Combigan 2 mg/ml + 5 mg/ml solution for ophthalmic use

Patient Information Leaflet

Introduction

Package Leaflet: Information for the patient

COMBIGAN 2 mg/ml + 5 mg/ml eye drops, solution.

brimonidine tartrate and timolol

Package leaflet contents

1. What COMBIGAN is and what it is used for
2. What you need to know before using COMBIGAN
3. How to use COMBIGAN
4. Possible side effects
5. Storage of COMBIGAN
6. Contents of the pack and other information

1. What is Combigan and what is it used for

COMBIGAN is an eye drop medicine used to control glaucoma. It contains two medicines (brimonidine and timolol), both of which reduce elevated pressure in the eye. Brimonidine belongs to a group of medicines called alpha-2 adrenergic receptor agonists. Timolol belongs to a group of medicines called beta-blockers.

COMBIGAN is used to reduce elevated pressure inside the eye when the use of beta-blocker eye drops alone is not sufficient.

Your eye contains a clear, watery fluid that nourishes the inside of the eye. This fluid is continuously drained out of the eye and replaced by newly produced fluid. If the fluid cannot drain out of the eye quickly enough, pressure inside the eye increases and may eventually damage your vision. COMBIGAN works by reducing the production of fluid and increasing the amount of fluid that drains out. This reduces the pressure inside the eye while new fluid continues to be produced.

2. What you need to know before using COMBIGAN

Do not use COMBIGAN ophthalmic solution:

• If you are allergic (hypersensitive) to brimonidine tartrate, timolol, beta-blockers, or to 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, wheezing, feeling weak, difficulty breathing, itching, or redness around the eye.

• If you have or have had breathing problems such as asthma, severe chronic obstructive bronchitis (a serious lung disease that may cause wheezing, difficulty breathing, and/or constant cough)

• If you have heart problems such as slow heart rate, heart failure, 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 these apply to you, do not use COMBIGAN until you have consulted your doctor.

Warnings and precautions

Talk to your doctor before using COMBIGAN if:

• You have or have had:

  • Coronary heart disease (symptoms may include chest pain or tightness, shortness of breath, or suffocation), heart failure, low blood pressure
  • Heart rhythm disorders, such as slow heart rate
  • Peripheral circulatory disorders (such as Raynaud's disease or Raynaud's syndrome)
  • Diabetes, as timolol may mask the signs and symptoms of low blood sugar
  • Overactive thyroid gland, as timolol may mask the signs and symptoms
  • Kidney or liver problems
  • Tumor of the adrenal gland
  • Eye surgery to reduce pressure in the eye

• If you have or have had any allergies (e.g. hay fever, eczema) or a severe allergic reaction, be aware that you may need a higher dose of adrenaline than usual to treat a serious reaction.

• Inform your doctor that you are using COMBIGAN before undergoing surgery, as timolol may alter the effects of certain medicines used during anesthesia.

Children and adolescents

COMBIGAN must not be used in children under 2 years of age and is generally not recommended for children and adolescents aged 2 to 17 years.

Other medicines and COMBIGAN

COMBIGAN may interact with or be affected by other medicines you are using, including other eye drops for glaucoma.

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, even those for other conditions unrelated to your eye problem, including over-the-counter medicines.

A number of medicines may interfere with COMBIGAN, so it is very important to inform your doctor if you are taking:

• Painkillers
• Medicines to help you sleep or for anxiety
• Medicines for high blood pressure (hypertension)
• Medicines for heart conditions (e.g. irregular heartbeat), such as beta-blockers, digoxin, or quinidine (used to treat heart problems and some types of malaria)
• Medicines for diabetes or high blood sugar
• Medicines for depression such as fluoxetine and paroxetine
• Other eye drops used to reduce high eye pressure (glaucoma)
• Medicines for severe allergic reactions
• Medicines affecting hormones in your body, such as adrenaline and dopamine
• Medicines affecting the muscles in your blood vessels
• Medicines for stomach acid or stomach ulcers
• If you change the dose of any of your medicines or drink alcohol regularly, inform your doctor
• If you are to undergo anesthesia, inform your doctor or dentist that you are using COMBIGAN.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine. Do not use COMBIGAN during pregnancy unless considered necessary by your doctor.

