AZARGA 10 mg/mL + 5 mg/mL EYE DROPS, SUSPENSION

2. What you need to know before you use AZARGA

Do not use AZARGA

• If you are allergic to brinzolamida, medicines called sulfonamides (including, for example, medicines used to treat diabetes and infections, also diuretics, timolol, beta-blockers (medicines used to lower blood pressure or treat heart disease) or any of the other ingredients of this medicine (listed in section 6).
• If you currently have or have had in the past respiratory problems such as asthma, severe chronic obstructive pulmonary disease (a serious lung condition that can cause wheezing, difficulty breathing and/or persistent cough) or other types of respiratory problems.
• If you have severe hay fever.
• If you have a slow heart rate, heart failure or heart rhythm disorders (irregular heartbeats).
• If you have too much acid in the blood (a disease called hyperchloremic acidosis).
• If you have severe kidney problems.

Warnings and precautions

Only use AZARGA in your eye(s).

If you have signs of hypersensitivity or severe reactions, stop using this medicine and consult your doctor.

Consult your doctor or pharmacist before starting to use AZARGA if you have or have had in the past:

• coronary heart disease (symptoms may include chest pain or discomfort, shortness of breath or choking), heart failure, low blood pressure,

• heart rhythm disorders such as slow heartbeat.
• respiratory problems, asthma or chronic obstructive pulmonary disease
• circulatory disorders (such as Raynaud's disease or Raynaud's syndrome)
• diabetes as timolol may mask the signs and symptoms of low blood sugar
• hyperthyroidism as timolol may mask the signs and symptoms of thyroid disease
• muscle weakness (myasthenia gravis)

• If you have a history of atopy (tendency to develop an allergic reaction) and severe allergic reactions, you may be more sensitive to suffering an allergic reaction while using AZARGA, and adrenaline may not be as effective in treating an allergic reaction. When receiving any other treatment, inform the doctor or nurse that you are using AZARGA.

Be careful with AZARGA:

Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in association with brinzolamida treatment. Stop using AZARGA and seek immediate medical attention if you notice any of the symptoms related to these severe skin reactions described in section 4.

Children and adolescents

AZARGA is not recommended in children and adolescents under 18 years of age.

Other medicines and AZARGA

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

AZARGA may affect, or be affected by, other medicines you are using, including other eye drops for the treatment of glaucoma. Consult your doctor if you are using or think you may use medicines to lower blood pressure such as parasymphathomimetics and guanethidine, or other heart medicines including quinidine (used to treat heart conditions and some types of malaria), amiodarone or other medicines to treat heart rhythm disorders and cardiac glycosides to treat heart failure. Also, consult your doctor if you are using or think you may use medicines to treat diabetes or to treat stomach ulcers, antifungal, antiviral or antibiotic medicines, or antidepressants such as fluoxetine and paroxetine.

Consult your doctor if you are using another carbonic anhydrase inhibitor (acetazolamide or dorzolamide).

Occasional increase in pupil size has been reported when Azarga is used with adrenaline (epinephrine).

Pregnancy and breastfeeding

If you are pregnant, think you may be pregnant or plan to become pregnant, you should not use AZARGA unless your doctor considers it necessary. Consult your doctor before using AZARGA.

Do not use AZARGA during breastfeeding, timolol may pass into breast milk.

Consult your doctor before using any medicine during breastfeeding.

Driving and using machines

Do not drive or use machines until your vision is clear. Immediately after applying AZARGA, you may notice that your vision becomes blurry for a while.

One of the active ingredients may worsen the ability to perform tasks that require mental alertness and/or physical coordination. If you notice these effects, be careful when driving or using machines.

AZARGA contains benzalkonium chloride

This medicine contains 3.34 µg of benzalkonium chloride per drop (= 1 dose), equivalent to 0.01% or 0.1 mg/ml.

AZARGA contains a preservative (benzalkonium chloride) that can be absorbed by soft contact lenses and may alter the color of contact lenses. Remove contact lenses before using this medicine and wait 15 minutes before putting them back. Benzalkonium chloride may cause eye irritation, especially if you have dry eyes or other corneal diseases. Consult your doctor if you feel any unusual sensation, itching or pain in the eye after using this medicine.

