Timbrix

Package leaflet: Information for the user

Timbrix

2 mg/mL + 5 mg/mL eye drops, solution
brimonidine tartrate/timolol
Equivalent medicine
Please read all of this leaflet carefully before you start using this medicine, as 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 they have the same symptoms as yours, because it could 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 Timbrix is and what it is used for
2. What you need to know before using Timbrix
3. How to use Timbrix
4. Possible side effects
5. How to store Timbrix
6. Contents of the pack and other information

1. What Timbrix is and what it is used for

Timbrix is an eye drop used to control glaucoma. It contains two different active substances (brimonidine and timolol) that work together to reduce elevated pressure inside the eye.
Brimonidine belongs to a group of medicines called alpha-2 adrenergic receptor agonists.
Timololo belongs to a group of medicines called beta-blockers. Timbrix has been prescribed to reduce elevated intraocular pressure when beta-blocker eye drops used alone are not sufficient.
The eye contains a clear aqueous fluid that supplies nutrients to the internal parts of the eye. This fluid is constantly drained from the eye, while new fluid is continuously produced to replace it. When this fluid cannot drain freely, pressure inside the eye increases, potentially impairing vision. Timbrix works by reducing the production of fluid in the eye and increasing the amount of fluid that drains out. This leads to a reduction in intraocular pressure, while the eye continues to receive its nutrients normally.

2. What you need to know before using Timbrix

Do not use Timbrix

• if you are allergic (hypersensitive) to brimonidine tartrate, timolol, beta-blockers, or any of the other components of this medicine (listed in section 6). Symptoms of an allergic reaction may include swelling of the face, lips, and throat, shortness of breath, feeling faint, difficulty breathing, itching, or redness around the eye.
• if you have or have previously had respiratory problems such as asthma, severe chronic obstructive pulmonary disease (severe lung disease that may cause shortness of breath, difficulty breathing, and/or long-lasting cough).
• if you have heart problems such as slow heart rate, heart failure, or irregular heartbeat (unless controlled by a pacemaker).
• if you are taking monoamine oxidase inhibitors (MAO inhibitors) or certain other antidepressant medicines.

If you think any of the above apply to you, do not use Timbrix before
consulting your doctor again.
Warnings and precautions
Talk to your doctor before using Timbrix

• if you have or have previously had
  • coronary heart disease (symptoms may include chest pain or tightness, shortness of breath, or suffocation)
  • low blood pressure
  • heart rhythm disorders, such as slow heartbeat
  • respiratory problems, asthma, or chronic obstructive pulmonary disease
  • a disease related to poor blood circulation (such as Raynaud's disease or Raynaud's syndrome)
  • diabetes, as timolol may mask signs and symptoms of low blood sugar
  • overactive thyroid gland, as timolol may mask its signs and symptoms
  • kidney or liver problems
  • a tumor of the adrenal gland
  • eye surgery to reduce eye pressure
• if you suffer or have suffered from any allergies (e.g. hay fever, eczema) or a severe allergic reaction, you should be aware that the usual dose of adrenaline used to treat a severe allergic reaction may need to be increased.

Before undergoing surgery, inform your doctor that you are using Timbrix, as timolol may alter the
effects of certain drugs used during anesthesia.
Children and adolescents
Timbrix must not be used in children under 2 years of age and should normally not be used in
children aged between 2 and 17 years.
Other medicines and Timbrix
Timbrix may affect or be affected by other medicines you are taking, including other eye drops for
the treatment of glaucoma.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicines, including those for any condition unrelated to eye disease and those obtained without a
prescription.
Some medicines may interact with Timbrix, so it is particularly important to inform your doctor if you are taking:

• painkillers
• medicines to help sleep or relieve anxiety
• medicines for high blood pressure (hypertension)
• medicines for heart problems (e.g. irregular heartbeat), such as beta-blockers, digoxin, or quinidine (used to treat heart diseases and some types of malaria)
• medicines for diabetes or high blood sugar
• medicines for depression such as fluoxetine and paroxetine
• another eye drop used to lower high eye pressure (glaucoma)
• medicines for treating severe allergic reactions
• medicines acting on certain hormones in the body, such as adrenaline and dopamine
• medicines acting on muscles in blood vessels
• medicines for treating heartburn or stomach ulcers

If the dose of any of your current medicines has changed or if you regularly consume alcohol, inform your
doctor.
If you are to receive an anesthetic, inform your doctor or dentist that you are taking Timbrix.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding,
please consult your doctor or pharmacist before taking this medicine.
Do not use Timbrix during pregnancy unless your doctor considers it necessary.
Do not use Timbrix if you are breastfeeding. Timolol may be excreted in breast milk. Ask your doctor
before taking any medicine while breastfeeding.
Driving and using machines
Timbrix may cause drowsiness, fatigue, or blurred vision in some patients. Do not drive or operate
machinery until these symptoms have resolved. If you experience any problems, consult your doctor.
Timbrix contains phosphates
This medicine contains 53.35 mg of phosphates per 5 mL of solution, equivalent to 10.87 mg/mL.
If you have severe damage to the outermost transparent layer of the eye (the cornea), phosphates may, in
very rare cases, cause cloudy spots on the cornea due to calcium deposits during treatment.

