A.Menarini Pharmaceuticals Ltd

Read all this leaflet carefully before you start using this medicine.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1. What Nebilet Plus is and what it is used for
2. Before you take Nebilet Plus
3. How to take Nebilet Plus
4. Possible side effects
5. How to store Nebilet Plus
6. Further information

Do not take Nebilet Plus

• if you are allergic (hypersensitive) to nebivolol or to hydrochlorothiazide or to any of the other ingredients of Nebilet Plus (see end of Section 2, and Section 6).
• if you are allergic (hypersensitive) to other sulphonamide-derived substances (like hydrochlorothiazide, which is a sulphonamide-derived drug)
• if you have one or more of the following disorders:
  • very slow heartbeat (less than 60 beats per minute)
  • certain other serious heart rhythm problems (e.g. sick sinus syndrome, sino-atrial block, 2nd and 3rd degree atrioventricular block).
  • heart failure, which has just occurred or which has recently become worse, or you are receiving treatment for circulatory shock due to acute heart failure by intravenous drip feed to help your heart work
  • low blood pressure
  • serious circulation problems in the arms or legs
  • untreated phaeochromocytoma, a tumour located on top of the kidneys (in the adrenal glands)
  • severe kidney problems, complete absence of urine (anuria)
  • a metabolic disorder (metabolic acidosis), e.g., diabetic ketoacidosis.
  • asthma or wheezing (now or in the past)
  • liver function disorder
  • high blood calcium, low blood potassium, low blood sodium levels that are persistent and resistant to treatment
  • high uric acid levels with gout symptoms

Take special care with Nebilet Plus

• Inform your doctor if you have or develop one of the following problems:
  • a type of chest pain due to spontaneously occurring heart cramp, called Prinzmetal angina
  • 1st degree heart block (a kind of mild heart conduction impairment that affects heart rhythm)
  • abnormally slow heartbeat
  • untreated chronic heart failure
  • lupus erythematosus (a disorder of the immune system, i.e. your body’s defence system)
  • psoriasis (a skin disease characterised by scaly pink patches) or if you have ever had psoriasis
  • overactive thyroid gland: this medicine may mask the signs of an abnormally fast heart rate due to this condition
  • poor circulation in the arms or legs, e.g. Raynaud’s disease or syndrome, cramp-like pains when walking
  • allergy: this medicine may intensify your reaction to pollen or other substances you are allergic to
  • prolonged breathing problems
  • diabetes: this medicine could conceal the warning signs of a low sugar level (e.g. palpitations, fast heartbeat); your doctor will also tell you to check your blood sugar more often while taking Nebilet Plus, as the dose of your antidiabetic drugs may need to be adjusted
  • kidney problems: your doctor will check your kidney function to make sure it does not get worse. If you have serious kidney problems do not take Nebilet Plus (see section ‘Do not take Nebilet Plus’)
  • if you tend to have low blood potassium, and especially if you suffer from prolonged QT syndrome (a kind of ECG abnormality) or you are taking digitalis (to help your heart pump); you are more likely to have low blood potassium if you suffer from liver cirrhosis, or have had too rapid a loss of water due to a strong diuretic treatment, of if your intake of potassium with food and drinks is inadequate
  • if you have to have surgery, always inform your anaesthetist that you are on Nebilet Plus before being anaesthetised.
• Nebilet Plus may increase blood fat levels and uric acid. It may affect the levels of certain chemicals in your blood, called electrolytes: your doctor will check them from time to time via a blood test.
• The hydrochlorothiazide in Nebilet Plus may cause your skin to be oversensitive to sunlight or artificial UV light. Stop taking Nebilet Plus and tell your doctor if you get a rash, itchy spots or sensitive skin during treatment (see also Section 4).
• Anti-dope test: Nebilet Plus could cause a positive anti-dope test.

Children and adolescents

Because of the lack of data on the use of the product in children and adolescents, Nebilet Plus is not recommended for use in them.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. Certain medicines cannot be used at the same time, while other drugs require specific changes (in the dose, for example).

Always tell your doctor if you are using or receiving any of the following medicines in addition to Nebilet Plus:

• Medicines that, as well as Nebilet Plus, may influence the blood pressure and/or heart function:
  • Medicines for controlling blood pressure or medicines for heart problems (such as amiodarone, amlodipine, cibenzoline, clonidine, digoxin, diltiazem, disopyramide, dofetilide, felodipine, flecainide, guanfacine, hydroquinidine, ibutilide, lacidipine, lidocaine, mexiletine, methyldopa, moxonidine, nicardipine, nifedipine, nimodipine, nitrendipine, propafenone, quinidine, rilmenidine, sotalol, verapamil)
  • Sedatives and therapies for psychosis (a mental illness) e.g. amisulpiride, barbiturates (also used for epilepsy), chlorpromazine, cyamemazine, droperidol, haloperidol, levomepromazine, narcotic drugs, phenothiazine (also used for vomiting and nausea), pimozide, sulpiride, sultopride, thioridazine, tiapride trifluoperazine
  • Medicines for depression e.g. amitriptyline, fluoxetine, paroxetine
  • Medicines used for anaesthesia during an operation
  • Medicines for asthma, blocked nose or certain eye disorders such as glaucoma (increased pressure in the eye) or dilation (widening) of the pupil
• Medicines whose effect or toxicity may be increased by Nebilet Plus:
  • Lithium, used as a mood stabilizer
  • Cisapride (used for digestive problems)
  • Bepridil (used for angina)
  • Diphemanil (used for excessive sweating)
  • Medicines used for infections: erythromycin given by infusion or injection, pentamidine and sparfloxacin, amphotericin and penicillin G sodium, halofantrine (used for malaria)
  • Vincamine (used for brain circulation problems)
  • Mizolastine and terfenadine (used for allergy
  • Diuretics and laxatives
  • Medicines used to treat acute inflammation: steroids (e.g cortisone and prednisone), ACTH (adrenocorticotropic hormone) and medicines derived from salicylic acid (e.g. acetylsalicylic acid/aspirin and other salicylates)
  • Carbenoxolone (used for heartburn and stomach ulcer)
  • Calcium salts, used as supplements for bone health
  • Medicines used to relax muscles (e.g. tubocurarine)
  • Diaxozide, used to treat low blood sugar and high blood pressure
  • Amantadine, an antiviral medicine
  • Cyclosporine, used to suppress the body’s immune response
  • Iodinated contrast media, used for contrast in X-ray scans
  • Anti-cancer medicines (e.g. cyclophosphamide, fluorouracil, methotrexate)
• Medicines whose effect may be decreased by Nebilet Plus:
  • Blood sugar-lowering medicines (insulin and oral antidiabetic drugs, metformin)
  • Medicines for gout (e.g. allopurinol, probenecid and sulfinpyrazone)
  • Medicines like noradrenalin, used to treat low blood pressure or slow heart rate
• Medicines for pain and inflammation (non-steroidal anti-inflammatory drugs), as they may reduce the blood pressure lowering effect of Nebilet Plus
• Medicines for treating excessive stomach acid or ulcers (antacid), e.g. cimitedine: you should take Nebilet Plus during a meal and the antacid between meals.

Taking Nebilet Plus with food and drink

Nebilet Plus can be taken with food or on an empty stomach, but the tablet is best taken with some water.

Take care when drinking alcohol while you are taking Nebilet Plus, as you may feel faint or dizzy. If this happens to you, do not drink any alcohol, including wine, beer or alcopops.

Pregnancy and breast-feeding

You must tell your doctor if you are pregnant or if you think that you are. Usually, your doctor will advise you to take another medicine instead of Nebilet Plus, as Nebilet Plus is not recommended during pregnancy. This is because the active ingredient hydrochlorothiazide crosses the placenta. The use of Nebilet Plus during pregnancy may cause potentially harmful foetal and neonatal effects.

Tell your doctor if you are breast-feeding or about to start breast-feeding. Nebilet Plus is not recommended for mothers who are breast-feeding.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving or operating machines

This medicine may cause dizziness or fatigue. If affected, do not drive or operate machinery.

Important information about some of the ingredients of Nebilet Plus

This product contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

If you take more Nebilet Plus than you should

If you accidentally take an overdose of this medicine, tell your doctor or pharmacist immediately. The most frequent symptoms and signs of overdose are very slow heart beat (bradycardia), low blood pressure with possible fainting, breathlessness such as in asthma, acute heart failure, excessive urination with consequent dehydration, nausea and somnolence, muscle spasms, heart rhythm disturbances (especially if you are also taking digitalis or medicines for heart rhythm problems).

If you forget to take Nebilet Plus

If you forget a dose of Nebilet Plus, but remember a little later on that you should have taken it, take that day’s dose as usual. However, if a long delay has occurred (e.g. several hours), so that the next due dose is near, skip the forgotten dose and take the next, scheduled, normal dose at the usual time. Do not take a double dose. Repeated skipping, however, should be avoided.

If you stop taking Nebilet Plus

Always consult your doctor before stopping Nebilet Plus treatment.

What Nebilet Plus contains

• The active substance is nebivolol 5 mg (as nebivolol hydrochloride: 2.5 mg of d-nebivolol and 2.5 mg of l-nebivolol) and 25 mg of hydrochlorothiazide
• The other ingredients are:
  • tablet core: lactose monohydrate, polysorbate 80 (E433), hypromellose (E464), maize starch, croscarmellose sodium (E468), cellulose microcrystalline (E460), silica colloidal anhydrous (E551), magnesium stearate (E572)
  • coating: macrogol 40 stearate Type I, titanium dioxide (E171), carmines (carminic acid aluminium lake, E120), hypromellose (E464), cellulose microcrystalline (E460).

What Nebilet Plus looks like and contents of the pack

Nebilet Plus is available as almost violet, round, slight biconvex film-coated tablets with “5/25” embossed on one side in packs of 7, 14, 28, 30, 56, 90 film-coated tablets.

Tablets are provided in blisters (PP/COC/PP/Aluminium blister).

(Not all pack sizes may be marketed)

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