Brimonidine Tartrate/Timolol Maleate Ophthalmic Solution 2 mg/mL; 5 mg/mL Solution
Other active recalls for Brimonidine Tartrate And Timolol Maleate (different manufacturers) — 3 · tap to view
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the beta-Adrenergic Blocker class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Ophthalmic brimonidine is used to lower pressure in the eyes in patients who have glaucoma (a condition in which increased pressure in the eye can lead to gradual loss of vision) or ocular hypertension (increased pressure in the eyes). Brimonidine is in a class of drugs called alpha adrenergic agonists. Brimonidine works by decreasing the amount of fluid in the eyes.
Read the full MedlinePlus article ↗Patient education
Supplement & herbal interactions
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII F5UM2KM3W7
Benzalkonium chloride is a chemical compound that works as a preservative and antimicrobial agent in medications. It prevents bacterial and fungal growth in liquid formulations to keep the product safe during storage and use.
-
UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
-
UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
-
UNII 70WT22SF4B
A mineral salt that acts as a buffer to maintain the pH balance of the medication. It helps stabilize the drug's potency and prevents unwanted chemical changes during storage.
-
UNII 593YOG76RN
A salt made from sodium and phosphate that helps regulate acidity and maintain proper pH balance in the medicine. It also acts as a buffer to keep the product stable.
-
UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
6 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $2.795 | $13.97 / 5 ml |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Brimonidine Tartrate/Timolol Maleate Ophthalmic Solution 2 mg/mL; 5 mg/mL 65145-0164-01 | Caplin | 1 bottle | $1.839 | AB | Availability likely | save 34% |
| Brimonidine Tartrate and Timolol Maleate 2 mg/mL; 5 mg/mL 70069-0653-01 | Somerset | 1 bottle | $1.839 | AB | Availability likely | save 34% |
| Brimonidine Tartrate and Timolol Maleate 2 mg/mL; 5 mg/mL 00781-7186-70 | Sandoz | 10 ml | $2.461 | AB | Availability likely | save 12% |
| Brimonidine Tartrate/Timolol Maleate Ophthalmic Solution 2 mg/mL; 5 mg/mL 65145-0163-01 | Caplin | 1 bottle | $2.461 | AB | Availability likely | save 12% |
| Brimonidine Tartrate/Timolol Maleate 2 mg/mL; 5 mg/mL 68462-0281-32 | Glenmark | 1 bottle | $2.461 | AB | Availability likely | save 12% |
| Brimonidine Tartrate and Timolol Maleate 2 mg/mL; 5 mg/mL 70069-0652-01 | Somerset | 1 bottle | $2.461 | AB | Availability likely | save 12% |
| Brimonidine Tartrate and Timolol Maleate 2 mg/mL; 5 mg/mL 00832-1425-05 | Upsher-Smith | 1 bottle | $2.795 | AB | Availability likely | — |
| Brimonidine Tartrate/Timolol Maleate Ophthalmic Solution 2 mg/mL; 5 mg/mL 60505-0589-01 | Apotex | 1 bottle | $2.795 | AB | Availability likely | — |
| Brimonidine Tartrate and Timolol Maleate 2 mg/mL; 5 mg/mL 62332-0706-05 | Alembic | 1 bottle | $2.795 | AB | Availability likely | — |
| Brimonidine Tartrate/Timolol Maleate Ophthalmic Solution 2 mg/mL; 5 mg/mLthis 65145-0162-01 | Caplin | 1 bottle | $2.795 | AB | Availability likely | — |
| Brimonidine Tartrate/Timolol Maleate Ophthalmic Solution 2 mg/mL; 5 mg/mL 69315-0330-05 | Leading | 1 bottle | $2.795 | AB | Availability likely | — |
| Brimonidine Tartrate and Timolol Maleate 2 mg/mL; 5 mg/mL 70069-0651-01 | Somerset | 1 bottle | $2.795 | AB | Availability likely | — |
| Brimonidine Tartrate And Timolol Maleate 2 mg/mL; 5 mg/mL 71921-0188-05 | Florida | 1 bottle | $2.795 | AB | Availability likely | — |
| Brimonidine tartrate and Timolol maleate 2 mg/mL; 5 mg/mL 72603-0931-05 | NorthStar | 1 bottle | $2.795 | AB | Availability likely | — |
| Combigan 2 mg/mL; 5 mg/mL 00023-9211-03 | Allergan, | 1 bottle | — | AB | FDA listed | — |
| Brimonidine Tartrate and Timolol Maleate 2 mg/mL; 5 mg/mL 46708-0706-05 | Alembic | 1 bottle | — | AB | FDA listed | — |
| Brimonidine Tartrate and Timolol maleate Ophthalmic Solution 2 mg/mL; 5 mg/mL 68083-0624-01 | Gland | 1 bottle | — | AB | FDA listed | — |
| Brimonidine Tartrate and Timolol maleate Ophthalmic Solution 2 mg/mL; 5 mg/mL 68083-0625-01 | Gland | 1 bottle | — | AB | FDA listed | — |
| Brimonidine Tartrate and Timolol maleate Ophthalmic Solution 2 mg/mL; 5 mg/mL 68083-0664-01 | Gland | 1 bottle | — | AB | FDA listed | — |
| Brimonidine Tartrate/Timolol Maleate 2 mg/mL; 5 mg/mL 72485-0634-05 | ARMAS | 1 bottle | — | AB | FDA listed | — |
| Brimonidine Tartrate and Timolol maleate Ophthalmic Solution 2 mg/mL; 5 mg/mL 73043-0029-01 | Devatis | 1 bottle | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 65145-0162-01 You're viewing this | 1 BOTTLE, DROPPER in 1 CARTON (65145-162-01) / 5 mL in 1 BOTTLE, DROPPER | 2025-03-10 | Active |
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS & USAGE 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 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.
⏱️ Dosage and Administration ▾
2 DOSAGE & ADMINISTRATION The recommended dose is one drop of brimonidine tartrate/timolol maleate ophthalmic solution 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. One drop in the affected eye(s), twice daily approximately 12 hours apart.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS & STRENGTHS Solution containing 2 mg/mL brimonidine tartrate and 5 mg/mL timolol (6.8 mg/mL timolol maleate). Solution containing 2 mg/mL brimonidine tartrate and 5 mg/mL timolol.
⛔ Contraindications ▾
4 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 )
4.1Reactive Airway Disease Including Asthma, COPD 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 )] .
4.2Sinus Bradycardia, AV Block, Cardiac Failure, Cardiogenic Shock 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.
4.3Neonates and Infants (Under the Age of 2 Years) Brimonidine tartrate/timolol maleate ophthalmic solution is contraindicated in neonates and infants (under the age of 2 years).
4.4Hypersensitivity Reactions 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.
⚠️ Warnings and Cautions ▾
5 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 Patients with Diabetes Mellitus ( 5.7 ) Masking of Thyrotoxicosis ( 5.8 ) Ocular Hypersensitivity ( 5.9 )
5.1Potential for Severe Respiratory or Cardiac Reactions Brimonidine tartrate/timolol maleate ophthalmic solution contains timolol maleate; and although administered topically can be absorbed systemically. Therefore, the same types of adverse reactions found with systemic administration of beta-adrenergic blocking agents may occur with topical administration. For example, severe respiratory reactions and cardiac reactions including death due to bronchospasm in patients with asthma, and rarely death in association with cardiac failure have been reported following systemic or ophthalmic administration of timolol maleate [ see Contraindications (4.1) ] .
Additionally, ophthalmic beta-blockers may impair compensatory tachycardia and increase risk of hypotension.
5.2Cardiac Failure 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, brimonidine tartrate/timolol maleate ophthalmic solution should be discontinued [ see Contraindications (4.2) ] .
5.3Obstructive Pulmonary Disease Patients with chronic obstructive pulmonary disease (e.g., chronic bronchitis, emphysema) of mild or moderate severity, bronchospastic disease, or a history of bronchospastic disease (other than bronchial asthma or a history of bronchial asthma, in which brimonidine tartrate/timolol maleate ophthalmic solution is contraindicated [see Contraindications (4.1)] ) should, in general, not receive beta-blocking agents, including brimonidine tartrate/timolol maleate ophthalmic solution.
5.4Potentiation of Vascular Insufficiency Brimonidine tartrate/timolol maleate ophthalmic solution may potentiate syndromes associated with vascular insufficiency. Brimonidine tartrate/timolol maleate ophthalmic solution should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension, or thromboangiitis obliterans.
5.5Increased Reactivity to Allergens While taking beta-blockers, patients with a history of atopy or a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenge with such allergens. Such patients may be unresponsive to the usual doses of epinephrine used to treat anaphylactic reactions.
5.6Potentiation of Muscle Weakness Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, and generalized weakness). Timolol has been reported rarely to increase muscle weakness in some patients with myasthenia gravis or myasthenic symptoms.
5.7Masking of Hypoglycemic Symptoms in Patients with Diabetes Mellitus Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor blocking agents may mask the signs and symptoms of acute hypoglycemia.
5.8Masking of Thyrotoxicosis Beta-adrenergic blocking agents may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be mana…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Most common adverse reactions occurring in approximately 5 to 15% of patients included allergic conjunctivitis, conjunctival folliculosis, conjunctival hyperemia, eye pruritus, ocular burning, and stinging. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Caplin Steriles at 1-866-978-6111 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Brimonidine Tartrate/Timolol Maleate Ophthalmic Solution In clinical trials of 12 months duration with brimonidine tartrate/timolol maleate ophthalmic solution, the most frequent reactions associated with its use occurring in approximately 5% to 15% of the patients included: allergic conjunctivitis, conjunctival folliculosis, conjunctival hyperemia, eye pruritus, ocular burning, and stinging.
The following adverse reactions were reported in 1% to 5% of patients: asthenia, blepharitis, corneal erosion, depression, epiphora, eye discharge, eye dryness, eye irritation, eye pain, eyelid edema, eyelid erythema, eyelid pruritus, foreign body sensation, headache, hypertension, oral dryness, somnolence, superficial punctate keratitis, and visual disturbance. Other adverse reactions that have been reported with the individual components are listed below. Brimonidine Tartrate (0.1%-0.2%) Abnormal taste, allergic reaction, blepharoconjunctivitis, blurred vision, bronchitis, cataract, conjunctival blanching, conjunctival edema, conjunctival hemorrhage, conjunctivitis, cough, dizziness, dyspepsia, dyspnea, fatigue, flu syndrome, follicular conjunctivitis, gastrointestinal disorder, hypercholesterolemia, hypotension, infection (primarily colds and respiratory infections), hordeolum, insomnia, keratitis, lid crusting, lid disorder, muscular pain, nasal dryness, ocular allergic reaction, pharyngitis, photophobia, rash, rhinitis, sinus infection, sinusitis, superficial punctate keratopathy, tearing, upper respiratory symptoms, visual field defect, vitreous detachment, vitreous disorder, vitreous floaters, and worsened visual acuity.
Timolol (Ocular Administration) Body as a whole : chest pain; Cardiovascular : Arrhythmia, bradycardia, cardiac arrest, cardiac failure, cerebral ischemia, cerebral vascular accident, claudication, cold hands and feet, edema, heart block, palpitation, pulmonary edema, Raynaud’s phenomenon, syncope, and worsening of angina pectoris; Digestive : anorexia, diarrhea, nausea; Immunologic : Systemic lupus erythematosus; Nervous System/Psychiatric : Increase in signs and symptoms of myasthenia gravis, insomnia, nightmares, paresthesia, behavioral changes and psychic disturbances including confusion, hallucinations, anxiety, disorientation, nervousness, and memory loss; Skin : Alopecia, psoriasiform rash or exacerbation of psoriasis; Hypersensitivity : Signs and symptoms of systemic allergic reactions, including anaphylaxis, angioedema, urticaria, and generalized and localized rash; Respiratory : Bronchospasm (predominantly in patients with pre-existing bronchospastic disease) [ see Contraindications(4.1) ] , dyspnea, nasal congestion respiratory failure, upper respiratory infections; Endocrine : Masked symptoms of hypoglycemia in diabetes patients [ see Warnings and Precautions (5.7) ] ; Special Senses : diplopia, choroidal detachment following filtration surgery, cystoid macular edema, decreased corneal sensitivity, pseudopemphigoid, ptosis, refractive changes, tinnitus; Urogenital : Decreased libido, impotence, Peyronie’s disease, retroperitoneal fibrosis.
6.2Postmarketing Experience The following reactions have been identified during post-marketing use of brimonidine tartrate ophthalmic solutions, timolol ophthalmic solutions, or both in combination, in clinical…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Antihypertensives/cardiac glycosides may lower blood pressure. ( 7.1 ) Concomitant use with systemic beta-blockers may potentiate systemic beta-blockade. ( 7.2 ) Oral or intravenous calcium antagonists may cause atrioventricular conduction disturbances, left ventricular failure, and hypotension.
( 7.3 ) Catecholamine-depleting drugs may have additive effects and produce hypotension and/or marked bradycardia. ( 7.4 ) Use with CNS depressants may result in an additive or potentiating effect. ( 7.5 ) Digitalis and calcium antagonists may have additive effects in prolonging atrioventricular conduction time.
( 7.6 ) CYP2D6 inhibitors may potentiate systemic beta-blockade. ( 7.7 ) Tricyclic antidepressants may potentially blunt the hypotensive effect of systemic clonidine. ( 7.8 ) Monoamine oxidase inhibitors may result in increased hypotension.
( 7.9 )
7.1Antihypertensives/Cardiac Glycosides Because brimonidine tartrate/timolol maleate ophthalmic solution may reduce blood pressure, caution in using drugs such as antihypertensives and/or cardiac glycosides with brimonidine tartrate/timolol maleate ophthalmic solution is advised.
7.2Beta-adrenergic Blocking Agents Patients who are receiving a beta-adrenergic blocking agent either orally or intravenously and brimonidine tartrate/timolol maleate ophthalmic solution should be observed for potential additive effects of beta-blockade, both systemic and on intraocular pressure. The concomitant use of two topical beta- adrenergic blocking agents is not recommended.
7.3Calcium Antagonists Caution should be used in the co-administration of beta-adrenergic blocking agents, such as brimonidine tartrate/timolol maleate ophthalmic solution, and oral or intravenous calcium antagonists because of possible atrioventricular conduction disturbances, left ventricular failure, and hypotension. In patients with impaired cardiac function, co-administration should be avoided.
7.4Catecholamine-depleting Drugs Close observation of the patient is recommended when a beta blocker is administered to patients receiving catecholamine-depleting drugs such as reserpine, because of possible additive effects and the production of hypotension and/or marked bradycardia, which may result in vertigo, syncope, or postural hypotension.
7.5CNS Depressants Although specific drug interaction studies have not been conducted with brimonidine tartrate/timolol maleate ophthalmic solution, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics) should be considered.
7.6Digitalis and Calcium Antagonists The concomitant use of beta-adrenergic blocking agents with digitalis and calcium antagonists may have additive effects in prolonging atrioventricular conduction time.
7.7CYP2D6 Inhibitors Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g., quinidine, SSRIs) and timolol.
7.8Tricyclic Antidepressants 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/timolol maleate ophthalmic solution in humans can lead to resulting interference with the IOP-lowering effect. Caution, however, is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines.
7.9Monoamine Oxidase Inhibitors Monoamine oxidase (MAO) inhibitors may theoretically interfere with the metabolism of brimonidine and potentially result in an increased systemic side effect such as hypotension. Caution, however, is advised in patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amines.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Not for use in children below the age of 2 years. Use with caution in children ≥ 2 years of age. ( 8.4 )
8.1Pregnancy 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.
8.3Nursing Mothers 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.
8.4Pediatric Use 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.
8.5Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and other adult patients.
🤰 Pregnancy ▾
8.1Pregnancy 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.
🧒 Pediatric Use ▾
8.4Pediatric Use 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.
🧓 Geriatric Use ▾
8.5Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and other adult patients.
🆘 Overdosage ▾
10 OVERDOSAGE 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Brimonidine tartrate/timolol maleate ophthalmic solution is comprised of two components: brimonidine tartrate and timolol. Each of these two components decreases elevated intraocular pressure, whether or not associated with glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss.
The higher the level of intraocular pressure, the greater the likelihood of glaucomatous field loss and optic nerve damage. Brimonidine tartrate/timolol maleate ophthalmic solution is a relatively selective alpha-2 adrenergic receptor agonist with a non-selective beta-adrenergic receptor inhibitor. Both brimonidine and timolol have a rapid onset of action, with peak ocular hypotensive effect seen at two hours post-dosing for brimonidine and one to two hours for timolol.
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. Timolol maleate is a beta 1 and beta 2 adrenergic receptor inhibitor that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity.
12.3Pharmacokinetics Absorption Systemic absorption of brimonidine and timolol was assessed in healthy volunteers and patients following topical dosing with brimonidine tartrate/timolol maleate ophthalmic solution. Normal volunteers dosed with one drop of brimonidine tartrate/timolol maleate ophthalmic solution twice daily in both eyes for seven days showed peak plasma brimonidine and timolol concentrations of 30 pg/mL and 400 pg/mL, respectively. Plasma concentrations of brimonidine peaked at 1 to 4 hours after ocular dosing.
