Nebkliq

Patient Information Leaflet

Nebkliq 5 mg/5 mg film-coated tablets, 5 mg/10 mg film-coated tablets

nebivolol/amlodipine
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, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What is Nebkliq and what is it used for

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

• Nebivolol is a cardiovascular medicine belonging to the group of "selective beta-blockers" (i.e. acting selectively on the cardiovascular system). It prevents the increase in heart rate and controls the heart's pumping force. It also has a vasodilatory effect on blood vessels, thereby helping to lower blood pressure.
• Amlodipine belongs to a group of substances called "calcium antagonists". Amlodipine prevents calcium from entering the walls of blood vessels, thereby preventing their constriction and reducing blood pressure.

NEBKLIQ is used to treat high blood pressure in adult patients who are already receiving
the same doses of nebivolol and amlodipine as separate tablets.

2. What you need to know before taking Nebkliq

Do not take Nebkliq if:

• you are allergic to nebivolol, amlodipine, or to a specific group of calcium antagonists called dihydropyridines, or to any of the other ingredients of this medicine (listed in section 6);
• you have liver problems;
• you have newly developed or recently worsened heart failure, or if you are receiving intravenous infusion treatment for circulatory shock due to acute heart failure to help support heart function;
• you have certain other serious heart rhythm disorders (e.g. second- or third-degree atrioventricular block, cardiac conduction disorders);
• you have asthma or wheezing (currently or in the past);
• you have untreated phaeochromocytoma, a tumour of the adrenal glands located above the kidneys;
• you have a metabolic disorder (metabolic acidosis);
• you have a very slow heart rate (less than 60 beats per minute);
• you have low or very low blood pressure;
• you have severe circulatory problems in the arms or legs;
• you have narrowing of the aortic heart valve (aortic stenosis) or cardiogenic shock (a condition in which the heart is unable to supply sufficient blood to the body);
• you have heart failure following a heart attack.

Do not take Nebkliq if you have any of the symptoms listed above. If in doubt, speak with your doctor before taking Nebkliq.

Warnings and precautions

Talk to your doctor or pharmacist before taking Nebkliq.

Tell your doctor if:

• you have an abnormally slow heart rate;
• you have a type of chest pain caused by spontaneous coronary spasm known as "Prinzmetal's angina";
• you have untreated chronic heart failure;
• you have first-degree heart block (a mild type of cardiac conduction disorder affecting heart rhythm);
• you have poor circulation in the arms or legs, e.g. Raynaud's disease or syndrome, cramp-like pains when walking;
• you have prolonged breathing problems;
• you have diabetes: this medicine does not affect blood glucose levels, but it may mask warning signs of low blood sugar (e.g. palpitations, rapid heartbeat);
• you have an overactive thyroid gland: this medicine may mask signs of abnormally fast heart rate due to this condition;
• you have allergies: this medicine may intensify your reaction to pollen or other substances you are allergic to;
• you have psoriasis (a skin disease – scaly pink patches) or have had psoriasis in the past;
• if you are scheduled for surgery, always inform the anaesthetist before anaesthesia that you are taking Nebkliq;
• you have recently had a heart attack;
• you have recently had heart failure or problems with heart valves or heart muscle;
• you have a severe increase in blood pressure (hypertensive crisis).

As with any medicine that lowers blood pressure, an excessive drop in blood pressure in patients with impaired blood flow to the heart or brain may cause a heart attack or stroke. Your doctor must therefore monitor your blood pressure carefully.

See also the information under the heading "Do not take NEBKLIQ".

Children and adolescents

Due to lack of data on use in children and adolescents under 18 years of age, Nebkliq is not recommended for use in these age groups.

Other medicines and Nebkliq

Tell your doctor if you are taking, have recently taken, or might take any other medicines.

In particular, inform your doctor if you are taking:

• Other antihypertensive medicines, as they may increase the effect of Nebkliq.

• Amiodarone, cibenzoline, clonidine, digoxin, diltiazem, disopyramide, felodipine, flecainide, guanfacine, hydroquinidine, lacidipine, lidocaine, methyldopa, mexiletine, moxonidine, nicardipine, nifedipine, nimodipine, nitrendipine, propafenone, quinidine, rilmenidine, verapamil, medicines used to control blood pressure or for heart problems.

• Barbiturates (a group of drugs used as sedatives and for the treatment of psychosis, but also for epilepsy, anxiety, insomnia, and convulsive disorders), as the effect of Nebkliq may be increased.