3. How to use AZARGA

Follow the instructions for administration of this medicine exactly as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

In the event that AZARGA replaces a previous eye drop used for the treatment of glaucoma, discontinue the use of the previous medicine and start using AZARGA the next day. In case of doubt, consult your doctor or pharmacist.

To avoid possible contamination of the dropper tip and the suspension, be careful not to touch the eyelids, the area around them, or other surfaces with the dropper. Keep the bottle tightly closed when not in use.

The following instruction is useful to reduce the amount of medicine that passes into the bloodstream after applying the eye drops:

• Keep the eyelid closed while pressing the edge of the eye next to the nose with your finger for at least 2 minutes.

The recommended dose is

One drop in the affected eye(s), twice a day.

AZARGA should only be applied to both eyes if your doctor has recommended it. Follow the treatment for the entire period of time indicated by your doctor .

How to use

1 2 3

• Take the AZARGA bottle and stand in front of a mirror.
• Wash your hands.

• Shake well before use.
• Remove the cap. After removing the cap, you should remove the security ring if it is loose before using this medicine.

• Hold the bottle, upside down, between your thumb and index finger.
• Tilt your head back. Gently pull the lower eyelid down to form a pocket, where the drop should fall (Figure 1).
• Bring the tip of the bottle close to the eye. You can use a mirror to help you.
• Do not touch the eye, eyelid, surrounding areas, or other surfaces with the dropper because the drops may become contaminated.
• Gently press the base of the bottle to release one drop of AZARGA at a time.
• Do not squeeze the bottle: it is designed to deliver a single drop with a gentle pressure on the base (Figure 2).
• After using AZARGA, press the edge of the eye next to the nose with your finger for 2 minutes (Figure 3). This helps prevent AZARGA from passing into the rest of the body.
• If you are applying drops in both eyes, repeat all the previous steps with the other eye.
• Close the bottle tightly immediately after using the product.
• Use a single bottle before opening the next one.

If a drop falls outside the eye, try again.

If you are using another eye drop or ointment, wait at least 5 minutes between applying each medicine. Eye ointments should be administered last.

If you use more AZARGA than you should, you can rinse your eyes with warm water. Do not apply more drops until it is time for your next dose.

You may experience a decrease in heart rate, decrease in blood pressure, heart failure, difficulty breathing, and effects on the nervous system.

If you forget to use AZARGA, continue with the next scheduled dose. Do not apply a double dose to make up for forgotten doses. Do not apply more than one drop twice a day in the affected eye(s).

If you stop treatment with AZARGAwithout consulting your doctor, the pressure in your eye will not be controlled, which could lead to vision loss.

If you have any other questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop using AZARGA and seek immediate medical attention if you notice any of the following symptoms:

• severe redness and itching of the eye, red patches, target-shaped or circular, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin rashes can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).

Unless the effects are severe, continue with the treatment as usual. If these effects worry you, talk to your doctor or pharmacist. Do not stop using Azarga without consulting your doctor first.

Common(may affect up to 1 in 10 people)

• Eye effects:inflammation of the eye surface, blurred vision, signs and symptoms of eye irritation (e.g., burning, stinging, itching, tearing, redness), eye pain.
• Other adverse effects:decreased heart rate, changes in taste.

Uncommon(may affect up to 1 in 100 people)

• Eye effects:corneal erosion (damage to the outer layer of the eyeball), inflammation of the eye surface with damaged surface, inflammation inside the eye, corneal spots, abnormal sensation in the eyes, eye discharge, dry eye, tired vision, itching of the eyes, red eye, eyelid redness.
• Other adverse effects:decreased white blood cell count, decreased blood pressure, cough, blood in urine present, general weakness.

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

• Eye effects:corneal disorder, sensitivity to light, increased tear production, crusts on the eyelid.
• Other adverse effects:difficulty sleeping (insomnia), sore throat, runny nose.