Do not use COMBIGAN while breastfeeding. Timolol may pass into breast milk. Consult your doctor before using any medicine during breastfeeding.

Driving and using machines

COMBIGAN may cause drowsiness, fatigue, or blurred vision. Do not drive or operate tools or machinery until these symptoms have resolved. If you experience any of these, speak to your doctor.

COMBIGAN contains benzalkonium chloride

This medicine contains 0.25 mg of benzalkonium chloride in each 5 ml of solution, equivalent to 0.05 mg/ml.

Benzalkonium chloride may be absorbed by soft contact lenses, altering their color. Remove contact lenses before using this medicine and wait 15 minutes before reinserting them.

Benzalkonium chloride may cause eye irritation, especially if you have dry eye or other corneal conditions (the transparent layer at the front of the eye). Consult your doctor if you experience a foreign body sensation, stinging, or pain in the eye after using this medicine.

COMBIGAN contains phosphates:

This medicine contains 52.9 mg of phosphates in each 5 ml of solution, equivalent to 10.58 mg/ml.

If you have severe corneal damage (the transparent layer at the front of the eye), treatment with phosphates may, in very rare cases, lead to blurred vision due to calcium accumulation.

3. How to use COMBIGAN

Follow exactly the instructions for using this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again. COMBIGAN must not be used in children under 2 years of age, and routine use is not recommended in children and adolescents (between 2 and 17 years of age).

The recommended dose is one drop of COMBIGAN twice daily, approximately 12 hours apart. Do not change the dose or stop using it without consulting your doctor.

If you are using COMBIGAN together with other eye drops, wait at least five minutes between applying COMBIGAN and the other eye drops.

Instructions for use

Do not use the container if the safety seal is broken when you first open the product.

Wash your hands before opening the container. Tilt your head backwards and look up at the ceiling.

1. Gently pull down the lower eyelid until a small pocket forms.
2. Invert the bottle and squeeze it to release one drop into each eye requiring treatment.
3. Release the lower eyelid and close the eye.
4. Keep the eye closed and press your finger against the tear duct (where the eye meets the nose) for two minutes. This helps prevent COMBIGAN from passing into the rest of the body.

If the drop misses the eye, try again.

To help prevent infection, avoid letting the tip of the container touch the eye or any other surface. Close the container immediately after use.

If you use more COMBIGAN than you should

Adults

If you use more COMBIGAN than you should, it is unlikely to cause harm. Use the next drop at your usual time. If you are concerned, speak to your doctor or pharmacist.

Infants and children

There have been some cases of overdose in infants and children treated with brimonidine (one of the components of COMBIGAN) as part of glaucoma treatment. Symptoms observed included drowsiness, floppiness, low body temperature, paleness, and breathing difficulties. If this occurs, contact your doctor immediately.

Adults and children

In case of accidental ingestion of COMBIGAN, contact your doctor immediately.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number 91-562 04 20.

If you forget to use COMBIGAN

If you forget to use COMBIGAN, apply one drop to each eye requiring treatment as soon as you remember, then continue with your regular routine. Do not double the dose to make up for a missed dose.

If you stop using COMBIGAN

To work properly, COMBIGAN must be used every day.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

If you notice any of the following adverse effects, please contact your doctor immediately:

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

The likelihood of experiencing an adverse effect is classified into the following categories:

The following adverse effects may occur with COMBIGAN

Affecting the eye

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

• Eye redness, burning sensation

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

• Stinging or pain in the eye
• Allergic reaction in the eye or surrounding skin
• Small breaks on the surface of the eye (with or without inflammation)
• Swelling, redness of the eyelids
• Eye irritation or sensation of foreign body
• Itching of the eye and eyelid
• Follicles or white spots on the layer covering the surface of the eye, through which we see
• Vision disturbances
• Tearing
• Dry eyes
• Sticky eyes

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

• Difficulty seeing clearly
• Swelling or inflammation of the layer covering the surface of the eye, through which we see
• Tired eyes
• Light sensitivity
• Pain in the eyelid
• Whitening of the layer covering the surface of the eye, through which we see
• Swelling or inflamed areas beneath the surface of the eye
• Floaters in front of the eyes

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

• Blurred vision

Affecting the body:

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
• Dizziness
• Fainting
• Dry nose
• Taste disturbances
• Nausea
• Diarrhea

Frequency 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 allergic reaction to one of the components of the product.

