Combigan 0.2/0.5% Opth Soln 5ml
It is used to treat glaucoma.It is used to lower high eye pressure.
Drug Class
Antiglaucoma Agents
Pharmacologic Class
Alpha-2 Adrenergic Agonist (Brimonidine) & Beta-Adrenergic Blocker (Timolol)
Pregnancy Category
Category C
FDA Approved
Oct 2005
DEA Schedule
Not Controlled
Overview
What is this medicine?
Combigan is an eye drop that contains two medicines, brimonidine and timolol. It is used to lower high pressure inside the eye, which can damage your vision if not treated. Brimonidine works by reducing the amount of fluid your eye makes and helping fluid drain better. Timolol works by reducing the amount of fluid your eye makes. Together, they help keep your eye pressure at a healthy level.
How to Use This Medicine
Proper Use of This Medication
To use this eye 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 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 eye medication, administer each one at least 5 minutes apart.
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 eye 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 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 eye medication, administer each one at least 5 minutes apart.
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
- Administer drops at approximately 12-hour intervals.
- 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.
- Avoid touching the dropper tip to the eye or any other surface to prevent contamination.
- Wash hands before and after use.
- Do not discontinue use without consulting your doctor, as eye pressure may increase.
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:
openAngleGlaucoma:
One drop in the affected eye(s) twice daily, approximately 12 hours apart.
ocularHypertension:
One drop in the affected eye(s) twice daily, approximately 12 hours apart.
Pediatric Dosing
Neonatal:
Not established; contraindicated in infants and children under 2 years of age due to potential for apnea and bradycardia.
Infant:
Not established; contraindicated in infants and children under 2 years of age due to potential for apnea and bradycardia.
Child:
Not established for routine use. Use with caution in children 2-17 years of age due to potential for systemic adverse effects (e.g., somnolence, decreased alertness).
Adolescent:
Not established for routine use. Use with caution in children 2-17 years of age due to potential for systemic adverse effects (e.g., somnolence, decreased alertness).
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, but monitor for systemic effects.
Moderate:
No specific dose adjustment recommended, but monitor for systemic effects.
Severe:
Use with caution. Timolol and its metabolites are primarily excreted by the kidneys. Brimonidine metabolites are renally excreted. Monitor for increased systemic adverse effects.
Dialysis:
Consider with caution. Systemic exposure may be increased. Monitor for systemic effects.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended, but monitor for systemic effects.
Moderate:
Use with caution. Brimonidine is extensively metabolized by the liver. Timolol is partially metabolized by the liver. Monitor for increased systemic adverse effects.
Severe:
Use with caution. Brimonidine is extensively metabolized by the liver. Timolol is partially metabolized by the liver. Monitor for increased systemic adverse effects.
Pharmacology
Mechanism of Action
Combigan is a fixed combination of two medications, brimonidine tartrate and timolol maleate, which lower elevated intraocular pressure (IOP) by complementary mechanisms of action. Brimonidine is an alpha-2 adrenergic agonist that reduces aqueous humor production and increases uveoscleral outflow. Timolol is a non-selective beta-adrenergic receptor blocker that primarily reduces aqueous humor production.
Pharmacokinetics
Absorption:
Bioavailability:
Low systemic bioavailability after ocular administration for both components (approx. 10-20% for timolol, less for brimonidine).
Tmax:
Brimonidine: Approximately 1-4 hours (systemic). Timolol: Approximately 1-2 hours (systemic).
FoodEffect:
Not applicable for ophthalmic solution.
Distribution:
Vd:
Not available for ophthalmic use, but timolol has a Vd of approximately 1.7 L/kg systemically.
ProteinBinding:
Brimonidine: Approximately 29%. Timolol: Approximately 60%.
CnssPenetration:
Yes (Timolol), Limited (Brimonidine)
Elimination:
HalfLife:
Brimonidine: Approximately 2-3 hours (systemic). Timolol: Approximately 4-6 hours (systemic).
Clearance:
Not precisely quantified for ophthalmic use.
ExcretionRoute:
Brimonidine: Primarily renal excretion of metabolites. Timolol: Primarily renal excretion of metabolites and unchanged drug.
Unchanged:
Brimonidine: Very little unchanged drug excreted. Timolol: Approximately 20% unchanged drug excreted renally.
Pharmacodynamics
OnsetOfAction:
Within 30 minutes
PeakEffect:
Approximately 2-8 hours
DurationOfAction:
Up to 12 hours
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
Abnormal heartbeat
Chest pain
Dizziness or fainting
Muscle weakness
Heart problems, which can be rare but potentially deadly. If you experience:
+ 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 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, contact 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
Abnormal heartbeat
Chest pain
Dizziness or fainting
Muscle weakness
Heart problems, which can be rare but potentially deadly. If you experience:
+ 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 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, contact 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, dizziness, or fainting
- Shortness of breath, wheezing, or difficulty breathing (especially if you have asthma or COPD)
- Severe eye irritation, redness, or swelling that worsens
- 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. 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:
This medication is not suitable for children under 2 years of age. Do not administer it to a child 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.
To ensure your safety, verify that it is acceptable to take this medication with all your other medications and health conditions.
* Never start, stop, or adjust 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. 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:
This medication is not suitable for children under 2 years of age. Do not administer it to a child 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.
To ensure your safety, verify that it is acceptable to take this medication with all your other medications and health conditions.
* Never start, stop, or adjust 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 drug affects you.
This medication 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.
As directed by your doctor, schedule regular check-ups to monitor your eye pressure and vision.
Notify your doctor if you have an eye infection, suffer an eye injury, or are scheduled for eye surgery.
Prior to 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 in people 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 risk for an even more severe reaction if exposed to the allergen again. Additionally, if you rely on epinephrine to treat severe allergic reactions, discuss this with your doctor, as the effectiveness of epinephrine may be reduced while taking this medication.
This drug may also make it more challenging to recognize symptoms of hyperthyroidism, such as a rapid heartbeat. If you have hyperthyroidism and suddenly stop taking this medication, your condition may worsen and become life-threatening. Consult your doctor for guidance.
If you are pregnant, planning to become pregnant, or 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 drug affects you.
This medication 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.
As directed by your doctor, schedule regular check-ups to monitor your eye pressure and vision.
Notify your doctor if you have an eye infection, suffer an eye injury, or are scheduled for eye surgery.
Prior to 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 in people 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 risk for an even more severe reaction if exposed to the allergen again. Additionally, if you rely on epinephrine to treat severe allergic reactions, discuss this with your doctor, as the effectiveness of epinephrine may be reduced while taking this medication.
This drug may also make it more challenging to recognize symptoms of hyperthyroidism, such as a rapid heartbeat. If you have hyperthyroidism and suddenly stop taking this medication, your condition may worsen and become life-threatening. Consult your doctor for guidance.
If you are pregnant, planning to become pregnant, or 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
- Dizziness
- Somnolence (drowsiness)
- Fatigue
- Hypoglycemia (low blood sugar)
What to Do:
Seek immediate medical attention or call a poison control center (e.g., 1-800-222-1222). Treatment is symptomatic and supportive. Atropine may be used for bradycardia, isoproterenol for bronchospasm, and vasopressors for hypotension.
Drug Interactions
Contraindicated Interactions
- Monoamine Oxidase Inhibitors (MAOIs) (due to brimonidine component)
- Antidepressants that affect noradrenergic transmission (e.g., tricyclic antidepressants, mianserin) (due to brimonidine component)
Major Interactions
- Systemic Beta-Blockers (additive effects on heart rate and blood pressure)
- Calcium Channel Blockers (e.g., verapamil, diltiazem) (additive effects on AV conduction and heart rate)
- Cardiac Glycosides (e.g., digoxin) (additive effects on AV conduction and heart rate)
- Quinidine (can inhibit timolol metabolism via CYP2D6, leading to increased timolol systemic exposure)
- Clonidine (potential for additive or potentiating hypotensive effects)
- CNS Depressants (e.g., alcohol, barbiturates, opiates, sedatives, anesthetics) (additive CNS depressant effects with brimonidine)
Moderate Interactions
- Other Antihypertensives (potential for additive hypotensive effects)
- Pilocarpine (may reduce efficacy of timolol)
- Adrenergic psychotropic drugs (e.g., chlorpromazine, methylphenidate, reserpine) (potential for additive effects)
Minor Interactions
- Not specifically identified as minor, but general caution with other ophthalmic preparations.
Monitoring
Baseline Monitoring
Intraocular Pressure (IOP)
Rationale: To establish baseline and assess treatment efficacy.
Timing: Prior to initiation of therapy.
Ophthalmic Examination (e.g., slit lamp, fundoscopy)
Rationale: To assess ocular health and rule out other conditions.
Timing: Prior to initiation of therapy.
Heart Rate and Blood Pressure
Rationale: To assess baseline cardiovascular status due to potential systemic absorption of timolol.
