Combigan 0.2/0.5% Solution 10ml
It is used to treat glaucoma.It is used to lower high eye pressure.
Drug Class
Antiglaucoma Agent, Ophthalmic
Pharmacologic Class
Alpha-2 Adrenergic Agonist; Non-selective Beta-Adrenergic Blocker
Pregnancy Category
Category C
FDA Approved
Oct 2007
DEA Schedule
Not Controlled
Overview
What is this medicine?
Combigan is an eye drop used to lower high pressure inside the eye, which can damage your vision and lead to glaucoma. It contains two medicines: one that reduces the amount of fluid your eye makes and another that helps fluid drain better from your eye.
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. For optimal results, use this medication only in your eyes.
Preparation and Administration
1. Remove your contact lenses before using this medication. You can put them back in 15 minutes after administration, unless your eyes are irritated or infected.
2. Avoid touching the container tip to your eye, lid, or surrounding skin, as this can introduce bacteria and lead to severe eye problems or vision loss.
3. Wash your hands thoroughly before and after using the medication.
4. Tilt your head back, and gently drop the medication into your eye.
5. After administration, 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.
6. 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 each administration.
Continuing Treatment
Continue using this medication as directed, even if your symptoms improve.
Important Safety Precautions
Do not use the medication if the solution changes color, becomes cloudy, or contains particles.
Do not use the medication if the container is leaking.
Storage and Disposal
1. Store the medication at room temperature, protected from light and moisture. Avoid storing it in a bathroom.
2. Keep all medications in a safe place, out of the reach of children and pets.
3. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. Consult your pharmacist for guidance on disposal, and consider participating in local drug take-back programs.
Missed Dose
If you miss a dose, use it as soon as you remember. However, 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 the same time or take extra doses.
To use this medication correctly, follow your doctor's instructions and read all the information provided. For optimal results, use this medication only in your eyes.
Preparation and Administration
1. Remove your contact lenses before using this medication. You can put them back in 15 minutes after administration, unless your eyes are irritated or infected.
2. Avoid touching the container tip to your eye, lid, or surrounding skin, as this can introduce bacteria and lead to severe eye problems or vision loss.
3. Wash your hands thoroughly before and after using the medication.
4. Tilt your head back, and gently drop the medication into your eye.
5. After administration, 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.
6. 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 each administration.
Continuing Treatment
Continue using this medication as directed, even if your symptoms improve.
Important Safety Precautions
Do not use the medication if the solution changes color, becomes cloudy, or contains particles.
Do not use the medication if the container is leaking.
Storage and Disposal
1. Store the medication at room temperature, protected from light and moisture. Avoid storing it in a bathroom.
2. Keep all medications in a safe place, out of the reach of children and pets.
3. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. Consult your pharmacist for guidance on disposal, and consider participating in local drug take-back programs.
Missed Dose
If you miss a dose, use it as soon as you remember. However, 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 the same time or take extra doses.
Lifestyle & Tips
- Do not touch the dropper tip to any surface to avoid contamination.
- Wait at least 5 minutes between instilling Combigan and other eye drops.
- Remove contact lenses before instilling drops and wait at least 15 minutes before reinserting them.
- Inform your doctor about all medications you are taking, especially for heart conditions, blood pressure, or depression.
- Avoid driving or operating machinery if you experience blurred vision or dizziness after instilling the drops.
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.
Condition-Specific Dosing:
glaucoma:
One drop in the affected eye(s) twice daily, approximately 12 hours apart.
Pediatric Dosing
Neonatal:
Contraindicated (due to potential for apnea and bradycardia with brimonidine)
Infant:
Contraindicated (due to potential for apnea and bradycardia with brimonidine)
Child:
Not recommended for children under 16 years of age due to potential for systemic adverse effects.
Adolescent:
Not recommended for children under 16 years of age due to potential for systemic adverse effects.
Dose Adjustments
Renal Impairment:
Mild:
Use with caution; systemic exposure may be increased.
Moderate:
Use with caution; systemic exposure may be increased.
Severe:
Use with caution; systemic exposure may be increased.
Dialysis:
Use with caution; systemic exposure may be increased. Monitor for systemic adverse effects.
Hepatic Impairment:
Mild:
Use with caution; systemic exposure may be increased.
Moderate:
Use with caution; systemic exposure may be increased.
Severe:
Use with caution; systemic exposure may be increased.
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 combination results in additive intraocular pressure (IOP) lowering effects.