• Phenothiazines (a group of medicines used as sedatives and for the treatment of psychosis, but also for nausea and vomiting), as the effect of Nebkliq may be increased.

• Thioridazine (a group of medicines used as sedatives and for the treatment of psychosis), as the effect of Nebkliq may be increased.

• Amitriptyline, paroxetine, fluoxetine, medicines used for depression, as the effect of NEBKLIQ may be increased.

• Medicines used for anaesthesia during surgery.

• Medicines for asthma, nasal congestion, or certain eye disorders such as glaucoma (increased pressure in the eye) or pupil dilation (enlargement).

• Baclofen (an antispastic drug); amifostine (a protective medicine used during cancer therapy).

• Insulin and oral antidiabetic medicines: Nebkliq has no effect on blood glucose, but it may mask warning signs of low blood sugar (e.g. palpitations, rapid heartbeat).

• Medicines used to treat excessive stomach acidity or ulcers (antacids): take Nebkliq with food and take the antacid between meals.

• Ketoconazole, itraconazole (antifungal medicines)

• Ritonavir, indinavir, nelfinavir (so-called protease inhibitors used to treat HIV)

• Rifampicin, erythromycin, clarithromycin (antibiotics)

• Hypericum perforatum (St. John's wort)

• Dantrolene (infusion for severe abnormalities in body temperature)

• Tacrolimus, sirolimus, temsirolimus and everolimus (medicines used to modify immune system function)

• Simvastatin (a medicine that lowers cholesterol levels in the blood)

• Cyclosporine (an immunosuppressant)

Nebkliq with food, drinks and alcohol

Nebkliq can be taken with or without food.

Grapefruit and grapefruit juice must not be consumed by people taking Nebkliq. This is because grapefruit and grapefruit juice can lead to increased blood levels of the active substance amlodipine, resulting in an unpredictable increase in the antihypertensive effect of Nebkliq.

If you are taking Nebkliq, be cautious when drinking alcohol, as you may feel faint or dizzy. In such cases, do not consume any alcoholic beverages, including wine, beer or alcopops.

Pregnancy and breastfeeding

Pregnancy

As adequate clinical data in pregnant women are not available, Nebkliq is not recommended during pregnancy. Nebkliq may be considered only if no safer alternatives are available and only after careful individual assessment of the risk-benefit ratio by the doctor. Therefore, inform your doctor immediately if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. Do not forget to ask your doctor for advice before taking this medicine.

If Nebkliq is taken during pregnancy, careful monitoring of the foetus and newborn may be necessary.

Breastfeeding

If you are breastfeeding or planning to breastfeed, consult your doctor before taking this medicine. Nebkliq is not recommended for breastfeeding mothers; your doctor may choose another medicine if you wish to breastfeed.

Driving and using machines

Nebkliq may affect your ability to drive or operate machinery. If this medicine causes you discomfort, dizziness, fatigue, or headache, do not drive or operate machinery and contact a doctor immediately.

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 Nebkliq

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor.
The recommended dose is one tablet daily, preferably at the same time each day.
Nebkliq may be taken before, during, or after meals, or alternatively, it may be taken independently of meals. The tablet should be taken with some water, but must not be chewed. Do not take Nebkliq with grapefruit juice.
The break line on the tablet is intended to facilitate splitting the tablet in case you have difficulty swallowing it whole.

If you take more Nebkliq than you should
If you accidentally take an excessive dose of this medicine, inform your doctor immediately.
The most common symptoms and signs of overdose are low blood pressure with fainting (hypotension) and possible increase in heart rate (reflex tachycardia), very slow heartbeat (bradycardia), shortness of breath as in asthma (bronchospasm), and acute heart failure.
Excess fluid may accumulate in the lungs (pulmonary edema), causing breathlessness, which may develop up to 24–48 hours after ingestion.

If you forget to take Nebkliq
If you forget to take a dose of Nebkliq but remember shortly afterwards, take the dose for that day as usual. However, if there has been a significant delay (e.g. several hours) and the next dose is nearly due, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for the forgotten tablet. Nevertheless, avoid repeatedly skipping doses.

If you stop taking Nebkliq
Always consult your doctor before stopping treatment with Nebkliq.
If you have any doubts about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Consult your doctor immediately if you experience any of the following side effects
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 causing severe breathing difficulties
• Severe skin reactions, including intense skin rashes, hives, redness of the skin all over the body, severe itching, skin rash with blisters, skin peeling and swelling, mucosal inflammation (Stevens-Johnson syndrome, toxic epidermal necrolysis) or other allergic reactions
• Heart attack, abnormal heartbeat
• Inflammation of the pancreas which may cause severe abdominal and back pain accompanied by a feeling of malaise.

