Patient information on Combigan

 Manufactured by: Allergan.

What is Combigan used for?

Combigan treats open-angle glaucoma, a condition involving a rise in the eyes pressure because of the inability of the ocular fluid to get discharged.

What is the dosage form Combigan? It is a solution intended to be inserted in the eyes only.

What should you know about Combigan?

  • Monitor blood glucose levels regularly if you are diabetic and using blood glucose lowering medications, as this drug can mask the signs of reduced blood sugar which can prove fatal to the patient.
  • Combigan eye drops are not to be used unless told by the ophthalmologist if you have asthma or another sort of obstructive condition in your lungs.
  • Combigan should not be administered if you have developed a serious heart condition, or are suffering from heart failure.
  • Children should not use Combigan.
  • Combigan can produce hypersensitivity reactions in susceptible patients which may require medical help.
  • Systemic adverse effects of this drug can occur even on topical use.
  • Consult your doctor before using Combigan, if you suffer from depression or conditions that reduce the blood flow to brain or heart or any other area of the body, or if you experience severe orthostatic hypotension i.e. a headache or dizziness on standing up from sitting or lying posture because of the rushing and pooling of blood to the lower extremities.
  • You might be asked to have a thyroid test if your doctor suspects an effect of Combigan on them.
  • Do not use Combigan in the situations or conditions which may have traumatized or injured your eye.
  • Remove contact lenses before instilling Combigan drops in the damaged eye.
  • This drug can make you tired and sleepy; avoid performing activities that require mental skills.

Dosing Considerations: as told by the ophthalmologist.

How to take the drug?

  • Your hands should be washed before and after using Combigan.
  • Administer the drug in exact quantity as prescribed.
  • Do not use it longer than recommended before consulting your ophthalmologist.
  • Agents in Combigan can discolor contact lenses, so remove the contacts before instilling the drops and wait for about 15 minutes before reinserting them.
  • Store this product at 15°-25°C.

What kind of side-effects does this drug have?

Inflamed conjunctiva, Itching, burning and stinging dryness, redness, pain in the eyes, Blurry vision, Visual disturbances, General feeling of weakness, Erosion of the cornea, a condition in which corneal outermost layer fails to attach to the underlying basement membrane, Depressive mood swings, Watery discharge from the eyes, Swollen eyelids, Foreign body sensation, fatigue, Headache, High blood pressure.

Contra-indications and precautions:

  • Combigan is prohibited in patients with heart failure and in blockage of cardiac vessels.
  • Combigan use is unsafe in children.
  • Timolol used in this drug can worsen the active respiratory conditions of asthma and chronic obstructive pulmonary disease.
  • Combigan is not to be used alone for acute angle-closure glaucoma treatment.
  • Avoid its use unless recommended by your physician if you have muscle weakness or paralysis.
  • Diabetic patients require regular blood sugar monitoring as this drug may hide the hypoglycemic i.e. low sugar levels.
  • It can also mask the symptoms of hyperthyroidism, which could be clinically significant.
  • It can cause syncope, severe dizziness and low pulse which may require monitoring.

How can Combigan interact with the other drugs?

  • Calcium Antagonists: calcium channel blockers e.g. amlodipine, nifedipine, diltiazem, verapamil etc. when given together with Combigan can result in failure of the left side of the heart, severe low blood pressure.
  • Other beta-blockers: Timolol itself is a beta receptor blocker, and use of more than one such agent can lead to augmented response/effects.
  • CYP2D6 Inhibitors: collective treatment of CYP2D6 inhibitors (e.g., quinidine, SSRIs) and Timolol results in decreased heart rate and depression medically designated as systemic beta-blockade.
  • Alcohol: use of alcohol with Combigan can cause profound CNS depression.
  • Monoamine Oxidase Inhibitors: when given with the agent brimonidine can lead to severely low blood pressure conditions.
  • Antihypertensives/Cardiac Glycosides: co-use of these medicines can reduce the blood pressures to a dangerously low level.

Can this drug be used by all kinds of people?

  • In pediatrics: it is not safe to give Combigan to children under 2.
  • In geriatrics: Combigan is safe for elderlies unless objected by the professionals.
  • In nursing mothers: not known if brimonidine gets secreted in human milk but it is well known that timolol gets secreted in it. Your doctor will only prescribe this drug when it is truly required and no other alternatives can be used.
  • In pregnancy: It should only be used when your doctor is certain of the benefits of this drug during your pregnancy as it is a category C

What is its mechanism of action?

Combigan possesses two active agents namely; Timolol and Brimonidine.

Combigan is a moderately particular alpha-2 adrenergic receptor agonist with a non-specific beta-adrenergic receptor inhibitor. Both brimonidine and timolol have a quick onset of activity.

What is the pharmacokinetics of the drug?

Absorption: brimonidine and timolol reach their peak plasma levels after absorption within 1-4 hours and 1-3 hours respectively.

Distribution: the binding of brimonidine to proteins present in the plasma is yet to be studied whereas about 60% of timolol binds to these proteins.

Metabolism and excretion: brimonidine is vastly metabolized by enzymatic systems present in the liver. Contrary, timolol has limited metabolism in the liver. The chief route of excretion for these compounds is urine.

Toxicology of brimonidine: it is not cancer causing drug. Brimonidine tartrate was not found mutagenic and did not cause alterations at the chromosomal level.

Toxicology of Timolol:

Test subjects developed adrenal tumors by timolol. Animal subjects also developed lung cancer and females developed mammary gland tumors after receiving timolol at higher doses.

Neither of the drugs had any adverse action on the reproducing organs of the animals.

What are the ingredients used in Combigan?

Active ingredients: brimonidine tartrate 0.2% and timolol 0.5%.

Inactive ingredients: benzalkonium chloride 0.005%; sodium phosphate, monobasic; sodium phosphate, dibasic; purified water; and hydrochloric acid and/or sodium hydroxide to adjust pH.

What is important for your doctor to be aware of?

You should always inform your doctor about the other health problems (if you have any) and if you are undergoing treatment with other medications for a condition diagnosed previously.


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