Brimonidine is a selective alpha-2 adrenergic agonist indicated for use as an ophthalmic agent to reduce intraocular pressure in patients with open-angle glaucoma and ocular hypertension, and as a topical agent to treat persistent facial erythema of rosacea. In addition, a lower strength ophthalmic solution (0.025%) has been approved to relieve ocular redness associated with minor ocular irritation. When administered via the ophthalmic route to patients with open-angle glaucoma and ocular hypertension, brimonidine reduces intraocular pressure by approximately 2 to 6 mmHg. Because this reduction in intraocular pressure is achieved with only minimal effect on cardiovascular or pulmonary hemodynamics, brimonidine may be a treatment option for patients in whom topical beta-blocker therapy is contraindicated. When administered topically to patients with acne rosacea, brimonidine significantly improved facial redness as compared to vehicle control.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
-Apply smoothly and evenly as a thin layer across the face avoiding the eyes and lips.
-Wash hands after application.
-Not for oral, ophthalmic, or intravaginal use.
Ophthalmic Administration
-Brimonidine is applied topically to the eye.
-Wash hands before and after use. Tilt the head back slightly and pull the lower eyelid down with the index finger to form a pouch. Squeeze one drop into the pouch and gently close eyes for 1 to 2 minutes. Do not blink.
-Care should be taken to avoid contamination. Do not touch the tip of the dropper to the eye, fingertips, or other surface. To avoid the risk of infection, use one open bottle per individual patient.
-Brimonidine may be used concomitantly with other topical ophthalmic agents. Administer each agent at least 5 minutes apart.
Single use vials
-Twist tab completely off to open vial.
-Instill drop to affected eye(s).
-Discard vial immediately. Do not save or reuse vial.
-Contact lenses should be removed prior to instilling brimonidine; contacts can be reinserted 10 minutes after the dose is instilled.
Multi dose bottle (brimonidine 0.025%)
-Contact lenses should be removed prior to instilling brimonidine; contacts can be reinserted 10 minutes after the dose is instilled.
Multi dose bottle (brimonidine 0.1%, 0.15%, 0.2% solution)
-Contact lenses should be removed prior to instilling brimonidine; they can be reinserted 15 minutes after the dose is instilled.
Cardiovascular adverse events reported during the use of brimonidine ophthalmic solution include hypertension (up to 9%), hypotension (1% to 4%), and palpitations or arrhythmias (less than 3%). Other adverse events noted with use of the ophthalmic solution during postmarketing reports include bradycardia and sinus tachycardia. Additionally, bradycardia, tachycardia, and hypotension were noted in postmarketing reports with infants receiving brimonidine ophthalmic solution. Bradycardia and hypotension (including orthostatic hypotension), some requiring hospitalization, have also been reported with postmarketing use of the topical gel. In some cases, the topical gel was administered in unapproved dosing regimens and for unapproved indications (i.e., after laser procedures).
When brimonidine is administered ophthalmically, blurred vision has been reported at an incidence of 1% to 30%. Blurred vision has also been reported with topical application of brimonidine gel at an incidence of 1%. Local side effects were noted in patients receiving brimonidine ophthalmic solution including ocular or conjunctival hyperemia (10% to 30%), ocular burning (5% to 30%), stinging (1% to 30%), foreign body sensation (1% to 30%), conjunctival follicles (5% to 30%), ocular allergic reactions (5% to 30%), ocular pruritus (10% to 30%), allergic conjunctivitis (10% to 20%), visual disturbance (5% to 9%), corneal erosion or staining (less than 1% to 9%), photophobia (1% to 9%), erythematous eyelid (1% to 9%), ocular pain (1% to 9%), xerophthalmia (1% to 9%), tearing (1% to 9%), eyelid edema (1% to 9%), conjunctival edema (1% to 9%), blepharitis (1% to 9%), ocular irritation (1% to 9%), conjunctival blanching (3% to 9%), abnormal vision or visual impairment (3% to 9%), blepharoconjunctivitis (1% to 4%), cataracts (1% to 4%), conjunctival or ocular hemorrhage (up to 4%), conjunctivitis (1% to 4%), epiphora (1% to 4%), conjunctival or ocular discharge (up to 4%), follicular conjunctivitis (1% to 4%), keratitis (1% to 4%), eyelid disorder (1% to 4%), superficial punctate keratopathy (1% to 4%), visual field defect (1% to 4%), vitreous detachment (1% to 4%), vitreous disorder (1% to 4%), vitreous floaters (1% to 4%), worsened visual acuity (1% to 4%), eyelid crusting (less than 3%), and hordeolum (less than 1%). Products not preserved with benzalkonium chloride may cause less allergic conjunctivitis or pruritus. Adverse events noted during postmarketing reports include iritis, miosis, and keratoconjunctivitis sicca. In an open label study of brimonidine topical gel in patients with acne rosacea, increased ocular pressure (ocular hypertension) was reported at an incidence of 4%.
Nervous system or phychiatric side effects noted in patients receiving brimonidine ophthalmic solution include headache (1% to 30%), fatigue (1% to 30%), drowsiness (1% to 30%), dizziness (1% to 9%), asthenia (1% to 9%), insomnia (up to 4%), depression (less than 3%), anxiety (less than 3%), and syncope (less than 3%). Headache (4%) and paresthesias (1%) were reported in patients treated with brimonidine topical gel in clinical trials of patients with acne rosacea. Coma, hypothermia, hypotonia, lethargy, and somnolence have been noted in postmarketing reports in infants receiving brimonidine ophthalmic solution. Episodes of dizziness, have been reported during postmarketing use of the topical gel.
Upper respiratory symptoms were reported in 3% to 9% of patients receiving brimonidine ophthalmic solution. Other respiratory symptoms reported in 1% to 4% of patients include bronchitis, cough, dyspnea, pharyngitis, rhinitis, and sinusitis. Nasal dryness was noted in less than 3% of patients. Naso-pharyngitis (5%) and nasal congestion (1%) were reported in patients treated with brimonidine topical gel in clinical trials of patients with acne rosacea. Apnea and respiratory depression were noted in postmarketing reports with infants receiving brimonidine ophthalmic solution.
Gastrointestinal (GI) symptoms were reported in 3% to 9% of patients receiving brimonidine ophthalmic solution. Specific adverse events include abnormal taste or dysgeusia (up to 4%), xerostomia (5% to 30%), dyspepsia (1% to 4%), and unspecified GI disorder (1% to 4%). Nausea was noted during postmarketing reports.
Allergic reactions and rash (unspecified) were reported in 1% to 4% of patients using brimonidine ophthalmic solution during clinical trials. During postmarketing surveillance, hypersensitivity reactions have been noted with use of both the ophthalmic solution and the topical gel. Specifically for the topical gel, cases of angioedema, lip swelling, swollen tongue, and throat tightness have been reported. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
Musculoskeletal pain was noted in 3% to 9% of patients receiving brimonidine ophthalmic solution.
Infection, including influenza, influenza, colds, respiratory infections, and sinus infections, were reported in 1% to 4% of patients receiving brimonidine ophthalmic solution.
Hypercholesterolemia was noted in 1% to 4% of patients receiving brimonidine ophthalmic solution.
Allergic contact dermatitis was reported in approximately 1% of subjects across the clinical development program of brimonidine topical gel. Of 2 subjects who underwent patch testing with individual product ingredients, one was found to be sensitive to brimonidine tartrate and the other sensitive to the preservative phenoxyethanol. Erythema (4% to 8%) was among the most frequently reported adverse events in clinical trials of brimonidine topical gel. For some subjects, the effects of the gel began to diminish hours after application, resulting in rebound erythema that was worse than baseline. In addition, during postmarketing use, some patients developed erythema in previously unaffected areas that were outside of the treatment site (i.e., neck and chest). Intermittent flushing (3% to 10%) was another adverse events frequently reported during clinical trials. The onset of flushing following topical application ranged from 30 minutes to several hours. As with erythema, postmarketing reports have noted new onset flushing in some drug recipients. In addition, some patients experienced increased flushing or increased depth of erythema with flushing. Both erythema and flushing appear to resolve after discontinuation of therapy. Other adverse dermatologic reactions have been reported with brimonidine ophthalmic solution and topical gel. In clinical trials of brimonidine topical gel, skin burning sensation (2% to 4%), skin warmth, (1%), acne vulgaris (1%), and skin pain (1%) were reported more frequently with brimonidine than the vehicle. Rosacea was reported at an incidence of 5% in a one-year open-label study of brimonidine topical gel. During postmarketing use of the gel, urticaria and pallor (excessive whitening) at or outside the application site have been observed. Skin reactions (including erythema, eyelid pruritus, rash, and vasodilation) have been reported during postmarketing use of brimonidine ophthalmic solution.
Although brimonidine has minimal effects on blood pressure and other cardiopulmonary hemodynamics, it should be used with caution in patients with severe, unstable, or uncontrolled cardiac disease, cerebrovascular disease or coronary artery disease.
Some brimonidine ophthalmic solutions contain benzalkonium chloride, a preservative that may be absorbed by soft contact lenses. Patients should remove contact lenses prior to instilling brimonidine ophthalmic solutions containing benzalkonium chloride and wait 15 minutes before replacing them. Contacts may be placed back into the eye after 10 minutes for brimonidine ophthalmic solutions (0.025%) for eye redness.
Brimonidine should be used with caution in patients with Raynaud's phenomenon, thromboangiitis obliterans (Buerger's disease), depression, scleroderma, Sjogren's syndrome, and orthostatic hypotension.
Brimonidine has not been studied in patients with renal impairment or hepatic disease. It should be used carefully in these patient populations.
Brimonidine 0.1%, 0.15%, and 0.2% ophthalmic solutions are contraindicated for use in neonates, infants, and children younger than 2 years. During postmarketing use of these ophthalmic solutions in infants, the following adverse events were noted: apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence. Brimonidine 0.025% ophthalmic solution is not indicated for use in patients younger than 5 years of age, and the topical gel is only approved for use in adults 18 years or older.
Brimonidine is classified as FDA pregnancy risk category B. There are no adequate and well-controlled studies in pregnant women. According to the manufacturer, brimonidine should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
According to the manufacturer, a decision should be made whether to discontinue nursing or to discontinue brimonidine, taking into account the importance of the drug to the mother. It is not known whether brimonidine is excreted in breast milk. However, limited data in nursing mothers using brimonidine ophthalmic products have not demonstrated adverse reactions in nursing infants. To minimize the amount of drug that reaches the systemic circulation and breast milk, apply pressure over the tear duct by the corner of the eye for 1 minute after ophthalmic administration. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
For the treatment of increased intraocular pressure in patients with open-angle glaucoma or ocular hypertension:
Ophthalmic dosage (0.1%, 0.15%, 0.2% ophthalmic solution):
Adults: Instill 1 drop in the affected eye(s) 3 times daily, approximately 8 hours apart.
Children and Adolescents 2 to 17 years: Instill 1 drop in the affected eye(s) 3 times daily, approximately 8 hours apart.
For the treatment of persistent (nontransient) facial erythema of acne rosacea:
Topical dosage:
Adults: Apply a pea-sized amount as a thin layer topically to the entire face (i.e., forehead, chin, nose, and each cheek) once daily.
For the treatment of eye redness due to minor ocular pain or irritation:
Ophthalmic dosage (0.025% ophthalmic solution):
Adults: Instill 1 drop into affected eye(s) every 6 to 8 hours as needed. Max: 4 doses daily.
Children and Adolescents 5 to 17 years: Instill 1 drop into affected eye(s) every 6 to 8 hours as needed. Max: 4 doses daily.
Maximum Dosage Limits:
-Adults
3 drops/day/affected eye 0.1%, 0.15%, or 0.2% ophthalmic solution; 4 drops/day/affected eye 0.025% ophthalmic solution; 1 application/day topically brimonidine gel.
-Geriatric
3 drops/day/affected 0.1%, 0.15%, or 0.2% ophthalmic solution; 4 drops/day/affected eye 0.025% ophthalmic solution; 1 application/day topically brimonidine gel.
-Adolescents
3 drops/day/affected eye 0.1%, 0.15%, or 0.2% ophthalmic solution; 4 drops/day/affected eye 0.025% ophthalmic solution; safety and efficacy of brimonidine topical gel have not been established.
-Children
5 years and older: 3 drops/day/affected eye 0.1%, 0.15%, or 0.2% ophthalmic solution; 4 drops/day/affected eye 0.025% ophthalmic solution; safety and efficacy of brimonidine topical gel have not been established.
2 to 4 years: 3 drops/day/affected eye 0.1%, 0.15%, or 0.2% ophthalmic solution; safety and efficacy of brimonidine topical gel or 0.025% ophthalmic solution have not been established.
less than 2 years: Use of ophthalmic solution not recommended; safety and efficacy of brimonidine topical gel have not been established.
-Infants
Use of brimonidine ophthalmic solution not recommended; safety and efficacy of brimonidine topical gel have not been established.
-Neonates
Use of brimonidine ophthalmic solution not recommended; safety and efficacy of brimonidine topical gel have not been established.
Patients with Hepatic Impairment Dosing
Brimonidine has not been studied in patients with hepatic impairment; use caution in treating these patients.
Patients with Renal Impairment Dosing
Brimonidine has not been studied in patients with renal impairment; use caution in treating these patients.
*non-FDA-approved indication
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Acetaminophen; Codeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Acetaminophen; Hydrocodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Acetaminophen; Oxycodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Alfentanil: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Alprazolam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Amitriptyline: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Amobarbital: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of anxiolytics, sedatives, and hypnotics.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Aspirin, ASA; Oxycodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Barbiturates: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Belladonna; Opium: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Benzhydrocodone; Acetaminophen: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Benzodiazepines: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Butalbital; Acetaminophen: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Butalbital; Acetaminophen; Caffeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists. (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists. (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Cardiac glycosides: (Minor) Alpha-agonists as a class, may reduce heart rate and blood pressure. Although ophthalmic brimonidine administration generally does not have clinically significant effects on pulse and blood pressure, it should be used with caution with cardiac glycosides.
Celecoxib; Tramadol: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Chlordiazepoxide: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Chlordiazepoxide; Amitriptyline: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines. (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Chlordiazepoxide; Clidinium: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Chlorpheniramine; Codeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Chlorpheniramine; Hydrocodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Clomipramine: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Clonazepam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Clorazepate: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Codeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Codeine; Guaifenesin: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Codeine; Phenylephrine; Promethazine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Codeine; Promethazine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Desipramine: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Diazepam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Digoxin: (Minor) Alpha-agonists as a class, may reduce heart rate and blood pressure. Although ophthalmic brimonidine administration generally does not have clinically significant effects on pulse and blood pressure, it should be used with caution with cardiac glycosides.
Doxepin: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Estazolam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Eszopiclone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of anxiolytics, sedatives, and hypnotics.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Fentanyl: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Flurazepam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Homatropine; Hydrocodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Hydrocodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Hydrocodone; Ibuprofen: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Hydromorphone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Ibuprofen; Oxycodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Imipramine: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Isocarboxazid: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Levorphanol: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Linezolid: (Moderate) Use brimonidine with caution with MAOIs because they can affect the metabolism and uptake of circulating amines. Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Lorazepam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Meperidine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Meprobamate: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of anxiolytics, sedatives, and hypnotics.
Methadone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Methohexital: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Midazolam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Monoamine oxidase inhibitors: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Morphine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Morphine; Naltrexone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Nortriptyline: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Oliceridine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Opiate Agonists: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Oxazepam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Oxycodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Oxymorphone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Pentobarbital: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Perphenazine; Amitriptyline: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Phenelzine: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Phenobarbital: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Primidone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Protriptyline: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Quazepam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Rasagiline: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Remifentanil: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Remimazolam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Secobarbital: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Selegiline: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Sufentanil: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Tapentadol: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Temazepam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Tramadol: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Tramadol; Acetaminophen: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Tranylcypromine: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Triazolam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Tricyclic antidepressants: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Trimipramine: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Zaleplon: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of anxiolytics, sedatives, and hypnotics.
Zolpidem: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of anxiolytics, sedatives, and hypnotics.
Brimonidine is a potent alpha-2 adrenergic receptor agonist that shows up to 1,700-fold selectivity for alpha-2 receptors over alpha-1 receptors. When administered via the ophthalmic route, brimonidine decreases intraocular pressure by 2 mechanisms: reducing aqueous humor production (primary short-term mechanism) and stimulating aqueous humor outflow through the uveoscleral pathway (primary long-term mechanism). In addition to lowering intraocular pressure, data from animal studies suggest brimonidine may provide a neuroprotective effect against the progressive neuropathy that is associated with glaucoma. When administered topically, brimonidine binds to alpha-adrenergic receptors on smooth muscles surrounding the vessels of the superficial and deep dermal plexuses. By binding to these receptors, brimonidine causes vasoconstriction, thereby diverting blood flow away from the central face and reducing facial erythema associated with rosacea.
Brimonidine is administered as an ophthalmic solution to the eye or topically to the skin. Once in systemic circulation, brimonidine has a plasma elimination half-life of approximately 2 to 5 hours. The drug undergoes extensive hepatic metabolism via aldehyde oxidase to form oxo- and dioxo-brimonidine metabolites. Elimination of brimonidine and its metabolites occurs primarily via the kidneys (60% to 75%), with approximately 87% of an orally administered dose being excreted within 120 hours, of which, 74% is found in urine.
Affected cytochrome P450 isoenzymes: None
-Route-Specific Pharmacokinetics
Topical Route
Following topical administration of 1 gram of brimonidine 0.33% gel to the face once daily for 29 days, the mean Cmax and AUC were highest on day 15 with values of 46 +/- 62 pg/mL and 417 +/- 264 pg x hour/mL, respectively. On day 29, the systemic drug exposure was slightly lower indicating no further drug accumulation.
Other Route(s)
Ophthalmic Route
Following ophthalmic administration of brimonidine, the Tmax occurred in 0.5 to 4 hours with a systemic half-life of approximately 2 to 3 hours. The time to peak hypotensive effect on IOP is about 2 hours.