Bivis

PACKAGE LEAFLET: INFORMATION FOR THE USER

BIVIS 20 mg/5 mg film-coated tablets, 40 mg/5 mg film-coated tablets, 40 mg/10 mg film-coated tablets

olmesartan medoxomil/amlodipine
Please read all of this leaflet carefully before 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, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Bivis is and what it is used for

Bivis contains two substances called olmesartan medoxomil and amlodipine (as amlodipine
besylate). Both are used to control hypertension.

• Olmesartan medoxomil belongs to a group of medicines known as "angiotensin II receptor antagonists". These reduce blood pressure by relaxing blood vessels.
• Amlodipine belongs to a group of substances known as "calcium antagonists". Amlodipine prevents calcium from entering the vessel wall, thereby reducing vessel constriction and lowering blood pressure.

The combined action of both substances helps counteract vascular constriction, allowing blood vessels to relax and blood pressure to decrease.
Bivis is used to treat high blood pressure (also known as "arterial hypertension") in patients whose blood pressure is not adequately controlled by olmesartan medoxomil or amlodipine alone.

2. What you should know before taking Bivis

Do not take Bivis

• if you are allergic to olmesartan medoxomil or amlodipine, or to a specific group of calcium antagonists, the dihydropyridines, or to any of the other ingredients of this medicine (listed in section 6). 1 of 9

If you think you may be allergic, speak with your doctor before taking Bivis.

• if you are more than three months pregnant (it is best to avoid taking Bivis even in the early stages of pregnancy – see section “Pregnancy and breastfeeding”).
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.
• if you have severe liver problems, if bile secretion is impaired or its outflow from the gallbladder is blocked (for example, by gallstones), or if you develop jaundice (yellowing of the skin and eyes).
• if your blood pressure is very low.
• if you suffer from inadequate blood supply to tissues, with symptoms such as low blood pressure, weak pulse, or rapid heartbeat (shock, including cardiogenic shock). Cardiogenic shock means shock due to serious heart problems.
• if blood flow from your heart is obstructed (for example, due to narrowing of the aorta (aortic stenosis)).
• if you have reduced cardiac output (causing shortness of breath or peripheral swelling) following a heart attack (acute myocardial infarction).

Warnings and precautions
Talk to your doctor or pharmacist before taking Bivis.
Consult your doctor if you are taking any of the following medicines used to treat
high blood pressure:

• an “ACE inhibitor” (for example enalapril, lisinopril, ramipril), especially if you have kidney problems related to diabetes;
• aliskiren.

Your doctor may check your kidney function, blood pressure, and
levels of electrolytes (for example potassium) in your blood at regular intervals.
See also the section “Do not take Bivis”.
Consult your doctor if you also have any of the following health conditions:

• Kidney problems or kidney transplant.
• Liver disease.
• Heart failure or problems with heart valves or heart muscle.
• Severe vomiting, diarrhoea, treatment with high doses of diuretics, or if you are on a low-salt diet.
• Elevated potassium levels in the blood.
• Problems with the adrenal glands (hormone-producing glands located above the kidneys).

Inform your doctor if you develop severe and prolonged diarrhoea accompanied by significant weight loss.
Your doctor will evaluate your symptoms and decide whether to continue this
antihypertensive treatment.
Contact your doctor if, after taking Bivis, you experience abdominal pain, nausea, vomiting, or
diarrhoea. The doctor will decide whether treatment should continue. Do not stop
taking Bivis on your own initiative.
As with any medicine that lowers blood pressure, excessive reduction
of blood pressure in patients with circulatory disorders of the heart or brain could lead to
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a heart attack or stroke. Your doctor will therefore carefully monitor your
blood pressure.
You must inform your doctor if you think you may be pregnant (or if there is a possibility of
becoming pregnant). Bivis is not recommended during early pregnancy and must not
be taken if you are more than three months pregnant, as it may cause serious harm to the unborn child if taken during this period (see section “Pregnancy and
breastfeeding”).
Children and adolescents
Bivis is not recommended for children and adolescents under 18 years of age.
Other medicines and Bivis
Inform your doctor or pharmacist if you are taking, have recently taken, or might
take any other medicines, including any of the following:

• Other medicines that lower blood pressure may increase the effect of Bivis. Your doctor may consider it necessary to adjust the dose and/or take other precautions. If you are taking an ACE inhibitor or aliskiren (see also the sections: "Do not take Bivis" and "Warnings and precautions").
• Potassium supplements, potassium-containing salt substitutes, diuretics, or heparin (used to thin the blood and prevent thrombosis). Taking these medicines together with Bivis may increase potassium levels in the blood.
• Lithium (a medicine used to treat mood swings and certain types of depression) used together with Bivis may increase lithium toxicity. If you need to take lithium, your doctor will monitor your blood lithium levels.
• Non-steroidal anti-inflammatory drugs (NSAIDs, medicines used to reduce pain, swelling, and other symptoms of inflammation, including arthritis) used together with Bivis may increase the risk of kidney failure. The effect of Bivis may be reduced by NSAIDs.
• Colesevelam hydrochloride, a medicine that reduces cholesterol levels in the blood, which may reduce the effect of Bivis. Your doctor may advise you to take Bivis at least 4 hours before colesevelam hydrochloride.
• Some antacids (used for indigestion or stomach acidity) may slightly reduce the effect of Bivis.
• Medicines for HIV/AIDS (for example ritonavir, indinavir, nelfinavir) or for treating fungal infections (for example ketoconazole, itraconazole).
• Diltiazem, verapamil, medicines used for heart rhythm problems and high blood pressure.
• Rifampicin, erythromycin, clarithromycin (antibiotics), medicines used for tuberculosis or other infections.
• St. John’s wort (Hypericum perforatum), a herbal remedy.
• Dantrolene (infusion for severe disturbances in body temperature).
• Simvastatin, a substance used to reduce cholesterol and fat (triglyceride) levels in the blood.
• Tacrolimus, sirolimus, temsirolimus, everolimus, and cyclosporine, used to control your body’s immune response and thus allow your body to accept transplanted organs.

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Inform your doctor or pharmacist if you are taking, have recently taken, or might
take any other medicines.
Bivis with food and drinks
Bivis can be taken with or without food. The tablet should be swallowed with some liquid (such as a glass of water). If possible, take your daily dose at the same time each day, for example with breakfast.
People taking Bivis must not consume grapefruit or grapefruit juice, as grapefruit and its juice may increase blood levels of the active ingredient amlodipine, which could lead to an unpredictable increase in the hypotensive effect of Bivis.
Elderly
If you are over 65 years old, your doctor will regularly monitor your blood pressure with each dose increase, to avoid excessive lowering.
Black patients
As with other similar medicines, the blood pressure-lowering effect of Bivis may be somewhat reduced in black patients.
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). Usually, your doctor will advise you to stop taking Bivis before becoming pregnant or as soon as you find out you are pregnant, and will recommend another medicine instead of Bivis.
Bivis is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to the unborn child if taken after the third month of pregnancy.
If you become pregnant while taking Bivis, inform your doctor and seek medical advice immediately.
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. Bivis is not recommended for women who are breastfeeding, and your doctor may choose another treatment if you wish to breastfeed, especially if the baby is a newborn or was born prematurely.
If you are pregnant, think you may be pregnant, plan to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Driving and using machines
You may experience drowsiness, discomfort, dizziness, or headache during treatment for high blood pressure. If this occurs, do not drive or operate machinery until symptoms resolve. Consult your doctor.
This medicine contains less than 1 mmol of sodium (23 mg) per film-coated tablet, i.e. it is essentially sodium-free.

3. How to take Bivis

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Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

• The recommended dose of Bivis is one tablet daily.
• The tablets can be taken with or without food. Swallow the tablets with some liquid (such as a glass of water). Do not chew the tablets. Do not take with grapefruit juice.
• If possible, take your daily dose at the same time each day, for example with breakfast.

If you take more Bivis than you should
If you take more tablets than you should, you may experience a drop in blood pressure with symptoms such as dizziness, increased or decreased heart rate.
If you take more tablets than prescribed or if a child accidentally swallows any, go immediately to your doctor or nearest emergency department, taking the medicine pack or this leaflet with you.
Excess fluid may accumulate in the lungs (pulmonary edema), causing shortness of breath, which may develop up to 24–48 hours after ingestion.

If you forget to take Bivis
If you forget to take a dose, take your usual dose the next day. Do not take a double dose to make up for the missed dose.

If you stop taking Bivis
It is important to continue taking Bivis unless your doctor tells you to stop.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them. If they do occur, they are mostly mild and do not require discontinuation of treatment.

Although not occurring in all individuals, the following side effects may be serious:

During treatment with Bivis, allergic reactions may occur, which can affect the whole body, with swelling of the face, mouth and/or larynx (site of the vocal cords), associated with itching and skin rash. If this happens, stop taking Bivis and contact your doctor immediately.

Bivis may cause excessive lowering of blood pressure in sensitive individuals or as a consequence of an allergic reaction. This could lead to severe dizziness or fainting. If this happens, stop taking Bivis, contact your doctor immediately and remain lying down.

Frequency not known: If you experience yellowing of the whites of the eyes, dark urine, or skin itching, even if you have been on Bivis therapy for a long time, contact your doctor immediately. Your doctor will assess your symptoms and decide how to proceed with treatment for high blood pressure.

Other possible side effects of Bivis:

Common (may affect up to 1 in 10 people):
Dizziness; headache; swelling of ankles, feet, legs, hands or arms; fatigue.

Uncommon (may affect up to 1 in 100 people):
Dizziness upon standing; lack of energy; tingling or numbness in hands or feet; vertigo; awareness of heartbeat; faster heartbeat; low blood pressure with symptoms such as dizziness, feeling of emptiness in the head, difficulty breathing; cough; nausea; vomiting; indigestion; diarrhoea; constipation; dry mouth; upper abdominal pain; skin rash; cramps; pain in arms and legs; back pain; feeling of urgency to urinate; loss of sexual interest; inability to achieve or maintain erection; weakness.

Some blood test abnormalities have also been observed, including the following:
Increased or decreased potassium in the blood, increased creatinine in the blood, increased uric acid in the blood, increased liver function tests (levels of gamma-glutamyl transferase).

Rare (may affect up to 1 in 1,000 people):
Hypersensitivity to the medicine; fainting; flushing and sensation of warmth in the face; red, itchy welts (urticaria); facial swelling.

Side effects reported with olmesartan medoxomil or amlodipine used alone, but not with Bivis or with higher frequency:

Olmesartan medoxomil

Common (may affect up to 1 in 10 people):
Bronchitis; sore throat; stuffy or runny nose; cough; abdominal pain; gastrointestinal flu; diarrhoea; indigestion; nausea; bone or joint pain; back pain; blood in urine; urinary tract infection; chest pain; flu-like symptoms; pain. Laboratory test abnormalities such as increased fats (hypertriglyceridaemia); increased plasma urea or uric acid; increased liver and muscle function test values.

Uncommon (may affect up to 1 in 100 people):
Reduced number of a type of blood cell called platelets, which may lead to easier bruising or prolonged bleeding time; immediate allergic reactions affecting the whole body, which may cause breathing difficulties or rapid drop in blood pressure, possibly leading to weakness (anaphylactic reactions); angina (chest pain or discomfort, known as angina pectoris); itching; skin rash; allergic skin rash; skin rash with urticaria, facial swelling; muscle pain; feeling of malaise.

Rare (may affect up to 1 in 1,000 people):
Swelling of the face, mouth and/or larynx (site of the vocal cords); acute renal failure and kidney failure; lethargy; intestinal angioedema: intestinal swelling presenting with symptoms such as abdominal pain, nausea, vomiting and diarrhoea.

Amlodipine

Very common (may affect more than 1 in 10 people):
Oedema (fluid retention)

Common (may affect up to 1 in 10 people):
Abdominal pain; nausea; swollen ankles; drowsiness; flushing and sensation of warmth in the face; visual disturbances (including double vision and blurred vision); awareness of heartbeat; diarrhoea; constipation; indigestion; cramps; weakness; shortness of breath.

Uncommon (may affect up to 1 in 100 people):
Restless sleep; sleep disorders; mood disturbances including anxiety; depression; irritability; tremors; taste disturbances; fainting; ringing in the ears (tinnitus); worsening of angina pectoris (chest pain or discomfort); irregular heartbeat; stuffy or runny nose; hair loss; red spots or patches on the skin due to minor bleeding (purpura); skin discoloration; excessive sweating; skin rash; itching; red, itchy welts (urticaria); muscle or joint pain; urinary problems; need to urinate at night; increased need to urinate; breast enlargement in men; chest pain; pain, discomfort; 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):
Reduction in the number of white blood cells in the blood, which may increase the risk of infections; reduction in the number of a type of blood cell called platelets, which may lead to easier bruising or prolonged bleeding time; increased blood glucose; increased muscle stiffness or increased resistance to passive movement (hypertonia); tingling or numbness in hands or feet; heart attack; inflammation of blood vessels; inflammation of the liver or pancreas; inflammation of the stomach wall; gum enlargement; elevated liver enzymes; yellowing of the skin and eyes; increased skin sensitivity to light; allergic reactions: itching, skin rash, swelling of the face, mouth and/or larynx (site of the vocal cords) together with itching and skin rash; severe skin reactions including severe rash, urticaria, redness of the skin over the entire body surface, severe itching, blisters, peeling and swelling of the skin, inflammation of mucous membranes (Stevens-Johnson syndrome, toxic epidermal necrolysis), sometimes life-threatening.

Not known (frequency cannot be estimated from available data):
Tremor, rigid posture, mask-like facial expression, slow movements and unbalanced, shuffling gait.

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 the following website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Bivis

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after “Exp.”.
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist
how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Bivis contains
The active substances are olmesartan medoxomil and amlodipine (as besylate).
Each film-coated tablet contains 20 mg of olmesartan medoxomil and 5 mg of
amlodipine (as besylate).
Each film-coated tablet contains 40 mg of olmesartan medoxomil and 5 mg of
amlodipine (as besylate).
Each film-coated tablet contains 40 mg of olmesartan medoxomil and 10 mg of
amlodipine (as besylate).
The other components are
Tablet core: pregelatinized maize starch, microcrystalline cellulose, anhydrous colloidal silica, sodium croscarmellose, magnesium stearate.
Coating: polyvinyl alcohol, macrogol 3350, talc, titanium dioxide (E171), yellow iron (III) oxide (E172) (only in Bivis 40 mg/5 mg film-coated tablets and Bivis 40 mg/10 mg film-coated tablets), and red iron (III) oxide (E172) (only in Bivis 40 mg/10 mg film-coated tablets).

Description of the appearance of Bivis and contents of the pack
Bivis 20 mg/5 mg, film-coated tablets, round, white, with the code C73 engraved on one side;
Bivis 40 mg/5 mg, film-coated tablets, round, cream-coloured, with the code C75 engraved on one side;
Bivis 40 mg/10 mg, film-coated tablets, round, brownish, with the code C77 engraved on one side.
Bivis is available in packs of 14, 28, 30, 56, 90, 98, 10x28 and 10x30 film-coated tablets in OPA/Aluminium/PVC/Aluminium blisters, and in packs of 10x1, 50x1 and 500x1 film-coated tablets with unit-dose divisible blisters.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
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Marketing Authorization Holder
Menarini International Operations Luxembourg S.A. - 1, Avenue de la Gare, L-1611
Luxembourg.
Concessionaire for sales: Laboratori Guidotti S.p.A., Via Livornese 897, La Vettola - Pisa
Manufacturer
Daiichi Sankyo Europe GmbH
Luitpoldstrasse 1
85276 Pfaffenhofen (Germany)
Berlin-Chemie AG
Glienicker Weg 125
12489 Berlin (Germany)
Laboratorios Menarini, S.A.
Alfons XII, 587
08918 Badalona (Barcelona),
Spain
Fine Foods & Pharmaceuticals NTM S.p.A.
Via Grignano, 43
24041 - Brembate (BG), Italy

This medicinal product is authorized in the Member States of the European Economic Area
under the following names:
Netherlands (RMS): Belfor 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Austria: Amelior 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Belgium: Forzaten 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Bulgaria: Tespadan 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Cyprus: Orizal 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Estonia: Sanoral 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
France: Axeler 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Germany: Vocado 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Greece: Orizal 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Ireland: Konverge 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Italy: Bivis 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Latvia: Sanoral 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Lithuania: Sanoral 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Luxembourg: Forzaten 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Malta: Konverge 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Poland: Elestar 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Portugal: Zolnor 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Czech Republic: Sintonyn 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Romania: Inovum 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Slovakia: Folgan 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Slovenia: Olectan 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Spain: Balzak 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
Hungary: Duactan 20 mg/5 mg, 40 mg/5 mg, 40 mg/10 mg
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