The following additional side effects have been reported. If any of these cause you problems, contact your doctor.
Other possible side effects of Nebkliq:
Very common side effects (may affect more than 1 in 10 people):

• Swollen hands or feet (oedema)

Common side effects (may affect up to 1 in 10 people):

• Tiredness
• abdominal pain, nausea
• dizziness
• headache
• drowsiness
• burning, unusual pricking, numbness, or tingling sensations
• palpitations
• flushing
• altered bowel habits (including diarrhoea and constipation)
• indigestion
• swollen ankles
• muscle cramps
• weakness
• visual disturbances, double vision

Uncommon side effects (may affect up to 1 in 100 people):

• slow heartbeat or other heart problems
• low blood pressure
• cramp-like leg pains during walking
• feelings of depression
• vomiting
• shortness of breath like in asthma, due to sudden spasms of the muscles around the airways (bronchospasm)
• nightmares
• insomnia
• mood changes (including anxiety)
• taste disturbances
• numbness or tingling sensation in limbs; loss of pain sensation
• fainting
• tremor
• ringing in the ears
• arrhythmia (including ventricular tachycardia and atrial fibrillation)
• heart failure
• cough
• sneezing/runny nose caused by inflammation of the inner lining of the nose
• dry mouth
• flatulence
• hair loss
• increased sweating
• itching, red spots on the skin, skin colour changes
• joint or muscle pain
• back pain
• inability to get and maintain an erection
• discomfort or enlargement of the breasts in men
• discomfort during urination, increased need to urinate at night, increased frequency of urination
• pain, feeling unwell
• weight decrease or increase

Rare side effects (may affect up to 1 in 1,000 people):

• confusion

Very rare side effects (may affect up to 1 in 10,000 people):

• decrease in white blood cell count, decrease in platelet count which may cause unusual bruising or easy bleeding
• worsening of psoriasis (a skin disease – scaly pink patches)
• excessively high blood sugar levels (hyperglycaemia)
• increased muscle tension
• nerve disorder which may cause muscle weakness, tingling or numbness
• inflammation of blood vessels, often with skin rash
• abdominal swelling (gastritis)
• swollen gums
• abnormal liver function, inflammation of the liver (hepatitis), yellowing of the skin (jaundice), increased liver enzyme which may affect certain medical tests
• sensitivity to light

Not known (frequency cannot be estimated from the available data):

• tremors, rigid posture, mask-like facial expression, slow movements, shuffling and unbalanced 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 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 NEBKLIQ

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.
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 Nebkliq contains

• The active substances are nebivolol (as nebivolol hydrochloride) and amlodipine (as amlodipine besilate).
  Nebkliq 5 mg/5 mg: each film-coated tablet contains 5 mg of nebivolol (as
  nebivolol hydrochloride: 2.5 mg d-nebivolol and 2.5 mg l-nebivolol) and 5 mg of amlodipine (as
  amlodipine besilate).
  Nebkliq 5 mg/10 mg: each film-coated tablet contains 5 mg of nebivolol (as
  nebivolol hydrochloride: 2.5 mg d-nebivolol and 2.5 mg l-nebivolol) and 10 mg of amlodipine (as
  amlodipine besilate).

• The inactive ingredients are: Tablet core: microcrystalline cellulose, sodium croscarmellose, maize starch, hypromellose, polysorbate 80, anhydrous colloidal silica, magnesium stearate. Film coating: Nebkliq 5 mg/5 mg: OPADRY® 02B220019 yellow (composed of: hypromellose, titanium dioxide, macrogol 400, yellow iron oxide (E172)); Nebkliq 5 mg/10 mg: OPADRY® Y-1-7000 white (composed of: hypromellose, titanium dioxide, macrogol 400).

Description of the appearance of Nebkliq and contents of the pack
Nebkliq 5 mg/5 mg film-coated tablets are yellow, oval-shaped, with a unilateral score line.
Nebkliq 5 mg/10 mg film-coated tablets are white, oval-shaped, with a unilateral score line.
Nebkliq is available in PVC/PVDC-Al blisters in pack sizes of 7, 14, 28, 30, and 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, 1611 Luxembourg
Luxembourg
Manufacturer
Saneca Pharmaceuticals, a.s.
Nitrianska 100
920 27 Hlohovec
Slovakia

The medicinal product is authorised in the European Economic Area (EEA) Member States under the following name:
Estonia: Nebkliq
Italy: Nebkliq