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ALPHAGAN® P
open-angle glaucoma or ocular hypertension by approximately 2-6 mmHg.
A clinical study was conducted to evaluate the safety, efficacy, and (brimonidine tartrate ophthalmic solution) 0.1% and 0.15% acceptability of ALPHAGAN® P (brimonidine tartrate ophthalmic solution)
0.1% compared with ALPHAGAN® administered three-times-daily in
DESCRIPTION
patients with open-angle glaucoma or ocular hypertension. Those results ALPHAGAN® P (brimonidine tartrate ophthalmic solution) is a relatively
indicated that ALPHAGAN® P (brimonidine tartrate ophthalmic solution)
selective alpha-2 adrenergic agonist for ophthalmic use. The chemical 0.1% is equivalent in IOP lowering effect to ALPHAGAN® (brimonidine
name of brimonidine tartrate is 5-bromo-6-(2-imidazolidinylideneamino) tartrate ophthalmic solution) 0.2%, and effectively lowers IOP in patients with quinoxaline L-tartrate. It is an off-white to pale yellow powder. It has a open-angle glaucoma or ocular hypertension by approximately 2-6 mmHg.
molecular weight of 442.24 as the tartrate salt, and is both soluble inwater (0.6 mg/mL) and in the product vehicle (1.4 mg/mL) at pH 7.7.
INDICATIONS AND USAGE
ALPHAGAN® P is indicated for the lowering of intraocular pressure in
patients with open-angle glaucoma or ocular hypertension.
CONTRAINDICATIONS
ALPHAGAN® P 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.
PRECAUTIONS
General:
In solution, ALPHAGAN® P (brimonidine tartrate ophthalmic solution) has
Although brimonidine tartrate ophthalmic solution had minimal effect on a clear, greenish-yellow color. It has an osmolality of 250-350 mOsmol/kg the blood pressure of patients in clinical studies, caution should be and a pH of 7.4-8.0 (0.1%) or 6.6-7.4 (0.15%).
exercised in treating patients with severe cardiovascular disease.
ALPHAGAN® P has not been studied in patients with hepatic or renal
Each mL of ALPHAGAN® P contains:
impairment; caution should be used in treating such patients.
Active ingredient: brimonidine tartrate 0.1% (1.0 mg/mL) or 0.15%
ALPHAGAN® P should be used with caution in patients with depression,
cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic Inactives: sodium carboxymethylcellulose; sodium borate; boric acid;
hypotension, or thromboangiitis obliterans. Patients prescribed sodium chloride; potassium chloride; calcium chloride; magnesium IOP-lowering medication should be routinely monitored for IOP.
chloride; Purite® 0.005% (0.05mg/mL) as a preservative; purified water; Information for Patients:
with hydrochloric acid and/or sodium hydroxide to adjust pH.
As with other drugs in this class, ALPHAGAN® P may cause fatigue and /or
drowsiness in some patients. Patients who engage in hazardous activities
CLINICAL PHARMACOLOGY
should be cautioned of the potential for a decrease in mental alertness.
Mechanism of action:
ALPHAGAN® P is an alpha adrenergic receptor agonist. It has a peak
Drug Interactions:
ocular hypotensive effect occurring at two hours post-dosing.
Although specific drug interaction studies have not been conducted with Fluorophotometric studies in animals and humans suggest that ALPHAGAN® P, the possibility of an additive or potentiating effect with
brimonidine tartrate has a dual mechanism of action by reducing aqueous CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics) humor production and increasing uveoscleral outflow.
should be considered. Alpha-agonists, as a class, may reduce pulse and blood pressure. Caution in using concomitant drugs such as Pharmacokinetics:
anti-hypertensives and/or cardiac glycosides is advised.
After ocular administration of either a 0.1% or 0.2% solution, plasma Tricyclic antidepressants have been reported to blunt the hypotensive concentrations peaked within 0.5 to 2.5 hours and declined with a effect of systemic clonidine. It is not known whether the concurrent use of systemic half-life of approximately 2 hours.
these agents with ALPHAGAN® P in humans can lead to resulting
In humans, systemic metabolism of brimonidine is extensive. It is interference with the IOP lowering effect. No data on the level of circulating metabolized primarily by the liver. Urinary excretion is the major route of catecholamines after ALPHAGAN® P administration are available.
elimination of the drug and its metabolites. Approximately 87% of an Caution, however, is advised in patients taking tricyclic antidepressants orally-administered radioactive dose was eliminated within 120 hours, which can affect the metabolism and uptake of circulating amines.
Carcinogenesis, Mutagenesis, and Impairment of Fertility:
Clinical Evaluations:
No compound-related carcinogenic effects were observed in either mice Elevated IOP presents a major risk factor in glaucomatous field loss. The or rats following a 21-month and 24-month study, respectively. In these higher the level of IOP, the greater the likelihood of optic nerve damage and studies, dietary administration of brimonidine tartrate at doses up to visual field loss. Brimonidine tartrate has the action of lowering intraocular 2.5 mg/kg/day in mice and 1.0 mg/kg/day in rats achieved 150 and pressure with minimal effect on cardiovascular and pulmonary parameters.
120 times or 90 and 80 times, respectively, the plasma drug Clinical studies were conducted to evaluate the safety, efficacy, and ) estimated in humans treated with one drop of acceptability of ALPHAGAN® P (brimonidine tartrate ophthalmic solution)
ALPHAGAN® P 0.1% or 0.15% into both eyes 3 times per day.
0.15% compared with ALPHAGAN® administered three-times-daily in
Brimonidine tartrate was not mutagenic or cytogenic in a series of in vitro patients with open-angle glaucoma or ocular hypertension. Those results and in vivo studies including the Ames test, chromosomal aberration assay indicated that ALPHAGAN® P (brimonidine tartrate ophthalmic solution)
in Chinese Hamster Ovary (CHO) cells, a host-mediated assay and 0.15% is comparable in IOP lowering effect to ALPHAGAN® (brimonidine
cytogenic studies in mice, and dominant lethal assay.
tartrate ophthalmic solution) 0.2%, and effectively lowers IOP in patients with Pregnancy:
The following events have been identified during post-marketing use of Teratogenic effects: Pregnancy Category B.
brimonidine tartrate ophthalmic solutions in clinical practice. Because they Reproductive studies performed in rats and rabbits with oral doses of are reported voluntarily from a population of unknown size, estimates of 0.66 mg base/kg revealed no evidence of impaired fertility or harm to the frequency cannot be made. The events, which have been chosen for fetus due to ALPHAGAN® P. Dosing at this level produced an exposure in
inclusion due to either their seriousness, frequency of reporting, possible rats and rabbits that is 190 and 100 times or 120 and 60 times higher, causal connection to brimonidine tartrate ophthalmic solutions, or a respectively, than the exposure seen in humans following multiple combination of these factors, include: bradycardia; depression; iritis; ophthalmic doses of ALPHAGAN® P 0.1% or 0.15%.
keratoconjunctivitis sicca; miosis; nausea; skin reactions (including There are no adequate and well-controlled studies in pregnant women. In erythema, eyelid pruritus, rash, and vasodilation) and tachycardia. Apnea; animal studies, brimonidine crossed the placenta and entered into the bradycardia; hypotension; hypothermia; hypotonia; and somnolence have fetal circulation to a limited extent. ALPHAGAN® P should be used during
been reported in infants receiving brimonidine tartrate ophthalmic solutions.
pregnancy only if the potential benefit to the mother justifies the potential OVERDOSAGE
No information is available on overdosage in humans. Treatment of an oral Nursing Mothers:
overdose includes supportive and symptomatic therapy; a patent airway It is not known whether this drug is excreted in human milk; although in animal studies brimonidine tartrate was excreted in breast milk. A decisionshould be made whether to discontinue nursing or to discontinue the drug, DOSAGE AND ADMINISTRATION
taking into account the importance of the drug to the mother.
The recommended dose is one drop of ALPHAGAN® P in the affected
eye(s) three times daily, approximately 8 hours apart.
Pediatric Use:
ALPHAGAN® P ophthalmic solution may be used concomitantly with other
In a well-controlled clinical study conducted in pediatric glaucoma patients topical ophthalmic drug products to lower intraocular pressure. If more (ages 2 to 7 years) the most commonly observed adverse events with than one topical ophthalmic product is being used, the products should be brimonidine tartrate ophthalmic solution 0.2% dosed three times daily administered at least 5 minutes apart.
were somnolence (50%-83% in patients ages 2 to 6 years) and decreasedalertness. In pediatric patients 7 years of age or older (>20kg), HOW SUPPLIED
somnolence appears to occur less frequently (25%). Approximately 16% ALPHAGAN® P is supplied sterile in opaque teal LDPE plastic bottles and
of patients on brimonidine tartrate ophthalmic solution discontinued from droppers with purple high impact polystyrene (HIPS) caps as follows: the study due to somnolence.
The safety and effectiveness of brimonidine tartrate ophthalmic solution have not been studied in pediatric patients below the age of 2 years.
Brimonidine tartrate ophthalmic solution is not recommended for use in pediatric patients under the age of 2 years. (Also refer to Adverse Geriatric Use:
No overall differences in safety or effectiveness have been observed between elderly and other adult patients.
ADVERSE REACTIONS
Adverse events occurring in approximately 10-20% of the subjects NOTE: Store at 15°-25° C (59-77°F).
receiving brimonidine ophthalmic solution (0.1-0.2%) included: allergicconjunctivitis, conjunctival hyperemia, and eye pruritus. Adverse events occurring in approximately 5-9% included: burning sensation, conjunctivalfolliculosis, hypertension, ocular allergic reaction, oral dryness, and 2005 Allergan, Inc.
Adverse events occurring in approximately 1-4% of the subjects receivingbrimonidine ophthalmic solution (0.1-0.2%) included: allergic reaction, asthenia, blepharitis, blepharoconjunctivitis, blurred vision, bronchitis,cataract, conjunctival edema, conjunctival hemorrhage, conjunctivitis, US Pat. 5,424,078; 5,736,165; 6,194, 415; 6,248,741; 6,465,464; cough, dizziness, dyspepsia, dyspnea, epiphora, eye discharge, eye 6,562,873; 6,627,210; 6,641,834; 6,673,337 dryness, eye irritation, eye pain, eyelid edema, eyelid erythema, fatigue, flu syndrome, follicular conjunctivitis, foreign body sensation, gastrointestinal disorder, headache, hypercholesterolemia, hypotension, infection (primarily colds and respiratory infections), insomnia, keratitis, lid disorder,pharyngitis, photophobia, rash, rhinitis, sinus infection, sinusitis,somnolence, stinging, superficial punctate keratopathy, tearing, visual fielddefect, vitreous detachment, vitreous disorder, vitreous floaters, andworsened visual acuity.
The following events were reported in less than 1% of subjects: cornealerosion, hordeolum, nasal dryness, and taste perversion.

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