 unborn child if taken after the third month of pregnancy.
• Inform your doctor if you are breastfeeding or planning to breastfeed. Cotareg is not recommended for women who are breastfeeding, and your doctor may choose another treatment for you if you wish to breastfeed, especially if the baby is a newborn or was born prematurely.

Driving and using machines
Before driving a vehicle, operating machinery, or performing other activities requiring concentration, you should be aware of how you react to Cotareg. Like many other medicines used to treat high blood pressure, Cotareg may rarely cause dizziness and affect your ability to concentrate.
For athletes: using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

3. How to take Cotareg

Take this medicine exactly as your doctor has told you. This will help you achieve the best results and reduce the risk of side effects. If you are unsure, consult your doctor or pharmacist.
People with high blood pressure often do not notice any symptoms and may feel perfectly well. For this reason, it is very important that you keep regular appointments with your doctor, even when you feel well.
Your doctor will tell you exactly how many Cotareg tablets you should take. Depending on your response to treatment, your doctor may adjust your dose to a higher or lower level.

• The recommended dose of Cotareg is one tablet daily.
• Do not change the dose and do not stop taking the tablets without first consulting your doctor.
• This medicine should be taken every day at the same time, usually in the morning.
• You may take Cotareg with or without food.
• Swallow the tablet with a glass of water.

If you take more Cotareg than you should
If you experience severe dizziness and/or fainting, lie down and contact your doctor immediately.
If you have accidentally taken too many tablets, contact your doctor, pharmacist or hospital.
If you forget to take Cotareg
If you forget to take 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 the forgotten dose.
If you stop taking Cotareg
Stopping treatment with Cotareg may cause your high blood pressure to worsen. Do not stop taking this medicine unless your doctor tells you to.
If you have any questions about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some side effects can be serious and require immediate medical attention

• Contact your doctor immediately if you have symptoms of angioedema, such as:
• swelling of the face, tongue or throat
• difficulty swallowing
• hives and difficulty breathing
• Severe skin diseases causing rash, redness of the skin, blistering on lips, eyes or mouth, peeling of the skin, fever (toxic epidermal necrolysis)
• Decreased vision or eye pain due to high eye pressure (possible sign of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma)
• Fever, sore throat, more frequent infections (agranulocytosis)
• Severe shortness of breath, fever, weakness and confusion (acute respiratory distress).

These side effects are very rare or frequency not known.
If you experience any of these symptoms, stop taking Cotareg and contact your doctor immediately
(see also section 2 “Warnings and precautions”).
Other side effects are:
Uncommon (may affect up to 1 in 100 people)

• cough
• low blood pressure
• sensation of emptiness in the head
• dehydration (with symptoms such as thirst, dry mouth and tongue, infrequent urination, dark urine, dry skin)
• muscle pain
• fatigue
• tingling or numbness
• blurred vision
• noises in the ears (e.g. ringing, buzzing)

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

• dizziness
• diarrhoea
• joint pain

Not known (frequency cannot be estimated from the available data)

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

The following side effects have been reported with medicines containing valsartan or
hydrochlorothiazide alone
Valsartan
Uncommon (may affect up to 1 in 100 people)

• sensation of dizziness
• abdominal pain

Not known (frequency cannot be estimated from the available data)

• appearance of blisters on the skin (sign of bullous dermatitis)
• rash with or without itching together with one or more of the following signs or symptoms: fever, joint pain, muscle pain, swollen lymph nodes and/or flu-like symptoms
• rash, red-purple spots, fever, itching (symptoms of inflammation of blood vessels)
• low platelet count in the blood (sometimes with unusual bleeding or bruising)
• increased potassium levels in the blood (sometimes with muscle cramps, abnormal heart rhythm)
• allergic reactions (with symptoms such as rash, itching, hives, difficulty breathing or swallowing, dizziness)
• swelling, especially of the face and throat, rash, itching
• increased liver function test values
• decreased haemoglobin levels and percentage of red blood cells in the blood (which, in severe cases, may both cause anaemia)
• renal failure
• low sodium levels in the blood (which may cause fatigue, mental confusion, muscle cramps and/or seizures in severe cases)

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

• low potassium levels in the blood
• increased blood lipids

Common (may affect up to 1 in 10 people)