Additional adverse reactions have been observed with brimonidine or timolol, and therefore could also occur with COMBIGAN.

The following adverse reactions have additionally been observed with brimonidine:

• Eye inflammation, small pupils, difficulty sleeping, cold-like symptoms, breathing difficulties, stomach and digestive symptoms, general allergic reactions, skin reactions including redness, facial swelling, itching, skin rash, and dilation of blood vessels

Like any other eye medicine, COMBIGAN (brimonidine/timolol) is absorbed into the bloodstream. The absorption of timolol, a beta-blocking component of COMBIGAN, may cause adverse reactions similar to those observed with intravenous and/or oral beta-blockers. The incidence of adverse reactions following topical ophthalmic administration is lower than with oral or injected medications.

The following adverse reactions have been observed with the use of beta-blockers in treating eye diseases:

• Generalized allergic reactions, including swelling under the skin (may occur in areas such as the face or limbs, and may lead to airway obstruction and difficulty swallowing or breathing), urticaria (itchy rash), localized or generalized skin rash, itching, sudden severe allergic reaction that may be life-threatening
• Low blood sugar levels
• Difficulty sleeping (insomnia), nightmares, memory loss, hallucinations
• Stroke, reduced blood supply to the brain, worsening of symptoms of myasthenia gravis (a muscle disorder), unusual sensations (such as tingling)
• Inflammation of the cornea, detachment of the retinal layer containing blood vessels after filtration surgery, which may cause vision disturbances, reduced corneal sensitivity, fluid-filled cysts forming at the back of the eye causing blurred vision, corneal erosion (damage to the front layer of the eyeball), drooping eyelid (eye appears half-closed), double vision. Chronic conjunctivitis (swelling or inflammation of the transparent layer covering the eye surface) with scarring of the conjunctiva (outer transparent layer of the eye); reduced vision
• Chest pain, edema (fluid accumulation), changes in speed or rhythm of heartbeat, certain heart rhythm disorders, heart attack, heart failure
• Raynaud's phenomenon, cold hands and feet
• Constriction of lung airways (mainly in patients with pre-existing disease), breathing difficulties, cough
• Indigestion, abdominal pain, vomiting
• Hair loss, white-silver colored skin rash (psoriasiform rash) or worsening of psoriasis, skin rash
• Muscle pain not caused by exercise
• Sexual dysfunction, decreased libido
• Muscle weakness/fatigue

Other adverse effects reported with eye drops containing phosphate:

Very rare cases of corneal calcification associated with the use of eye drops containing phosphates have been reported in some patients with significantly damaged corneas.

Reporting of adverse effects:

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of COMBIGAN

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

Store the container in the outer packaging to protect it from light.

Do not use more than one container at the same time.

Do not use this medicine after the expiry date stated on the carton and on the container after EXP. The expiry date refers to the last day of the month indicated.

Discard the container four weeks after first opening, even if there are still some drops remaining. This will help prevent infections. To help you remember, write the date of first opening in the space provided on the carton.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused containers and medicines at the SIGRE Point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of unused containers and medicines. This will help protect the environment.

6. Contents of the pack and other information

Composition of COMBIGAN

• The active substances are brimonidine tartrate and timolol.
• One ml of solution contains 2 mg of brimonidine tartrate and timolol maleate equivalent to 5 mg of timolol.
• The other components are: benzalkonium chloride (as a preservative), monobasic sodium phosphate monohydrate, dibasic sodium phosphate heptahydrate, and purified water. Small amounts of hydrochloric acid or sodium hydroxide may be added to adjust the pH level (determination of the acidity or alkalinity of the solution).

Appearance of the product and contents of the container

COMBIGAN is a clear, slightly greenish-yellow eye drop solution in a plastic container with a screw cap. Each container is filled to approximately half its capacity and contains 5 ml of solution. Boxes containing 1 or 3 containers are available. Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

AbbVie Spain, S.L.U.

Avenida de Burgos 91,

28050 Madrid

Spain

Manufacturer:

Allergan Pharmaceuticals Ireland

Castlebar Road

Westport, Co Mayo

Ireland

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Date of the most recent review of this leaflet: 11/2025

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

To request a copy of this leaflet in large print, please contact the local representative of the marketing authorization holder.