Document
DailyMed Label: BRIMONIDINE TARTRATE
Title
DailyMed Label: Brimonidine Tartrate
Date
2010
Document type
DailyMed Prescription
Name
Brimonidine Tartrate
Generic name
brimonidine tartrate
Manufacturer
Physicians Total Care, Inc.
Product information
NDC: 54868-6094
Product information
NDC: 54868-6094
Description
Brimonidine Tartrate Ophthalmic Solution, 0.15% (1.5 mg
brimonidine tartrate per mL equivalent to 1.0 mg brimonidine free base per mL)
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 to pale yellow powder. It has a
molecular weight of 442.24 as the tartrate salt, and is both soluble in water
(1.5 mg/mL) and in the product vehicle (3.0 mg/mL) at pH 7.2. The structural
formula is:
In solution, Brimonidine Tartrate Ophthalmic Solution, 0.15% has a clear,
greenish-yellow color. It has an osmolality of 250 - 350 mOsmol/kg and a pH of
6.6-7.4.
Each mL of Brimonidine Tartrate Ophthalmic Solution, 0.15% contains: Active ingredient: brimonidine tartrate 0.15% (1.5 mg/mL)
Inactives: povidone; boric acid; sodium borate; calcium
chloride; magnesium chloride; potassium chloride; mannitol; sodium chloride;
POLYQUAD* 0.001% (0.01 mg/mL); purified water; with hydrochloric acid and/or
sodium hydroxide to adjust pH.
image of chemical structure and formula
Indications
Brimonidine Tartrate Ophthalmic Solution, 0.15% is indicated for the lowering of
intraocular pressure in patients with open-angle glaucoma or ocular
hypertension.
Dosage
The recommended dose is one drop of Brimonidine Tartrate
Ophthalmic Solution, 0.15% in the affected eye(s) three-times-daily,
approximately 8 hours apart.
Brimonidine Tartrate Ophthalmic Solution, 0.15% may be used concomitantly
with other topical ophthalmic drug products to lower intraocular pressure. If
more than one topical ophthalmic product is being used, the products should be
administered at least 5 minutes apart.
Contraindications
Brimonidine Tartrate Ophthalmic Solution, 0.15% 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: Although Brimonidine Tartrate Ophthalmic Solution, 0.15% had
minimal effect on the blood pressure of patients in clinical studies, caution
should be exercised in treating patients with severe cardiovascular disease.
Brimonidine Tartrate Ophthalmic Solution, 0.15% has not been studied in
patients with hepatic or renal impairment; caution should be used in treating
such patients.
Brimonidine Tartrate Ophthalmic Solution, 0.15% should be used with caution
in patients with depression, cerebral or coronary insufficiency, Raynaud's
phenomenon, orthostatic hypotension, or thromboangiitis obliterans. Patients
prescribed IOP-lowering medication should be routinely monitored for IOP.
Information for Patients: As with other drugs in this class, Brimonidine Tartrate
Ophthalmic Solution, 0.15% 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 Brimonidine Tartrate Ophthalmic Solution, 0.15%, the possibility
of an additive or potentiating effect with CNS depressants (alcohol,
barbiturates, opiates, sedatives, or anesthetics) should be considered. Alpha-2
agonists, as a class, may reduce pulse and blood pressure. Caution in using
concomitant drugs such as beta-blockers (ophthalmic and systemic),
anti-hypertensives 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 Brimonidine Tartrate Ophthalmic Solution, 0.15% in humans can
interfere with its IOP-lowering effect. No data on the level of circulating
catecholamines after Brimonidine Tartrate Ophthalmic Solution, 0.15%
administration are available. Caution, however, is advised in patients taking
tricyclic antidepressants, which can affect the metabolism and uptake of
circulating amines.
Carcinogenesis, Mutagenesis, and Impairment of
Fertility: No compound-related carcinogenic effects were observed in either
mice or rats following a 21-month and a 24-month study, respectively. In these
studies, dietary administration of brimonidine tartrate at doses up to
2.5 mg/kg/day in mice and 1.0 mg/kg/day in rats achieved 60 and 50 times,
respectively, the plasma drug concentration estimated in humans treated with one
drop of Brimonidine Tartrate Ophthalmic Solution, 0.15% into both eyes.
Brimonidine tartrate was not mutagenic or cytogenic in a series of in vitro and in vivo studies
including the Ames test, chromosomal aberration assay in Chinese hamster ovary
(CHO) cells, a host-mediated assay and cytogenic studies in mice, and dominant
lethal assay.
Pregnancy: Teratogenic Effects: Pregnancy Category: B
Reproductive studies performed in rats and rabbits with oral
doses of 0.66 mg base/kg revealed no evidence of harm to the fetus due to
Brimonidine Tartrate Ophthalmic Solution, 0.15%. Dosing at this level produced
an exposure in rats and rabbits that is 80 and 40 times higher than the exposure
seen in humans, respectively.
There are no adequate and well-controlled studies in pregnant women. In
animal studies, brimonidine crossed the placenta and entered into the fetal
circulation to a limited extent. Brimonidine Tartrate Ophthalmic Solution, 0.15%
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 this drug is excreted in human milk. In
animal studies, brimonidine tartrate was 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: In a well-controlled clinical study conducted in pediatric
glaucoma patients (ages 2 to 7 years) the most commonly observed adverse events
with brimonidine tartrate ophthalmic solution 0.2% dosed three-times-daily were
somnolence (50%-83% in patients ages 2 to 6 years) and decreased alertness. In
pediatric patients 7 years of age or older (>20 kg), somnolence appears to
occur less frequently (25%). Approximately 16% of patients on brimonidine
tartrate ophthalmic solution discontinued from 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 REACTIONS
section.)
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
included: allergic conjunctivitis, conjunctival hyperemia, and eye pruritis.
How supplied
Brimonidine Tartrate Ophthalmic Solution, 0.15% is supplied
sterile in opaque white LDPE plastic bottles and natural tips with purple
polypropylene caps as follows:
10 mL in 10 mL bottle NDC 54868-6094-0
Storage: Store at 15°-25° C (59° - 77°F).
Rx Only
Distributed by:
Falcon Pharmaceuticals, Ltd.
Fort Worth, Texas 76134
Manufactured by:
Alcon Laboratories, Inc.
Fort Worth, Texas 76134
Printed in USA
*POLYQUAD is a registered trademark of Alcon Research, Ltd.
**ALPHAGAN P is a registered trademark of Allergan, Inc.
349040-1008
Clinical pharmacology
Mechanism of Action: Brimonidine Tartrate Ophthalmic Solution, 0.15% is an alpha-2
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.
Pharmacokinetics: In a pharmacokinetic study, 14 healthy subjects (4 males and
10 females) received a single topical ocular administration of Brimonidine
Tartrate Ophthalmic Solution, 0.15%, one drop per eye. The peak plasma
concentrations (C max ) and AUC
0-inf were 73 ± 19 pg/mL and 375 ± 89 pg•hr/mL, respectively. T max was 1.7 ± 0.7 hours after dosing. The systemic half-life
was approximately 2.1 hours.
Brimonidine is metabolized primarily by the liver. In
vitro metabolism data from human microsomal fractions and liver slices
indicate that brimonidine undergoes extensive hepatic metabolism.
Urinary excretion is the major route of elimination of brimonidine and its
metabolites. Approximately 87% of an orally administered radioactive dose of
brimonidine was eliminated within 120 hours, with 74% of the radioactivity
recovered in the urine.
Special Populations
Brimonidine Tartrate Ophthalmic Solution, 0.15% has not been studied in
patients with hepatic or renal impairment. Because of the low systemic drug
exposure following topical ocular administration of Brimonidine Tartrate
Ophthalmic Solution, 0.15%, no dose adjustment is necessary when treating
patients with hepatic or renal impairment.
Clinical Evaluations: 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. Brimonidine tartrate has the action of lowering
intraocular pressure with minimal effect on cardiovascular and pulmonary
parameters.
A clinical study was conducted to evaluate the safety and efficacy of
Brimonidine Tartrate Ophthalmic Solution, 0.15% compared to Alphagan® P**
administered three-times-daily in patients with open-angle glaucoma or ocular
hypertension. The results indicated that Brimonidine Tartrate Ophthalmic
Solution, 0.15% is equivalent in IOP-lowering effect to Alphagan® P (brimonidine
tartrate ophthalmic solution), 0.15%, and effectively lowers IOP in patients
with open-angle glaucoma or ocular hypertension by 2 - 6 mm Hg.
Package label
Brimonidine Tartrate Opthalmic Solution
image of Brimonidine Tartrate package label
14 organizations
1 product
Product
BRIMONIDINE TARTRATEOrganization
STAT RX USA LLCOrganization
A-S Medication SolutionsOrganization
Sandoz Inc. Organization
Padagis Israel Pharmaceuticals LtdOrganization
Pacific Pharma, Inc.Organization
Akorn - Strides LLC Organization
Alembic Pharmaceuticals Inc.Organization
bryant ranch prepackOrganization
BAUSCH & LOMB INCORPORATEDOrganization
Florida Pharmaceutical Products, LLCOrganization
Apotex Corp.Organization
Somerset Therapeutics, LLCOrganization
Alembic Pharmaceuticals LimitedOrganization
Physicians Total Care, Inc.