Peak plasma concentrations of timolol occurred approximately 1 to 3 hours post-dose. In a crossover study of brimonidine tartrate/timolol maleate ophthalmic solution, brimonidine tartrate 0.2%, and timolol 0.5% administered twice daily for 7 days in healthy volunteers, the mean brimonidine area-under-the-plasma-concentration-time curve (AUC) for brimonidine tartrate/timolol maleate ophthalmic solution was 128 ± 61 pg•hr/mL versus 141 ± 106 pg•hr/mL for the respective monotherapy treatments; mean C max values of brimonidine were comparable following brimonidine tartrate/timolol maleate ophthalmic solution treatment versus monotherapy (32.7 ± 15 pg/mL versus 34.7 ± 22.6 pg/mL, respectively).
Mean timolol AUC for brimonidine tartrate/timolol maleate ophthalmic solution was similar to that of the respective monotherapy treatment (2919 ± 1679 pg•hr/mL versus 2909 ± 1231 pg•hr/mL, respectively); mean C max of timolol was approximately 20% lower following brimonidine tartrate/timolol maleate ophthalmic solution treatment versus monotherapy. In a parallel study in patients dosed twice daily with brimonidine tartrate/timolol maleate ophthalmic solution, twice daily with timolol 0.5%, or three times daily with brimonidine tartrate 0.2%, one-hour post dose plasma concentrations of timolol and brimonidine were approximately 30-40% lower with brimonidine tartrate/timolol maleate ophthalmic solution than their respective monotherapy values.
The lower plasma brimonidine concentrations with brimonidine tartrate/timolol maleate ophthalmic solution appears to be due to twice-daily dosing for brimonidine tartrate/timolol maleate ophthalmic solution versus three-times dosing with brimonidine tartrate 0.2%. Distribution The protein binding of timolol is approximately 60%. The protein binding of brimonidine has not been studied.
Metabolism In humans, brimonidine is extensively metabolized-by the liver. Timolol is partially metabolized by the liver. Excretion In the crossover study in healthy volunteers, the plasma concentration of brimonidine declined with a systemic half-life of approximately 3 hours.
The apparent systemic half-life of timolol was about 7 hours a…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Brimonidine tartrate/timolol maleate ophthalmic solution is comprised of two components: brimonidine tartrate and timolol. Each of these two components decreases elevated intraocular pressure, whether or not associated with glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss.
The higher the level of intraocular pressure, the greater the likelihood of glaucomatous field loss and optic nerve damage. Brimonidine tartrate/timolol maleate ophthalmic solution is a relatively selective alpha-2 adrenergic receptor agonist with a non-selective beta-adrenergic receptor inhibitor. Both brimonidine and timolol have a rapid onset of action, with peak ocular hypotensive effect seen at two hours post-dosing for brimonidine and one to two hours for timolol.
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. Timolol maleate is a beta 1 and beta 2 adrenergic receptor inhibitor that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Brimonidine tartrate/timolol maleate ophthalmic solution is supplied sterile, in a white low density polyethylene (LDPE) bottle with a white LDPE nozzle and dark blue HDPE caps as follows: 5 mL in 10 mL bottle NDC 65145-162-01 10 mL in 10 mL bottle NDC 65145-163-01 15 mL in 15 mL bottle NDC 65145-164-01 Storage: Store at 20° -25°C (68° -77°F) [See USP Controlled Room Temperature]. Protect from light.
📋 Description ▾
11 DESCRIPTION Brimonidine tartrate/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/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 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/timolol maleate ophthalmic solution 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; water for injection; and hydrochloric acid and/or sodium hydroxide to adjust pH. brimonidine-timolol-brimo-structure brimonidine-timolol-timo-structure
💬 Information for Patients ▾
17 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 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/timolol maleate ophthalmic solution 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/timolol maleate ophthalmic solution.
As with other similar medications, brimonidine tartrate/timolol maleate ophthalmic solution 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. Made in India Distributed by : Caplin Steriles USA Inc, Hamilton, NJ 08619.
Code: TN/Drugs/TN00003457 February, 2025 22201081 brimonidine-timolol-caplin-logo