ALPHAGAN® (brimonidine tartrate ophthalmic solution) 0.2% is a relatively selective alpha-2 adrenergic agonist for ophthalmic use. The chemical name of brimonidine tartrate is 5-bromo-6-(2-imidazolidinylideneamino) quinoxaline L-tartrate. It is an off-white, pale yellow to pale pink powder. In solution, ALPHAGAN® has a clear, greenish-yellow color. It has a molecular weight of 442.24 as the tartrate salt and is water soluble (34 mg/mL). The molecular formula is C 11 H 10 BrN 5 ·C 4 H 6 O 6 .

ALPHAGAN® (brimonidine tartrate ophthalmic solution) 0.2% is a sterile ophthalmic solution. Each mL of ALPHAGAN® Solution contains:

ACTIVE: brimonidine tartrate 2 mg (equivalent to 1.32 mg as brimonidine free base).

PRESERVATIVE: benzalkonium chloride (0.05 mg)

INACTIVES: polyvinyl alcohol; sodium chloride; sodium citrate; citric acid; and purified water. Hydrochloric acid and/or sodium hydroxide may be added to adjust pH (6.3-6.5).

Mechanism of Action

ALPHAGAN® is an alpha adrenergic receptor agonist. It has a peak ocular hypotensive effect occurring at two hours post-dosing. Fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow.

After ocular administration of a 0.2% solution, plasma concentrations peaked within 1 to 4 hours and declined with a systemic half-life of approximately 3 hours.

In humans, systemic metabolism of brimonidine is extensive. It is metabolized primarily by the liver. Urinary excretion is the major route of elimination of the drug and its metabolites. Approximately 87% of an orally-administered radioactive dose was eliminated within 120 hours, with 74% found in the urine.

Clinical Studies

Elevated IOP presents a major risk factor in glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss. ALPHAGAN® has the action of lowering intraocular pressure with minimal effect on cardiovascular and pulmonary parameters. In comparative clinical studies with timolol 0.5%, lasting up to one year, the IOP lowering effect ofALPHAGAN® was approximately 4-6 mm Hg compared with approximately 6 mm Hg for timolol. In these studies, both patient groups were dosed BID, however, due to the duration of action of ALPHAGAN®, it is recommended that ALPHAGAN® be dosed TID. Eight percent of the subjects were discontinued from studies due to inadequately controlled intraocular pressure, which in 30% of these patients occurred during the first month of therapy. Approximately 20% were discontinued due to adverse experiences.

ALPHAGAN® is indicated for lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension. The IOP lowering efficacy of ALPHAGAN® Ophthalmic Solution diminishes over time in some patients. This loss of effect appears with a variable time of onset in each patient and should be closely monitored.


ALPHAGAN® is contraindicated in patients with hypersensitivity to brimonidine tartrate or any component of this medication. It is also contraindicated in patients receiving monoamine oxidase (MAO) inhibitor therapy.


General: Although ALPHAGAN® had minimal effect on blood pressure of patients in clinical studies, caution should be exercised in treating patients with severe cardiovascular disease. ALPHAGAN® has not been studied in patients with hepatic or renal impairment; caution should be used in treating such patients. ALPHAGAN® should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud' phenomenon, orthostatic hypotension or thromboangiitis obliterans. During the studies there was a loss of effect in some patients. The IOP-lowering efficacy observed with ALPHAGAN® Ophthalmic Solution during the first month of therapy may not always reflect the long-term level of IOP reduction. Patients prescribed IOP-lowering medication should be routinely monitored for IOP.

Information for Patients: The preservative in ALPHAGAN®, benzalkonium chloride, may be absorbed by soft contact lenses. Patients wearing soft contact lenses should be instructed to wait at least 15 minutes after instilling ALPHAGAN® to insert soft contact lenses. As with other drugs in this class, ALPHAGAN® may cause fatigue and/or drowsiness in some patients. Patients who engage in hazardous activities should be cautioned of the potential for a decrease in mental alertness.

Drug Interactions: Although specific drug interaction studies have not been conducted with ALPHAGAN®, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics) should be considered. ALPHAGAN® did not have significant effects on pulse and blood pressure in clinical studies. However, since alpha-agonists, as a class, may reduce pulse and blood pressure, caution in using concomitant drugs such as beta-blockers (ophthalmic and systemic), antihypertensives and/or cardiac glycosides is advised. Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of these agents with ALPHAGAN® can lead to an interference in IOP lowering effect. No data on the level of circulating catecholamines after ALPHAGAN® is instilled are available. Caution, however, is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines.

Carcinogenesis, Mutagenesis, Impairment of Fertility: No compound-related carcinogenic effects were observed in 21 month and 2 year studies in mice and rats given oral doses of 2.5 mg/kg/day (as the free base) and 1.0 mg/kg/day, respectively (~77 and 118 times, respectively, the human plasma drug concentration following the recommended ophthalmic dose). ALPHAGAN® was not mutagenic or cytogenic in a series of in vitro and in vivo studies including the Ames test, host-mediated assay, chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells, cytogenic studies in mice and dominant lethal assay.

Pregnancy: Teratogenic Effects: Pregnancy Category B.

Reproduction studies performed in rats with oral doses of 0.66 mg base/kg revealed no evidence of impaired fertility or harm to the fetus due to ALPHAGAN®. Dosing at this level produced 100 times the plasma drug concentration level seen in humans following multiple ophthalmic doses. There are no studies of ALPHAGAN® in pregnant women, however in animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent. ALPHAGAN® should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

Nursing Mothers: It is not known whether ALPHAGAN® is excreted in human milk, although in animal studies, brimonidine tartrate has been shown to be excreted in breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Agitation, apnea, bradycardia, convulsions, cyanosis, depression, dyspnea, emotional instability, hypotension, hypothermia, hypotonia, hypoventilation, irritability, lethargy, somnolence, and stupor have been reported in pediatric patients.

Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and other adult patients.


Adverse events occurring in approximately 10-30% of the subjects, in descending order of incidence, included oral dryness, ocular hyperemia, burning and stinging, headache, blurring, foreign body sensation, fatigue/drowsiness, conjunctival follicles, ocular allergic reactions, and ocular pruritus. Events occurring in approximately 3-9% of the subjects, in descending order included corneal staining/erosion, photophobia, eyelid erythema, ocular ache/pain, ocular dryness, tearing, upper respiratory symptoms, eyelid edema, conjunctival edema, dizziness, blepharitis, ocular irritation, gastrointestinal symptoms, asthenia, conjunctival blanching, abnormal vision and muscular pain. The followingadverse reactions were reported in less than 3% of thepatients: lid crusting, conjunctival hemorrhage, abnormal taste, insomnia, conjunctival discharge, depression, hypertension, anxiety, palpitations/arrhythmias, nasal dryness and syncope.


No information is available on overdosage in humans. Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained.


The recommended dose is one drop of ALPHAGAN® in the affected eye(s) three times daily, approximately 8 hours apart.


ALPHAGAN® (brimonidine tartrate ophthalmic solution) 0.2% is supplied sterile in white opaque plastic dropper bottles as follows:

5 mL    NDC 0023-8665-05

10 mL  NDC 0023-8665-10

15 mL  NDC 0023-8665-15

NOTE: Store at or below 25° C (77° F).

Rx only


©2000 Allergan, Inc., Irvine, CA 92612


NOTE: These photos can be used only for identification by shape, color, and imprint. They do not depict actual or relative size.

The product samples shown here have been supplied by the manufacturer and reproduced in full color by PDR as a quick-reference identification aid. While every effort has been made to assure accurate reproduction, please remember that any visual identification should be considered preliminary. In cases of poisoning or suspected overdosage, the drug' identity should be verified by chemical analysis.