3. How to use Timbrix

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

Use in children and adolescents
Timbrix must not be used in children under 2 years of age.
Timbrix should normally not be used in children and adolescents (from 2 to 17 years of age).

Adults
The recommended dose is one drop of Timbrix twice daily, approximately 12 hours apart. Do not change the dose or stop using the medicine without speaking to your doctor.
If you are using Timbrix with another eye drop, wait at least 5 minutes between applying Timbrix and the other eye drop.

Instructions for use
Before instilling the eye drops:

• Wash your hands before opening the bottle.
• Do not use this medicine if the tamper-evident seal on the neck of the bottle is already broken before your first use.
• At first use, before releasing a drop into the eye, practice using the dropper bottle by gently squeezing it to release a drop away from the eye.
• Once you are confident you can release one drop at a time, choose a comfortable position for instilling the drops (you may sit, lie on your back, or stand in front of a mirror).

Instillation:

1. Hold the bottle directly under the cap and twist the cap to open it. Do not touch anything with the tip of the bottle to avoid contaminating the solution.

2. Tilt your head backward and hold the bottle over the eye.
3. Pull the lower eyelid down while looking upward. Gently squeeze the bottle in the middle to release one drop into the eye. There may be a short delay between squeezing the bottle and the drop coming out. Do not squeeze too hard.

If you have any doubts about administering this medicine, consult your doctor, pharmacist, or nurse.

4. Blink several times so that the drop spreads across the eye.

5. After using Timbrix, press with your finger at the inner corner of the eye toward the nose for two minutes. This helps prevent Timbrix from spreading into the rest of the body.

6. Repeat steps 2–5 to instill a drop into the other eye, if your doctor has instructed you to do so. Sometimes only one eye needs treatment, and your doctor will tell you if this applies to you and which eye requires treatment.
7. After each use and before replacing the cap, shake the bottle once downward without touching the dropper tip, to remove any residual liquid from the tip. This step is necessary to ensure proper release of subsequent drops.

8. After the 28-day period of use following first opening, there may still be some Timbrix left in the bottle. Do not attempt to use any remaining medicine after completing the treatment course. Do not use the eye drops for more than 28 days after first opening the bottle.

If the drop did not enter the eye, try again.
To avoid contamination, do not let the tip of the bottle touch the eyes or any other object. Immediately after use, replace the cap and close the bottle tightly. If you have any doubts about administering this medicine, consult your doctor, pharmacist, or nurse.

If you use more Timbrix than you should
Adults
If you use more Timbrix than you should, it is unlikely to cause harm. Take your next dose at the usual time. If you are concerned, consult your doctor or pharmacist.
Newborns and children
Several cases of overdose have been reported in newborns and children who received brimonidine (one of the active substances in Timbrix) as part of medical treatment for glaucoma. Symptoms of overdose include: drowsiness, weakness, low body temperature, paleness, and breathing difficulties. If this occurs, contact your doctor immediately.
Adults and children
If Timbrix has been accidentally swallowed, you must contact your doctor immediately.

If you forget to use Timbrix
If you forget to use Timbrix, instill one drop into the affected eye as soon as you remember, then continue with your regular schedule. Do not use a double dose to make up for a forgotten dose.

If you stop using Timbrix
To work properly, Timbrix must be used every day.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them. If you experience any of the following side effects, contact your doctor immediately:

• Heart failure (e.g. chest pain) or irregular heartbeat
• Increase or decrease in heart rate or low blood pressure

The following side effects may occur with Timbrix.

Eye disorders
Very common (may affect more than 1 in 10 people):

• Redness or burning sensation in the eyes

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

• Burning or pain in the eyes
• Allergic reaction in the eye or on the skin around the eye
• Small cracks on the surface of the eye (with or without inflammation)
• Swelling, redness or inflammation of the eyelid
• Irritation, sensation of a foreign body in the eye
• Itching of the eyes and eyelids
• White spots or follicles on the transparent layer covering the eye surface
• Visual disturbances
• Tearing
• Dry eyes
• Sticky eyes

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

• Difficulty seeing clearly
• Swelling or inflammation of the transparent layer covering the eye surface
• Tired eyes
• Light sensitivity
• Eyelid pain
• Discoloration of the transparent layer covering the eye surface
• Swelling or inflammation beneath the eye surface
• Floaters in front of the eyes

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

• Blurred vision

General body disorders:
Common (may affect up to 1 in 10 people):

