Combigan

Generic name: brimonidine and timolol ophthalmic
Drug class: Ophthalmic glaucoma agents

Medically reviewed by  A Ras MD.

What is Combigan?

Combigan is a prescription medicine that is used to treat glaucoma. It is used to lower high eye pressure.

Description

COMBIGAN® (brimonidine tartrate/timolol maleate ophthalmic solution) 0.2%/0.5%, sterile, is a relatively selective alpha-2 adrenergic receptor agonist with a non-selective beta-adrenergic receptor inhibitor (topical intraocular pressure lowering agent).

The structural formulae are:

Brimonidine tartrate:

5-bromo-6-(2-imidazolidinylideneamino) quinoxaline L-tartrate; MW= 442.24

Timolol maleate:

(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)-oxy]-2-propanol maleate (1:1) (salt); MW= 432.50 as the maleate salt

In solution, COMBIGAN® (brimonidine tartrate/timolol maleate ophthalmic solution) 0.2%/0.5% has a clear, greenish-yellow color. It has an osmolality of 260-330 mOsmol/kg and a pH during its shelf life of 6.5-7.3.

Brimonidine tartrate appears as an off-white, or white to pale-yellow powder and is soluble in both water (1.5 mg/mL) and in the product vehicle (3 mg/mL) at pH 7.2. Timolol maleate appears as a white, odorless, crystalline powder and is soluble in water, methanol, and alcohol.

Each mL of COMBIGAN® contains the active ingredients brimonidine tartrate 0.2% and timolol 0.5% with the inactive ingredients benzalkonium chloride 0.005%; sodium phosphate, monobasic; sodium phosphate, dibasic; purified water; and hydrochloric acid and/or sodium hydroxide to adjust pH.

  Mechanism of Action

COMBIGAN® is comprised of two components: brimonidine tartrate and timolol. Each of these two components decreases elevated intraocular pressure, whether or not associated with glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. The higher the level of intraocular pressure, the greater the likelihood of glaucomatous field loss and optic nerve damage.

COMBIGAN® is a relatively selective alpha-2 adrenergic receptor agonist with a non-selective beta-adrenergic receptor inhibitor. Both brimonidine and timolol have a rapid onset of action, with peak ocular hypotensive effect seen at two hours post-dosing for brimonidine and one to two hours for timolol.

Fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow.

Timolol maleate is a beta1 and beta2 adrenergic receptor inhibitor that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity.

Before taking Combigan, tell your doctor:

For all patients taking Combigan:

• If you are allergic to Combigan; any part of this medicine; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
• If you have any of these health problems: Asthma or other breathing problems like COPD (chronic obstructive pulmonary disease).
• If you have any of these health problems: Heart block, shock caused by heart problems, or slow heartbeat.
• If you have heart failure (weak heart).
• If you are using another drug like this one. If you are not sure, ask your doctor or pharmacist.
• If you are breast-feeding or plan to breast-feed.

Children:

• If your child is younger than 2 years of age. Do not give Combigan to a child younger than 2 years of age.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Combigan with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take Combigan?

• Tell all of your health care providers that you take Combigan. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert or have clear eyesight until you see how Combigan affects you.
• This medicine may hide the signs of low blood sugar. Talk with the doctor.
• Have your eye pressure and eyesight checked as you have been told by the doctor.
• Tell your doctor if you have an eye infection, eye injury, or will be having eye surgery.
• Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
• Very bad and sometimes deadly breathing problems have happened with Combigan in patients with asthma. Talk with the doctor.
• Very bad and sometimes deadly heart problems like heart failure have happened with Combigan. Talk with the doctor.
• If you have had a very bad allergic reaction, talk with your doctor. You may have a chance of an even worse reaction if you come into contact with what caused your allergy. If you use epinephrine to treat very bad allergic reactions, talk with your doctor. Epinephrine may not work as well while you are taking Combigan.
• This medicine may make it harder to tell if you have signs of an overactive thyroid like fast heartbeat. If you have an overactive thyroid and stop taking Combigan all of a sudden, it may get worse and could be life-threatening. Talk with your doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Combigan while you are pregnant.

How is Combigan best taken?

Use Combigan as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• For the eye only.
• Take out contact lenses before using Combigan. Lenses may be put back in 15 minutes after Combigan is given. Do not put contacts back in if your eyes are irritated or infected.
• Do not touch the container tip to the eye, lid, or other skin.
• Wash your hands before and after use.
• Tilt your head back and drop drug into the eye.
• After use, keep your eyes closed. Put pressure on the inside corner of the eye. Do this for 1 to 2 minutes. This keeps the drug in your eye.
• Blot extra solution from the eyelid.
• If more than 1 drug is being used in the same eye, use each drug at least 5 minutes apart.
• Use as you have been told, even if your signs get better.
• Do not use if solution changes color.
• Do not use if the solution is cloudy, leaking, or has particles.

What do I do if I miss a dose?

• Use a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not use 2 doses at the same time or extra doses.

What are the side effects of Combigan that I need to call my doctor about immediately?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Change in eyesight, eye pain, or very bad eye irritation.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• Slow heartbeat.
• A heartbeat that does not feel normal.
• Chest pain.
• Dizziness or passing out.
• Trouble breathing.
• Muscle weakness.

What are some other side effects of Combigan?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Eye irritation.
• Itching.
• Burning.
• Stinging.
• Feeling sleepy.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Combigan?

• Store at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.

Label

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