DAFIRO 10 mg/160 mg FILM-COATED TABLETS

2. What you need to know before you take Dafiro

Do not take Dafiro

• if you are allergic to amlodipine or any other calcium channel blocker. This may include itching, redness of the skin, or difficulty breathing.
• if you are allergic to valsartan or any of the other ingredients of this medicine (listed in section 6). If you think you may be allergic, inform your doctor before taking Dafiro.
• if you have severe liver problems or biliary problems such as biliary cirrhosis or cholestasis.
• if you are more than 3 months pregnant. (In any case, it is recommended to avoid taking this medicine also at the start of your pregnancy, see section Pregnancy).
• if you have severe low blood pressure (hypotension).
• if you have narrowing of the aortic valve (aortic stenosis) or cardiogenic shock (a situation where your heart is unable to supply enough blood to your body).
• if you have heart failure after a heart attack.
• if you have diabetes or kidney problems and are being treated with a blood pressure-lowering medicine that contains aliskiren.

Do not take Dafiro and inform your doctor if you are affected by any of the above.

Warnings and precautions

Consult your doctor before starting to take Dafiro:

• if you have been ill (with vomiting or diarrhea).
• if you have liver or kidney problems.
• if you have had a kidney transplant or have been told you have narrowing of the arteries to your kidneys.
• 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 the dosage carefully. Your doctor may also check 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 increased abnormally (called «hypertrophic cardiomyopathy»).
• if you have experienced swelling, particularly in the face and throat, while taking other medicines (including ACE inhibitors). If you have these symptoms, stop taking Dafiro and contact your doctor immediately. You should never take Dafiro again.
• if you experience abdominal pain, nausea, vomiting, or diarrhea after taking Dafiro. Your doctor will decide whether to continue treatment. 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 electrolyte levels (e.g., potassium) in your blood at regular intervals.

See also the information under the heading “Do not take Dafiro”.

Tell your doctor before taking Dafiro if you are affected by any of the above.

Children and adolescents

Dafiro is not recommended for use in children and adolescents (under 18 years).

Other medicines and Dafiro

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. Your doctor may need to modify your dose and/or take other precautions. In some cases, you may need to stop taking one of the medicines. This is especially applicable to the medicines listed below:

• an ACE inhibitor or aliskiren (see also the information under the headings “Do not take Dafiro” and “Warnings and precautions”);
• diuretics (a type of medicine that increases the amount of urine);
• lithium (a medicine used to treat certain types of depression);
• potassium-sparing diuretics, potassium supplements, salt substitutes that contain potassium, and other substances that may increase potassium levels;
• a certain type of pain medicine called non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclooxygenase-2 (COX-2) inhibitors. Your doctor may also check your 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 to treat 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 (in infusion for severe body temperature abnormalities);
• medicines used to protect against rejection in a transplant (cyclosporine).

Taking Dafiro with food and drinks

People taking Dafiro should not consume grapefruit or grapefruit juice. This is because grapefruit and grapefruit juice can lead to an increase in the levels of the active substance amlodipine in the blood, which can cause an unpredictable increase in the blood pressure-lowering effect of Dafiro.

Pregnancy and breastfeeding

Pregnancy

You should inform your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant. Your doctor will normally advise you to stop taking Dafiro before you become pregnant or as soon as you find out that you are pregnant, and will recommend that you take another medicine to lower your blood pressure instead. Dafiro is not recommended during the first 3 months of pregnancy and should not be used from the third month of pregnancy onwards as it may cause harm to your baby.

Breastfeeding

Inform your doctor if you are about to start or are already breastfeeding. It has been shown that amlodipine passes into breast milk in small amounts. Dafiro is not recommended for mothers who are breastfeeding, especially if they are breastfeeding newborn babies or premature infants. Your doctor may decide to give you a different treatment that is more suitable if you want to breastfeed, especially for newborn or premature babies.

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

This medicine may make you feel dizzy. This may affect your ability to concentrate. If you are unsure how this medicine will affect you, do not drive, use machines, or perform other activities that require concentration.

3. How to take Dafiro

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are unsure, consult your doctor again. This will help you get the best results and reduce the risk of side effects.

The normal dose of Dafiro is one tablet per day.

• It is preferable to take the medicine at the same time each day.
• Swallow the tablets with a glass of water.
• You can take Dafiro with or without food. Do not take Dafiro with grapefruit or grapefruit juice.

Depending on your response to the treatment, your doctor may suggest a higher or lower dose.

Do not exceed the prescribed dose.

Dafiro and elderly patients (65 years or older)

Your doctor should exercise caution when increasing your dose.

If you have any further questions on the use of this medicine, ask 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 can accumulate in the lungs (pulmonary edema) causing difficulty breathing that can develop up to 24-48 hours after ingestion.

If you forget to take Dafiro

If you forget to take this medicine, 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 forgotten doses.

If you stop taking Dafiro

Stopping your treatment with Dafiro may cause your condition to worsen. Do not stop taking your medicine unless your doctor tells you to.