Pharmacokinetics
Absorption:
Bioavailability:
Not available (for ophthalmic, systemic absorption occurs)
Tmax:
Brimonidine: 1-4 hours; Timolol: 1-3 hours (after ophthalmic administration)
FoodEffect:
Not applicable (ophthalmic)
Distribution:
Vd:
Not available (for ophthalmic)
ProteinBinding:
Brimonidine: Approximately 29%; Timolol: Approximately 60%
CnssPenetration:
Limited (for ophthalmic, but systemic absorption can lead to CNS effects)
Elimination:
HalfLife:
Brimonidine: Approximately 3 hours (terminal half-life 7-12 hours); Timolol: Approximately 2-4 hours
Clearance:
Not available (for ophthalmic)
ExcretionRoute:
Renal (primarily as metabolites)
Unchanged:
Brimonidine: <10%; Timolol: Approximately 20% (renal)
Pharmacodynamics
OnsetOfAction:
Approximately 30 minutes
PeakEffect:
Approximately 2-4 hours
DurationOfAction:
Approximately 12 hours
Confidence:
Medium
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
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 or an irregular heartbeat
Chest pain
Dizziness or fainting
Muscle weakness
Heart problems, which can be rare but potentially deadly. If you experience any of the following, call your doctor right away:
+ Shortness of breath
+ Sudden 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
Reporting Side Effects
This list is not exhaustive, and you may experience other 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, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
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 or an irregular heartbeat
Chest pain
Dizziness or fainting
Muscle weakness
Heart problems, which can be rare but potentially deadly. If you experience any of the following, call your doctor right away:
+ Shortness of breath
+ Sudden 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
Reporting Side Effects
This list is not exhaustive, and you may experience other 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 or sudden vision changes
- Signs of an allergic reaction (e.g., rash, itching, swelling of face/tongue/throat, severe dizziness, trouble breathing)
- Very slow heart rate or irregular heartbeat
- Severe dizziness or fainting
- Shortness of breath or wheezing
- New or worsening depression
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. Be sure to describe the symptoms you experienced.
Certain health conditions, such as:
+ Breathing problems, including 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 using another medication similar to this one. If you are unsure, consult your doctor or pharmacist.
Special Considerations for Children:
If the patient is under 2 years of age, do not administer this medication. It is not recommended for children younger than 2 years old.
Additional Important Information:
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. Verify that it is safe to take this medication with your existing medications and health conditions. Never start, stop, or change the dosage of any medication without 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. Be sure to describe the symptoms you experienced.
Certain health conditions, such as:
+ Breathing problems, including 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 using another medication similar to this one. If you are unsure, consult your doctor or pharmacist.
Special Considerations for Children:
If the patient is under 2 years of age, do not administer this medication. It is not recommended for children younger than 2 years old.
Additional Important Information:
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. Verify that it is safe to take this medication with your existing medications and health conditions. Never start, stop, or change the dosage of any medication without 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 drug affects you.
This medication may mask certain symptoms of low blood sugar, including 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, undergoing surgery, have an irregular diet, or are experiencing vomiting. If you have any questions or concerns, consult your doctor.
Regularly schedule appointments with your doctor to monitor your eye pressure and vision as advised. Additionally, notify your doctor if you have an eye infection, suffer an eye injury, or are scheduled to undergo 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, this medication has been associated with severe respiratory problems, which can be fatal, particularly in individuals with asthma. If you have any 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 if you are exposed to the allergen again. Furthermore, 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 make it more challenging to recognize symptoms of hyperthyroidism, such as a rapid heartbeat. If you have hyperthyroidism and abruptly stop taking this medication, your condition may worsen and become 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 you and your baby.
This medication may mask certain symptoms of low blood sugar, including 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, undergoing surgery, have an irregular diet, or are experiencing vomiting. If you have any questions or concerns, consult your doctor.
Regularly schedule appointments with your doctor to monitor your eye pressure and vision as advised. Additionally, notify your doctor if you have an eye infection, suffer an eye injury, or are scheduled to undergo 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, this medication has been associated with severe respiratory problems, which can be fatal, particularly in individuals with asthma. If you have any 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 if you are exposed to the allergen again. Furthermore, 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 make it more challenging to recognize symptoms of hyperthyroidism, such as a rapid heartbeat. If you have hyperthyroidism and abruptly stop taking this medication, your condition may worsen and become 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 you and your baby.
Overdose Information
Overdose Symptoms:
- Bradycardia (slow heart rate)
- Hypotension (low blood pressure)
- Bronchospasm (difficulty breathing)
- CNS depression (drowsiness, lethargy, coma)
- Apnea (cessation of breathing)
- Hypoglycemia (low blood sugar)
What to Do:
Seek immediate medical attention or call a poison control center (1-800-222-1222). Treatment is supportive and symptomatic. Consider activated charcoal if ingested. Atropine for bradycardia, vasopressors for hypotension, bronchodilators for bronchospasm.
Drug Interactions
Contraindicated Interactions
- Monoamine Oxidase Inhibitors (MAOIs) - due to potential for severe hypotension
- Antidepressants (tricyclic antidepressants, mianserin) - may interfere with the IOP-lowering effect of brimonidine
Major Interactions
- Oral beta-blockers - potential for additive systemic beta-blockade (e.g., bradycardia, hypotension)
- Calcium channel blockers - potential for additive systemic effects (e.g., bradycardia, hypotension)
- Cardiac glycosides (e.g., digoxin) - potential for additive effects on AV conduction and heart rate
- Other alpha-adrenergic agonists (e.g., phenylephrine) - potential for additive systemic effects
- CNS depressants (e.g., alcohol, barbiturates, opiates, sedatives, anesthetics) - potential for additive CNS depression
- Adrenergic psychotropic drugs (e.g., chlorpromazine, methylphenidate, reserpine) - potential for additive effects or interference with blood pressure regulation
Moderate Interactions
- Cimetidine, hydralazine, quinidine, fluoxetine, paroxetine - may increase timolol levels due to CYP2D6 inhibition
- Propafenone - may increase timolol levels due to CYP2D6 inhibition
- Clonidine - potential for additive hypotensive effects
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Intraocular Pressure (IOP)
Rationale: To establish baseline and assess treatment efficacy.
Timing: Prior to initiation of therapy
Heart Rate and Blood Pressure
Rationale: To assess for systemic beta-blocker effects.
Timing: Prior to initiation of therapy
Ophthalmic Examination (e.g., slit lamp, fundoscopy)
Rationale: To assess ocular health and rule out contraindications.
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 based on disease severity and progression risk
Action Threshold: IOP above target range, signs of disease progression
Heart Rate and Blood Pressure
Frequency: Periodically, especially in patients with cardiovascular or cerebrovascular disease
Target: Within normal limits for the patient
Action Threshold: Significant bradycardia (<50 bpm), hypotension, or other cardiovascular symptoms
Ocular Adverse Effects (e.g., hyperemia, burning, stinging, allergic conjunctivitis)
Frequency: At each follow-up visit
Target: Absence of severe or persistent adverse effects
Action Threshold: Persistent or worsening ocular irritation, signs of allergic reaction
Symptom Monitoring
- Blurred vision
- Ocular discomfort (burning, stinging, itching)
- Ocular hyperemia (redness)
- Allergic conjunctivitis
- Dry mouth
- Fatigue
- Dizziness
- Bradycardia
- Hypotension
- Respiratory symptoms (e.g., bronchospasm, dyspnea)
- Depression
Special Patient Groups
Pregnancy
Use only if the potential benefit justifies the potential risk to the fetus. Systemic absorption occurs. Brimonidine has shown developmental toxicity in animal studies. Timolol has been associated with adverse effects in animal studies and potential for fetal/neonatal bradycardia and hypoglycemia.
Trimester-Specific Risks:
First Trimester:
Potential for developmental toxicity; avoid if possible.
Second Trimester:
Potential for developmental toxicity; monitor for systemic effects.
Third Trimester:
Potential for fetal/neonatal bradycardia, hypoglycemia, and respiratory depression due to systemic absorption of timolol. Discontinue several days before delivery if possible.
Lactation
Timolol is excreted in human milk and can cause serious adverse reactions in nursing infants (e.g., bradycardia, respiratory depression). Brimonidine is also likely excreted in human milk. A decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
Moderate concern (L3) due to potential for systemic effects in the infant (bradycardia, respiratory depression, CNS depression).
Pediatric Use
Contraindicated in infants and children under 2 years of age due to potential for severe systemic adverse reactions (e.g., apnea, bradycardia, hypotension, hypothermia, CNS depression). Not recommended for children under 16 years of age due to potential for systemic adverse effects.
Geriatric Use
No overall differences in safety or effectiveness have been observed between elderly and younger patients. However, caution is advised due to potential for increased systemic sensitivity to beta-blockers and alpha-2 agonists in some elderly patients. Monitor for systemic adverse effects (e.g., bradycardia, hypotension, CNS effects).
Clinical Information
Clinical Pearls
- Combigan is a convenient twice-daily fixed combination that can improve patient adherence compared to multiple drops.
- Patients should be instructed on proper ophthalmic instillation technique to minimize systemic absorption and maximize local effect.
- Due to the timolol component, caution is advised in patients with pre-existing respiratory conditions (e.g., asthma, COPD), heart block, or severe bradycardia.
- The brimonidine component can cause somnolence and fatigue, especially in children and some adults. Patients should be warned about driving or operating machinery.
- Monitor for signs of allergic conjunctivitis, which can occur with brimonidine.
- Systemic absorption, though limited, can lead to drug interactions, particularly with other cardiovascular or CNS-acting medications.
Alternative Therapies
- Prostaglandin analogs (e.g., Latanoprost, Travoprost, Bimatoprost)
- Beta-blockers (e.g., Timolol, Betaxolol)
- Alpha-2 adrenergic agonists (e.g., Brimonidine)
- Carbonic anhydrase inhibitors (e.g., Dorzolamide, Brinzolamide, Acetazolamide)
- Rho kinase inhibitors (e.g., Netarsudil)
- Cholinergic agonists (e.g., Pilocarpine)
- Surgical interventions (e.g., trabeculectomy, MIGS)
- Laser procedures (e.g., SLT)
Cost & Coverage
Average Cost:
$150 - $300 per 10ml bottle
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (for brand), Tier 1 (for generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. 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 it's a good idea to check with your pharmacist. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide detailed information about the overdose, including the medication taken, the amount, and the time it occurred.