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

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

• swelling and blistering of the skin (due to increased sensitivity to sunlight)
• high calcium levels in the blood
• high blood sugar levels
• sugar in the urine
• worsening of the metabolic state of diabetes
• constipation, diarrhoea, stomach or intestinal disturbances, liver disorders which may present with yellowing of the skin and eyes
• irregular heartbeat
• headache
• sleep disturbances
• sadness (depression)
• low platelet count in the blood (sometimes with bleeding or bruising under the skin)
• dizziness
• tingling or numbness
• vision disturbances

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

• inflammation of blood vessels with symptoms such as skin rashes, red-purple spots, fever (vasculitis)
• rash, itching, hives, difficulty breathing or swallowing, dizziness (hypersensitivity reactions)
• facial rashes, joint pain, muscle disorders, fever (lupus erythematosus)
• severe pain in the upper abdomen (pancreatitis)
• difficulty breathing with fever, cough, wheezing, shortness of breath (respiratory distress, including pneumonia and pulmonary oedema)
• paleness, fatigue, shortness of breath, dark urine (haemolytic anaemia)
• fever, sore throat or mouth ulcers due to infections (leucopenia)
• confusion, fatigue, tremor and muscle cramp, shortness of breath (hypochloraemic alkalosis)

Not known (frequency cannot be estimated from the available data)

• fatigue, easy bruising and frequent infections (aplastic anaemia)
• severe decrease in urine output (possible sign of kidney disorder or renal failure)
• rash, redness of the skin, blistering on lips, eyes or mouth, peeling of the skin, fever (possible signs of erythema multiforme)
• muscle cramp
• fever (pyrexia)
• weakness (asthenia)
• skin and lip cancer (non-melanoma skin cancer)

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cotareg

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton. The expiry date refers to the last day of the month.
• Do not store above 30°C. Store in the original packaging to protect the medicine from moisture.
• Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering.
• Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Cotareg contains

• The active substances are valsartan and hydrochlorothiazide. Each film-coated tablet contains 80 mg, 160 mg or 320 mg of valsartan and 12.5 mg or 25 mg of hydrochlorothiazide, respectively.
• The tablet core contains microcrystalline cellulose, crospovidone, anhydrous colloidal silica, magnesium stearate.
• The tablet coating contains hypromellose, macrogol 8000 (only in 80 mg/12.5 mg and 160 mg/12.5 mg), macrogol 4000 (only in 160 mg/25 mg, 320 mg/12.5 mg and 320 mg/25 mg), talc, red iron oxide (E172, except for 320 mg/25 mg), yellow iron oxide (E172, only in 80 mg/12.5 mg, 160 mg/12.5 mg and 320 mg/12.5 mg), black iron oxide (E172, only in 160 mg/25 mg and 320 mg/12.5 mg), titanium dioxide (E171).

Description of the appearance of Cotareg and pack sizes
Cotareg 80 mg/12.5 mg film-coated tablets are light orange, ovaloid, with "HGH" engraved on one side and "CG" on the other side.
Cotareg 160 mg/12.5 mg film-coated tablets are dark red, ovaloid, with "HHH" engraved on one side and "CG" on the other side.
Cotareg 160 mg/25 mg film-coated tablets are brown, ovaloid, with "HXH" engraved on one side and "NVR" on the other side.
Cotareg 320 mg/12.5 mg film-coated tablets are pink, ovaloid, with bevelled edges, with "NVR" engraved on one side and "HIL" on the other side.
Cotareg 320 mg/25 mg film-coated tablets are yellow, ovaloid, with "CTI" engraved on one side and "NVR" on the other side.
The tablets are available in packs with blisters of 7 tablets (only Cotareg 320 mg/12.5 mg and 320 mg/25 mg), 14 tablets, 28 tablets as calendar pack, 30 tablets (only Cotareg 80 mg/12.5 mg), 56 tablets, 98 tablets as calendar pack or 280 tablets. Divisible unit-dose blisters are also available in packs of 56x1, 98x1 or 280x1 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Novartis Farma S.p.A.
Largo Umberto Boccioni 1
21040 Origgio VA
Italy

Manufacturer
Novartis Farma S.p.A.
Via Provinciale Schito 131
80058 Torre Annunziata NA
Italy

This medicinal product is authorized in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names: