Complete SPL Sections
1 INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
Brimonidine tartrate and 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 and timolol maleate ophthalmic solution, 0.2%/0.5% 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.
2 DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
The recommended dose is one drop of brimonidine tartrate and timolol maleate ophthalmic solution, 0.2%/0.5% in the affected eye(s) twice daily approximately 12 hours apart. If more than one topical ophthalmic product is to be used, the different products should be instilled at least 5 minutes apart.
3 DOSAGE FORMS AND STRENGTHS
DOSAGE FORMS & STRENGTHS SECTION
Solution containing 2 mg/mL brimonidine tartrate and 5 mg/mL timolol (6.8 mg/mL timolol maleate).
4 CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
5 WARNINGS AND PRECAUTIONS
WARNINGS AND PRECAUTIONS SECTION
6 ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
7 DRUG INTERACTIONS
DRUG INTERACTIONS SECTION
8 USE IN SPECIFIC POPULATIONS
USE IN SPECIFIC POPULATIONS SECTION
10 OVERDOSAGE
OVERDOSAGE SECTION
There have been reports of inadvertent overdosage with timolol ophthalmic solution resulting in systemic effects similar to those seen with systemic beta-adrenergic blocking agents such as dizziness, headache, shortness of breath, bradycardia, bronchospasm, and cardiac arrest. With the exception of hypotension, very limited information exists on accidental ingestion of brimonidine in adults. Symptoms of brimonidine overdose have been reported in neonates, infants, and children receiving brimonidine ophthalmic solutions as part of medical treatment of congenital glaucoma or by accidental oral ingestion [see Use in Specific Populations ( 8.4 )] . Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained.
11 DESCRIPTION
DESCRIPTION SECTION
Brimonidine tartrate and timolol maleate ophthalmic solution, 0.2%/0.5%, sterile, is a relatively selective alpha-2 adrenergic receptor agonist with a non-selective beta-adrenergic receptor inhibitor (topical intraocular pressure lowering agent). The structural formulae are: Brimonidine tartrate: 5-bromo-6-(2-imidazolidinylideneamino) quinoxaline L-tartrate; MW= 442.24 Timolol maleate: (-)-1-( tert -butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)-oxy]-2-propanol maleate (1:1) (salt); MW= 432.50 as the maleate salt In solution, brimonidine tartrate and timolol maleate ophthalmic solution, 0.2%/0.5% has a clear, greenish-yellow color. It has an osmolality of 260 to 330 mOsmol/kg and a pH during its shelf life of 6.5 to 7.3. Brimonidine tartrate appears as an off-white or white to pale-yellow powder and is soluble in both water (1.5 mg/mL) and in the product vehicle (3 mg/mL) at pH 7.2. Timolol maleate appears as a white, odorless, crystalline powder and is soluble in water, methanol, and alcohol. Each mL of brimonidine tartrate and timolol maleate ophthalmic solution, 0.2%/0.5% contains Actives: brimonidine tartrate 0.2% (2 mg), timolol maleate 6.8 mg equivalent to timolol 0.5% (5 mg). Preservative: benzalkonium chloride 0.005%. Inactives: purified water; sodium phosphate, monobasic; sodium phosphate, dibasic; hydrochloric acid and/or sodium hydroxide to adjust pH.
12 CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
13 NONCLINICAL TOXICOLOGY
NONCLINICAL TOXICOLOGY SECTION
14 CLINICAL STUDIES
CLINICAL STUDIES SECTION
Clinical studies were conducted to compare the IOP-lowering effect over the course of the day of brimonidine tartrate and timolol maleate ophthalmic solution, 0.2%/0.5% administered twice a day (BID) to individually-administered brimonidine tartrate ophthalmic solution, 0.2% administered three times per day (TID) and timolol maleate ophthalmic solution, 0.5% BID in patients with glaucoma or ocular hypertension. Brimonidine tartrate and timolol maleate ophthalmic solution, 0.2%/0.5% BID provided an additional 1 to 3 mmHg decrease in IOP over brimonidine treatment TID and an additional 1 to 2 mmHg decrease over timolol treatment BID during the first 7 hours post dosing. However, the IOP-lowering of brimonidine tartrate and timolol maleate ophthalmic solution, 0.2%/0.5% BID was less (approximately 1 to 2 mmHg) than that seen with the concomitant administration of 0.5% timolol BID and 0.2% brimonidine tartrate TID. Brimonidine tartrate and timolol maleate ophthalmic solution, 0.2%/0.5% administered BID had a favorable safety profile versus concurrently administered brimonidine TID and timolol BID in the self-reported level of severity of sleepiness for patients over age 40.
16 HOW SUPPLIED/STORAGE AND HANDLING
HOW SUPPLIED SECTION
Brimonidine tartrate and timolol maleate ophthalmic solution, 0.2%/0.5% is supplied sterile, in a white LDPE plastic bottle with a natural LDPE dropper tip and a blue polypropylene cap as follows: NDC 0781-7186-75 – 5 mL fill in 8 mL bottle NDC 0781-7186-70 – 10 mL fill in 10 mL bottle NDC 0781-7186-85 – 15 mL fill in 15 mL bottle Storage: Store at 15° to 25°C (59° to 77°F). Protect from light.
17 PATIENT COUNSELING INFORMATION
INFORMATION FOR PATIENTS SECTION
Patients with bronchial asthma, a history of bronchial asthma, severe chronic obstructive pulmonary disease, sinus bradycardia, second or third degree atrioventricular block, or cardiac failure should be advised not to take this product [see Contraindications ( 4.1 , 4.2 )] . Patients should be instructed that ocular solutions, if handled improperly or if the tip of the dispensing container contacts the eye or surrounding structures, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions or by inadvertent contact with the dropper tip [see Warnings and Precautions ( 5.10 )] . Always replace the cap after using. If solution changes color or becomes cloudy, do not use. Do not use the product after the expiration date marked on the bottle. Patients also should be advised that if they have ocular surgery or develop an intercurrent ocular condition (e.g., trauma or infection), they should immediately seek their physician’s advice concerning the continued use of the present multidose container. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart. Patients should be advised that brimonidine tartrate and timolol maleate ophthalmic solution, 0.2%/0.5% contains benzalkonium chloride which may be absorbed by soft contact lenses. Contact lenses should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following administration of brimonidine tartrate and timolol maleate ophthalmic solution, 0.2%/0.5%. As with other similar medications, brimonidine tartrate and timolol maleate ophthalmic solution, 0.2%/0.5% 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.
0.2%/0.5% Label
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 0781-7186-75 Brimonidine Tartrate/ Timolol Maleate Ophthalmic Solution 0.2%/0.5%* FOR USE IN THE EYES ONLY Rx only Sterile 5mL SANDOZ