What is it used for?

• Open angle glaucoma.
• Raised pressure in the eye (ocular hypertension).

How does it work?

• Combigan eye drops contain two active ingredients, brimonidine tartrate and timolol maleate. These are both medicines that decrease raised pressure within the eye. They work in different ways to produce a combined effect greater than either medicine produces on its own.
• The pressure within the eyeball is naturally maintained by a continuous flow of liquid called aqueous humour through the eyeball. Aqueous humour is produced by a part of the eye called the ciliary body. It drains out of the eyeball through channels called the trabecular meshwork. If the outflow of aqueous humour is blocked, as in glaucoma, the aqueous humour builds up inside the eye, increasing the pressure within the eyeball. This pressure needs to be reduced, as otherwise it can damage the optic nerve and impair vision as a result.
• Brimonidine is a type of medicine called an alpha agonist. It works by stimulating alpha receptors found on the blood vessels that supply the ciliary body. This causes the blood vessels to constrict, and reduces the amount of watery fluid that filters out of the blood vessels to form aqueous humour. Brimonidine therefore works by reducing the inflow of aqueous humour into the eyeball, which decreases the pressure within the eye.
• Timolol is a type of medicine called a beta-blocker. These medicines block beta-receptors in various parts of the body. Blocking the beta receptors in the eye reduces the amount of aqueous humour that is produced. Timolol therefore also reduces the inflow of aqueous humour into the eyeball and so decreases the pressure within the eye.
• The combination of these two medicines is used to lower the pressure in the eye when a beta-blocker eye drop does not lower the pressure enough on its own.
• Eye drops are used to produce a local effect in the eye, with minimal effect on other parts of the body. You can further minimise the amount of medicine that is absorbed into your bloodstream and increase the local action in the eye by pressing on your tear duct (the corner of the eye closest to the nose) while putting in the eye drops and for a minute after.

Use with caution in

• Severe or unstable and uncontrolled disease involving the heart and blood vessels (cardiovascular disease).
• History of severe heart disease.
• Heart failure.
• Decreased blood supply to the heart (coronary insufficiency), eg people with angina.
• A severe form of angina pectoris, not caused by exertion (Prinzmetal's angina).
• Decreased blood supply to the brain (cerebral insufficiency), eg people who have had a stroke or mini-stroke (transient ischaemic attack).
• Low blood pressure (hypotension).
• People who experience drops in blood pressure when going from lying down to sitting or standing, that result in dizziness and light-headedness (postural hypotension).
• Severe disorders of blood circulation.
• Narrowing of the blood vessels in the hands, causing numb and painful fingers (Raynaud's disease).
• Progressive disease involving narrowing of the blood vessels in the legs (thromboangiitis obliterans).
• Increase in the acidity of the blood (metabolic acidosis).
• Untreated tumour of the adrenal gland (phaeochromocytoma).
• Decreased kidney function.
• Decreased liver function.
• Diabetes.
• People who suffer from drops in blood sugar (hypoglycaemia).
• Overactive thyroid gland (hyperthyroidism).
• Depression.
• History of allergies.
• Psoriasis.
• Abnormal muscle weakness (myaesthenia gravis).

Not to be used in

• Asthma or history of asthma.
• Severe chronic obstructive pulmonary disease (COPD).
• Slow heart rate caused by the pacemaker of the heart (sinus bradycardia).
• Serious defect in the heart's electrical message pathways resulting in decreased function of the heart (2nd or 3rd degree heart block).
• Uncontrolled heart failure.
• Failure of the heart to maintain adequate circulation of blood (cardiogenic shock).
• People taking monoamine oxidase inhibitor (MAOI) or tricyclic antidepressants or mianserin.
• Breastfeeding.
• Babies and infants under two years of age.
• This medicine is also not recommended for children or adolescents aged 2 to 17 years of age, because its safety and effectiveness have not been established in this age group. There is a high risk of sleepiness if used in children who are aged two to seven years or weigh less than 20kg.
• This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

• Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.
• The safety of this medicine during pregnancy has not been established. It should not be during pregnancy unless considered essential by your doctor, as it may be absorbed into the bloodstream and could be harmful to the unborn baby. Seek medical advice from your doctor.
• It is not known if brimonidine passes into breast milk, however, timolol does pass into breast milk after application to the eye. These eye drops should not be used by breastfeeding mothers. Seek medical advice from your doctor.

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect.

Very common (affects more than 1 in 10 people)

• Red eye due to increased blood supply (hyperaemia).
• Burning sensation in the eye.

Common (affects between 1 in 10 and 1 in 100 people)

• Eye stinging, itching, irritation, dryness, pain or discharge.
• Inflammation of the membrane that lines the inside of the eyelids and outside of the eyeball, causing redness and discharge (conjunctivitis).
• Inflammation of the eyelids (blepharitis).
• Corneal erosion.
• Sensation of something being in the eye.
• Eyelid swelling, redness or itching.
• Sleepiness.
• Feeling weak or fatigued.
• Headache.
• Dry mouth.
• Increased blood pressure.
• Depression.

Uncommon (affects between 1 in 100 and 1 in 1000 people)

• Dislike of light (photophobia).
• Dizzines or fainting.
• Awareness of your heart beat (palpitations).
• Nasal inflammation or dryness.
• Abnormal taste.
• Heart failure.

The side effects listed above may not include all of the side effects reported by the medicine's manufacturer.

For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

• The brimonidine and timolol in these eye drops could be absorbed into the bloodstream in low amounts after application to the eye and could therefore interact with other medicines that you are taking by mouth, injection, skin patch or suppository. You should tell your doctor or pharmacist what medicines you are already using, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before starting any new medicines while using this one, to ensure that the combination is safe.

If you are using more than one type of eye drop you should administer them at least five minutes apart, to prevent the second drop washing away the first. Use eye gels or ointments last.

The manufacturer states that these eye drops should not be used by people taking any of the following medicines:

• monoamine oxidase inhibitor (MAOIs), eg the antidepressants phenelzine, tranylcypromine or isocarboxacid (these eye drops should not be started until 14 days after stopping treatment with an MAOI)
• tricyclic antidepressants, eg amitriptyline, imipramine
• related antidepressants, eg mianserin.

In people with diabetes, timolol can prolong the lowering of blood sugar (hypoglycaemia) caused by insulin or other antidiabetic medicines. People with diabetes should monitor their blood sugar while using these eye drops, as timolol can also mask the signs of hypoglycaemia.

The timolol in these eye drops may enhance the effects of the following medicines taken by mouth, which may result in low blood pressure and/or a slowed heart rate:

• beta-blockers, eg atenolol
• calcium channel blockers, eg nifedipine, verapamil, diltiazem
• digoxin
• medicines for abnormal heart rhythms (antiarrhythmics), eg amiodarone
• medicines for high blood pressure.

If the medicine clonidine is suddenly stopped it can cause an increase in blood pressure. This increase in blood pressure may be worse in people taking beta-blockers, including eye drops such as this one.

Beta-blockers oppose the action of medicines for asthma that open the airways, which is why these eye drops should not be used by people with asthma or other breathing difficulties.

References:

https://www.combigan.com/patient/Default.aspx

https://www.netdoctor.co.uk/medicines/eye-care/a7195/combigan-eye-drops-brimonidine-timolol/

https://www.webmd.com/drugs/2/drug-149680/combigan-ophthalmic-eye/details

https://www.medicines.org.uk/emc/product/3909/pil

https://chealth.canoe.com/drug/getdrug/combigan