Timing: Prior to initiation of therapy.
Medical History (especially cardiovascular, respiratory, and psychiatric conditions)
Rationale: To identify contraindications or precautions.
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 continues to progress, consider dose adjustment or alternative therapy.
Heart Rate and Blood Pressure
Frequency: Periodically, especially in patients with pre-existing cardiovascular conditions.
Target: Within normal limits for the patient.
Action Threshold: Significant bradycardia (<50 bpm), hypotension, or worsening of cardiovascular symptoms.
Ocular Examination (e.g., visual acuity, slit lamp, optic nerve assessment)
Frequency: Periodically, as determined by ophthalmologist (e.g., annually or more frequently if indicated).
Target: Stable ocular health, no signs of progression.
Action Threshold: Worsening vision, new ocular symptoms, or signs of glaucoma progression.
Symptom Monitoring
- Ocular irritation (burning, stinging, itching, foreign body sensation)
- Ocular hyperemia (redness)
- Blurred vision
- Dry eyes
- Allergic conjunctivitis
- Bradycardia (slow heart rate)
- Hypotension (low blood pressure)
- Dizziness or lightheadedness
- Fatigue or lethargy
- Somnolence (drowsiness)
- Respiratory symptoms (e.g., bronchospasm, dyspnea), especially in patients with asthma or COPD
- Depression
- Insomnia
Special Patient Groups
Pregnancy
Category C. Use only if the potential benefit justifies the potential risk to the fetus. Systemic absorption of timolol can occur, and beta-blockers have been associated with adverse effects in the fetus/neonate (e.g., bradycardia, hypoglycemia). Brimonidine has shown reproductive toxicity in animal studies at high doses.
Trimester-Specific Risks:
First Trimester:
Potential for fetal exposure; avoid if safer alternatives exist.
Second Trimester:
Potential for fetal exposure; monitor for fetal growth and heart rate.
Third Trimester:
Potential for fetal bradycardia, hypoglycemia, and respiratory depression in the neonate, especially if used close to delivery. Monitor neonate for first 24-48 hours after birth.
Lactation
L3 (Moderate Risk). Both brimonidine and timolol are excreted in human milk. Due to the potential for serious adverse reactions in nursing infants (e.g., apnea, bradycardia, somnolence from brimonidine; beta-blockade effects from timolol), 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:
Bradycardia, apnea, somnolence, hypotension, hypoglycemia.
Pediatric Use
Contraindicated in infants and children under 2 years of age due to potential for apnea and bradycardia. Use with caution in children 2-17 years of age due to potential for systemic adverse effects (e.g., somnolence, decreased alertness). Safety and efficacy have not been established in pediatric patients.
Geriatric Use
No overall differences in safety or effectiveness have been observed between elderly and younger patients. However, caution is advised due to the potential for increased systemic adverse reactions in elderly patients, particularly those with underlying cardiovascular or respiratory conditions. Monitor heart rate and blood pressure.
Clinical Information
Clinical Pearls
- Combigan is a convenient fixed-dose combination that can improve patient adherence compared to separate drops.
- Patients should be instructed on proper instillation technique to minimize systemic absorption and maximize ocular efficacy.
- Due to the timolol component, caution is advised in patients with bronchial asthma, severe COPD, sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, or cardiogenic shock.
- Brimonidine can cause somnolence and fatigue, especially in children. Patients should be warned about operating machinery or driving if affected.
- Patients should be advised to remove soft contact lenses prior to instillation and wait at least 15 minutes before reinserting, as the preservative (benzalkonium chloride) can be absorbed by soft contact lenses.
Alternative Therapies
- Prostaglandin analogs (e.g., latanoprost, travoprost, bimatoprost)
- Other topical beta-blockers (e.g., timolol maleate, betaxolol)
- Topical carbonic anhydrase inhibitors (e.g., dorzolamide, brinzolamide)
- Other topical alpha-agonists (e.g., apraclonidine)
- Miotics (e.g., pilocarpine)
- Oral carbonic anhydrase inhibitors (e.g., acetazolamide)
- Surgical interventions (e.g., trabeculectomy, minimally invasive glaucoma surgery)
- Laser procedures (e.g., Selective Laser Trabeculoplasty - SLT)
Cost & Coverage
Average Cost:
$150 - $300+ per 5ml bottle
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (Brand), Tier 1 (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 this 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, including the amount taken and the time it happened, to ensure you receive the best possible care.