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

• Eye effects:eye allergy, vision changes, optic nerve damage, increased eye pressure, deposits on the eye surface, decreased sensation in the eye, inflammation or infection of the conjunctiva (white part of the eye), abnormal vision, double or reduced vision, increased pigmentation of the eye, lump on the eye surface, eye swelling, sensitivity to light, decreased eyelash growth or number, drooping of the upper eyelids (causing the eye to be half-closed), inflammation of the eyelid and eyelid glands, inflammation of the cornea and detachment of the layer under the retina that contains blood vessels which can cause vision changes after filtration surgery, decreased corneal sensitivity, corneal erosion.
• Heart and circulation:changes in heart rhythm or frequency, slow heart rate, palpitations, type of heart rhythm disorder, abnormal increase in heart rate, chest pain, reduced heart function, heart attack, increased blood pressure, reduced blood flow to the brain, stroke, edema (fluid accumulation), congestive heart failure (heart disease with difficulty breathing and swelling of the feet and legs due to fluid accumulation), swelling of the limbs, decreased blood pressure, discoloration of the fingers and toes and, occasionally, other parts of the body (Raynaud's phenomenon), coldness in hands and feet.
• Respiratory:constriction of the airways in the lungs (mainly in patients with pre-existing disease), shortness of breath or difficulty breathing, cold symptoms, chest congestion, sinus infection, sneezing, stuffy nose, dry nose, nosebleeds, asthma, throat irritation.
• Nervous system and general disorders:hallucinations, depression, nightmares, memory loss, headache, nervousness, irritability, fatigue, tremors, abnormal sensation, fainting, dizziness, drowsiness, general weakness or severe, unusual sensations such as tingling.
• Gastrointestinal:nausea, vomiting, diarrhea, gas or abdominal discomfort, throat inflammation, dry or abnormal mouth sensation, indigestion, stomach pain.
• Blood:abnormal liver function test values, increased blood chloride levels, or decreased red blood cell count in blood tests.
• Allergic reactions:increased allergy symptoms, generalized allergic reactions including swelling under the skin that can occur in areas such as the face and limbs and can obstruct the airways, causing difficulty swallowing or breathing, hives, localized and generalized rash, itching, sudden and severe allergic reaction that can be life-threatening.
• Ear:ringing in the ears, feeling of dizziness or vertigo.
• Skin:rash, redness or inflammation of the skin, abnormal or decreased sensation in the skin, hair loss, rash with a white silvery appearance (psoriasiform rash) or worsening of psoriasis.
• Muscle:muscle pain not caused by exercise, in joints, back, or generalized, muscle spasms, pain in the limbs, muscle weakness/fatigue, increased signs and symptoms of myasthenia gravis (muscle disorder).
• Kidney:kidney pain that occurs as lower back pain, frequent urination.
• Reproduction:sexual dysfunction, decreased sexual desire, male sexual problems.
• Metabolism:low blood sugar levels.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of AZARGA

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the bottle and carton after “EXP”. The expiry date is the last day of the month shown.

This medicine does not require any special storage conditions.

To avoid infections, discard the bottle 4 weeks after first opening. Write the date of opening on the space provided on the label and carton.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and further information

AZARGA composition

• The active substances are brinzolamide and timolol. One ml of suspension contains 10 mg of brinzolamide and 5 mg of timolol (as maleate).

• The other ingredients are benzalkonium chloride (see section 2 “AZARGA contains benzalkonium chloride”), carbomer 974P, disodium edetate, mannitol (E421), purified water, sodium chloride, tiloxapol, hydrochloric acid and/or sodium hydroxide.

Very small amounts of hydrochloric acid and/or sodium hydroxide are added to maintain normal acidity levels (pH levels).

Appearance and package contents of the product

AZARGA is a liquid (a uniform white to off-white suspension) presented in a carton containing a 5 ml plastic bottle with a screw cap, or in a carton containing three 5 ml plastic bottles with screw caps.

Only certain pack sizes may be marketed.

Marketing authorisation holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

Novartis Pharma GmbH

Roonstraße 25

D-90429 Nuremberg

Germany

Novartis Manufacturing NV

Rijksweg 14

2870 Puurs-Sint-Amands

Belgium

Novartis Farmacéutica, S.A.

Gran Via de les Corts Catalanes, 764

08013 Barcelona

Spain

Siegfried El Masnou, S.A.,

Camil Fabra 58,

08320 El Masnou,

Barcelona,

Spain

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

For further information about this medicine, please contact the local representative of the marketing authorisation holder:

Date of last revision of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu