Brimonidine (Ophthalmic)
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VA CLASSIFICATION
Primary: OP114
Commonly used brand name(s): Alphagan.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Category:
Antiglaucoma agent (ophthalmic)—
antihypertensive, ocular—
Indications
Accepted
Glaucoma, open-angle (treatment) or
Hypertension, ocular (treatment)—Brimonidine is used in the treatment of open-angle glaucoma or ocular hypertension {01}.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Molecular weight—
442.24 {01}
Other characteristics
The pH of brimonidine tartrate ophthalmic solution is 6.3 to 6.5 {01}.
Mechanism of action/Effect:
Brimonidine is a relatively selective alpha 2-adrenergic agonist {01}. It appears to act by decreasing aqueous humor production and increasing aqueous outflow {01}.
Other actions/effects:
Brimonidine has minimal cardiovascular or pulmonary effects after application to the conjunctiva {01}.
Absorption:
Some systemic absorption occurs after ocular instillation {01}.
Half-life:
For systemically absorbed brimonidine—Approximately 3 hours {01}.
Time to peak plasma concentration
Approximately 1 to 4 hours after ocular instillation {01}.
Time to peak effect:
Approximately 2 hours {01}.
Elimination:
For systemically absorbed brimonidine—Primarily renal, as unchanged brimonidine and metabolites {01}.
Precautions to Consider
Carcinogenicity
Brimonidine was not carcinogenic in a 21-month study in mice given oral doses of 2.5 mg per kg of body weight (mg/kg) per day or in a 2-year study in rats given oral doses of 1 mg/kg per day {01}. These doses provided plasma concentrations equivalent to 77 and 118 times, respectively, the human plasma concentration occurring after ocular instillation of a recommended dose {01}.
Mutagenicity
Brimonidine was not mutagenic in several in vitro and in vivo studies including the Ames test, host-mediated assay, chromosomal aberration test in Chinese hamster ovary (CHO) cells, dominant lethal assay, and cytogenetic studies in mice {01}.
Pregnancy/Reproduction
Fertility—
Brimonidine did not impair fertility in rats given oral doses of 0.66 mg/kg, which produced plasma concentrations equivalent to 100 times the human plasma concentration occurring after ocular instillation of multiple doses {01}.
Pregnancy—
Studies in humans have not been done {01}.
Animal studies have shown that limited quantities of brimonidine cross the placenta and enter the fetal circulation {01}. However, no harm to the fetus occurred in rats given oral doses of 0.66 mg/kg of brimonidine, which produced plasma concentrations equivalent to 100 times the human plasma concentration occurring after ocular instillation of multiple doses {01}.
FDA Pregnancy Category B {01}.
Breast-feeding
It is not known whether brimonidine is distributed into human breast milk {01}. However, brimonidine was detected in breast milk in animal studies {01}.
Pediatrics
No information is available on the relationship of age to the effects of brimonidine in pediatric patients. Safety and efficacy have not been established {01}.
Geriatrics
No information is available on the relationship of age to the effects of brimonidine in geriatric patients.
Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
Antihypertensives or
Beta-adrenergic blocking agents or
Other cardiovascular agents (although ophthalmic brimonidine had little effect on pulse or blood pressure in clinical studies, caution in concurrent use with these medications is recommended because alpha-adrenergic agonists such as brimonidine may decrease pulse rate and blood pressure {01})
Central nervous system (CNS) depressants (caution in concurrent use is recommended because of the possibility of additive CNS depression {01})
» Monoamine oxidase (MAO) inhibitors (brimonidine should not be administered during {01}, or within 14 days following, the administration of an MAO inhibitor)
Tricyclic antidepressants (whether tricyclic antidepressants may interfere with the ocular antihypertensive effect of ophthalmic brimonidine has not been determined, but they have been reported to decrease the antihypertensive effect of systemic clonidine {01})
(although the effect of ophthalmic brimonidine on systemic catecholamine concentrations has not been determined, caution is recommended in its concurrent use with tricyclic antidepressants because the antidepressants may alter the metabolism and uptake of circulating catecholamines {01})
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Except under special circumstances, this medication should not be used when the following medical problem exists:
» Sensitivity to brimonidine or other ingredients in the formulation{01}
Risk-benefit should be considered when the following medical problems exist
» Cardiovascular disease, severe or
Cerebral insufficiency or
Coronary insufficiency or
Hypotension, orthostatic or
Raynaud's disease or
Thromboangiitis obliterans (caution is advised, although ocular instillation of brimonidine had minimal effect on blood pressure in clinical trials {01})
Hepatic function impairment or
Renal function impairment (caution is recommended because studies have not been done in patients with these conditions {01})
Mental depression (caution is recommended; some patients experienced mental depression during clinical trials with brimonidine {01})
Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
» Intraocular pressure (should be monitored regularly to determine that an adequate response to treatment is achieved and maintained; in clinical trials the efficacy of brimonidine decreased over time in some patients {01})
Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)–not necessarily inclusive:
Those indicating need for medical attention
Incidence more frequent (10 to 30%)
Allergic reaction{01} (redness of eye or inner lining of eyelid; swelling of eyelid; itching; tearing)
conjunctival follicles{01}
headache{01}
ocular hyperemia{01} (redness of eye)
Incidence less frequent (9% or lower)
Ache or pain in eye{01}
blepharitis{01} (redness, swelling, and/or itching of eyelid)
blurred vision or other change in vision{01}
conjunctival discharge{01} (oozing in eye)
conjunctival hemorrhage{01} (bloody eye)
corneal erosion{01}
dizziness{01}
edema of conjunctiva or eyelid{01} (swelling of eye or eyelid)
foreign body sensation{01} (feeling of something in the eye)
gastrointestinal symptoms{01} (nausea or vomiting)
increased blood pressure{01}
mental depression{01}
muscle pain{01}
syncope{01} (fainting)
upper respiratory symptoms{01} (runny or stuffy nose; sneezing)
Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent (10 to 30%)
Burning, stinging, or tearing{01}
drowsiness or tiredness{01}
dryness of mouth{01}
Incidence less frequent (9% or lower)
Anxiety{01}
conjunctival blanching{01} (paleness of eye or inner lining of eyelid)
corneal staining{01} (discoloration of white part of eye)
crusting on eyelid or corner of eye{01}
dryness of eye{01}
muscle weakness{01}
photophobia{01} (increased sensitivity of eye to light)
pounding heartbeat{01}
taste changes{01}
trouble in sleeping{01}
Overdose
There is no experience with brimonidine overdose {01}. For information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).
Treatment of overdose
Treatment may consist of maintaining a patent airway and other supportive measures required to relieve observed symptoms {01}.
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Brimonidine (Ophthalmic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance)
Before using this medication
» Conditions affecting use, especially:
Sensitivity to brimonidine
Other medications, especially monoamine oxidase inhibitors
Other medical problems, especially severe cardiovascular disease
Proper use of this medication
Waiting at least 10 minutes between instillation of two different ophthalmic solutions
Proper administration technique; using a second drop if necessary; not touching applicator tip to any surface; keeping container tightly closed
» Importance of not using more medication than the amount prescribed
» Proper dosing
Missed dose: Using as soon as possible; not using if almost time for next dose; using next dose at regularly scheduled time; not doubling doses
» Proper storage
Precautions while using this medication
» Regular visits to physician to check eye pressure during therapy
» Medication may cause dizziness, drowsiness, or tiredness; using caution when driving, using machines, or doing anything else requiring alertness
» Contacting physician immediately if syncope occurs
» Soft contact lens users: Preservative in product may be absorbed by soft contact lenses; waiting at least 15 minutes after instilling medication before inserting lenses
Possible photophobia; wearing sunglasses or avoiding bright light
Side/adverse effects
Signs of potential side effects, especially allergic reaction, conjunctival follicles, headache, ocular hyperemia, ache or pain in eye, blepharitis, blurred vision or other change in vision, conjunctival discharge, conjunctival hemorrhage, corneal erosion, dizziness, edema of conjunctiva or eyelid, foreign body sensation, gastrointestinal symptoms, increased blood pressure, mental depression, muscle pain, syncope, or upper respiratory symptoms
General Dosing Information
The intraocular pressure (IOP) lowering effect of brimonidine decreases over time {01}. Although the onset of loss of effect is variable, in clinical studies some patients experienced inadequate control of IOP during the first month of treatment {01}.
Ophthalmic Dosage Forms
BRIMONIDINE TARTRATE OPHTHALMIC SOLUTION
Usual adult dose
Open-angle glaucoma or
Ocular hypertension
Topical, to the conjunctiva, 1 drop in the affected eye(s) three times a day {01}.
Usual pediatric dose
Safety and efficacy have not been established {01}.
Strength(s) usually available
U.S.—
0.2% (2 mg of brimonidine tartrate, equivalent to 1.32 mg of brimonidine base, per mL) (Rx) [Alphagan (benzalkonium chloride 0.05 mg per mL) (polyvinyl alcohol) (sodium chloride) (citric acid) (hydrochloric acid and/or sodium hydroxide to adjust pH)]
Packaging and storage:
Store at or below 25 °C (77 °F) {01}.
Auxiliary labeling:
• For the eye.
Developed: 04/01/1997
Revised: 07/15/1998
References
- Alphagan package insert (Allergan—US), New 9/96, Rec 10/96.
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