Valsartan + hydrochlorothiazide krka

Package leaflet: Information for the patient

Valsartan + hydrochlorothiazide Krka, 80 mg + 12.5 mg, film-coated tablets
Valsartan + hydrochlorothiazide Krka, 160 mg + 12.5 mg, film-coated tablets
Valsartan + hydrochlorothiazide Krka, 160 mg + 25 mg, film-coated tablets
Valsartan + hydrochlorothiazide Krka, 320 mg + 12.5 mg, film-coated tablets
Valsartan + hydrochlorothiazide Krka, 320 mg + 25 mg, film-coated tablets
valsartanum + hydrochlorothiazidum
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

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

1. What Valsartan + hydrochlorothiazide Krka is and what it is used for

Valsartan + hydrochlorothiazide Krka contains two active substances, valsartan and hydrochlorothiazide.
Both substances help control high blood pressure (hypertension).

• Valsartan belongs to a group of medicines known as "angiotensin II receptor antagonists", used in the treatment of high blood pressure. Angiotensin II is a substance produced in the human body that causes blood vessels to narrow, thereby increasing blood pressure. Valsartan works by blocking the action of angiotensin II. As a result, blood vessels dilate and blood pressure decreases.
• Hydrochlorothiazide belongs to a group of medicines called thiazide diuretics (also known as "water tablets"). Hydrochlorothiazide increases urine output, which also helps lower blood pressure.

Valsartan + hydrochlorothiazide Krka is used to treat high blood pressure that cannot be adequately controlled with a single active substance.
High blood pressure increases the workload on the heart and blood vessels. If left untreated, it may lead to damage of blood vessels in the brain, heart, and kidneys, potentially causing stroke, heart failure, or kidney failure. High blood pressure increases the risk of heart attack. Lowering blood pressure to normal levels reduces the risk of developing these conditions.

2. Important information before using Valsartan + hydrochlorothiazide Krka

When not to use Valsartan + hydrochlorothiazide Krka:

• if the patient is allergic to valsartan, hydrochlorothiazide, sulphonamide derivatives (chemicals similar to hydrochlorothiazide), or to any of the other ingredients of this medicine (listed in section 6);
• during pregnancy beyond 3 months (use of Valsartan + hydrochlorothiazide Krka should also be avoided during early pregnancy - see section "Pregnancy and breastfeeding");
• if the patient has severe liver disease, damage to the small bile ducts in the liver (biliary cirrhosis), resulting in 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;
• 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 function disorders and is being treated with a blood pressure-lowering medicine containing aliskiren.

If any of the above situations apply, do not take
Valsartan + hydrochlorothiazide Krka. Consult your doctor.
Warnings and precautions
Before starting treatment with Valsartan + hydrochlorothiazide Krka, discuss the following
with your doctor or pharmacist:

• if the patient is taking potassium-sparing medicines, potassium supplements, potassium-containing salt substitutes, or other medicines that increase blood potassium levels, such as heparin; regular monitoring of blood potassium levels by the doctor may be necessary;
• if the patient has low blood potassium levels;
• if the patient has diarrhoea or severe vomiting;
• if the patient is taking high doses of diuretic tablets (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 carefully regarding the initial dose of the medicine. Your doctor may also check your kidney function.
• if the patient has renal artery stenosis;
• 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; if the patient has this condition, treatment with Valsartan + hydrochlorothiazide Krka is not recommended;
• if the patient has liver or kidney disease;
• inform your doctor if, after taking another medicine (including ACE inhibitors), the patient has ever previously experienced swelling of the tongue and face due to an allergic reaction called angioedema. If such symptoms occur while taking Valsartan + hydrochlorothiazide Krka, stop taking the medicine immediately and never take it again. See also section 4 "Possible side effects".
• if the patient develops fever, rash, and joint pain, which may indicate systemic lupus erythematosus (SLE, an autoimmune disease);
• if the patient has diabetes, gout, or high blood cholesterol or triglyceride levels;
• if the patient has previously had allergic reactions after taking other blood pressure-lowering medicines from this group (angiotensin II receptor antagonists), or if the patient has allergies or asthma;
• if the patient experiences worsening of vision or eye pain. These may be symptoms of fluid accumulation in the uvea (excessive fluid accumulation between choroid and sclera) or increased intraocular pressure, and may occur within hours to weeks after starting treatment with Valsartan + hydrochlorothiazide Krka. Without treatment, these symptoms may lead to complete vision loss. If the patient

previously had an allergy to penicillin or sulphonamides, they may be at increased
risk of developing these symptoms.

• Valsartan + hydrochlorothiazide Krka may increase skin sensitivity to sunlight;
• if the patient has previously had skin cancer or if unexpected skin changes occur during treatment. Treatment with hydrochlorothiazide, especially at high doses over a long period, may increase the risk of certain types of skin cancer and lip cancer (non-melanoma skin cancer). While taking Valsartan + hydrochlorothiazide Krka, 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 Valsartan + hydrochlorothiazide Krka, seek immediate medical help;
• if the patient is taking any of the following medicines used to treat high blood pressure:
• ACE inhibitors (e.g. enalapril, lisinopril, ramipril), especially if the patient has kidney problems related to diabetes,
• aliskiren.

If any of the above conditions apply to the patient, contact the doctor.
The treating doctor 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 Valsartan + hydrochlorothiazide Krka:".
If the patient experiences abdominal pain, nausea, vomiting, or diarrhoea after taking
Valsartan + hydrochlorothiazide Krka, discuss this with the doctor. The doctor will decide on further
treatment. Do not make independent decisions about stopping Valsartan + hydrochlorothiazide Krka.
It is essential to inform the doctor about pregnancy, suspected pregnancy, or plans to become pregnant. Use of Valsartan + hydrochlorothiazide Krka is not recommended during the first trimester of pregnancy and must not be taken after 3 months of pregnancy, as it may seriously harm the unborn child (see section "Pregnancy and breastfeeding").
Children and adolescents
Valsartan + hydrochlorothiazide Krka is not recommended for use in children and adolescents (under 18 years of age).
Valsartan + hydrochlorothiazide Krka and other medicines
Inform your doctor or pharmacist about all medicines currently taken, recently taken, or planned to be taken.
The effect of the medicine may change if Valsartan + hydrochlorothiazide Krka is taken simultaneously with certain other medicines. Dose adjustments, additional precautions, or in some cases discontinuation of one of the medicines may be necessary. This particularly applies to medicines such as:

• 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 decrease blood potassium levels, such as diuretics (water tablets), corticosteroids, laxatives, carbenoxolone, amphotericin, or penicillin G.
• certain antibiotics (rifampicin group), a medicine used to prevent transplant rejection (cyclosporine), or an antiretroviral medicine used to treat HIV/AIDS (ritonavir). These medicines may enhance the effect of Valsartan + hydrochlorothiazide Krka.
• medicines that may cause "torsade de pointes" (irregular heartbeat), such as antiarrhythmic medicines (used to treat heart conditions) and certain antipsychotic medicines;
• medicines that may decrease blood sodium levels, such as antidepressants, antipsychotics, anticonvulsants;
• medicines used to treat gout, such as allopurinol, probenecid, sulfinpyrazone;
• therapeutic doses of vitamin D and calcium supplements;
• medicines used to treat diabetes (oral antidiabetic medicines such as metformin or insulin);
• other blood pressure-lowering medicines, including methyldopa;
• 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 and 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 (COX-2) inhibitors and acetylsalicylic acid > 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 during anaesthesia);
• amantadine (a medicine used to treat Parkinson's disease and to treat and prevent certain virus-related illnesses);
• cholestyramine and colestipol (medicines mainly used to lower high blood lipid levels);
• alcohol, sedatives, and anaesthetics (medicines with sedative or pain-relieving effects, used e.g. during surgical procedures);
• iodine-containing contrast agents (used in imaging procedures).

The treating doctor may need to adjust the dose and/or apply additional
precautions:

• If the patient is taking an ACE inhibitor or aliskiren (see also information under the headings "When not to use Valsartan + hydrochlorothiazide Krka:" and "Warnings and precautions").

Valsartan + hydrochlorothiazide Krka with food, drink, and alcohol
Valsartan + hydrochlorothiazide Krka may be taken with or without food.
Avoid consuming alcohol without consulting your doctor. Alcohol may intensify the lowering of
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 plans to become pregnant, she should consult her doctor or pharmacist before using this medicine.
Pregnancy
It is essential to inform the doctor about pregnancy, suspected pregnancy, or plans to become pregnant. The doctor will usually recommend discontinuing Valsartan + hydrochlorothiazide Krka before conception or immediately after pregnancy is confirmed and will prescribe an alternative medicine. Use of Valsartan + hydrochlorothiazide Krka is not recommended during the first trimester of pregnancy and must not be taken after 3 months of pregnancy, as it may seriously harm the unborn child.
Breastfeeding
Inform the doctor about breastfeeding or plans to breastfeed.
Use of Valsartan + hydrochlorothiazide Krka is not recommended during breastfeeding.
The doctor may choose an alternative medicine if the patient intends to breastfeed, especially if the infant is a newborn or premature.
Driving and operating machinery
Before driving, using tools, operating machinery, or performing other tasks requiring concentration, the patient should ensure how Valsartan + hydrochlorothiazide Krka affects them. Like many other medicines used to treat high blood pressure, Valsartan + hydrochlorothiazide Krka may rarely cause dizziness and affect the ability to concentrate.
Valsartan + hydrochlorothiazide Krka contains lactose and sodium
If the patient has been informed by a doctor that they have an intolerance to certain sugars, they should consult their doctor before taking this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, therefore it can be considered essentially "sodium-free".

3. How to use Valsartan + hydrochlorothiazide Krka

This medicine should always be taken exactly as directed by your doctor or pharmacist. If in doubt,
you should consult your doctor or pharmacist. This will help achieve the best treatment results and
reduce the risk of adverse effects.
Patients with high blood pressure often do not experience any symptoms of the condition.
Many feel quite well. Therefore, it is very important to attend regular check-ups with your doctor,
even when feeling well.
Your doctor will specify the exact number of tablets of Valsartan + hydrochlorothiazide Krka to take.
Depending on your response to treatment, your doctor may decide to increase or decrease the dose
of the medicine.

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

Taking more Valsartan + hydrochlorothiazide Krka than prescribed
If you experience severe dizziness and/or fainting, lie down immediately and contact your doctor
without delay.
If you accidentally take too many tablets, contact your doctor, pharmacist, or hospital immediately.
Missing a dose of Valsartan + hydrochlorothiazide Krka
If you miss a dose, take it as soon as you remember. However, if it is almost time for your next dose,
do not take the missed dose.
Do not take a double dose to make up for a missed dose.
Stopping Valsartan + hydrochlorothiazide Krka treatment
Stopping treatment 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 effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Some adverse effects may be serious and require immediate medical attention.
You should contact your doctor immediately if you experience symptoms of angioedema, such as:

• swelling of the face, tongue or throat,
• difficulty swallowing,
• hives and breathing difficulties. If any of these symptoms occur, you must immediately stop taking Valsartan + hydrochlorothiazide Krka and contact your doctor (see also section 2 "Warnings and precautions").

Other adverse effects include:
Not common (may occur in less than 1 in 100 patients):

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

Very rare (may occur in less than 1 in 10,000 patients):

• dizziness
• diarrhea
• joint pain

Unknown frequency (frequency cannot be determined from available data):

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

The following adverse effects have been reported after using medicines containing either
valsartan or hydrochlorothiazide alone:
Valsartan
Not common (may occur in less than 1 in 100 patients):

• sensation of spinning
• abdominal pain

Very rare (may occur in less than 1 in 10,000 patients):

• intestinal angioedema: swelling in the intestine with symptoms such as abdominal pain, nausea, vomiting and diarrhea

Unknown frequency (frequency cannot be determined from available data):

• skin rash with or without skin itching, associated with some of the following symptoms: fever, joint pain, muscle pain, swollen lymph nodes and/or flu-like symptoms
• rash, purple-red spots, fever, itching (symptoms of vasculitis)
• low platelet count (sometimes with unusual bleeding or skin purpura)
• high potassium levels in the blood (sometimes with muscle cramps, heart rhythm disturbances)
• allergic reactions (with symptoms such as rash, itching, hives, difficulty breathing or swallowing, dizziness)
• swelling, mainly of the face and throat, rash, itching
• increased liver enzyme activity
• decreased hemoglobin levels and reduced number of red blood cells in the blood (both may lead to anemia in severe cases)
• kidney failure
• low sodium levels in the blood (which may cause fatigue, confusion, muscle tremors and/or seizures in severe cases)

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

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

Common (may occur in less than 1 in 10 patients):

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

Rare (may occur in less than 1 in 1,000 patients):

• swelling and blisters on the skin (due to increased sensitivity to sunlight)
• high calcium levels in the blood
• high blood sugar levels
• presence of glucose in urine
• worsening of metabolic disturbances in diabetes
• constipation, diarrhea, stomach or intestinal discomfort, liver function disorders which may occur together with yellowing of the skin and eyes
• irregular heartbeat
• headache
• sleep disturbances
• depression
• low platelet count (sometimes with subcutaneous bleeding or bruising)
• dizziness
• tingling or numbness sensation
• visual disturbances

Very rare (may occur in less than 1 in 10,000 patients):

• vasculitis with symptoms such as rash, purple-red spots, fever
• rash, itching, hives, difficulty breathing or swallowing, dizziness (hypersensitivity reactions)
• severe skin diseases causing rash, redness of the skin, formation of blisters on the lips, oral mucosa and conjunctiva, skin peeling, fever (toxic epidermal necrolysis)
• 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 edema)
• acute respiratory failure (symptoms include severe shortness of breath, fever, weakness and confusion)
• fever, sore throat, frequent infections (agranulocytosis)
• pale skin, fatigue, shortness of breath, dark urine color (hemolytic anemia)
• fever, sore throat or oral ulcers due to infection (leukopenia)
• confusion, fatigue, muscle tremors and cramps, rapid breathing (hypochloremic alkalosis)

Unknown frequency (frequency cannot be determined from available data):

• malignant skin and lip tumors (non-melanoma skin cancers)
• weakness, bruising and frequent infections (aplastic anemia)
• significantly reduced urine output (possible signs of kidney dysfunction or kidney failure)
• worsening of vision or eye pain due to increased pressure (possible signs of fluid accumulation in the vascular layer surrounding the eye – excessive accumulation of fluid between choroid and sclera – or acute angle-closure glaucoma)
• rash, redness of the skin, blistering on lips, eyes or oral mucosa, skin peeling, fever (possible signs of erythema multiforme)
• muscle cramps
• fever
• weakness (asthenia)

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of 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
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Valsartan + hydrochlorothiazide Krka

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Do not store above 30°C.
Store in the original packaging to protect from light and moisture.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging and other information

What Valsartan + hydrochlorothiazide Krka contains

• The active substances are valsartan and hydrochlorothiazide. Each coated tablet of Valsartan + hydrochlorothiazide Krka contains 80 mg of valsartan and 12.5 mg of hydrochlorothiazide. Each coated tablet of Valsartan + hydrochlorothiazide Krka contains 160 mg of valsartan and 12.5 mg of hydrochlorothiazide. Each coated tablet of Valsartan + hydrochlorothiazide Krka contains 160 mg of valsartan and 25 mg of hydrochlorothiazide. Each coated tablet of Valsartan + hydrochlorothiazide Krka contains 320 mg of valsartan and 12.5 mg of hydrochlorothiazide. Each coated tablet of Valsartan + hydrochlorothiazide Krka contains 320 mg of valsartan and 25 mg of hydrochlorothiazide.
• The other ingredients are: microcrystalline cellulose, monohydrate lactose, magnesium stearate, sodium croscarmellose, povidone K-25 and anhydrous colloidal silica in the tablet core; and in the tablet coating: hypromellose 2910 6 cP, titanium dioxide (E 171), macrogol 4000, iron oxide red (E 172) – only in tablets 80 mg + 12.5 mg, 160 mg + 12.5 mg, 160 mg + 25 mg and 320 mg + 12.5 mg, iron oxide yellow (E 172) – only in tablets 80 mg + 12.5 mg, 160 mg + 25 mg and 320 mg + 25 mg. See section 2 "Valsartan + hydrochlorothiazide Krka contains lactose and sodium".

What Valsartan + hydrochlorothiazide Krka looks like and contents of the pack
Coated tablets 80 mg + 12.5 mg are pink, oval, biconvex. Tablet dimensions: length: 10 mm, width: 5 mm.
Coated tablets 160 mg + 12.5 mg are reddish-brown, oval, biconvex. Tablet dimensions: length: 14 mm, width: 6 mm.
Coated tablets 160 mg + 25 mg are light brown, oval, biconvex. Tablet dimensions: length: 14 mm, width: 6 mm.
Coated tablets 320 mg + 12.5 mg are pink, oval, biconvex. Tablet dimensions: length: 16 mm, width: 8.5 mm.
Coated tablets 320 mg + 25 mg are light yellow, oval, biconvex, with a division line on one side. Tablet dimensions: length: 16 mm, width: 8.5 mm. The tablet can be divided into equal doses.
Pack sizes: 28, 30, 56 or 60 coated tablets in blisters, packed in a cardboard box.

Marketing Authorisation Holder:
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

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

For further information on the names of this medicinal product in the European Economic Area countries, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
Tel. 22 57 37 500