Package Leaflet: Information for the User

Amlodipino/Valsartán Krka 10 mg/160 mg Film-Coated Tablets

Read this package leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this package leaflet, as 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 pass it on to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist. See section 4.

Amlodipino/Valsartán Krka tablets contain two substances called amlodipino and valsartán. Both substances help control high blood pressure.

• Amlodipino belongs to a group of substances called «calcium channel blockers». Amlodipino prevents calcium from entering the blood vessel wall, preventing blood vessel constriction.
• Valsartán belongs to a group of substances called «angiotensin II receptor antagonists». Angiotensin II is produced by the body and causes blood vessels to constrict, thereby increasing blood pressure. Valsartán acts by blocking the effect of angiotensin II.

This means that both substances help prevent blood vessel constriction. As a result, blood vessels relax and blood pressure decreases.

Amlodipino/Valsartán Krka is used to treat high blood pressure in adults whose blood pressure is not adequately controlled with amlodipino or valsartán alone.

Do not take Amlodipino/Valsartán Krka:

• if you are allergic to amlodipino or any other calcium channel blocker. This may include symptoms such as itching, skin redness, or difficulty breathing.
• if you are allergic to valsartán or any of the other components of this medication (including those listed in section 6). If you think you may be allergic, inform your doctor before taking Amlodipino/Valsartán Krka.
• if you have severe liver problems or bile duct problems such as biliary cirrhosis or cholestasis.
• if you are more than 3 months pregnant. (In any case, it is best to avoid taking this medication also at the beginning of your pregnancy, see Pregnancy section).
• if you have a severe decrease in blood pressure (hypotension).
• if you have a narrowing of the aortic valve (aortic stenosis) or cardiogenic shock (a situation in which your heart cannot supply enough blood to your body).
• if you have heart failure after a heart attack.
• if you have high blood sugar levels and have type 2 diabetes (also known as non-insulin-dependent diabetes mellitus) or have a kidney function disorder and are taking a medication to lower blood pressure that contains aliskiren.

Do not take Amlodipino/Valsartán Krka and inform your doctor if you are affected by any of the above cases.

Warnings and precautions

Consult your doctor before starting to take Amlodipino/Valsartán Krka:

• if you have been sick (with vomiting or diarrhea).
• if you have liver or kidney problems.
• if you have had a kidney transplant or if you have been told that you have a narrowing of the kidney arteries.
• if you have a disease that affects the adrenal glands called "primary hyperaldosteronism".
• if you have had heart failure or have had a heart attack. Follow your doctor's instructions to start taking the medication carefully.Your doctor may also check your kidney function.
• if your doctor has told you that you have a narrowing of the heart valves (which is called "aortic or mitral stenosis") or that the thickness of your heart muscle has increased abnormally (which is called "hypertrophic obstructive cardiomyopathy").
• if you have experienced swelling, particularly in the face and throat, while taking other medications (including ACE inhibitors). If you have these symptoms, stop taking Amlodipino/Valsartán Krka and contact your doctor immediately. Never take Amlodipino/Valsartán Krka again.
• if you are taking any of the following medications used to treat high blood pressure:
• • an ACE inhibitor (such as enalapril, lisinopril, ramipril), particularly if you have kidney problems related to diabetes.
  • aliskiren.

Your doctor may check your kidney function, blood pressure, and electrolyte levels (such as potassium) in your blood at regular intervals.

See also the information under the heading “Do not take Amlodipino/Valsartán Krka”.

Inform your doctor before taking Amlodipino/Valsartán Krka if you are affected by any of the cases mentioned.

Children and adolescents

Amlodipino/Valsartán Krka is not recommended for use in children or adolescents (under 18 years old).

Use of Amlodipino/Valsartán Krka with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication. Your doctor may need to adjust your dose and/or take other precautions. In some cases, you may need to stop taking one of the medications. This applies especially to the medications listed below:

• an ACE inhibitor or aliskiren (see also the information under the headings “Do not take Amlodipino/Valsartán Krka” and “Warnings and precautions”);
• diuretics (a type of medication that increases urine production);
• lithium (a medication used to treat certain types of depression);
• potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, and other substances that may increase potassium levels;
• a certain type of medication used to treat pain called nonsteroidal anti-inflammatory drugs (NSAIDs) or selective COX-2 inhibitors. Your doctor may also check your kidney function;
• anticonvulsants (e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone);
• St. John's Wort;
• nitroglycerin and other nitrates, or other substances called "vasodilators";
• medications used to treat HIV/AIDS (e.g. ritonavir, indinavir, nelfinavir);
• medications used to treat fungal infections (e.g. ketoconazole, itraconazole);
• antibiotics (medications used to treat bacterial infections) such as rifampicin, erythromycin, clarithromycin, telithromycin;
• verapamil, diltiazem (heart medications);
• simvastatin (a medication used to control high cholesterol levels);
• dantrolene (for severe abnormalities of body temperature);
• medications used to prevent rejection in a transplant (cyclosporin, tacrolimus).

Taking Amlodipino/Valsartán Krka with food and drinks

People taking Amlodipino/Valsartán Krka should not consume grapefruit or grapefruit juice. This is because grapefruit and grapefruit juice may cause an increase in the blood levels of the active ingredient amlodipino, which may lead to unpredictable reductions in blood pressure.

Pregnancy and breastfeeding

Pregnancy

You should inform your doctor if you are pregnant, if you suspect you may be pregnant, or if you plan to become pregnant. Your doctor will usually advise you to stop taking Amlodipino/Valsartán Krka before becoming pregnant or as soon as you become pregnant, and recommend taking another antihypertensive medication instead. Amlodipino/Valsartán Krka is not recommended for use during the first 3 months of pregnancy and should not be administered after the third month of pregnancy as it may cause serious harm to your baby when administered from that time.

Breastfeeding

Amlodipino has been shown to pass into breast milk in small amounts. Inform your doctor if you are planning to start or are breastfeeding, as Amlodipino/Valsartán Krka is not recommended for use during this period. Your doctor may decide to administer a more suitable treatment if you want to breastfeed, especially in newborns or premature babies.

Consult your doctor or pharmacist before using any medication.

Driving and operating machinery

This medication may make you feel dizzy, which may affect your ability to concentrate. Therefore, if you are unsure how this medication will affect you, do not drive, operate machinery, or perform other activities that require concentration.

Amlodipino/Valsartán Krka contains sodium

This medication contains less than 23 mg of sodium (1mmol) per tablet; this is, essentially "sodium-free".

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor again. This will help you obtain the best results and reduce the risk of adverse effects.

The normal dose of Amlodipino/Valsartán Krka is one tablet per day.

• It is preferable to take the medication at the same time every day.
• Swallow the tablets with a glass of water.
• You can take Amlodipino/Valsartán Krka with or without food. Do not take Amlodipino/Valsartán Krka with grapefruit or grapefruit juice.

Your doctor may suggest a higher or lower dose depending on your response to treatment. Do not exceed the prescribed dose.

Amlodipino/Valsartán Krka and Older Adults (65 years or older)

Your doctor should exercise caution when increasing the dose.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

If You Take More Amlodipino/Valsartán Krka Than You Should

If you have taken too many tablets of Amlodipino/Valsartán Krka, or if someone else has taken your tablets, consult a doctor immediately.

Excess fluid may accumulate in the lungs (pulmonary edema) causing difficulty breathing that may develop up to 24-48 hours after ingestion.

If You Forget to Take Amlodipino/Valsartán Krka

If you forget to take this medication, take it as soon as you remember. Then take the next dose at the usual time. However, if it is almost time for the next dose, do not take the missed dose. Do not take a double dose to make up for the missed doses.

If You Stop Taking Amlodipino/Valsartán Krka

Stopping your treatment with Amlodipino/Valsartán Krka may cause your condition to worsen. Do not stop taking your medication unless your doctor tells you to.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, Amlodipino/Valsartán Krka can cause side effects, although not everyone will experience them.

Some side effects can be serious and require immediate medical attention:

A few patients have experienced these serious side effects(which can affect up to 1 in 1,000 patients).Notify your doctor immediately if you notice any of the following:

Allergic reaction with symptoms such as skin rash, itching, swelling of the face, lips, or tongue, difficulty breathing, low blood pressure (feeling faint, dizziness).

Other possible side effects of Amlodipino/Valsartán Krka:

Frequent (can affect up to 1 in 10 patients):Common cold; stuffy nose, sore throat, and discomfort swallowing; headache; swelling in the arms, hands, legs, ankles, or feet; fatigue; asthenia (weakness); flushing and warming of the face and/or neck.

Infrequent (can affect up to 1 in 100 patients):Dizziness; nausea and abdominal pain; dry mouth; drowsiness, tingling, or numbness in the hands or feet; vertigo, rapid heartbeat including palpitations; dizziness when standing up; cough; diarrhea; constipation; skin rash, redness of the skin; joint inflammation, back pain; joint pain.

Rare (can affect up to 1 in 1,000 patients):Anxiety; ringing in the ears (tinnitus); fainting; increased urine production or urgent need to urinate; inability to achieve or maintain an erection; feeling of heaviness; low blood pressure with symptoms such as dizziness, fainting; excessive sweating; skin rash all over the body, itching, muscle spasms.Notify your doctor if any of the mentioned cases severely affect you.

Side effects reported with amlodipine or valsartan alone and not observed with Amlodipino/Valsartán Krka or observed with a higher frequency than with Amlodipino/Valsartán Krka:

Amlodipine

Consult your doctor immediately if you experience any of the following serious side effects, which are very rare after taking this medication:

• Sudden hissing sounds while breathing (sibilant breathing), chest pain, shortness of breath, or difficulty breathing.
• Swelling of the eyelids, face, or lips.
• Swelling of the tongue and throat that causes severe difficulty breathing.
• Severe skin reactions that include intense skin rash, blisters, redness of the skin all over the body, severe itching, blistering, peeling, and inflammation of the skin, inflammation of mucous membranes (Stevens-Johnson syndrome, toxic epidermal necrolysis, or other allergic reactions).
• Heart attack, abnormal heartbeat.
• Pancreatitis that can cause severe abdominal pain and back pain accompanied by severe discomfort.

The following side effects have been reported. If any of these cause problems or last more than a week, consult your doctor.

Frequent (can affect up to 1 in 10 patients):Dizziness, somnolence; palpitations (feeling the heartbeat); hot flashes, swelling of the ankles (edema); abdominal pain, nausea.

Infrequent (can affect up to 1 in 100 patients):Mood changes, anxiety, depression, somnolence, tremor, altered taste, fainting; visual disturbances, visual deterioration, ringing in the ears; decreased blood pressure; nasal congestion and secretion caused by inflammation of the nasal mucosa (rhinitis); indigestion, vomiting (discomfort); hair loss, increased sweating, itching skin, skin discoloration; urinary disorders, increased need to urinate at night, increased frequency of urination; erectile dysfunction, breast tenderness in men, discomfort, muscle pain, muscle cramps; weight gain or loss.

Rare (can affect up to 1 in 1,000 patients):Confusion.

Very rare (can affect up to 1 in 10,000 patients):Decreased white blood cell count, decreased platelet count that can cause easy bleeding or unusual bruising (damage to red blood cells); high blood sugar (hyperglycemia); inflammation of the gums, abdominal swelling (gastritis); abnormal liver function, inflammation of the liver (hepatitis), yellowing of the skin (jaundice), increased liver enzymes that can affect some medical tests; muscle tension; inflammation of blood vessels often with skin eruptions, light sensitivity; movement disorders combining rigidity, tremor, and/or movement disturbances.

Frequency unknown(cannot be estimated from available data): tremor, rigid posture, mask-like face, slow movements, and walking with dragging feet and imbalance.

Valsartan

Frequency unknown (the frequency cannot be estimated from available data):Decreased red blood cell count, fever, sore throat, or mouth ulcers due to infection; spontaneous bleeding or skin hematomas; increased potassium in the blood; abnormal liver function test results; decreased kidney function and severely decreased kidney function; swelling, mainly of the face and throat; muscle pain; skin rash, red purpura spots; fever; itching; allergic reaction, blistering skin disease (sign of a disease called dermatitis bullosa).

Notify your doctor immediately if you experience any of the mentioned cases.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging and the blister pack after CAD. The expiration date is the last day of the month indicated.

Do not store at a temperature above 30°C.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and medicines you no longer need at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. By doing so, you will help protect the environment.

Composition of Amlodipine/Valsartan Krka

• The active ingredients are Amlodipine and Valsartan 10 mg / 160 mg film-coated tablets:

Each film-coated tablet contains 10 mg of amlodipine (as amlodipine besylate) and 160 mg of valsartan.

• The other components are microcrystalline cellulose, magnesium stearate, sodium croscarmellose, povidone K25, sodium lauryl sulfate, mannitol, and anhydrous colloidal silica in the tablet core and polyvinyl alcohol, titanium dioxide (E171), macrogol 3000, talc, and iron oxide yellow (E172) in the coating.

See section 2: “Amlodipine/Valsartan Krka contains sodium”

Appearance of the product and contents of the package

Amlodipine/Valsartan Krka 10 mg/160 mg film-coated tablets (tablets): this medication is presented as pale yellow-brown, oval, and biconvex film-coated tablets (tablet diameter: 13x8 mm, thickness: 3.8 mm-5.4 mm).

5 mg/160 mg and 10 mg/160 mg tablets: Blister (OPA/Alu/PVC-Alu laminates): 28, 30, 56, 90, 98, and 100 tablets, in a box.

Only some package sizes may be marketed.

Marketing Authorization 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-Str. 5, 27472 Cuxhaven, Germany

Krka-farma d.o.o., V. Holjevca 20/E, 10450 Jastrebarsko, Croatia

For further information about this medication, please contact the local representative of the Marketing Authorization Holder:

KRKA Farmacéutica, S.L., C/ Anabel Segura 10, Pta. Baja, Oficina 1, 28108 Alcobendas, Madrid, Spain

This medication is authorized in the Member States of the EEA, with the following names:

Last review date of this leaflet: August 2022

The detailed and updated information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) ( http://www.aemps.gob.es/ )