Combigan Information
Combigan () Indications And Usage
Combigan () Dosage And Administration
The recommended dose is one drop of 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.
Combigan () Dosage Forms And Strengths
Solution containing 2 mg/mL brimonidine tartrate and 5 mg/mL timolol (6.8 mg/mL timolol maleate).
Combigan () Contraindications
Asthma, COPD
Sinus Bradycardia, AV Block, Cardiac Failure, Cardiogenic Shock
5.2
Hypersensitivity Reactions
Local hypersensitivity reactions have occurred following the use of different components of is contraindicated in patients who have exhibited a hypersensitivity reaction to any component of this medication in the past.
Combigan () Warnings And Precautions
Combigan ()
CONTRAINDICATIONS
4
Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe failure.
In patients without a history of cardiac failure, continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of cardiac failure, should be discontinued (see also , ).
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The necessity or desirability of withdrawal of beta-adrenergic blocking agents prior to major surgery is controversial. Beta-adrenergic receptor blockade impairs the ability of the heart to respond to beta-adrenergically mediated reflex stimuli. This may augment the risk of general anesthesia in surgical procedures. Some patients receiving beta-adrenergic receptor blocking agents have experienced protracted severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been reported. For these reasons, in patients undergoing elective surgery, some authorities recommend gradual withdrawal of beta-adrenergic receptor blocking agents.
If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of adrenergic agonists.
Combigan () Use In Specific Populations
Pregnancy Category C: 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 (1.65 mg/kg/day) and rabbits (3.33 mg/kg/day) achieved AUC exposure values 580 and 37-fold higher, respectively, than similar values estimated in humans treated with , 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, should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
Combigan ()
The safety and effectiveness of have been established in the age group 2 – 16 years of age. Use of in this age group is supported by evidence from adequate and well-controlled studies of 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.
Combigan () Overdosage
No information is available on overdosage with in humans. 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. Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained.
Combigan () Description
The structural formulae are:
Brimonidine tartrate:
5-bromo-6-(2-imidazolidinylideneamino) quinoxaline L-tartrate; MW= 442.24
Timolol maleate:
(-)-1-(-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/timolol maleate ophthalmic solution) 0.2%/0.5% has a clear, greenish-yellow color. It has an osmolality of 260-330 mOsmol/kg and a pH during its shelf life of 6.5-7.3.
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 (3.0 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 contains the active ingredients brimonidine tartrate 0.2% and timolol 0.5% with the inactive ingredients benzalkonium chloride 0.005%; sodium phosphate, monobasic; sodium phosphate, dibasic; purified water; and hydrochloric acid and/or sodium hydroxide to adjust pH.
Combigan () Clinical Pharmacology
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Fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action by reducing aqueous humor production and increasing nonpressure dependent uveoscleral outflow.
Timolol maleate is a beta and beta adrenergic receptor inhibitor that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity.
Combigan () Clinical Studies
Clinical studies were conducted to compare the IOP-lowering effect over the course of the day of 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. BID provided an additional 1 to 3 mm Hg decrease in IOP over brimonidine treatment TID and an additional 1 to 2 mm Hg decrease over timolol treatment BID during the first 7 hours post dosing. However, the IOP-lowering of BID was less (approximately 1-2 mm Hg) than that seen with the concomitant administration of 0.5% timolol BID and 0.2% brimonidine tartrate TID. 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.
Combigan () How Supplied/storage And Handling
5 mL in 10 mL bottle NDC 0023-9211-0510 mL in 10 mL bottle NDC 0023-9211-10
Combigan () Patient Counseling Information
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 , ).
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 (see , ).
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 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 .
As with other similar medications, 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.
© 2011 Allergan, Inc., Irvine, CA 92612, U.S.A.® marks owned by Allergan, Inc.U.S. Patents 6,194,415; 6,465,464; 7,030,149; 7,320,976; 7,323,463; and 7,642,258Made in the U.S.A.
72060US12C
Combigan ()
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