• High blood pressure
• Depression
• Drowsiness
• Headache
• Dry mouth
• General weakness

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

• Heart failure
• Irregular heartbeat
• Sensation of emptiness in the head
• Fainting
• Nasal congestion
• Taste disturbances
• Nausea
• Diarrhea

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

• Increase or decrease in heart rate
• Low blood pressure
• Facial redness

Some of these effects may be due to an allergy to any of the components. Other side effects have been observed with brimonidine or timolol and may therefore also occur with Timbrix.
The following additional side effects have been observed with the use of brimonidine:

• Inflammation inside the eye, constricted pupils, difficulty sleeping, feeling of cold, shortness of breath, gastrointestinal and digestive symptoms, general allergic reactions, skin reactions including redness, facial swelling, itching, rashes, and blood vessel dilation.

Like other eye medications, Timbrix (brimonidine/timololo) is absorbed into the bloodstream.
Absorption of timolol, the beta-blocking component of Timbrix, may cause side effects similar to those observed with systemically administered beta-blockers (e.g., intravenous and/or oral). The incidence of side effects following topical ophthalmic administration is lower than that following systemic administration (e.g., oral or injectable). The listed side effects include those observed with the class of beta-blockers used in the treatment of ocular diseases:

• Generalized allergic reactions, including subcutaneous swelling (which may occur in areas such as the face and limbs and may obstruct airways, causing possible difficulty in swallowing or breathing), urticaria (itchy rash), localized and generalized skin rash, itching, sudden severe allergic reaction that may be life-threatening
• Low blood glucose levels
• Difficulty sleeping (insomnia), nightmares, memory loss, hallucinations
• Stroke, reduced blood flow to the brain, worsening of signs and symptoms of myasthenia gravis (a muscle disorder), unusual sensations (such as tingling)
• Corneal inflammation, detachment of the layer beneath the retina containing blood vessels following filtering surgery which may cause visual disturbances, decreased corneal sensitivity, corneal erosion (damage to the front layer of the eyeball), drooping of the upper eyelid (causing partial closure of the eye), double vision
• Chest pain, edema (fluid accumulation), changes in heart rhythm or rate, a type of heart rhythm disorder, heart attack, heart failure
• Raynaud's phenomenon, cold hands and feet
• Constriction of the airways in the lungs (mainly in patients with pre-existing respiratory disease), difficulty breathing, cough
• Indigestion, abdominal pain, vomiting
• Hair loss, white-silver colored skin eruptions (psoriasiform rash) or worsening of psoriasis, skin rash
• Muscle pain not caused by physical exercise
• Sexual dysfunction, reduced sexual desire
• Muscle weakness/fatigue

Other side effects reported with eye drops containing phosphates:
Very rare cases of corneal calcification have been reported in association with the use of eye drops containing phosphate in some patients with significantly damaged corneas.

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
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Timbrix

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the bottle label and on the carton after Exp. The expiry date refers to the last day of that month.
Use only one bottle at a time.
Discard the bottle 28 days after first opening, even if there are still eye drops remaining.
This will help prevent infections. To help you remember, write down the date of opening in the space provided on the packaging.
After first opening, this medicine does not require any special storage conditions.
Do not dispose of any medicine 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 other information

What Timbrix contains

• The active substances are brimonidine tartrate and timolol.
• One mL of solution contains 2 mg of brimonidine tartrate, equivalent to 1.3 mg of brimonidine, and 5 mg of timolol, equivalent to 6.8 mg of timolol maleate.
• The other components are disodium hydrogen phosphate heptahydrate, sodium dihydrogen phosphate dihydrate, water for injections, hydrochloric acid and/or sodium hydroxide (to adjust pH).

Description of the appearance of Timbrix and contents of the pack
Timbrix is a clear, yellowish-green aqueous solution, practically free from particles, contained in an 11 mL LDPE white opaque bottle with a white Novelia dispenser (HDPE and silicone) and a white HDPE cap.
Each bottle is half-filled and contains 5 mL of solution.
Packs containing 1 or 3 bottles are available.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
FB VISION SpA
Via San Giovanni Scafa, snc
63074 - San Benedetto del Tronto (AP)
Italy

Manufacturers
EXCELVISION
Zone Industrielle De La Lombardière,
27, Rue De La Lombardière
07100 Annonay
France

Pharmathen S.A.
Dervenakion 6
15351 Pallini, Attiki
Greece

This medicinal product is authorised in the European Economic Area countries under the following names:
Germany: Bazofex 2mg/mL + 5 mg/mL Augentropfen, Lösung
Italy: Timbrix
Greece: Bazofex 2 mg/ml + 5 mg/ml οφθαλμικές σταγόνες, διάλυμα
Austria: Bazofex 2 mg/ml + 5 mg/ml Augentropfen, Lösung