BRIMONIDINE TARTRATE/TIMOLOL MALEATE OPHTHALMIC SOLUTION- brimonidine tartrate and timolol maleate solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

Brimonidine Tartrate (UNII: 4S9CL2DY2H) (brimonidine - UNII:E6GNX3HHTE), timolol maleate (UNII: P8Y54F701R) (Timolol Anhydrous - UNII:5JKY92S7BR)

Available from:

Apotex Corp.

Administration route:

OPHTHALMIC

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Brimonidine Tartrate/Timolol Maleate Ophthalmic Solution 0.2%/0.5% is an alpha-adrenergic receptor agonist with a beta-adrenergic receptor inhibitor indicated for the reduction of elevated intraocular pressure (IOP) in patients with glaucoma or ocular hypertension who require adjunctive or replacement therapy due to inadequately controlled IOP; the IOP-lowering of brimonidine tartrate/timolol maleate ophthalmic solution dosed twice a day was slightly less than that seen with the concomitant administration of 0.5% timolol maleate ophthalmic solution dosed twice a day and 0.2% brimonidine tartrate ophthalmic solution dosed three times per day. Brimonidine tartrate/timolol maleate ophthalmic solution is contraindicated in patients with reactive airway disease including bronchial asthma; a history of bronchial asthma; severe chronic obstructive pulmonary disease [see Warnings and Precautions (5.1, 5.3)] . Brimonidine tartrate/timolol maleate ophthalmic solution is contraindicated in patients with sinus bradycardia; second or third degree atrioventricular block; overt cardiac failure [see Warnings and Precautions (5.2)] ; cardiogenic shock. Brimonidine tartrate/timolol maleate ophthalmic solution is contraindicated in neonates and infants (under the age of 2 years). Local hypersensitivity reactions have occurred following the use of different components of brimonidine tartrate/timolol maleate ophthalmic solution. Brimonidine tartrate/timolol maleate ophthalmic solution is contraindicated in patients who have exhibited a hypersensitivity reaction to any component of this medication in the past. Teratogenicity studies have been performed in animals. Brimonidine tartrate was not teratogenic when given orally during gestation days 6 through 15 in rats and days 6 through 18 in rabbits. The highest doses of brimonidine tartrate in rats (2.5 mg/kg/day) and rabbits (5 mg/kg/day) achieved AUC exposure values 580 and 37-fold higher, respectively, than similar values estimated in humans treated with brimonidine tartrate/timolol maleate ophthalmic solution, 1 drop in both eyes twice daily. Teratogenicity studies with timolol in mice, rats, and rabbits at oral doses up to 50 mg/kg/day [4,200 times the maximum recommended human ocular dose of 0.012 mg/kg/day on a mg/kg basis (MRHOD)] demonstrated no evidence of fetal malformations. Although delayed fetal ossification was observed at this dose in rats, there were no adverse effects on postnatal development of offspring. Doses of 1,000 mg/kg/day (83,000 times the MRHOD) were maternotoxic in mice and resulted in an increased number of fetal resorptions. Increased fetal resorptions were also seen in rabbits at doses 8,300 times the MRHOD without apparent maternotoxicity. There are no adequate and well-controlled studies in pregnant women; however, in animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent. Because animal reproduction studies are not always predictive of human response, brimonidine tartrate/timolol maleate ophthalmic solution should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Timolol has been detected in human milk following oral and ophthalmic drug administration. It is not known whether brimonidine tartrate is excreted in human milk, although in animal studies, brimonidine tartrate has been shown to be excreted in breast milk. Because of the potential for serious adverse reactions from brimonidine tartrate/timolol maleate ophthalmic solution in nursing infants, 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. Brimonidine tartrate/timolol maleate ophthalmic solution is contraindicated in children under the age of 2 years [see Contraindications (4.3)] . During post-marketing surveillance, apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence have been reported in infants receiving brimonidine. The safety and effectiveness of brimonidine tartrate and timolol maleate have not been studied in children below the age of 2 years. The safety and effectiveness of brimonidine tartrate/timolol maleate ophthalmic solution have been established in the age groups 2 – 16 years of age. Use of brimonidine tartrate/timolol maleate ophthalmic solution in these age groups is supported by evidence from adequate and well-controlled studies of brimonidine tartrate/timolol maleate ophthalmic solution in adults with additional data from a study of the concomitant use of brimonidine tartrate ophthalmic solution 0.2% and timolol maleate ophthalmic solution in pediatric glaucoma patients (ages 2 to 7 years). In this study, brimonidine tartrate ophthalmic solution 0.2% was dosed three times a day as adjunctive therapy to beta-blockers. The most commonly observed adverse reactions were somnolence (50%-83% in patients 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. No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

Product summary:

Brimonidine Tartrate/Timolol Maleate Ophthalmic Solution is supplied sterile, in white opaque plastic LDPE bottles with white translucent plastic LDPE droppers and dark blue opaque HDPE plastic caps as follows: Storage: Store at 20° - 25°C (68° - 77°F) [See USP Controlled Room Temperature]. Protect from light.

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

BRIMONIDINE TARTRATE/TIMOLOL MALEATE OPHTHALMIC SOLUTION-
BRIMONIDINE TARTRATE AND TIMOLOL MALEATE SOLUTION
APOTEX CORP.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
BRIMONIDINE
TARTRATE/TIMOLOL MALEATE OPHTHALMIC SOLUTION SAFELY AND EFFECTIVELY.
SEE FULL
PRESCRIBING INFORMATION FOR BRIMONIDINE TARTRATE/TIMOLOL MALEATE
OPHTHALMIC SOLUTION.
BRIMONIDINE TARTRATE/TIMOLOL MALEATE OPHTHALMIC SOLUTION 0.2%/0.5%
FOR TOPICAL ADMINISTRATION
INITIAL U.S. APPROVAL: 2007
INDICATIONS AND USAGE
Brimonidine Tartrate/Timolol Maleate Ophthalmic Solution is an
alpha-adrenergic receptor agonist with a
beta-adrenergic receptor inhibitor indicated for the reduction of
elevated intraocular pressure (IOP) in
patients with glaucoma or ocular hypertension who require adjunctive
or replacement therapy due to
inadequately controlled IOP; the IOP-lowering of brimonidine
tartrate/timolol maleate ophthalmic solution
dosed twice a day was slightly less than that seen with the
concomitant administration of timolol maleate
ophthalmic solution, 0.5% dosed twice a day and brimonidine tartrate
ophthalmic solution, 0.2% dosed
three times per day. (1)
DOSAGE AND ADMINISTRATION
One drop in the affected eye(s), twice daily approximately 12 hours
apart. (2)
DOSAGE FORMS AND STRENGTHS
Solution containing 2 mg/mL brimonidine tartrate and 5 mg/mL timolol.
(3)
CONTRAINDICATIONS
Bronchial asthma, a history of bronchial asthma, severe chronic
obstructive pulmonary disease. (4.1,
5.1, 5.3)
Sinus bradycardia, atrioventricular block, overt cardiac failure,
cardiogenic shock. (4.2, 5.2)
Neonates and infants (under the age of 2 years). (4.3)
Hypersensitivity to any component of this product. (4.4)
WARNINGS AND PRECAUTIONS
Potential for Severe Respiratory or Cardiac Reactions (5.1)
Cardiac Failure (5.2)
Obstructive Pulmonary Disease (5.3)
Potentiation of Vascular Insufficiency (5.4)
Increased Reactivity to Allergens (5.5)
Potentiation of Muscle Weakness (5.6)
Masking of Hypoglycemic Symptoms in P