Package leaflet: Information for the patient

Valarox, 10 mg + 80 mg, film-coated tablets
Valarox, 20 mg + 80 mg, film-coated tablets
Valarox, 10 mg + 160 mg, film-coated tablets
Valarox, 20 mg + 160 mg, film-coated tablets
Rosuvastatin + Valsartan
Please read this leaflet carefully before using this medicine, because it contains
important information for you.

Keep this leaflet so that you can read it again if necessary.
If you have any questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

What Valarox is and what it is used for
Important information before taking Valarox
How to take Valarox
Possible side effects
How to store Valarox
Contents of the pack and other information

1. What Valarox is and what it is used for

Valarox contains two active substances – rosuvastatin and valsartan.
Valarox is indicated for the treatment of high blood pressure and elevated cholesterol levels, and (or) for the prevention of cardiovascular events.

2. Important information before using Valarox

When not to use Valarox

if the patient is allergic to valsartan, rosuvastatin, or any of the other ingredients of this medicine (listed in section 6);
if the patient is pregnant or breastfeeding; if pregnancy occurs while taking Valarox, treatment must be stopped immediately and the doctor must be informed; women of childbearing potential should use effective contraceptive methods while taking Valarox;
if the patient has liver disease;
if the patient has severe kidney function impairment;
if the patient experiences recurrent or unexplained muscle pain or weakness;
if the patient is taking the combination of sofosbuvir with velpatasvir and voxilaprevir (used to treat viral hepatitis C);
if the patient is taking cyclosporine (a medicine used to prevent rejection of transplanted organs);
if the patient has diabetes or kidney impairment and is being treated with aliskiren, a blood pressure-lowering medicine.

If any of the above points apply to the patient (or if the patient has any doubts), the patient should
consult their doctor again.
Warnings and precautions
Before starting Valarox, discuss the following with your doctor or pharmacist:

if the patient has kidney problems or is on dialysis;
if the patient has liver problems;
if the patient experiences recurrent or unexplained muscle pain; if muscle pain occurred previously in the patient or their family, or if muscle disorders occurred in the past while taking other cholesterol-lowering medicines; if unexplained muscle pain occurs, especially if accompanied by malaise or fever, the doctor should be informed immediately;
if the patient regularly drinks large amounts of alcohol;
if the thyroid gland is not functioning properly;
if the patient is taking other cholesterol-lowering medicines called fibrates; read the leaflet carefully, even if the patient has previously taken other cholesterol-lowering medicines;
if the patient is taking medicines used to treat HIV infection, e.g. ritonavir with lopinavir and (or) atazanavir; see section "Valarox with other medicines";
if the patient is over 70 years old (as the doctor must select an appropriate starting dose);
if the patient has severe respiratory insufficiency;
if the patient is of Asian descent: Japanese, Chinese, Filipino, Vietnamese, Korean, or Indian; the doctor must select an appropriate starting dose of Valarox;
if the patient has renal artery stenosis;
in patients who have recently undergone kidney transplantation (new kidney transplant);
in patients treated after a recent heart attack or due to heart failure, the doctor may assess kidney function;
in patients with severe heart disease other than heart failure or myocardial infarction;
if the patient has ever experienced swelling of the tongue and face due to an allergic reaction called angioedema while taking other medicines (including ACE inhibitors). This should be reported to the doctor. If such symptoms occur, Valarox must be stopped immediately and the doctor contacted. The patient should never take Valarox again. See also section 4 "Possible side effects".
in patients taking medicines that increase blood potassium levels, such as: potassium supplements or potassium-containing salt substitutes, potassium-sparing medicines, and heparin. Periodic monitoring of blood potassium levels may be necessary;
in patients with aldosteronism, a condition in which the adrenal glands produce excessive amounts of a hormone called aldosterone. Valarox is not recommended in patients with aldosteronism;
in patients who have lost large amounts of fluid (dehydration) due to diarrhea, vomiting, or high doses of diuretics (water tablets);
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 problems related to diabetes;
aliskiren.
if the patient is taking an ACE inhibitor together with a medicine belonging to the group known as mineralocorticoid receptor antagonists (MRA) (e.g. spironolactone, eplerenone) or beta-blockers (e.g. metoprolol);
if the patient is taking or has taken within the last 7 days an oral or injectable medicine containing fusidic acid (used to treat bacterial infections); taking Valarox with fusidic acid may lead to severe muscle problems (rhabdomyolysis);
if the patient has ever experienced severe skin rash, skin peeling, blisters, and/or oral ulcers after taking rosuvastatin or other similar medicines;
if the patient has or has had myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing) or ocular myasthenia (a disease causing weakness of eye muscles), as statins may sometimes worsen symptoms or cause myasthenia (see section 4).

