Nesyrgy

Patient Information Leaflet

Nesyrgy, 5 mg + 5 mg, film-coated tablets
Nesyrgy, 5 mg + 10 mg, film-coated tablets
Nebivololum + Amlodipinum
Please read 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 further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet Contents

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

1. What Nesyrgy is and what it is used for

Nesyrgy contains two active substances called nebivolol and amlodipine. Both of these substances help lower high blood pressure.

• Nebivolol is a cardiovascular medicine belonging to a group of drugs known as selective beta-blockers. It prevents the heart from beating too fast and controls the force of the heart's contractions. It also widens blood vessels, which helps lower blood pressure.
• Amlodipine belongs to a group of medicines called calcium channel blockers. Amlodipine inhibits the influx of calcium into the walls of blood vessels, preventing their constriction and thereby lowering blood pressure.

Nesyrgy is used to treat high blood pressure in adult patients who have previously been treated with nebivolol and amlodipine as separate tablets at the same dose.

2. Important information before using Nesyrgy

When not to use Nesyrgy

• if the patient is allergic to nebivolol, amlodipine, or any calcium antagonist of the dihydropyridine group, or to any of the other ingredients of this medicine (listed in section 6).
• if the patient has liver disorders
• if the patient has heart failure which has recently developed or worsened, or if the patient is receiving intravenous therapy to support heart function due to cardiogenic shock in acute heart failure
• if the patient has certain severe heart rhythm disorders (e.g. second- or third-degree atrioventricular block, cardiac conduction disorders)
• if the patient has asthma or wheezing (currently or in the past)
• if the patient has untreated phaeochromocytoma: a tumour located in the adrenal glands on top of the kidneys
• if the patient has metabolic disorders (metabolic acidosis)
• if the patient has a very slow heart rate (less than 60 beats per minute)
• if the patient has low or very low blood pressure
• if the patient has severe circulatory disorders in the upper or lower limbs
• if the patient has aortic valve stenosis or cardiogenic shock (a condition in which the heart is unable to deliver sufficient blood to the body)
• if the patient suffers from heart failure following a heart attack.

Do not take Nesyrgy if any of the above conditions apply.
If in doubt, discuss this with your doctor before starting treatment with Nesyrgy.
Warnings and precautions
Before starting treatment with Nesyrgy, discuss it with your doctor or pharmacist.
Tell your doctor if the patient has:

• abnormally slow heart rate
• chest pain caused by spontaneous coronary artery spasm (Prinzmetal's angina)
• untreated chronic heart failure
• first-degree heart block (a mild conduction disorder affecting heart rhythm)
• circulatory disorders in the hands or feet, e.g. Raynaud’s disease or syndrome, cramping pain while walking
• persistent breathing difficulties
• diabetes: this medicine does not affect blood sugar levels, but may mask warning signs of low blood sugar (e.g. palpitations, rapid heartbeat), and may increase the risk of severe hypoglycaemia when used together with certain types of antidiabetic medicines called sulfonylureas (such as gliclazide, glimepiride, glipizide, glyburide, tolbutamide, or repaglinide)
• hyperthyroidism: this medicine may mask symptoms of abnormally rapid heartbeat associated with this condition
• allergies: this medicine may worsen reactions to pollen or other substances to which the patient is allergic
• psoriasis (a skin disease characterised by scaly, red patches) or a history of psoriasis
• planned surgery – always inform the anaesthetist that the patient is taking Nesyrgy before receiving anaesthesia
• recent heart attack
• recent heart failure or disorders affecting heart valves or heart muscle
• significant increase in blood pressure (hypertensive crisis)

As with other medicines that lower blood pressure, excessive reduction of blood pressure in patients with circulatory disorders of the heart or brain may lead to heart attack or stroke. Your doctor will recommend careful monitoring of blood pressure in such patients.
See also the information under the heading “When not to use Nesyrgy”.
Children and adolescents
Nesyrgy is not recommended for children and adolescents under 18 years of age due to lack of data on use in this age group.
Nesyrgy and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
In particular, inform your doctor if the patient is taking:

• Other blood pressure-lowering medicines – may enhance the effect of Nesyrgy.
• Amiodarone, cibenzoline, clonidine, digoxin, diltiazem, disopyramide, felodipine, flecainide, guanfacine, hydroquinidine, lacidipine, lidocaine, methyldopa, mexiletine,

moxonidine, nicardipine, nifedipine, nimodipine, nitrendipine, propafenone, quinidine,
rilmenidine, verapamil – medicines that lower blood pressure or are used to treat heart disorders.

