Dafiro

Patient Information Leaflet: Information for the User

Dafiro 5 mg/80 mg film-coated tablets, 5 mg/160 mg film-coated tablets, 10 mg/160 mg film-coated tablets

amlodipine/valsartan
Please read this leaflet carefully before 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 their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Dafiro is and what it is used for

Dafiro tablets contain two substances called amlodipine and valsartan. Both of these
substances help control high blood pressure.

• Amlodipine belongs to a group of substances known as “calcium channel blockers”. Amlodipine prevents calcium from entering the walls of blood vessels and thereby prevents the narrowing of blood vessels.
• Valsartan belongs to a group of substances known as “angiotensin II receptor antagonists”. Angiotensin II is produced by the body and causes blood vessels to narrow, thereby increasing blood pressure. Valsartan works by blocking the effect of angiotensin II. This means that both substances help prevent the narrowing of blood vessels. As a result, blood vessels relax and blood pressure decreases.

Dafiro is used to treat high blood pressure in adults whose blood pressure is not sufficiently controlled with amlodipine or valsartan alone.

2. What you should know before taking Dafiro

Do not take Dafiro

• if you are allergic to amlodipine or any other calcium antagonist. This may cause itching, skin redness, or difficulty breathing.
• if you are allergic to valsartan or to any of the other ingredients of this medicine (listed in section 6). If you think you may be allergic, consult your doctor or pharmacist before taking Dafiro.
• if you have severe liver problems or bile-related disorders such as biliary cirrhosis or cholestasis.
• if you are more than 3 months pregnant (it is better to avoid taking Dafiro even in the early stages of pregnancy; see section Pregnancy).
• if you have very low blood pressure (hypotension).
• if you have narrowing of the aortic valve (aortic stenosis) or cardiogenic shock (a condition in which your heart is unable to supply sufficient blood to the body).
• if you have heart failure following a heart attack.
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren. If any of these situations apply to you, do not take Dafiro and consult your doctor.

Warnings and precautions
Talk to your doctor before taking Dafiro:

• if you have felt unwell (vomiting or diarrhoea).
• if you have liver or kidney problems.
• if you have had a kidney transplant or if you have been told you have narrowing of the renal arteries.
• if you suffer from a disease affecting the adrenal glands called “primary hyperaldosteronism”.
• if you have had heart failure or a heart attack. Follow your doctor’s instructions carefully regarding initial dosing. Your doctor may also monitor your kidney function.
• if your doctor has told you that you have narrowing of the heart valves (called “aortic or mitral stenosis”) or that the thickness of your heart muscle has abnormally increased (a condition called “obstructive hypertrophic cardiomyopathy”).
• if you have previously experienced swelling, particularly of the face and throat, while taking other medicines (including angiotensin-converting enzyme inhibitors). If you experience these symptoms, stop taking Dafiro immediately and contact your doctor right away. You must never take Dafiro again.
• if after taking Dafiro you experience abdominal pain, nausea, vomiting, or diarrhoea. Your doctor will decide whether treatment should continue. Do not stop taking Dafiro on your own.
• 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.

Your doctor may check your kidney function, blood pressure, and levels of electrolytes (such as potassium) in your blood at regular intervals.
See also the section “Do not take Dafiro”.
If any of these conditions apply to you, inform your doctor before taking Dafiro.
Children and adolescents
Dafiro is not recommended for use in children and adolescents (under 18 years of age).
Other medicines and Dafiro
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Your doctor may need to adjust the dose and/or take additional precautions. In some cases, it may be necessary to stop taking one of the medicines. This is particularly important for the following medicines:

• ACE inhibitors or aliskiren (see also the sections “Do not take Dafiro” and “Warnings and precautions”);
• diuretics (a type of medicine that increases the amount of urine produced);
• lithium (a medicine used to treat certain types of depression);
• potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other substances that may increase potassium levels;
• certain types of painkillers known as non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclooxygenase-2 inhibitors (COX-2 inhibitors). Your doctor may also monitor kidney function;
• anticonvulsant agents (e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone);
• St. John’s wort;
• nitroglycerin and other nitrates or other substances called “vasodilators”;
• medicines used for HIV/AIDS (e.g. ritonavir, indinavir, nelfinavir);
• medicines used to treat fungal infections (e.g. ketoconazole, itraconazole);
• medicines used to treat bacterial infections (such as rifampicin, erythromycin, clarithromycin, telithromycin);
• verapamil, diltiazem (heart medicines);
• simvastatin (a medicine used to control high cholesterol levels);
• dantrolene (infusion for severe body temperature abnormalities);
• tacrolimus (used to control immune response to allow the body to accept a transplanted organ);
• medicines used to prevent transplant rejection (ciclosporin).

