Valsartan and hydrochlorothiazide HCS

Package leaflet: Information for the user

Valsartan and hydrochlorothiazide HCS 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
Generic medicine
Please read this leaflet carefully before you take 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. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
• 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 Valsartan and hydrochlorothiazide HCS is and what it is used for
2. What you need to know before taking Valsartan and hydrochlorothiazide HCS
3. How to take Valsartan and hydrochlorothiazide HCS
4. Possible side effects
5. How to store Valsartan and hydrochlorothiazide HCS
6. Contents of the pack and other information

1. What Valsartan and hydrochlorothiazide HCS is and what it is used for

Valsartan and hydrochlorothiazide HCS film-coated tablets contain two active substances called valsartan and hydrochlorothiazide, which 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 is lowered.
• Hydrochlorothiazide belongs to a group of medicines called thiazide diuretics. Hydrochlorothiazide increases urine production, which helps reduce blood pressure.

Valsartan and hydrochlorothiazide HCS is used to treat high blood pressure that is not adequately controlled by a single agent.
High blood pressure increases the workload on the heart and arteries. If left untreated, it can damage blood vessels in the brain, heart, and kidneys, and may lead to heart attack, heart failure, or kidney failure. High blood pressure also increases the risk of heart attacks. Lowering blood pressure to normal levels reduces the risk of developing these conditions.

2. What you need to know before taking Valsartan and hydrochlorothiazide HCS

Do not take Valsartan and hydrochlorothiazide HCS

• if you are allergic to valsartan, hydrochlorothiazide, sulphonamide derivatives (chemically related substances to hydrochlorothiazide), or to any of the other ingredients of this medicine (listed in section 6).
• if you are more than 3 months pregnant (it is also better to avoid Valsartan and hydrochlorothiazide HCS in the early stages of pregnancy – see the pregnancy section).
• if you have a severe liver disease, destruction of the small bile ducts within the liver (biliary cirrhosis) leading to bile accumulation in the liver (cholestasis).
• if you have a severe kidney disease.
• if you are unable to produce urine (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 these cases apply to you, do not take this medicine and speak with your doctor.
Warnings and precautions
Talk to your doctor or pharmacist before taking Valsartan and hydrochlorothiazide HCS:

• if you are taking potassium-sparing medicines, potassium supplements, potassium-containing salt substitutes, or other medicines that increase potassium levels in the blood, such as heparin. Your doctor may need to check your blood potassium levels regularly.
• if you have low blood potassium levels
• if you have diarrhoea or severe vomiting
• if you are taking high doses of diuretics
• if you have a severe heart disease
• if you suffer from heart failure or have recently had a heart attack. Follow your doctor’s instructions carefully regarding the initial dose. Your doctor may also monitor your kidney function.
• if you suffer from narrowing of the renal artery
• if you have recently received a kidney transplant
• if you suffer from hyperaldosteronism, a condition in which your adrenal glands produce too much aldosterone hormone. If this applies to you, the use of Valsartan and hydrochlorothiazide HCS is not recommended.
• if you have liver or kidney disease
• inform your doctor if you have ever experienced swelling of the tongue and face due to an allergic reaction called angioedema while taking another medicine (including ACE inhibitors). If these symptoms occur while taking Valsartan and hydrochlorothiazide HCS, stop taking it immediately and do not take it again. See also 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, high cholesterol or high triglyceride levels in the blood
• if you have had allergic reactions with other antihypertensive agents of the same class (angiotensin II receptor antagonists) or if you have allergies or asthma
• if you experience a decrease in vision or eye pain. These could be symptoms of increased intraocular pressure and may occur within a few hours up to several weeks after taking Valsartan and hydrochlorothiazide HCS. If untreated, these symptoms can lead to permanent vision loss. If you previously had an allergy to penicillin or sulphonamides, you may be at higher risk of developing these symptoms.
• it may cause increased skin sensitivity to sunlight.
• 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 any of these cases apply to you, consult your doctor.
Your doctor may monitor your kidney function, blood pressure, and levels of electrolytes (e.g. potassium) in your blood at regular intervals.
See also the section "Do not take Valsartan and hydrochlorothiazide HCS".
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant).
Valsartan and hydrochlorothiazide HCS 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 your baby (see the pregnancy section).
Children and adolescents
The use of Valsartan and hydrochlorothiazide HCS in children and adolescents (under 18 years of age) is not recommended.
For athletes: using the drug without therapeutic need constitutes doping and may result in a positive anti-doping test.
Other medicines and Valsartan and hydrochlorothiazide HCS
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 Valsartan and hydrochlorothiazide HCS is taken together with certain other medicines. Your doctor may need to adjust the dose, take additional precautions, or in some cases, discontinue one of the two medicines. 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. These include potassium supplements or potassium-containing salt substitutes, potassium-sparing medicines, and heparin
• medicines that may reduce blood potassium levels, such as diuretics, corticosteroids, laxatives, carbenoxolone, amphotericin, or penicillin G
• certain antibiotics (rifamycin group), a medicine used to prevent transplant rejection (cyclosporine), or an antiretroviral medicine used to treat HIV/AIDS infection (ritonavir). These medicines may increase the effect of Valsartan and hydrochlorothiazide HCS.
• medicines that may cause "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 treating gout, such as allopurinol, probenecid, sulfinpyrazone
• therapeutic vitamin D and calcium supplements
• medicines for treating diabetes (oral agents such as metformin or insulin)
• other medicines to lower blood pressure, including methyldopa
• medicines to increase blood pressure, such as noradrenaline or adrenaline
• digoxin and 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 to treat cancer), such as methotrexate or cyclophosphamide
• painkillers such as non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors (Cox-2 inhibitors) and acetylsalicylic acid at doses exceeding 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 as an adjunct in anaesthesia)
• amantadine (a medicine used to treat Parkinson’s disease and also used to treat or prevent certain viral infections)
• cholestyramine and colestipol (medicines mainly used to treat high blood lipid levels)
• cyclosporine, a medicine used in organ transplantation to prevent rejection
• alcohol, sleeping pills, and anaesthetics (medicines with sedative or pain-relieving effects used, for example, during surgery)
• iodinated contrast agents (used in radiological examinations)
• if you are taking an ACE inhibitor or aliskiren (see also the sections "Do not take Valsartan and hydrochlorothiazide HCS" and "Warnings and precautions").

Valsartan and hydrochlorothiazide HCS with food, drinks, and alcohol
You may take Valsartan and hydrochlorothiazide HCS with or without food.
Avoid consuming alcohol until you have discussed it with your doctor. Alcohol may further lower your blood pressure and/or increase the risk of dizziness or fainting.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before taking this medicine.
Pregnancy
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Normally, your doctor will advise you to stop taking Valsartan and hydrochlorothiazide HCS before becoming pregnant or as soon as you know you are pregnant, and will recommend another medicine instead. Valsartan and hydrochlorothiazide HCS 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 your baby if used after the third month of pregnancy.
Breastfeeding
Inform your doctor if you are breastfeeding or starting to breastfeed.
Valsartan and hydrochlorothiazide HCS is not recommended for breastfeeding mothers, and if you wish to breastfeed, your doctor may choose another treatment for you, especially if your baby is a newborn or was born prematurely.
Driving and using machines
Before driving, operating tools or machinery, or performing activities requiring concentration, make sure you know how Valsartan and hydrochlorothiazide HCS affects you. Like many other medicines used to treat high blood pressure, Valsartan and hydrochlorothiazide HCS may occasionally cause dizziness and affect your ability to concentrate.
Valsartan and hydrochlorothiazide HCS contains lactose. If your doctor has informed you that you have an intolerance to certain sugars, consult your doctor before taking this medicine.

3. How to take Valsartan and hydrochlorothiazide HCS

Take this medicine exactly as prescribed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist. This will help you achieve the best results and reduce the risk of side effects.
People with high blood pressure often do not experience any noticeable symptoms and may feel perfectly well. For this reason, it is important to attend all your doctor's appointments regularly, even if you feel well. Your doctor will tell you exactly how many tablets of Valsartan and hydrochlorothiazide HCS you should take. Depending on your response to treatment, your doctor may adjust your dose, increasing or decreasing it as needed.

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

If you take more Valsartan and hydrochlorothiazide HCS 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 right away.
If you forget to take Valsartan and hydrochlorothiazide HCS
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 the forgotten dose.
If you stop taking Valsartan and hydrochlorothiazide HCS
Stopping your treatment with Valsartan and hydrochlorothiazide HCS may cause your condition to worsen. Do not stop taking this medicine unless your doctor tells you to do so.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some side effects may be serious and require immediate medical attention:
If you develop the following symptoms of angioedema, seek immediate medical help:

• swelling of the face, tongue or throat
• difficulty swallowing
• hives and difficulty breathing If you experience any of these symptoms, stop taking Valsartan and hydrochlorothiazide HCS immediately and contact your doctor immediately (see also section 2 "Take special care with Valsartan and hydrochlorothiazide HCS"). Other side effects include: 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-coloured urine, dry skin)
• muscle pain
• fatigue
• tingling or numbness
• blurred vision
• noises (e.g. ringing or buzzing) in the ears

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
• severely reduced urine production
• low levels of sodium in the blood (which may cause fatigue, confusion, muscle cramps and/or seizures in severe cases)
• low levels of potassium in the blood (sometimes with muscle weakness, muscle cramps, irregular heartbeat)
• low levels of white blood cells in the blood (with symptoms such as fever, skin infections, sore throat or mouth ulcers due to infections, weakness)
• increased levels of bilirubin in the blood (which may, in severe cases, cause yellowing of the skin and eyes)
• increased levels of blood urea nitrogen and creatinine in the blood (which may indicate abnormal kidney function)
• increased levels of uric acid in the blood (which, in severe cases, may trigger gout)
• syncope (fainting)

The following side effects have been reported for products containing valsartan or hydrochlorothiazide used as
monotherapy:
Valsartan
Uncommon (may affect up to 1 in 100 people):

• dizziness
• abdominal pain

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

• blisters on the skin (signs of bullous dermatitis)
• rash with or without itching, together with some of the following signs and symptoms: fever, joint pain, muscle pain, swollen lymph nodes and/or flu-like symptoms
• skin rash, purplish-red spots, fever, itching (signs of inflammation of blood vessels)
• low levels of platelets in the blood (sometimes with unusual bleeding or bruising)
• increased levels of potassium in the blood (sometimes with muscle cramps, irregular heartbeat)
• 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
• reduced haemoglobin levels and percentage of red blood cells in the blood (which may, in severe cases, lead to anaemia)
• renal failure
• low levels of sodium in the blood (which may cause fatigue, confusion, muscle cramps and/or seizures in severe cases) Hydrochlorothiazide Very common (may affect more than 1 in 10 people):
• low levels of potassium in the blood
• increased levels of lipids in the blood

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

• low levels of sodium in the blood
• low levels of magnesium in the blood
• high levels of uric acid in the blood
• rash with itching and other types of skin rash
• reduced 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):

• skin swelling and pustules (due to increased sensitivity to sunlight)
• high levels of calcium in the blood
• high blood sugar levels
• sugar in the urine
• worsening of diabetic metabolic state
• constipation, diarrhoea, gastrointestinal discomfort, liver disorders which may occur together with yellowing of the skin and eyes
• irregular heartbeat
• headache
• sleep disorders
• low mood (depression)
• low levels of platelets 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 rash, purplish-red spots, fever (vasculitis)

• skin rash, itching, hives, difficulty breathing or swallowing, dizziness (hypersensitivity reactions)

• severe skin disease causing rash, redness of the skin, pustules on the lips, eyes or mouth, skin peeling, fever (toxic epidermal necrolysis)

• facial rash, joint pain, muscle disorders, fever (cutaneous lupus erythematosus)

• severe stomach pain (pancreatitis)

• difficulty breathing with fever, cough, breathlessness, shortness of breath (respiratory distress including pneumonia and pulmonary oedema)

