Package leaflet: Information for the user

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

amlodipine/valsartan
Generic medicine
Please read all of this leaflet carefully before you start taking this medicine, because 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, because it may be harmful.
If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

What Avior is and what it is used for
What you need to know before taking Avior
How to take Avior
Possible side effects
How to store Avior
Contents of the pack and other information

1. What Avior is and what it is used for

Avior tablets contain two active 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, thereby preventing the narrowing of the 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, thus 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. Avior is used to treat high blood pressure in adults whose blood pressure is not adequately controlled with amlodipine or valsartan alone.

2. What you should know before taking Avior

Do not take Avior

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 are allergic, consult your doctor or pharmacist before taking Avior.
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 Avior 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 enough 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 applies to you, do not take Avior and consult your doctor.

Warnings and precautions
Consult your doctor before taking Avior:

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 previously had heart failure or a heart attack. Follow your doctor’s instructions carefully regarding the initial dosage. 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 Avior immediately and contact your doctor right away. You must never take Avior again.
if you have kidney problems involving reduced blood flow to the kidneys (renal artery stenosis).
if you are taking any of the following medicines used to treat high blood pressure:
an angiotensin-converting enzyme (ACE) inhibitor (e.g. enalapril, lisinopril, ramipril), especially if you have kidney problems related to diabetes;
aliskiren.

Your doctor may periodically check your kidney function, blood pressure, and levels of electrolytes (such as potassium) in your blood.
See also the information under the section “Do not take Avior”.
If any of these conditions apply to you, inform your doctor before taking Avior.
Children and adolescents
The use of Avior in children and adolescents (under 18 years of age) is not recommended.
Other medicines and Avior
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Your doctor may consider it necessary to adjust the dose and/or take other 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 information under “Do not take Avior” and “Warnings and precautions”);
diuretics (a type of medicine also known as “water tablets” that increase 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);
medicines used to prevent transplant rejection (cyclosporine).

Avior with food and drink
Grapefruit and grapefruit juice must not be consumed by people taking Avior. This is because grapefruit and grapefruit juice can increase blood levels of the active substance amlodipine, which may cause an unpredictable increase in the blood pressure-lowering effect of Avior.
Pregnancy and breastfeeding
Pregnancy
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 Avior before becoming pregnant or as soon as pregnancy is confirmed, and will recommend an alternative medicine instead of Avior. Avior is not recommended during early pregnancy (first 3 months) and must not be taken after 3 months of pregnancy, as it may cause serious harm to the unborn child if taken beyond 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. Avior is not recommended for women who are breastfeeding, and your doctor may choose an alternative treatment 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 activity requiring concentration.

3. How to take Avior

Take this medicine exactly as prescribed 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 Avior is one tablet daily.

It is preferable to take the medicine at the same time every day.
Swallow the tablets with a glass of water.
Avior can be taken with or without food. Do not take Avior with grapefruit or grapefruit juice. Depending on your response to treatment, your doctor may recommend a lower or higher dosage.

Do not take more than the prescribed dose.
Avior and elderly patients (65 years and older)
Your doctor should exercise caution when increasing the dose.
If you have any doubts about how to use this medicine, speak to your doctor or pharmacist.
If you take more Avior than you should
If you have taken too many Avior tablets or if someone else has taken your tablets, contact your doctor immediately.
If you forget to take Avior
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, skip the missed dose. Do not take a double dose to make up for a forgotten tablet.
If you stop taking Avior
Stopping treatment with Avior 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 everybody gets them.
Some side effects can be serious and require immediate medical attention:
A small number of patients have experienced these life-threatening side effects (may affect up to 1
in 1,000 people). If you notice any of the following side effects, contact your doctor immediately:
allergic reactions with symptoms such as rash, itching, swelling of the face, lips or tongue, difficulty breathing, low blood pressure (feeling of weakness, sensation of emptiness in the head).

Other possible side effects of Avior:
Common (may affect up to 1 in 10 people): Influenza; nasal congestion, sore throat and discomfort during swallowing, headache; swelling of arms, hands, legs, ankles or feet; fatigue; asthenia (weakness); flushing and/or sensation 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 hands or feet; vertigo; increased heart rate, including palpitations; dizziness upon standing; 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; increased amount of urine or more urgent need to urinate, inability to achieve or maintain an erection, sensation of heaviness; low blood pressure with symptoms such as dizziness, sensation of emptiness in the head; excessive sweating; rashes over the entire body; itching; muscle spasms.
If any of these effects become severe, inform your doctor.

Side effects reported with amlodipine or valsartan alone, not observed with Avior or observed with higher frequency than with Avior:

Amlodipine
If you notice any of the following very rare and serious side effects, consult your doctor immediately:
Sudden onset of wheezing, chest pain, shortness of breath 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 skin redness, severe itching, blisters, peeling and swelling of the skin, inflammation of mucous membranes (Stevens-Johnson syndrome, toxic epidermal necrolysis) or other allergic reactions.
Heart attack, irregular heartbeat.
Inflammation of the pancreas 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 effects, or if they persist for more than one week, contact your doctor.
Common (may affect up to 1 in 10): Dizziness; drowsiness; palpitations (awareness of heartbeat); flushing, swelling of the ankles (oedema); abdominal pain, feeling unwell (nausea).
Uncommon (may affect up to 1 in 100): Mood changes, anxiety, depression, insomnia, tremor, altered taste, 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 (feeling unwell); hair loss; increased sweating; skin itching; change in skin colour; difficulty urinating, 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): Confusion.
Very rare (may affect up to 1 in 10,000): Reduction in the number 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 clinical 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; formation of blisters on the skin (sign of a condition called bullous dermatitis).

If you experience any of these side effects, inform your doctor immediately.

Reporting of side effects
If you experience any side effect, 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 at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Avior

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". 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 this medicine if you notice that the packaging is damaged or shows signs of tampering.

6. Contents of the Pack and Other Information

What Avior Contains

The active substances in Avior are amlodipine (as amlodipine besylate) and valsartan. Each tablet contains 5 mg of amlodipine and 80 mg of valsartan.
The active substances in Avior are amlodipine (as amlodipine besylate) and valsartan. Each tablet contains 5 mg of amlodipine and 160 mg of valsartan.
The active substances in Avior are amlodipine (as amlodipine besylate) and valsartan. Each tablet contains 10 mg of amlodipine and 160 mg of valsartan.
The other components are microcrystalline cellulose (E460), povidone (E1201), sodium croscarmellose (E468), talc (E553b), magnesium stearate (E570), hypromellose (E464), macrogol (E1521), titanium dioxide (E171); [ film-coated tablets 5 mg/80 mg and 5 mg/160 mg only]: iron oxide, yellow (E172).

Description of the Appearance of Avior and Contents of the Pack
Avior 5 mg/80 mg tablets are 8 mm, round, biconvex, and yellow, with "I" engraved on one side and "LD" on the other.
Avior 5 mg/160 mg tablets are 13.5 mm long and 7 mm wide, oval, biconvex, and yellow, with "2" engraved on one side and "LD" on the other.
Avior 10 mg/160 mg tablets are 13.5 mm long and 7 mm wide, oval, biconvex, and white, with "3" engraved on one side and "LD" on the other.
Pack sizes: 28 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Dymalife Pharmaceutical S.r.l.,
Via Bagnulo, 95,
Piano di Sorrento (Napoli),
80063, Italy

Manufacturer
Balkanpharma Dupnitza AD
3 Samokovsko Shosse Str.,
Dupnitsa
2600, Bulgaria