In a small number of people, statins may affect the liver. This can be detected by a simple
blood test showing increased liver enzyme activity. For this reason, the doctor usually performs
liver function tests before and during treatment with Valarox.
Patients with diabetes or at risk of developing diabetes will be under close medical supervision
while taking this medicine. Individuals with high blood sugar and fat levels, overweight, and high
blood pressure may be at increased risk of developing diabetes.
The treating doctor may monitor kidney function, blood pressure, and blood electrolyte levels (e.g. potassium) at regular intervals.
Serious skin reactions, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with the use of rosuvastatin. If any of the symptoms described in section 4 occur, Valarox should be discontinued and medical advice sought immediately.
If the patient experiences abdominal pain, nausea, vomiting, or diarrhea after taking Valarox, this should be discussed with the doctor. The doctor will decide on further treatment. Do not stop taking Valarox on your own.
See also the information in the subsection "When not to use Valarox".
If any of the above situations apply, the patient must inform their doctor before starting Valarox.
Valarox with other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, including over-the-counter medicines.
Tell your doctor if you are taking any of the following medicines:

cyclosporine (a medicine used, for example, after organ transplantation);
medicines used to thin the blood, e.g.: warfarin, acenocoumarol, or fluindione (their blood-thinning effect and risk of bleeding may be increased when taken with this medicine), ticagrelor, or clopidogrel;
fibrates (e.g. gemfibrozil, fenofibrate) or any other medicine used to lower cholesterol (e.g. ezetimibe);
medicines for indigestion (used to neutralize stomach acid);
erythromycin (an antibiotic);
oral contraceptives;
hormone replacement therapy;
other blood pressure-lowering medicines, especially diuretics;
medicines that increase blood potassium levels, such as: potassium supplements or potassium-containing salt substitutes, potassium-sparing medicines, and heparin;
certain painkillers known as non-steroidal anti-inflammatory drugs (NSAIDs);
certain antibiotics (rifamycins), a medicine used to prevent transplant rejection (cyclosporine), or antiretroviral medicines used to treat HIV/AIDS (ritonavir with lopinavir and (or) atazanavir). These medicines may enhance the effect of Valarox;
lithium, a medicine used to treat certain mental disorders;
if the patient is taking an ACE inhibitor together with certain other medicines used to treat heart failure known as mineralocorticoid receptor antagonists (MRA) (e.g. spironolactone, eplerenone) or beta-blockers (e.g. metoprolol);
if fusidic acid is needed to treat a bacterial infection, taking Valarox should be temporarily stopped. The doctor will inform the patient when it is safe to restart Valarox. Taking Valarox with fusidic acid may rarely lead to muscle weakness, tenderness, or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.
regorafenib (used to treat cancer);
darolutamide (used to treat cancer);
capmatinib (used to treat cancer);
fostamatinib (used to treat low platelet count);
febuxostat (used to treat and prevent high blood uric acid levels);
teriflunomide (used to treat multiple sclerosis);
roxadustat (used to treat anemia in patients with chronic kidney disease);
tafamidis (used to treat a disease called transthyretin amyloidosis);
any of the following medicines used to treat viral infections, including HIV or hepatitis C virus, taken alone or in combination with other medicines (see: Warnings and precautions): ritonavir, lopinavir, atazanavir, sofosbuvir, voxilaprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir.

The effect of these medicines may be altered by Valarox or they may alter the effect of Valarox.
Valarox with food and drink
Valarox can be taken independently of meals.
Pregnancy and breastfeeding
Do not take Valarox during pregnancy or while breastfeeding. If the patient becomes pregnant while taking Valarox, she should immediately stop
taking the medicine and contact her doctor. Women of childbearing potential should use effective contraception while taking Valarox.
Consult a doctor or pharmacist before using this medicine.
Driving and operating machinery
Do not drive, operate machinery, or perform any other tasks requiring concentration until the patient knows how the medicine affects them.
Like many other medicines used to treat high blood pressure, Valarox may rarely cause dizziness and affect concentration.
If dizziness occurs, consult a doctor.
Valarox contains lactose and sodium
If the patient has previously been diagnosed with intolerance to certain sugars, they should consult their doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning it is considered "sodium-free".

3. How to use Valarox

This medicine should always be used as directed by a doctor or pharmacist. If in doubt,
consult a doctor or pharmacist.
Recommended dose in adults
The recommended dose is one tablet per day.
Valarox may be taken before or after a meal. The medicine should be taken at the same time each
day, with water. Do not take Valarox with grapefruit juice.
Use in children and adolescents
Valarox must not be used in children and adolescents.
Regular monitoring of cholesterol levels
It is important to visit your doctor regularly to monitor cholesterol levels, to ensure that levels
have reached and remain at the appropriate values.
Your doctor may decide to increase the dose so that the patient receives the appropriate amount
of Valarox.
Taking more Valarox than recommended
Contact a doctor or the nearest hospital for advice. In the event of severe dizziness and (or) fainting,
lie down. If the patient goes to hospital or is receiving treatment for another condition, inform
medical staff about taking Valarox.
If a dose of Valarox is missed
There is no cause for concern. Take the next dose at the usual time. Do not take a double dose to
make up for a missed dose.
Stopping Valarox
Talk to your doctor if you wish to stop taking Valarox. Stopping Valarox may cause a worsening of
the disease. Discontinuation of Valarox may lead to a renewed increase in cholesterol levels. Do not
stop taking the medicine unless your doctor advises otherwise.
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.
You should be aware of the adverse reactions that may occur. These reactions are usually mild
or moderate and typically resolve within a short period of time.
If any of the following adverse reactions occur in a patient after taking the medicine, the treatment with Valarox must be discontinued and the patient must immediately contact a doctor:

difficulty breathing, with or without swelling of the face, lips, tongue and (or) throat;
swelling of the face, lips, tongue and (or) throat, which may cause difficulty swallowing;
severe itching of the skin (urticarial rash);
formation of blisters on the skin, mouth, eyes and/or genital organs (Stevens-Johnson syndrome);
lupus-like syndrome (including rash, joint disorders and effects on blood cells);
muscle rupture;
red, flat, disc-shaped or circular spots on the trunk, often with blisters in the center, skin peeling, oral, throat, nose, genital or ocular ulcers. These potentially life-threatening skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome);
widespread rash, high body temperature and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

If any of these symptoms occur, treatment with Valarox must be discontinued and the patient must immediately contact a doctor (see section 2 “Warnings and precautions”).
Additionally, treatment with Valarox must be discontinued and the patient must immediately contact a doctor if the patient experiences any unusual muscle pain that lasts longer than expected. Muscle-related symptoms are more common in children and adolescents than in adults.
As with other statins, a small number of people have experienced unpleasant muscle symptoms, which rarely worsened, progressing into potentially life-threatening muscle damage known as rhabdomyolysis.

Common adverse reactions (may occur in up to 1 in 10 patients):

dizziness
low blood pressure with symptoms such as dizziness and fainting upon standing, or without these symptoms
impaired kidney function (symptoms of kidney dysfunction)
headache
abdominal pain
constipation
nausea
muscle pain
feeling of weakness
diabetes. The risk of developing diabetes is higher if the patient has high blood sugar and fat levels, is overweight, and has high blood pressure. During treatment with this medicine, the doctor will monitor the patient.

Uncommon adverse reactions (may occur in up to 1 in 100 patients):

angioedema (see “Some symptoms requiring immediate medical attention”)
sudden loss of consciousness (fainting)
sensation of spinning (vertigo)
severe impairment of kidney function (symptoms of severe kidney failure)
muscle cramps, heart rhythm disturbances (symptoms of hyperkalemia)
shortness of breath, breathing difficulties when lying down, swelling of feet or legs (symptoms of heart failure)
cough
diarrhea
fatigue
weakness
rash, itching or other skin reactions
increased protein in urine – usually resolves spontaneously without the need to discontinue Valarox

Rare adverse reactions (may occur in up to 1 in 1,000 patients):

severe allergic reaction – symptoms include swelling of the face, lips, tongue and (or) throat, difficulty swallowing and breathing, severe skin itching (with raised hives). If the patient suspects an allergic reaction, treatment with Valarox must be immediately discontinued and medical help sought
muscle damage in adults – as a precaution, treatment with Valarox must be discontinued and the doctor contacted immediately if the patient experiences any unusual muscle pain lasting longer than expected
severe abdominal pain (pancreatitis)
increased liver enzyme activity in blood
reduced platelet count, increasing the risk of bleeding or bruising (thrombocytopenia)

Very rare adverse reactions (may occur in up to 1 in 10,000 patients):

jaundice (yellowing of the skin and eyes)
hepatitis
trace amounts of blood in urine
nerve damage in arms and legs (e.g. numbness)
joint pain
memory loss
gynecomastia (enlargement of breasts in men)
intestinal angioedema: intestinal swelling with symptoms such as abdominal pain, nausea, vomiting and diarrhea

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

allergic reactions presenting as rash, itching and urticaria; symptoms may include: fever, joint swelling and joint pain, muscle pain, lymph node swelling and/or flu-like symptoms (serum sickness-like symptoms)
purple-red spots, fever, itching (symptoms of vasculitis)
fever, sore throat or oral ulceration due to infection (symptoms of low white blood cell count, known as neutropenia)
decreased hemoglobin concentration and reduced number of red blood cells in blood (in severe cases may lead to anemia)
increased potassium concentration in blood (in severe cases may cause muscle cramps and heart rhythm disturbances)
decreased sodium concentration in blood (in severe cases may cause fatigue, confusion, muscle twitching, seizures or coma)
increased liver enzyme activity (may indicate liver damage), including increased bilirubin concentration in blood (in severe cases may cause yellowing of skin and eyes)
increased blood urea nitrogen and increased serum creatinine concentration (may indicate kidney dysfunction)
shortness of breath
swelling
sleep disturbances, including insomnia and nightmares
sexual dysfunction
depression
breathing disorders, including persistent cough and/or shortness of breath or fever
tendon damage
persistent muscle weakness
myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing)
ocular myasthenia (a disease causing weakness of eye muscles). You should talk to a doctor if the patient experiences weakness in arms or legs worsening after periods of activity, double vision or drooping eyelids, difficulty swallowing or shortness of breath.

The frequency of some adverse reactions may vary depending on the condition being treated. For example, adverse reactions such as dizziness or impaired kidney function occurred less frequently in adult patients treated for high blood pressure than in adult patients treated for heart failure or after a recent myocardial infarction.
If any of these symptoms occur, the doctor must be informed immediately.

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

5. How to store Valarox

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after the abbreviation
"EXP". The expiry date refers to the last day of the specified month.
The batch number is indicated on the packaging after the abbreviation "Lot".
Store in the original packaging to protect from moisture.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. Proper disposal helps protect the environment.

6. Contents of the pack and other information

What Valarox contains

The active substances are valsartan and rosuvastatin (as rosuvastatin calcium).
10 mg + 80 mg: each film-coated tablet contains 10 mg rosuvastatin (as rosuvastatin calcium) and 80 mg valsartan.
20 mg + 80 mg: each film-coated tablet contains 20 mg rosuvastatin (as rosuvastatin calcium) and 80 mg valsartan.
10 mg + 160 mg: each film-coated tablet contains 10 mg rosuvastatin (as rosuvastatin calcium) and 160 mg valsartan.
20 mg + 160 mg: each film-coated tablet contains 20 mg rosuvastatin (as rosuvastatin calcium) and 160 mg valsartan.
Other ingredients are:
Tablet core: microcrystalline cellulose, lactose monohydrate, sodium croscarmellose, colloidal anhydrous silica, magnesium stearate, mannitol, povidone K25, sodium lauryl sulfate, and yellow iron oxide (E172).
Tablet coating:
10 mg + 80 mg: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, red iron oxide (E172).
20 mg + 80 mg: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, red iron oxide (E172).
10 mg + 160 mg: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, red iron oxide (E172), yellow iron oxide (E172).
20 mg + 160 mg: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, yellow iron oxide (E172).
See section 2 "Valarox contains lactose and sodium".

What Valarox looks like and contents of the pack
10 mg + 80 mg film-coated tablets (tablets): dark pink, round, slightly biconvex film-coated tablets with bevelled edges, marked with "K4" on one side; tablet diameter 8.7–9.3 mm.
20 mg + 80 mg film-coated tablets (tablets): dark pink, capsule-shaped, slightly biconvex film-coated tablets with bevelled edges, marked with "K3" on one side; tablet dimensions 14.7–15.3 mm x 6.7–7.3 mm.
10 mg + 160 mg film-coated tablets (tablets): dark pink, oval, slightly biconvex film-coated tablets with bevelled edges, marked with "K2" on one side; tablet dimensions 16.7–17.3 mm x 7.7–8.3 mm.
20 mg + 160 mg film-coated tablets (tablets): light brownish-yellow, oval, slightly biconvex film-coated tablets with bevelled edges, marked with "K1" on one side; tablet dimensions 16.7–17.3 mm x 7.7–8.3 mm.
Pack sizes: 10, 14, 20, 28, 30, 56, 60, 84, 90 and 100 film-coated tablets in a cardboard box.
Not all pack sizes may be marketed.

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

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

For further information on the names of this medicinal product in the other 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