• fever, sore throat, more frequent infections (agranulocytosis)

• pale skin, fatigue, shortness of breath, dark urine (haemolytic anaemia)

• fever, sore throat or mouth ulcers due to infections (leucopenia)

• confusion, fatigue, muscle cramps and spasms, rapid breathing (hypochloraemic alkalosis)

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

• weakness, bruising and frequent infections (aplastic anaemia)
• severely reduced urine production (possible signs of kidney disorder or kidney failure)
• reduced vision or eye pain due to high pressure (possible signs of acute angle-closure glaucoma)
• rash, redness of the skin, pustules on the lips, eyes or mouth, skin peeling, fever (possible signs of erythema multiforme)
• muscle cramp
• fever (pyrexia)
• weakness (asthenia)

Reporting of side effects
If you experience any side effect, 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 www.agenziafarmaco.gov.it/it/responsabili.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Valsartan and hydrochlorothiazide HCS

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

6. Pack contents and other information

What Valsartan and hydrochlorothiazide HCS contains

• The active substances are valsartan and hydrochlorothiazide. Each film-coated tablet of Valsartan and hydrochlorothiazide HCS 80 mg/12.5 mg contains 80 mg of valsartan and 12.5 mg of hydrochlorothiazide. Each film-coated tablet of Valsartan and hydrochlorothiazide HCS 160 mg/12.5 mg contains 160 mg of valsartan and 12.5 mg of hydrochlorothiazide. Each film-coated tablet of Valsartan and hydrochlorothiazide HCS 160 mg/25 mg contains 160 mg of valsartan and 25 mg of hydrochlorothiazide. Each film-coated tablet of Valsartan and hydrochlorothiazide HCS 320 mg/12.5 mg contains 320 mg of valsartan and 12.5 mg of hydrochlorothiazide. Each film-coated tablet of Valsartan and hydrochlorothiazide HCS 320 mg/25 mg contains 320 mg of valsartan and 25 mg of hydrochlorothiazide.
• The other ingredients are microcrystalline cellulose, lactose monohydrate, magnesium stearate, sodium croscarmellose, povidone and anhydrous colloidal silicon dioxide in the tablet core; and hypromellose, titanium dioxide (E171), macrogol, iron oxide red (E172) – only in the 80 mg/12.5 mg, 160 mg/12.5 mg, 160 mg/25 mg and 320 mg/12.5 mg film-coated tablets – iron oxide yellow (E172) – only in the 80 mg/12.5 mg, 160 mg/25 mg and 320 mg/25 mg film-coated tablets – in the coating.

Description of the appearance of Valsartan and hydrochlorothiazide HCS and pack contents
The 80 mg/12.5 mg film-coated tablets are pink, oval, biconvex.
The 160 mg/12.5 mg film-coated tablets are reddish-brown, oval, biconvex.
The 160 mg/25 mg film-coated tablets are light brown, oval, biconvex.
The 320 mg/12.5 mg film-coated tablets are pink, oval, biconvex.
The 320 mg/25 mg film-coated tablets are light yellow, oval, biconvex, with a score line on one side.
The tablet can be divided into two equal doses.
Valsartan and hydrochlorothiazide HCS 80 mg/12.5 mg, 160 mg/12.5 mg and 160 mg/25 mg film-coated tablets are available in packs of 14, 28, 30, 56, 60, 84, 90, 98, 280, 56 x 1, 98 x 1 and 280 x 1 film-coated tablets in blister packs.
Valsartan and hydrochlorothiazide HCS 320 mg/12.5 mg and 320 mg/25 mg film-coated tablets are available in packs of 10, 14, 28, 30, 56, 60, 84, 90, 98, 100, 280, 56 x 1, 98 x 1 and 280 x 1 film-coated tablets in blister packs.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
HCS bvba, H Kennisstraat 53, B 2650 Edegem, Belgium

Local representative for Italy
KRKA Farmaceutici Milano S.r.l., Viale Achille Papa 30, 20149 Milan, Italy

Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

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