Combigan 0.2/0.5% Solution 15ml
It is used to treat glaucoma.It is used to lower high eye pressure.
Drug Class
Antiglaucoma Agents, Ophthalmic
Pharmacologic Class
Alpha-2 Adrenergic Agonist (Brimonidine) & Non-selective Beta-Adrenergic Blocker (Timolol)
Pregnancy Category
Category C
FDA Approved
Apr 2007
DEA Schedule
Not Controlled
Overview
What is this medicine?
Combigan is an eye drop medication used to lower high pressure inside the eye, which can lead to glaucoma. It contains two medicines: brimonidine, which reduces fluid production and helps fluid drain from the eye, and timolol, which also reduces fluid production. Together, they work to protect your vision.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is for use in the eyes only.
Before Using
Remove your contact lenses before applying the medication. You can put them back in 15 minutes after use, but only if your eyes are not irritated or infected.
Wash your hands thoroughly before and after handling the medication.
Applying the Medication
Tilt your head back and gently drop the medication into your eye.
After applying, keep your eyes closed and apply gentle pressure to the inside corner of your eye for 1 to 2 minutes. This helps the medication stay in your eye.
Gently blot any excess solution from your eyelid.
Using Multiple Medications
If you are using more than one medication in the same eye, wait at least 5 minutes between applications.
Important Safety Precautions
Do not touch the container tip to your eye, lid, or surrounding skin, as this can contaminate the medication and lead to severe eye problems or vision loss.
Continue using the medication as directed, even if your symptoms improve.
Do not use the medication if the solution changes color, becomes cloudy, or contains particles.
Storage and Disposal
Store the medication at room temperature, protected from light and moisture. Do not store it in a bathroom.
Keep the medication out of reach of children and pets.
Dispose of unused or expired medication according to the instructions provided. Do not flush it down the toilet or pour it down the drain unless instructed to do so. Check with your pharmacist for guidance on proper disposal and potential drug take-back programs in your area.
Missed Dose
If you miss a dose, use it as soon as you remember.
If it is close to the time for your next dose, skip the missed dose and resume your regular schedule.
* Do not use two doses at once or take extra doses.
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is for use in the eyes only.
Before Using
Remove your contact lenses before applying the medication. You can put them back in 15 minutes after use, but only if your eyes are not irritated or infected.
Wash your hands thoroughly before and after handling the medication.
Applying the Medication
Tilt your head back and gently drop the medication into your eye.
After applying, keep your eyes closed and apply gentle pressure to the inside corner of your eye for 1 to 2 minutes. This helps the medication stay in your eye.
Gently blot any excess solution from your eyelid.
Using Multiple Medications
If you are using more than one medication in the same eye, wait at least 5 minutes between applications.
Important Safety Precautions
Do not touch the container tip to your eye, lid, or surrounding skin, as this can contaminate the medication and lead to severe eye problems or vision loss.
Continue using the medication as directed, even if your symptoms improve.
Do not use the medication if the solution changes color, becomes cloudy, or contains particles.
Storage and Disposal
Store the medication at room temperature, protected from light and moisture. Do not store it in a bathroom.
Keep the medication out of reach of children and pets.
Dispose of unused or expired medication according to the instructions provided. Do not flush it down the toilet or pour it down the drain unless instructed to do so. Check with your pharmacist for guidance on proper disposal and potential drug take-back programs in your area.
Missed Dose
If you miss a dose, use it as soon as you remember.
If it is close to the time for your next dose, skip the missed dose and resume your regular schedule.
* Do not use two doses at once or take extra doses.
Lifestyle & Tips
- Wash hands thoroughly before and after using eye drops.
- Do not touch the dropper tip to any surface (eye, finger, etc.) to prevent contamination.
- Tilt your head back, pull down your lower eyelid to form a pocket, and instill one drop. Close your eye gently for 1-2 minutes, applying pressure to the inner corner of your eye (near the nose) to minimize systemic absorption.
- If using other eye drops, wait at least 5 minutes between applications.
- Remove contact lenses before instilling drops and wait at least 15 minutes before reinserting them.
- Do not wear soft contact lenses if your eyes are irritated or red.
- Store at room temperature, away from light and moisture.
- Do not discontinue use without consulting your doctor, as this can lead to increased eye pressure and vision loss.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
One drop in the affected eye(s) twice daily, approximately 12 hours apart.
Pediatric Dosing
Neonatal:
Not established (Contraindicated in children under 2 years)
Infant:
Not established (Contraindicated in children under 2 years)
Child:
Not established (Use with caution in children 2-17 years; monitor for systemic effects)
Adolescent:
One drop in the affected eye(s) twice daily, approximately 12 hours apart (Use with caution; monitor for systemic effects)
Dose Adjustments
Renal Impairment:
Mild:
No specific adjustment recommended, use with caution.
Moderate:
No specific adjustment recommended, use with caution due to potential for increased systemic exposure.
Severe:
No specific adjustment recommended, use with caution due to potential for increased systemic exposure.
Dialysis:
Considerations: Use with caution; systemic exposure may be increased. Monitor for adverse effects.
Hepatic Impairment:
Mild:
No specific adjustment recommended, use with caution.
Moderate:
No specific adjustment recommended, use with caution due to potential for increased systemic exposure.
Severe:
No specific adjustment recommended, use with caution due to potential for increased systemic exposure.
Confidence:
Medium
Pharmacology
Mechanism of Action
Combigan is a fixed combination of two active ingredients: Brimonidine tartrate and Timolol maleate. Brimonidine is an alpha-2 adrenergic agonist that reduces aqueous humor production and increases uveoscleral outflow. Timolol is a non-selective beta-adrenergic blocker that reduces aqueous humor production. The combined action results in a synergistic reduction of intraocular pressure (IOP).
Pharmacokinetics
Absorption:
Bioavailability:
Brimonidine: Low systemic bioavailability (approx. 1-10% after ophthalmic administration). Timolol: Systemic absorption occurs after ophthalmic administration, with peak plasma concentrations typically reached within 1-2 hours.
Tmax:
Brimonidine: 1-4 hours (plasma). Timolol: 1-2 hours (plasma).
FoodEffect:
Not applicable for ophthalmic solution.
Distribution:
Vd:
Not available (for ophthalmic use, systemic Vd is less relevant).
ProteinBinding:
Brimonidine: Approximately 29%. Timolol: Approximately 60%.
CnssPenetration:
Limited (for ophthalmic use, but systemic absorption can lead to CNS effects).
Elimination:
HalfLife:
Brimonidine: Approximately 3 hours (terminal half-life). Timolol: Approximately 4-6 hours.
Clearance:
Not available (systemic clearance values are less relevant for ophthalmic use).
ExcretionRoute:
Brimonidine: Primarily renal (as metabolites). Timolol: Primarily renal (as metabolites and unchanged drug).
Unchanged:
Brimonidine: Minimal. Timolol: Approximately 20% unchanged in urine.
Pharmacodynamics
OnsetOfAction:
Within 30 minutes (for IOP reduction).
PeakEffect:
Approximately 2-8 hours.
DurationOfAction:
Up to 12 hours.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Attention Immediately
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ 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
+ Swelling of the mouth, face, lips, tongue, or throat
Changes in eyesight, eye pain, or severe eye irritation
Slow heartbeat
Abnormal heartbeat
Chest pain
Dizziness or fainting
Muscle weakness
In rare cases, this medication has been associated with serious heart problems, which can be fatal. If you experience any of the following symptoms, contact your doctor immediately:
Shortness of breath
Sudden significant weight gain
Swelling in the arms or legs
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms that bother you or do not go away, contact your doctor or seek medical help:
Eye irritation
Itching
* Burning or stinging
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ 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
+ Swelling of the mouth, face, lips, tongue, or throat
Changes in eyesight, eye pain, or severe eye irritation
Slow heartbeat
Abnormal heartbeat
Chest pain
Dizziness or fainting
Muscle weakness
In rare cases, this medication has been associated with serious heart problems, which can be fatal. If you experience any of the following symptoms, contact your doctor immediately:
Shortness of breath
Sudden significant weight gain
Swelling in the arms or legs
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms that bother you or do not go away, contact your doctor or seek medical help:
Eye irritation
Itching
* Burning or stinging
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Severe eye pain, redness, or swelling
- Vision changes or blurred vision that doesn't resolve
- Signs of an allergic reaction (rash, itching, hives, swelling of face/lips/tongue/throat, difficulty breathing)
- Dizziness, lightheadedness, or fainting
- Very slow or irregular heartbeat
- Shortness of breath, wheezing, or difficulty breathing
- Unusual tiredness or weakness
- Depression or mood changes
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the symptoms you experienced during an allergic reaction.
Certain health conditions, including:
+ Breathing problems, such as asthma or chronic obstructive pulmonary disease (COPD)
+ Heart block or heart failure (weak heart)
+ Shock caused by heart problems
+ Slow heartbeat
If you are currently taking another medication similar to this one. If you are unsure, consult your doctor or pharmacist.
Special Considerations for Children:
This medication is not recommended for children under 2 years of age. Do not administer this medication to a child younger than 2 years old.
Additional Important Information:
This list does not include all possible drug interactions or health problems that may be relevant to this medication.
Inform your doctor and pharmacist about all your medications, including prescription and over-the-counter drugs, natural products, and vitamins.
It is crucial to verify that it is safe to take this medication with all your other medications and health conditions.
Do not start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the symptoms you experienced during an allergic reaction.
Certain health conditions, including:
+ Breathing problems, such as asthma or chronic obstructive pulmonary disease (COPD)
+ Heart block or heart failure (weak heart)
+ Shock caused by heart problems
+ Slow heartbeat
If you are currently taking another medication similar to this one. If you are unsure, consult your doctor or pharmacist.
Special Considerations for Children:
This medication is not recommended for children under 2 years of age. Do not administer this medication to a child younger than 2 years old.
Additional Important Information:
This list does not include all possible drug interactions or health problems that may be relevant to this medication.
Inform your doctor and pharmacist about all your medications, including prescription and over-the-counter drugs, natural products, and vitamins.
It is crucial to verify that it is safe to take this medication with all your other medications and health conditions.
Do not start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Before engaging in activities that require alertness or clear vision, such as driving, wait until you understand how this medication affects you.
This drug may mask certain symptoms of low blood sugar, such as a rapid heartbeat, which can increase the risk of severe or prolonged hypoglycemia. This risk is particularly elevated in individuals with diabetes, children, and those who are fasting, including people undergoing surgery, experiencing abnormal eating patterns, or suffering from vomiting. If you have concerns, consult your doctor.
Regularly schedule appointments with your doctor to monitor your eye pressure and vision as advised.
Notify your doctor if you have an eye infection, suffer an eye injury, or are scheduled for eye surgery.
Before consuming alcohol, using marijuana or other cannabis products, or taking prescription or over-the-counter medications that may impair your reactions, discuss the potential risks with your doctor.
Although rare, severe respiratory problems have occurred in individuals taking this medication, sometimes with fatal outcomes, particularly in those with asthma. If you have questions or concerns, consult your doctor.
If you have a history of severe allergic reactions, inform your doctor, as you may be at a higher risk of an even more severe reaction upon re-exposure to the allergen. Additionally, if you rely on epinephrine to treat severe allergic reactions, consult your doctor, as this medication may reduce the effectiveness of epinephrine.
This drug may also obscure symptoms of hyperthyroidism, such as a rapid heartbeat. If you have hyperthyroidism and abruptly stop taking this medication, your condition may worsen, potentially becoming life-threatening. Consult your doctor for guidance.
If you are pregnant, plan to become pregnant, or are breastfeeding, discuss the benefits and risks of this medication with your doctor to ensure the best possible outcome for both you and your baby.
Before engaging in activities that require alertness or clear vision, such as driving, wait until you understand how this medication affects you.
This drug may mask certain symptoms of low blood sugar, such as a rapid heartbeat, which can increase the risk of severe or prolonged hypoglycemia. This risk is particularly elevated in individuals with diabetes, children, and those who are fasting, including people undergoing surgery, experiencing abnormal eating patterns, or suffering from vomiting. If you have concerns, consult your doctor.
Regularly schedule appointments with your doctor to monitor your eye pressure and vision as advised.
Notify your doctor if you have an eye infection, suffer an eye injury, or are scheduled for eye surgery.
Before consuming alcohol, using marijuana or other cannabis products, or taking prescription or over-the-counter medications that may impair your reactions, discuss the potential risks with your doctor.
Although rare, severe respiratory problems have occurred in individuals taking this medication, sometimes with fatal outcomes, particularly in those with asthma. If you have questions or concerns, consult your doctor.
If you have a history of severe allergic reactions, inform your doctor, as you may be at a higher risk of an even more severe reaction upon re-exposure to the allergen. Additionally, if you rely on epinephrine to treat severe allergic reactions, consult your doctor, as this medication may reduce the effectiveness of epinephrine.
This drug may also obscure symptoms of hyperthyroidism, such as a rapid heartbeat. If you have hyperthyroidism and abruptly stop taking this medication, your condition may worsen, potentially becoming life-threatening. Consult your doctor for guidance.
If you are pregnant, plan to become pregnant, or are breastfeeding, discuss the benefits and risks of this medication with your doctor to ensure the best possible outcome for both you and your baby.
Overdose Information
Overdose Symptoms:
- Bradycardia (slow heart rate)
- Hypotension (low blood pressure)
- Bronchospasm (difficulty breathing)
- Acute cardiac failure
- CNS depression (drowsiness, lethargy, somnolence, coma)
- Hypothermia
- Apnea
What to Do:
Seek immediate medical attention. Call 911 or your local emergency number. For poison control, call 1-800-222-1222. Treatment is supportive and symptomatic, including atropine for bradycardia, vasopressors for hypotension, bronchodilators for bronchospasm, and glucagon for refractory bradycardia/hypotension.
Drug Interactions
Contraindicated Interactions
- Monoamine Oxidase Inhibitors (MAOIs) (due to brimonidine component)
- Patients with bronchial asthma, a history of bronchial asthma, or severe chronic obstructive pulmonary disease (COPD) (due to timolol component)
- Sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, cardiogenic shock (due to timolol component)
Major Interactions
- Oral beta-adrenergic blocking agents (additive systemic beta-blockade)
- Calcium channel blockers (potential for AV conduction disturbances, left ventricular failure, and hypotension)
- Cardiac glycosides (potential for additive effects on AV conduction)
- Antiarrhythmics (e.g., amiodarone, quinidine - potential for additive cardiac effects)
- CNS depressants (e.g., alcohol, barbiturates, opiates, sedatives, anesthetics - additive CNS depression with brimonidine)
- Tricyclic antidepressants (may blunt the IOP-lowering effect of brimonidine)
- Adrenergic psychotropic drugs (e.g., chlorpromazine, methylphenidate, reserpine - potential for additive effects or hypotension)
Moderate Interactions
- Cimetidine, quinidine, fluoxetine, paroxetine (CYP2D6 inhibitors - may increase timolol plasma levels)
- Clonidine (potential for additive hypotensive effects)
- Systemic beta-agonists (e.g., albuterol - may reduce effectiveness of beta-blocker)
Minor Interactions
- Not specifically listed as minor, but general caution with other ophthalmic preparations to avoid washout.
Monitoring
Baseline Monitoring
Intraocular Pressure (IOP)
Rationale: To establish baseline and assess effectiveness of treatment.
Timing: Prior to initiation of therapy.
Heart Rate and Blood Pressure
Rationale: To assess for systemic beta-blocker effects (bradycardia, hypotension).
Timing: Prior to initiation of therapy.
Respiratory Status (e.g., lung sounds, history of asthma/COPD)
Rationale: To identify contraindications or risk of bronchospasm due to timolol.
Timing: Prior to initiation of therapy.
Cardiac History (e.g., heart failure, AV block)
Rationale: To identify contraindications or risk of cardiac adverse events due to timolol.
Timing: Prior to initiation of therapy.
Routine Monitoring
Intraocular Pressure (IOP)
Frequency: Regularly, as determined by ophthalmologist (e.g., 2-4 weeks after initiation, then every 3-6 months).
Target: Individualized target IOP, typically <21 mmHg or lower depending on disease severity.
Action Threshold: If IOP is not adequately controlled or increases, consider alternative therapy or adjunctive treatment.
Heart Rate and Blood Pressure
Frequency: Periodically, especially during initial therapy or dose changes.
Target: Maintain within patient's normal range; monitor for significant bradycardia (<50 bpm) or hypotension.
Action Threshold: Significant bradycardia, hypotension, or symptomatic cardiac effects warrant re-evaluation and potential discontinuation.
Ocular Examination (e.g., slit lamp, fundoscopy)
Frequency: Regularly, as part of glaucoma management.
Target: Not applicable.
Action Threshold: Development or worsening of ocular adverse effects (e.g., allergic conjunctivitis, blepharitis, blurred vision).
Symptom Monitoring
- Dizziness
- Fatigue
- Somnolence
- Blurred vision
- Eye irritation (redness, stinging, itching)
- Dry mouth
- Bradycardia
- Hypotension
- Shortness of breath or wheezing
- Signs of allergic reaction (rash, swelling)
Special Patient Groups
Pregnancy
Category C. Use only if the potential benefit justifies the potential risk to the fetus. Timolol has been associated with adverse effects in animal studies and has been detected in human breast milk. Brimonidine's effects on human pregnancy are not well-studied.
Trimester-Specific Risks:
First Trimester:
Potential for fetal harm, though data are limited. Avoid if possible.
Second Trimester:
Potential for fetal harm, though data are limited.
Third Trimester:
Potential for fetal harm, including bradycardia, hypotension, and respiratory depression in the neonate due to systemic absorption of timolol. Use with extreme caution or avoid.
Lactation
Timolol is excreted in human milk and has the potential for serious adverse reactions in nursing infants (e.g., bradycardia, respiratory depression). It is unknown whether brimonidine is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
Moderate to High risk due to timolol excretion in breast milk, potentially causing bradycardia, hypotension, and respiratory depression in the infant. Brimonidine risk is unknown but possible.
Pediatric Use
Contraindicated in infants and children under 2 years of age due to the potential for respiratory depression and CNS depression (e.g., apnea, bradycardia, hypotension, somnolence) associated with brimonidine. Use with caution in children 2-17 years of age, as systemic absorption can lead to significant adverse effects; monitor closely for somnolence and other systemic effects.
Geriatric Use
No overall differences in safety or effectiveness have been observed between elderly and younger patients. However, greater sensitivity of some older individuals to the systemic effects of timolol (e.g., cardiovascular, respiratory) cannot be ruled out. Monitor closely for systemic adverse effects.
Clinical Information
Clinical Pearls
- Combigan is a useful fixed-combination therapy for patients requiring more significant IOP reduction or who are not adequately controlled on monotherapy.
- Always remind patients about proper instillation technique to maximize efficacy and minimize systemic absorption.
- Counsel patients on potential systemic side effects, especially bradycardia, hypotension, and CNS depression (drowsiness, fatigue), which can affect driving or operating machinery.
- Due to the brimonidine component, avoid use in very young children (<2 years) due to risk of severe systemic adverse events.
- Patients with a history of asthma, COPD, or certain cardiac conditions are contraindicated due to the timolol component. Always review patient's medical history thoroughly.
Alternative Therapies
- Prostaglandin analogs (e.g., Latanoprost, Travoprost, Bimatoprost)
- Beta-blockers (e.g., Timolol, Betaxolol, Levobunolol)
- Alpha-2 adrenergic agonists (e.g., Brimonidine, Apraclonidine)
- Carbonic Anhydrase Inhibitors (e.g., Dorzolamide, Brinzolamide, Acetazolamide)
- Rho Kinase Inhibitors (e.g., Netarsudil)
- Cholinergic agonists (e.g., Pilocarpine)
- Surgical interventions (e.g., trabeculectomy, minimally invasive glaucoma surgery)
Cost & Coverage
Average Cost:
Check current market price per 5ml or 10ml bottle
Generic Available:
Yes
Insurance Coverage:
Tier 2 or 3 (for brand), Tier 1 (for generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.