Dafiro with food and drink
Grapefruit and grapefruit juice must not be consumed by people taking Dafiro. This is because grapefruit and grapefruit juice can increase blood levels of the active substance amlodipine, which may cause an unpredictable increase in Dafiro’s blood pressure-lowering effect.
Pregnancy and breastfeeding
Pregnancy
You must inform your doctor if you think you may be pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking Dafiro before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine. Dafiro is not recommended during early pregnancy (first 3 months) 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.
Breastfeeding
Inform your doctor if you are breastfeeding or planning to breastfeed. It has been shown that amlodipine passes into breast milk in small amounts. Dafiro is not recommended for breastfeeding women, and your doctor may choose an alternative treatment for you if you wish to breastfeed, especially if the baby is a newborn or was born prematurely.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
This medicine may cause dizziness. This may affect your ability to concentrate. Therefore, if you are unsure how this medicine affects you, do not drive, operate machinery, or perform any other activities requiring concentration.

3. How to take Dafiro

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor. This will help you achieve better results and reduce the risk of unwanted side effects.
The usual dose of Dafiro is one tablet daily.

• It is preferable to take the medicine every day at the same time.
• Swallow the tablets with a glass of water.
• Dafiro may be taken either with or without food. Do not take Dafiro with grapefruit or grapefruit juice.

Depending on your response to treatment, your doctor may recommend a lower or higher dose.
Do not take more than the prescribed dose.
Dafiro and elderly patients (65 years and over)
Your doctor should exercise caution when increasing the dose.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.
If you take more Dafiro than you should
If you have taken too many Dafiro tablets, or if someone else has taken your tablets, contact a doctor immediately. Excess fluid may accumulate in the lungs (pulmonary edema), causing shortness of breath, which may develop within 24–48 hours after ingestion.
If you forget to take Dafiro
If you forget to take your medicine, take it as soon as you remember. Then take your next dose at the usual time. 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 tablet.
If you stop taking Dafiro
Stopping treatment with Dafiro may cause your condition to worsen. Do not stop taking this medicine unless your doctor has told you to do so.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Some side effects can be serious and require immediate medical attention:
A small number of patients have experienced these serious side effects. If you notice any of the
following side effects, contact your doctor immediately:
Rare (may affect up to 1 in 1,000 people): allergic reactions with symptoms such as rash, itching,
swelling of the face, lips or tongue, difficulty breathing, low blood pressure (feeling weak, mild
confusion).
Very rare (may affect up to 1 in 10,000 people): intestinal angioedema: swelling in the intestine
causing symptoms such as abdominal pain, nausea, vomiting and diarrhoea.
Other possible side effects of Dafiro
Common (may affect up to 1 in 10 people): influenza; nasal congestion, sore throat and difficulty
swallowing, headache; swelling of the arms, hands, legs, ankles or feet; fatigue; asthenia (weakness);
flushing and/or feeling of warmth in the face and/or neck.
Uncommon (may affect up to 1 in 100 people): dizziness; nausea and abdominal pain; dry mouth;
drowsiness, tingling or numbness in the hands or feet; vertigo; fast heartbeat, including palpitations;
dizziness when standing up; cough; diarrhoea; constipation; skin rashes, redness of the skin; joint
swelling, back pain; joint pain.
Rare (may affect up to 1 in 1,000 people): feeling of anxiety; ringing in the ears (tinnitus); fainting;
passing larger amounts of urine than usual or more urgent need to urinate, inability to achieve or
maintain an erection, feeling of heaviness; low blood pressure with symptoms such as dizziness,
feeling of emptiness in the head; excessive sweating; skin rashes over the body; itching; muscle spasm.
If any of these side effects become severe, inform your doctor.
Side effects reported with amlodipine or valsartan alone, not observed with Dafiro or observed with
higher frequency than with Dafiro:
Amlodipine
If you notice any of the following very rare and serious side effects, consult your doctor
immediately:

• Sudden onset of shortness of breath, chest pain, laboured breathing or difficulty breathing.
• Swelling of the eyelids, face or lips.
• Swelling of the tongue and throat which may cause difficulty breathing.
• Severe skin reactions including severe rash, urticaria, widespread redness of the skin, severe itching, blisters, peeling and swelling of the skin, inflammation of mucous membranes (Stevens-Johnson syndrome, toxic epidermal necrolysis) or other allergic reactions.
• Myocardial infarction, arrhythmia.
• Pancreatic inflammation which may cause severe abdominal and back pain associated with a strong feeling of illness.

The following side effects have been reported. If you experience any of these side effects, or if they
persist for more than one week, contact your doctor.
Common (may affect up to 1 in 10 people): Dizziness, drowsiness; palpitations (awareness of your
heartbeat); flushing, swelling of the ankles (oedema); abdominal pain, nausea.
Uncommon (may affect up to 1 in 100 people): Mood changes, anxiety, depression, insomnia,
tremor, taste disturbances, fainting, loss of sensitivity to pain; visual disturbances, impaired vision,
ringing in the ears; low blood pressure; sneezing/runny nose due to inflammation of the nasal
mucosa (rhinitis); indigestion, vomiting; hair loss, increased sweating, skin itching, skin colour
change; urinary disorders, need to urinate at night, frequent need to urinate; inability to achieve an
erection, discomfort or breast enlargement in men, pain, malaise, muscle pain, muscle cramps;
weight gain or loss.
Rare (may affect up to 1 in 1,000 people): Confusion.
Very rare (may affect up to 1 in 10,000 people): Low levels of white blood cells and platelets in the
blood which may lead to unusual bruising or tendency to bleed (damage to red blood cells); high blood
sugar levels (hyperglycaemia); gum swelling, abdominal swelling (gastritis); abnormal liver function,
liver inflammation (hepatitis), yellowing of the skin (jaundice), increased liver enzymes which may
lead to changes in certain laboratory tests; increased muscle tension; inflammation of blood vessels,
often with skin rash, photosensitivity; disorders related to stiffness, tremor and/or movement
disorders.
Valsartan
Not known (frequency cannot be estimated from the available data): Decrease in red blood cells, fever,
sore throat or mouth pain due to infections; spontaneous bleeding or bruising; high potassium levels
in the blood; abnormal liver function tests; reduced kidney function and severe reduction in kidney
function; swelling, especially of the face and throat; muscle pain; skin rash, red-purple spots; fever;
itching; allergic reaction; blistering of the skin (a sign of a condition called bullous dermatitis).
If any of these side effects affect you, inform your doctor immediately.
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 listed in
Annex V. By reporting side effects, you can help provide more information on the safety of this
medicine.

5. How to store Dafiro

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after Exp or EXP. The expiry date refers to the last day of that month.
Do not store above 30°C.
Store in the original packaging to protect the medicine from moisture.
Do not use Dafiro packages that are damaged or show signs of tampering.

6. Package contents and other information

What Dafiro contains
Dafiro 5 mg/80 mg film-coated tablets
The active substances in Dafiro are amlodipine (as amlodipine besilate) and valsartan. Each tablet contains 5 mg of amlodipine and 80 mg of valsartan.
The other components are microcrystalline cellulose; crospovidone (type A); anhydrous colloidal silica; magnesium stearate; hypromellose (substitution type 2910 (3 mPa.s)); macrogol 4000; talc; titanium dioxide (E171); yellow iron oxide (E172).
Dafiro 5 mg/160 mg film-coated tablets
The active substances in Dafiro are amlodipine (as amlodipine besilate) and valsartan. Each tablet contains 5 mg of amlodipine and 160 mg of valsartan.
The other components are microcrystalline cellulose; crospovidone (type A); anhydrous colloidal silica; magnesium stearate; hypromellose (substitution type 2910 (3 mPa.s)); macrogol 4000; talc; titanium dioxide (E171); yellow iron oxide (E172).
Dafiro 10 mg/160 mg film-coated tablets
The active substances in Dafiro are amlodipine (as amlodipine besilate) and valsartan. Each tablet contains 10 mg of amlodipine and 160 mg of valsartan.
The other components are microcrystalline cellulose; crospovidone (type A); anhydrous colloidal silica; magnesium stearate; hypromellose (substitution type 2910 (3 mPa.s)); macrogol 4000; talc; titanium dioxide (E171); yellow iron oxide (E172); red iron oxide (E172).

Description of the appearance of Dafiro and package contents
Dafiro 5 mg/80 mg tablets are round, dark yellow in colour, marked with “NVR” on one side and “NV” on the other side. Approximate dimensions: 8.20 mm in diameter.
Dafiro 5 mg/160 mg tablets are oval, dark yellow in colour, marked with “NVR” on one side and “ECE” on the other side. Approximate dimensions: 14.2 mm (length) x 5.7 mm (width).
Dafiro 10 mg/160 mg tablets are oval, light yellow in colour, marked with “NVR” on one side and “UIC” on the other side. Approximate dimensions: 14.2 mm (length) x 5.7 mm (width).
Dafiro is available in packages containing 7, 14, 28, 30, 56, 90, 98 or 280 tablets and in multiple packs consisting of 4 boxes each containing 70 tablets or 20 boxes each containing 14 tablets. All packages are available in standard blisters; the 56, 98 and 280 tablet packages are additionally available in unit-dose divisible blisters.
Not all pack sizes may be available in your country.

Marketing Authorization Holder
Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland

Manufacturer
Novartis Farma S.p.A.
Via Provinciale Schito 131
80058 Torre Annunziata (NA)
Italy
Novartis Farmacéutica S.A.
Gran Via de les Corts Catalanes, 764
08013 Barcelona
Spain
Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nuremberg
Germany

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Novartis Pharma N.V. SIA Novartis Baltics Lietuvos filialas
Tél/Tel: +32 2 246 16 11 Tel: +370 5 269 16 50

България Luxembourg/Luxemburg
Novartis Bulgaria EOOD Novartis Pharma N.V.
Тел.: +359 2 976 98 28 Tél/Tel: +32 2 246 16 11

Česká republika Magyarország
Novartis s.r.o. Novartis Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 457 65 00

Danmark Malta
Novartis Healthcare A/S Novartis Pharma Services Inc.
Tlf: +45 39 16 84 00 Tel: +356 2122 2872

Deutschland Nederland
Novartis Pharma GmbH Novartis Pharma B.V.
Tel: +49 911 273 0 Tel: +31 88 04 52 111

Eesti Norge
SIA Novartis Baltics Eesti filiaal Novartis Norge AS
Tel: +372 66 30 810 Tlf: +47 23 05 20 00

Ελλάδα Österreich
Novartis (Hellas) A.E.B.E. Novartis Pharma GmbH
Τηλ: +30 210 281 17 12 Tel: +43 1 86 6570

España Polska
Esteve Pharmaceuticals, S.A. Novartis Poland Sp. z o.o.
Tel: +34 93 446 60 00 Tel.: +48 22 375 4888

France Portugal
Novartis Pharma S.A.S. Novartis Farma - Produtos Farmacêuticos, S.A.
Tél: +33 1 55 47 66 00 Tel: +351 21 000 8600

Hrvatska România
Novartis Hrvatska d.o.o. Novartis Pharma Services Romania SRL
Tel. +385 1 6274 220 Tel: +40 21 31299 01

Ireland Slovenija
Novartis Ireland Limited Novartis Pharma Services Inc.
Tel: +353 1 260 12 55 Tel: +386 1 300 75 50

Ísland Slovenská republika
Vistor hf. Novartis Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 5542 5439

Italia Suomi/Finland
Novartis Farma S.p.A. Novartis Finland Oy
Tel: +39 02 96 54 1 Puh/Tel: +358 (0)10 6133 200

Κύπρος Sverige
Novartis Pharma Services Inc. Novartis Sverige AB
Τηλ: +357 22 690 690 Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu