Combigan (brimonidine/timolol)

Combigan general information

What is Combigan used for?

Combigan eye drops are used to lower pressure within the eye known as intraocular pressure (IOP) caused by a build-up of fluid (aqueous humour). This increased pressure can cause glaucoma, which defines a group of eye disorders that affect the optic nerve, causing damage to the optic nerve fibres leading out of the back of the eye to the brain and may lead to gradual loss of sight, starting with peripheral vision and eventually to total blindness in that eye. Combigan eye drops are used to treat open angle glaucoma, which is the most common form of glaucoma; also ocular hypertension, which is increased IOP without ocular nerve damage. Combigan eye drops contain a combination of two glaucoma medications and are used for people who do not respond sufficiently to a single medication, where a single medication does not lower IOP sufficiently. Combining two medications also makes it easier to take than separate eye drops.

How does Combigan work?

Combigan eye drops contain a combination of two glaucoma medications with different mechanisms of action. Brimonidine is an alpha-2 adrenergic agonist that binds selectively to the alpha-1 adrenergic receptor that is found in many cells throughout the body, including the ciliary bodies of the eye. The ciliary bodies continually produce the eye fluid called aqueous humour, as a result of filtration from the capillaries (small blood vessels). Timolol is a non-selective beta-adrenergic receptor blocker that in its oral form is used to treat hypertension and prevent heart attack, however, in its ophthalmic form it is used to treat glaucoma. Normally eye fluid drains out of the eye through the spongy tissue called the trabecular network between the cornea and the iris, which is the conventional drainage route. If this drainage system becomes blocked, fluid is produced at a faster rate than it is drained away and this causes an increase in intraocular pressure (IOP) that can cause glaucoma. Brimonidine in Combigan eye drops has a dual mechanism of action and works by acting on the alpha-1 adrenergic receptors in the eye to reduce aqueous humor production and enhance uveoscleral outflow through the ciliary body where the aqueous is produced, which is the alternative route for drainage. Timolol in Combigan eye drops binds to the beta receptors on the ciliary epithelium and blocks their action, which reduces the production of aqueous humour. The combined action of brimonidine and timolol in Combigan eye drops has an additive effect with greater reduction in IOP when used together than when each medication is used separately. This helps restore the balance in the flow of fluid into and out of the eye to reduce IOP and the risk of damage to the optic nerve, which helps prevent loss of sight that can happen if glaucoma progresses untreated. Combigan has a rapid onset of action with a peak reduction in IOP within two hours of starting to use the eye drops.

What does Combigan contain?

Combigan eye drops contain the active ingredients brimonidine (0.2%), an alpha-2 adrenergic agonist and timolol (0.5%). They also contain benzalkonium chloride, sodium phosphate, monobasic monohydrate, sodium phosphate, dibasic heptahydrate, hydrochloric acid or sodium hydroxide to adjust pH, purified water.

Treating glaucoma with Combigan

Combigan eye drops contain a combination of two medications that are used together to treat glaucoma, which is caused by an increase in pressure within the eye known as intraocular pressure (IOP). The ciliary bodies of the eye continually produce the eye fluid called aqueous humour, as a result of filtration from the capillaries (small blood vessels). If there is a build-up of aqueous humour, this increases IOP and can result in damage to the optic nerve fibres leading out of the back of the eye to the brain, which may lead to gradual loss of sight, starting with peripheral vision and eventually to total blindness in that eye. Normally the eye fluid drains out of the eye through the spongy tissue called the trabecular network between the cornea and the iris, which is the conventional drainage route. If this drainage system becomes blocked, fluid is produced at a faster rate that it is drained away and this causes an increase in intraocular pressure (IOP) that can cause glaucoma. Brimonidine in Combigan eye drops is an alpha-2 adrenergic agonist that binds selectively to the alpha-1 adrenergic receptor and has a dual mechanism of action. It works by acting on the alpha-1 adrenergic receptors in the eye to reduce aqueous humor production and enhance uveoscleral outflow through the ciliary body where the aqueous is produced, which is the alternative route for drainage. Timolol in Combigan eye drops is a non-selective beta-adrenergic receptor blocker that binds to the beta receptors on the ciliary epithelium and blocks their action, which reduces the production of aqueous humour. The combined action of brimonidine and timolol in Combigan eye drops increases the reduction in IOP when used together to a greater extent than when each medication is used separately. This helps restore the balance in the flow of fluid into and out of the eye to reduce IOP and the risk of damage to the optic nerve, which helps prevent loss of sight that can happen if glaucoma progresses untreated.

What are the side effects of Combigan?

The most commonly reported side effects when taking Combigan eye drops include: burning, stinging, itching eyes, conjunctivitis, dry eyes, watering and redness of the eye, allergic reactions including redness and swelling of the eye, swelling of the eyelid (blepharitis), blurred vision, inflammation of the cornea (keratitis), sensitivity to light, irritation or feeling of having something in the eye, abnormal taste, nausea, diarrhoea, dryness of the mouth, upper respiratory symptoms, asthenia, headache, fatigue, drowsiness, dizziness, headache, weakness. Other reported side effects include cardiovascular effects like change in heart beat and palpitations.

When should Combigan not be used?

You should not use Combigan eye drops if you:

• are allergic to brimonidine, timolol or any ingredients in Combigan
• are pregnant or are breastfeeding
• have kidney or liver disease
• have a history of severe allergic reaction or anaphylactic reaction, as timolol may cause you to be more reactive
• wear soft contact lenses; you should remove your contacts and replace them after using Combigan eye drops
• have bronchial asthma or other obstructive lung disorders or a history of bronchospasm
• have certain heart conditions, such as severe, unstable, uncontrolled heart failure, cardiogenic shock or sick sinus syndrome
• have severe peripheral circulatory disturbance/disorders, such as Raynaud's syndrome
• have diabetes or over active thyroid as timolol may mask signs and symptoms
• have a very slow heart rate (severe bradycardia)
• are taking medicines that interact with Combigan, including: other beta-blockers, such as some medicines for high blood pressure or heart conditions, the antiarrhythmic quinidine, antidepressants including monoamine oxidase (MAO) inhibitor, tricyclics and SSRIs, digoxin for heart failure, the antipsychotic and antihypertensive reserpine, calcium channel blockers like nifedipine and diltiazem, the antihypertensives guanethidine and hydralazine, cimetidine for reflux

What medications interact with Combigan?

Several medications interact with Combigan and should either not be taken while you are taking Combigan or only after discussion and instruction from your doctor:

• Drugs that cause a serious reaction with Combigan: the antiarrhythmic quinidine, calcium channel blockers like nifedipine and diltiazem, digoxin for heart failure, the antipsychotic and antihypertensive reserpine, monoamine oxidase (MAO) inhibitors for depression
• Drugs that affect Combigan: SSRI antidepressants, cimetidine for reflux, the antihypertensive hydralazine
• Drugs that are affected by Combigan: other beta-blockers, such as some medicines for high blood pressure or heart conditions

How should Combigan be taken?

You should take your Combigan eye drops by applying one drop into the affected eye, twice daily, and following the instructions provided. If you are wearing contact lenses, you should remove them before applying your Combigan eye drops and then replace them at least 15 minutes after applying your eye drops. You should continue to use your Combigan eye drops daily for as long as recommended by your doctor, which may be for several months or years, as they will help maintain normal eye pressure but will not cure glaucoma.

How long should you take Combigan?

You should continue to use your Combigan eye drops daily for as long as recommended by your doctor, which may be for several months or years, as they will help maintain normal eye pressure but will not cure glaucoma.

Missed dose of Combigan

If you miss a dose of Combigan take it as soon as you remember, unless it is time to take the next dose, then skip the missed dose. Do not take a double dose.

How should Combigan be stored?

You should store your Combigan below 25°C in a cool dry place and protect from light.