Alphagan

Ocular Decongestants, Sympathomimetics
Other Miotics-Antiglaucoma Agents
Topical Rosacea Agents

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.

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 used to lower IOP. Administer each agent at least 5 minutes apart.[29281] [64299] [64300]
Contact lenses should be removed prior to instilling brimonidine; they can be reinserted 15 minutes after the dose is instilled.[64304]

visual impairment / Early / 3.0-9.0
ocular hypertension / Delayed / 4.0-4.0
keratitis / Delayed / 1.0-4.0
ocular hemorrhage / Delayed / 0-4.0
bradycardia / Rapid / 0-1.0
keratoconjunctivitis / Early / 0-1.0
coma / Early / 0-1.0
apnea / Delayed / 0-1.0
angioedema / Rapid / Incidence not known

conjunctival hyperemia / Early / 10.0-30.0
blurred vision / Early / 1.0-30.0
conjunctivitis / Delayed / 1.0-20.0
respiratory depression / Rapid / 1.0-10.0
hypertension / Early / 0-9.0
photophobia / Early / 1.0-9.0
blepharitis / Early / 1.0-9.0
erythema / Early / 4.0-8.0
hypotension / Rapid / 1.0-4.0
keratopathy / Delayed / 1.0-4.0
cataracts / Delayed / 1.0-4.0
epiphora / Early / 1.0-4.0
dyspnea / Early / 1.0-4.0
hypercholesterolemia / Delayed / 1.0-4.0
palpitations / Early / 0-3.0
depression / Delayed / 0-3.0
sinus tachycardia / Rapid / 0-1.0
iritis / Delayed / 0-1.0
hypotonia / Delayed / 0-1.0
contact dermatitis / Delayed / 1.0-1.0
orthostatic hypotension / Delayed / Incidence not known

ocular pruritus / Rapid / 10.0-30.0
foreign body sensation / Rapid / 1.0-30.0
fatigue / Early / 1.0-30.0
drowsiness / Early / 1.0-30.0
headache / Early / 1.0-30.0
xerostomia / Early / 5.0-30.0
flushing / Rapid / 3.0-10.0
xerophthalmia / Early / 1.0-9.0
ocular irritation / Rapid / 3.0-9.0
ocular pain / Early / 1.0-9.0
dizziness / Early / 1.0-9.0
asthenia / Delayed / 1.0-9.0
musculoskeletal pain / Early / 3.0-9.0
pharyngitis / Delayed / 1.0-5.0
ocular discharge / Delayed / 0-4.0
insomnia / Early / 0-4.0
rhinitis / Early / 1.0-4.0
cough / Delayed / 1.0-4.0
sinusitis / Delayed / 1.0-4.0
dyspepsia / Early / 1.0-4.0
dysgeusia / Early / 0-4.0
rash / Early / 1.0-4.0
influenza / Delayed / 1.0-4.0
infection / Delayed / 1.0-4.0
syncope / Early / 0-3.0
anxiety / Delayed / 0-3.0
nasal dryness / Early / 0-3.0
miosis / Early / 0-1.0
hypothermia / Delayed / 0-1.0
lethargy / Early / 0-1.0
paresthesias / Delayed / 1.0-1.0
nasal congestion / Early / 1.0-1.0
nausea / Early / 0-1.0
acne vulgaris / Delayed / 1.0-1.0
urticaria / Rapid / Incidence not known
pallor / Early / Incidence not known

Alphagan, Alphagan P, LUMIFY, Mirvaso

Rx, OTC

Selective alpha-2 adrenergic agonist
Used ophthalmically to reduce intraocular pressure in open-angle glaucoma and ocular hypertension and to relieve ocular redness due to irritation and topically to reduce persistent facial erythema of rosacea
Minimal cardiopulmonary effects

Instill 1 drop in the affected eye(s) 3-times daily, approximately 8 hours apart.

Apply a pea-size amount once daily to each of the 5 areas of the face: central forehead, chin, nose, each cheek.

Instill 1 drop into the affected eye(s) every 6 to 8 hours as needed. Do not use more than 4-times daily.

Brimonidine has not been studied in patients with hepatic impairment; use caution in treating these patients.

Brimonidine has not been studied in patients with renal impairment; use caution in treating these patients.

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Alphagan/Alphagan P/Brimonidine/Brimonidine Tartrate/LUMIFY Ophthalmic Sol: 0.025%, 0.1%, 0.15%, 0.2%
Alphagan/Brimonidine/Brimonidine Tartrate Ophthalmic Drops: 0.2%
Brimonidine/Mirvaso Topical Gel: 0.33%

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.

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.

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.

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.

Use of brimonidine ophthalmic solution not recommended; safety and efficacy of brimonidine topical gel have not been established.

Use of brimonidine ophthalmic solution not recommended; safety and efficacy of brimonidine topical gel have not been established.

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.[64303] [64304] 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.[64302]

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.[29281] [64299] [55747] [64304]
 
Affected cytochrome P450 isoenzymes: None

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.

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.

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.