• Barbiturates (a group of medicines used as sedatives and antipsychotics, but also in epilepsy, anxiety, insomnia, and convulsive disorders), as the effect of Nesyrgy may be enhanced.
• Phenothiazines (a group of medicines used as sedatives and antipsychotics, but also for nausea and vomiting), as the effect of Nesyrgy may be enhanced.
• Thioridazine (a group of medicines used as sedatives and antipsychotics), as the effect of Nesyrgy may be enhanced.
• Amitriptyline, fluoxetine, paroxetine – antidepressant medicines, as the effect of Nesyrgy may be enhanced.
• Medicines used for anaesthesia during surgery.
• Medicines used for asthma, nasal congestion, or certain eye conditions such as glaucoma (increased eye pressure) or to dilate the pupil.
• Baclofen (a muscle relaxant); amifostine (a protective agent used during cancer treatment).
• Medicines used in diabetes, such as insulin or oral antidiabetic medicines; Nesyrgy does not affect blood sugar levels, but may mask warning signs of low blood sugar (e.g. palpitations, rapid heartbeat). However, concomitant use of Nesyrgy with sulfonylurea medicines may increase the risk of severe hypoglycaemia (see also information in the section “Warnings and precautions”).
• Medicines used for acid-related disorders and peptic ulcer disease (medicines that reduce gastric acid secretion): Nesyrgy should be taken with food, and antacids should be taken between meals.
• Ketoconazole, itraconazole (antifungal medicines)
• Ritonavir, indinavir, nelfinavir (so-called protease inhibitors used in the treatment of HIV infection)
• Rifampicin, erythromycin, clarithromycin (antibiotics)
• St John's wort (Hypericum perforatum)
• Dantrolene (administered intravenously in severe disturbances of body temperature)
• Tacrolimus, sirolimus, temsirolimus, everolimus (medicines used to modify the immune system response)
• Simvastatin (a medicine used to reduce cholesterol levels)
• Cyclosporine (an immunosuppressant, a medicine that suppresses immune system function)

Taking Nesyrgy with food, drink, and alcohol
Nesyrgy can be taken with or without food.
Patients taking Nesyrgy should not consume grapefruit juice or grapefruits, as they may increase the blood concentration of the active substance – amlodipine, which could lead to unpredictable and enhanced blood pressure-lowering effects of Nesyrgy.
Exercise caution when drinking alcohol while taking Nesyrgy, as fainting or dizziness may occur. In such cases, alcohol, including wine, beer, and alcoholic carbonated beverages, should not be consumed.
Pregnancy and breastfeeding
Pregnancy
As adequate clinical data in pregnant women are not available, Nesyrgy is not recommended during pregnancy. Nesyrgy may be considered only if no safer alternatives are available and after careful individual assessment of risk versus benefit by the doctor. Therefore, if the patient is pregnant, suspects she may be pregnant, or is planning to become pregnant, she should inform her doctor. Medical advice should be sought before using this medicine.
If used during pregnancy, careful monitoring of the foetus and newborn may be necessary.
Breastfeeding
If the patient is breastfeeding or planning to breastfeed, seek medical advice before using this medicine. Nesyrgy is not recommended for breastfeeding mothers, and the doctor may recommend an alternative medicine if the patient wishes to breastfeed.
Driving and operating machinery
Nesyrgy may affect the ability to drive and operate machinery. If nausea, dizziness, fatigue, or headache occur during treatment, do not drive or operate machinery. Seek medical advice immediately.
This medicine contains less than 1 mmol (23 mg) of sodium per coated tablet, i.e. this medicine is considered “sodium-free”.

3. How to use Nesyrgy

This medicine should always be used as directed by a physician. In case of doubt, consult a doctor or pharmacist.
The recommended dose is one tablet per day, preferably taken at the same time each day.
Nesyrgy may be taken before, during, or after a meal, or independently of meals.
It is best to take the tablet with an adequate amount of water, without chewing it. Do not take Nesyrgy with grapefruit juice.
The break line on the tablet is intended only to facilitate splitting the tablet to make swallowing easier.

Use of a higher than recommended dose of Nesyrgy
In case of accidental overdose, inform your doctor or pharmacist immediately.
The most common subjective and objective symptoms of overdose include: low blood pressure that may lead to fainting (hypotension) possibly accompanied by increased heart rate (reflex tachycardia), very slow heart rate (bradycardia), breathlessness similar to that occurring in bronchial asthma (bronchospasm), acute heart failure.
Breathlessness caused by excess fluid accumulating in the lungs (pulmonary edema) may occur even 24–48 hours after taking the medicine.

Missed dose of Nesyrgy
If a dose of Nesyrgy is missed but remembered shortly afterwards, the missed dose should be taken as soon as possible on the same day. However, if a significant delay has occurred (e.g. several hours) and it is nearly time for the next scheduled dose, the missed dose should be skipped and the next dose taken at the usual time. Do not take a double dose to make up for a missed dose. Avoid repeatedly missing doses of this medicine.

Discontinuation of Nesyrgy
Before stopping the use of Nesyrgy, always consult your doctor.
If you have any further doubts regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
You should consult a doctor immediately if any of the following adverse effects occur 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 or throat, causing severe breathing difficulties
• Severe skin reactions, including severe skin rash, urticaria, redness of the entire body's skin, intense itching, blistering, peeling and swelling of the skin, mucosal inflammation (Stevens-Johnson syndrome, toxic epidermal necrolysis) or other allergic reactions
• Heart attack, abnormal heart function
• Pancreatitis, which may cause severe abdominal and back pain accompanied by a very poor general condition.

The following other adverse effects have been reported. You should contact your doctor if any of the following adverse effects cause a problem.
Other possible adverse effects of Nesyrgy:
Very common (may occur in more than 1 in 10 people):

• Swelling of hands or feet (oedema)

Common (may occur in less than 1 in 10 people):

• Fatigue
• Abdominal pain, nausea
• Dizziness
• Headache
• Drowsiness
• Sensation of burning, crawling, tingling, itching, numbness or pricking
• Palpitations
• Hot flushes
• Changes in bowel habits (including diarrhoea and constipation)
• Indigestion
• Ankle swelling
• Muscle cramps
• Weakness
• Visual disturbances, double vision

Uncommon (may occur in less than 1 in 100 people):

• Slow heart rate or other heart-related disorders
• Low blood pressure
• Cramping leg pain during walking
• Depressive disorders
• Vomiting
• Asthma-like breathlessness caused by sudden contraction of respiratory muscles (bronchospasm)
• Nightmares
• Insomnia
• Mood changes (including anxiety states)
• Taste disturbances
• Sensation of numbness or tingling in limbs; loss of pain sensation
• Fainting
• Tremor
• Tinnitus
• Arrhythmia (including ventricular tachycardia and atrial fibrillation)
• Heart failure
• Cough
• Sneezing/rhinitis due to inflammation of the nasal mucosa
• Dryness of the oral mucosa
• Flatulence
• Hair loss
• Excessive sweating
• Itchy skin, red skin patches, skin discoloration
• Joint or muscle pain
• Back pain
• Inability to achieve or maintain erection
• Discomfort or enlargement of breasts in males
• Discomfort during urination; increased need to urinate at night; increased frequency of urination
• Pain, malaise
• Increase or decrease in body weight

Rare (may occur in less than 1 in 1,000 people):

• Disorientation

Very rare (may occur in less than 1 in 10,000 people):

• Decreased white blood cell count, decreased platelet count, which may result in unusual bruising or prolonged bleeding
• Worsening of psoriasis (a skin disease – scaly pink patches)
• Increased blood glucose levels (hyperglycaemia)
• Increased muscle tone
• Nerve disorders, which may cause muscle weakness, tingling or numbness
• Vasculitis (often with skin rash)
• Abdominal bloating (gastric mucosal inflammation)
• Gum swelling
• Liver dysfunction, hepatitis, yellowing of the skin (jaundice), increased liver enzyme activity, which may affect certain medical tests
• Photosensitivity

Frequency not known (cannot be estimated from available data):

• Tremor, rigidity, mask-like facial expression, slowed movements, shuffling gait, unsteady walk.

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, you should inform your doctor or pharmacist.
Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store Nesyrgy

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 the stated month.
There are no special storage instructions for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Nesyrgy contains

• The active substances in this medicine are nebivolol (as nebivolol hydrochloride) and amlodipine (as amlodipine besylate). Nesyrgy, 5 mg + 5 mg: each film-coated tablet contains 5 mg nebivolol (as nebivolol hydrochloride: 2.5 mg d-nebivolol and 2.5 mg l-nebivolol) and 5 mg amlodipine (as amlodipine besylate). Nesyrgy, 5 mg + 10 mg: each film-coated tablet contains 5 mg nebivolol (as nebivolol hydrochloride: 2.5 mg d-nebivolol and 2.5 mg l-nebivolol) and 10 mg amlodipine (as amlodipine besylate).
• Other ingredients are: Tablet core: microcrystalline cellulose, sodium croscarmellose, maize starch, hypromellose, polysorbate 80, colloidal anhydrous silica, magnesium stearate. Tablet coating: Nesyrgy, 5 mg + 5 mg: OPADRY 02B220019 Yellow (consisting of: hypromellose, titanium dioxide, polyethylene glycol 400, yellow iron oxide (E 172)); Nesyrgy, 5 mg + 10 mg: OPADRY Y-1-7000 White (consisting of: hypromellose, titanium dioxide, polyethylene glycol 400).

What Nesyrgy looks like and contents of the pack
Nesyrgy 5 mg + 5 mg film-coated tablets are yellow, oval-shaped.
Nesyrgy 5 mg + 10 mg film-coated tablets are white, oval-shaped, with a breakline on one side.
Nesyrgy is available in PVC/PVDC/Aluminium or OPA/Aluminium/PVC/Aluminium blister packs, also referred to as Al/Al blisters, in pack sizes containing 14, 28, 30, 56, 84, or 90 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Menarini International Operations Luxembourg S.A.
1 Avenue de la Gare
L-1611 Luxembourg
Luxembourg

Manufacturer:
Saneca Pharmaceuticals, a.s.
Nitrianska 100
920 27 Hlohovec
Slovakia

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Berlin-Chemie/Menarini Polska Sp. z o.o.
Tel.: + 48 22 566 21 00
Fax: + 48 22 566 21 01

This medicine is authorised for marketing in the European Economic Area under the following names:
Estonia, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, France, Greece, Hungary, Italy, Latvia, Luxembourg, Poland, Romania, Slovenia, Slovakia, Spain: Nesyrgy
Austria, Ireland, Portugal: Nebkliq
Lithuania: Kliqqo