4. Possible side effects

Like all medicines, Dafiro can cause side effects, although not everybody gets them.

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

A few patients have experienced these serious side effects.If you notice any of the following, tell your doctor immediately:

Rare(may affect up to 1 in 1,000patients): Allergic reaction with symptoms such as skin rash, itching, swelling of the face, lips, or tongue, difficulty breathing, low blood pressure (feeling of fainting, dizziness).

Very rare (may affect up to 1 in 10,000patients):Intestinal angioedema: swelling in the intestine that occurs with symptoms such as abdominal pain, nausea, vomiting, and diarrhea.

Other possible side effects of Dafiro:

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

Uncommon(may affect up to 1 in 100patients): Dizziness; nausea and abdominal pain; dry mouth; drowsiness, tingling, or numbness of 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(may affect up to 1 in 1,000patients): Feeling anxious; ringing in the ears (tinnitus); fainting; increased urination or urgent need to urinate; inability to get or maintain an erection; feeling heavy; low blood pressure with symptoms such as dizziness, lightheadedness; excessive sweating; skin rash all over the body, itching, muscle spasms.

Tell your doctor if you are severely affected by any of the above.

Side effects reported with amlodipine or valsartan alone and not observed with Dafiro or observed with a higher frequency than with Dafiro:

Amlodipine

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

• Sudden wheezing, chest pain, shortness of breath, or difficulty breathing.
• Swelling of the eyelids, face, or lips.
• Swelling of the tongue and throat that causes great difficulty breathing.
• Severe skin reactions that include intense skin rash, hives, redness of the skin all over the body, severe itching, blistering, peeling, and inflammation of the skin, inflammation of the 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 a feeling of being very unwell.

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

Frequent(may affect up to 1 in 10patients): Dizziness, drowsiness; palpitations (feeling your heartbeat); flushing, swelling of the ankles (edema); abdominal pain, feeling unwell (nausea).

Uncommon(may affect up to 1 in 100patients): Mood changes, anxiety, depression, drowsiness, tremor, changes in taste, fainting, loss of pain sensation; visual disturbances, impaired vision, ringing in the ears; low blood pressure; runny nose/nasal congestion caused by inflammation of the nasal mucosa (rhinitis); indigestion, vomiting (nausea); hair loss, increased sweating, itching, skin discoloration; urinary disorders, increased need to urinate at night, increased frequency of urination; inability to get an erection, discomfort or breast enlargement in men, pain, feeling unwell, muscle pain, muscle cramps; weight gain or weight loss.

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

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

Valsartán

Frequency not known(frequency cannot be estimated from the available data): Decreased number of red blood cells, fever, sore throat, or mouth ulcers due to infection; spontaneous bleeding or bruising; high potassium levels 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, purple spots; fever; itching; allergic reaction, blistering skin disease (sign of a disease called bullous dermatitis).

If you experience any of the above, consult your doctor immediately.

If you experience side effects, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. 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. Storing Dafiro

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

Do not use this medicine after the expiry date which is stated on the carton and blister.

Do not store above 30°C.

Store in the original package to protect from moisture.

Do not use Dafiro if you notice that the packaging is damaged or shows signs of tampering.

6. Packaging Contents and Additional Information

Dafiro Composition

Dafiro 5mg/80mg film-coated tablets

The active ingredients of Dafiro are amlodipine (as amlodipine besylate) and valsartan. Each tablet contains 5 mg of amlodipine and 80 mg of valsartan.

The other ingredients 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 5mg/160mg film-coated tablets

The active ingredients of Dafiro are amlodipine (as amlodipine besylate) and valsartan. Each tablet contains 5 mg of amlodipine and 160 mg of valsartan.

The other ingredients 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 10mg/160mg film-coated tablets

The active ingredients of Dafiro are amlodipine (as amlodipine besylate) and valsartan. Each tablet contains 10 mg of amlodipine and 160 mg of valsartan.

The other ingredients 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).

Product Appearance and Packaging Contents

Dafiro 5 mg/80 mg tablets are round and dark yellow in color with «NVR» on one side and «NV» on the other side. Approximate size: diameter 8.20 mm.

Dafiro 5 mg/160 mg tablets are oval and dark yellow in color with «NVR» on one side and «ECE» on the other side. Approximate size: 14.2 mm (length) x 5.7 mm (width).

Dafiro 10 mg/160 mg tablets are oval and light yellow in color with «NVR» on one side and «UIC» on the other side. Approximate size: 14.2 mm (length) x 5.7 mm (width).

Dafiro is available in packs containing 7, 14, 28, 30, 56, 90, 98 or 280 tablets and in multipacks containing 4 packs, each with 70 tablets, or 20 packs, each with 14 tablets. All packs are available with standard blisters; the packs of 56, 98 and 280 tablets are also available with perforated unit dose blisters.

Not all pack sizes may be marketed in your country.

Marketing Authorisation 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

Roonstraße 25

D-90429 Nuremberg

Germany

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:

Date of Last Revision of this Leaflet:

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu