Version July 2025
Elevated intraocular pressure: Ophthalmic: Instill 1 drop in affected eye(s) twice daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Severe impairment (CrCl <30 mL/minute): Use is contraindicated (has not been studied); brinzolamide and metabolite are primarily excreted by the kidney.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Also see individual agents.
1% to 10%:
Gastrointestinal: Dysgeusia (2%)
Ophthalmic: Blurred vision (6%), eye irritation (4%), eye pain (3%), foreign body sensation of eye (1%)
<1%:
Cardiovascular: Decreased blood pressure
Dermatologic: Erythema of eyelid, hair disease, lichen planus
Nervous system: Insomnia
Ophthalmic: Abnormal sensation in eyes, allergic conjunctivitis, anterior chamber inflammation, asthenopia, blepharitis (including allergic), conjunctival hyperemia, corneal disease, corneal erosion, crusting of eyelid, eye discharge, eye pruritus, eyelid pruritus, hypotony of eye, increased lacrimation, injected sclera, ocular hyperemia, photophobia, punctate keratitis, xerophthalmia
Respiratory: Chronic obstructive pulmonary disease, cough, pharyngolaryngeal pain, rhinorrhea
Postmarketing:
Cardiovascular: Chest pain, decreased heart rate, increased blood pressure
Dermatologic: Alopecia, erythema of skin, skin rash
Gastrointestinal: Abdominal distress, diarrhea, nausea, xerostomia
Genitourinary: Hematuria
Hematologic & oncologic: Decreased white blood cell count
Hypersensitivity: Hypersensitivity reaction
Nervous system: Depression, dizziness, fatigue, hallucination, headache
Neuromuscular & skeletal: Myalgia
Ophthalmic: Corneal staining (vital dye staining cornea present), eyelid edema, visual impairment
Respiratory: Dyspnea, epistaxis, oropharyngeal pain
Hypersensitivity to brinzolamide, timolol, other beta-blockers, sulfonamides, or any component of the formulation; current or history of bronchial asthma; severe chronic obstructive pulmonary disease (COPD); severe allergic rhinitis and bronchial hyper-reactivity; sinus bradycardia, sick sinus syndrome, sino-atrial block, second-/third degree atrioventricular (AV) block, overt cardiac failure, cardiogenic shock; hyperchloremic acidosis; severe renal impairment (CrCl <30 mL/minute)
Note: Although sulfonamide hypersensitivity may be considered, cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur, or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004).
Concerns related to adverse events:
• Acid-base disturbances: Have been reported with oral carbonic anhydrase inhibitors; ophthalmic brinzolamide is systemically absorbed and may cause acid-base disturbances (eg, metabolic acidosis).
• Anaphylactic reactions: Use caution with history of atopy or severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
• Bacterial keratitis: Inadvertent contamination of multiple-dose ophthalmic solutions has caused bacterial keratitis.
• CNS effects: Impairment of mental alertness and/or physical coordination may occur.
• Ocular effects: Patients with compromised corneas (eg, patients with diabetes or low endothelial cell counts) or contact lens wearers may have an increased risk for corneal edema; use caution. Choroidal detachment has been reported with aqueous suppression therapy after filtration procedures. Benzalkonium chloride may cause keratopathies; monitor closely with prolonged use. May cause temporary blurred vision or other visual disturbances; patients should not perform dangerous tasks (eg, driving, operating machinery) until vision clears.
• Sulfonamide ("sulfa") allergy: The Health Canada–approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, 2 antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur, or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell–mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/toxic epidermal necrolysis), some clinicians choose to avoid exposure to these classes.
• Systemic effects: Systemic absorption may occur; adverse effects observed with beta-blockers and/or sulfonamides may occur with ophthalmic use. Beta-blocker therapy should not be withdrawn abruptly in order to avoid acute tachycardia, hypertension, and/or ischemia.
Disease-related concerns:
• Cardiovascular disease: Use is not recommended in cardiovascular disease (eg, coronary heart disease, Prinzmetal angina, heart failure) or hypotension; may worsen condition. Consider preexisting conduction abnormalities prior to initiating therapy (use may be contraindicated; refer to contraindications).
• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.
• Heart failure (HF): Use with caution in patients with compensated heart failure and monitor for a worsening of the condition; control heart failure prior to initiation of therapy.
• Hepatic impairment: Use with caution in patients with hepatic impairment; has not been studied.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; may worsen disease or other myasthenic symptoms (diplopia, ptosis, generalized weakness).
• Narrow-angle glaucoma: Use is not recommended in narrow-angle glaucoma; has not been studied.
• Peripheral vascular disease (PVD) and Raynaud's disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud's disease. Use with caution and monitor for progression of arterial obstruction.
• Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression.
• Renal impairment: Use with caution in patients with mild to moderate renal impairment; has not been studied and possible risk of metabolic acidosis.
• Respiratory disease: In general, patients with mild to moderate COPD or bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring.
• Thyroid disease: May mask signs of hyperthyroidism (eg, tachycardia). If thyrotoxicosis is suspected, carefully manage and monitor; abrupt withdrawal may exacerbate symptoms of hyperthyroidism or precipitate thyroid storm.
Special populations:
• Contact lens wearers: Formulation contains benzalkonium chloride which may be absorbed by soft contact lenses and discolor lenses; remove lens prior to administration and wait 15 minutes before reinserting.
Other warnings/precautions:
• Surgery: May block systemic effects of beta agonists (eg, epinephrine, norepinephrine); notify anesthesiologist if patient is receiving ophthalmic beta blocker therapy. Patients undergoing planned major surgery should be gradually tapered off therapy prior to procedure.
Not available in the US
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Ophthalmic:
Azarga: Brinzolamide 1% and timolol 0.5% (5 mL) [contains benzalkonium chloride, edetate (edta) disodium]
Ophthalmic: For topical ophthalmic use only. If using additional topical ophthalmic preparations, separate administration by at least 5 minutes. Remove contact lens prior to administration and wait 15 minutes before reinserting. Shake bottle well prior to administration. Gently close eyelid or apply finger pressure to lacrimal sac for 2 minutes after instillation to minimize possible systemic absorption. Instruct patients to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures. Ocular solutions can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may occur from using contaminated solutions. If changing from another ophthalmic antiglaucoma agent, discontinue use of first agent and initiate brinzolamide/timolol the following day.
Note: Not approved in the US
Elevated intraocular pressure: Treatment of elevated intraocular pressure (IOP) in adult patients with ocular hypertension or open-angle glaucoma for whom monotherapy provides an insufficient reduction in IOP
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May increase bradycardic effects of Beta-Blockers. Risk C: Monitor
Ajmaline: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Alpha2-Agonists: Beta-Blockers may increase rebound hypertensive effects of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Alpha2-Agonists may increase AV-blocking effects of Beta-Blockers. Sinus node dysfunction may also be enhanced. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Risk D: Consider Therapy Modification
Amantadine: Carbonic Anhydrase Inhibitors may increase serum concentration of Amantadine. Risk C: Monitor
Amiodarone: May increase bradycardic effects of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase serum concentration of Beta-Blockers. Risk C: Monitor
Antidiabetic Agents: Beta-Blockers (Nonselective) may increase hypoglycemic effects of Antidiabetic Agents. Beta-Blockers (Nonselective) may increase adverse/toxic effects of Antidiabetic Agents. Specifically, beta-blockers may mask the hypoglycemic symptoms of antidiabetic agents. Risk C: Monitor
Antipsychotic Agents (Phenothiazines): May increase hypotensive effects of Beta-Blockers. Beta-Blockers may decrease metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease metabolism of Beta-Blockers. Risk C: Monitor
Artemether and Lumefantrine: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Beta2-Agonists: Beta-Blockers (Nonselective) may decrease bronchodilatory effects of Beta2-Agonists. Risk X: Avoid
Bradycardia-Causing Agents: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Cafedrine: May increase bradycardic effects of Beta-Blockers. Beta-Blockers may decrease therapeutic effects of Cafedrine. Risk C: Monitor
Cannabis: Beta-Blockers may increase adverse/toxic effects of Cannabis. Specifically, the risk of hypoglycemia may be increased. Risk C: Monitor
Carbonic Anhydrase Inhibitors: May increase adverse/toxic effects of Carbonic Anhydrase Inhibitors. The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Management: Avoid concurrent use of different carbonic anhydrase inhibitors if possible. Monitor patients closely for the occurrence of kidney stones and with regards to severity of metabolic acidosis. Risk X: Avoid
Ceritinib: Bradycardia-Causing Agents may increase bradycardic effects of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider Therapy Modification
Cholinergic Agonists: Beta-Blockers may increase adverse/toxic effects of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Risk C: Monitor
CYP2D6 Inhibitors (Strong): May increase serum concentration of Timolol (Ophthalmic). Risk C: Monitor
Dipyridamole: May increase bradycardic effects of Beta-Blockers. Risk C: Monitor
Disopyramide: May increase bradycardic effects of Beta-Blockers. Beta-Blockers may increase negative inotropic effects of Disopyramide. Risk C: Monitor
DOBUTamine: Beta-Blockers may decrease therapeutic effects of DOBUTamine. Risk C: Monitor
Dronedarone: May increase bradycardic effects of Beta-Blockers. Dronedarone may increase serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Increase monitoring for clinical response and adverse effects. Risk D: Consider Therapy Modification
EPHEDrine (Systemic): Beta-Blockers may decrease therapeutic effects of EPHEDrine (Systemic). Risk C: Monitor
EPINEPHrine (Nasal): Beta-Blockers (Nonselective) may increase hypertensive effects of EPINEPHrine (Nasal). Risk C: Monitor
EPINEPHrine (Oral Inhalation): Beta-Blockers (Nonselective) may increase hypertensive effects of EPINEPHrine (Oral Inhalation). Risk C: Monitor
EPINEPHrine (Systemic): Beta-Blockers (Nonselective) may increase hypertensive effects of EPINEPHrine (Systemic). Risk C: Monitor
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): Beta-Blockers may increase vasoconstricting effects of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor
Etilefrine: Beta-Blockers may decrease therapeutic effects of Etilefrine. Etilefrine may increase bradycardic effects of Beta-Blockers. Risk C: Monitor
Etofylline: Beta-Blockers may decrease therapeutic effects of Etofylline. Risk X: Avoid
Etrasimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Fexinidazole: Bradycardia-Causing Agents may increase arrhythmogenic effects of Fexinidazole. Risk X: Avoid
Fingolimod: Bradycardia-Causing Agents may increase bradycardic effects of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider Therapy Modification
Grass Pollen Allergen Extract (5 Grass Extract): Beta-Blockers may increase adverse/toxic effects of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. Management: Consider alternatives to either grass pollen allergen extract (5 grass extract) or beta-blockers in patients with indications for both agents. Canadian product labeling specifically lists this combination as contraindicated. Risk D: Consider Therapy Modification
Insulin: Beta-Blockers (Nonselective) may increase hypoglycemic effects of Insulin. Beta-Blockers (Nonselective) may decrease therapeutic effects of Insulin. Risk C: Monitor
Isoproterenol: Beta-Blockers may decrease therapeutic effects of Isoproterenol. Risk C: Monitor
Ivabradine: Bradycardia-Causing Agents may increase bradycardic effects of Ivabradine. Risk C: Monitor
Lacosamide: Bradycardia-Causing Agents may increase AV-blocking effects of Lacosamide. Risk C: Monitor
Landiolol: Bradycardia-Causing Agents may increase bradycardic effects of Landiolol. Risk X: Avoid
Mavacamten: Beta-Blockers may increase adverse/toxic effects of Mavacamten. Specifically, negative inotropic effects may be increased. Risk C: Monitor
Mavorixafor: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid
Methacholine: Beta-Blockers may increase adverse/toxic effects of Methacholine. Risk C: Monitor
Midodrine: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Mivacurium: Beta-Blockers may increase therapeutic effects of Mivacurium. Risk C: Monitor
NIFEdipine (Topical): May increase adverse/toxic effects of Beta-Blockers. Risk C: Monitor
NIFEdipine: May increase hypotensive effects of Beta-Blockers. NIFEdipine may increase negative inotropic effects of Beta-Blockers. Risk C: Monitor
Nitrendipine: May increase therapeutic effects of Beta-Blockers. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Topical): May decrease therapeutic effects of Beta-Blockers. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents: May decrease antihypertensive effects of Beta-Blockers. Risk C: Monitor
Opipramol: Beta-Blockers may increase serum concentration of Opipramol. Opipramol may increase serum concentration of Beta-Blockers. Risk C: Monitor
Ozanimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Peginterferon Alfa-2b: May decrease serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Ponesimod: Bradycardia-Causing Agents may increase bradycardic effects of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider Therapy Modification
Reserpine: May increase hypotensive effects of Beta-Blockers. Reserpine may increase bradycardic effects of Beta-Blockers. Risk C: Monitor
Rivastigmine: May increase bradycardic effects of Beta-Blockers. Risk X: Avoid
Siponimod: Bradycardia-Causing Agents may increase bradycardic effects of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider Therapy Modification
Succinylcholine: Beta-Blockers may increase neuromuscular-blocking effects of Succinylcholine. Risk C: Monitor
Sulfonylureas: Beta-Blockers (Nonselective) may increase hypoglycemic effects of Sulfonylureas. Beta-Blockers (Nonselective) may decrease therapeutic effects of Sulfonylureas. Risk C: Monitor
Tasimelteon: Beta-Blockers may decrease therapeutic effects of Tasimelteon. Management: Consider avoiding nighttime administration of beta-blockers during tasimelteon therapy due to the potential for reduced tasimelteon efficacy. Risk D: Consider Therapy Modification
Theodrenaline: May increase bradycardic effects of Beta-Blockers. Beta-Blockers may decrease therapeutic effects of Theodrenaline. Risk C: Monitor
Theophylline Derivatives: Beta-Blockers (Nonselective) may decrease bronchodilatory effects of Theophylline Derivatives. Risk C: Monitor
White Birch Allergen Extract: Beta-Blockers may increase adverse/toxic effects of White Birch Allergen Extract. Specifically, beta-blockers may reduce the effectiveness of beta-agonists that may be required to treat systemic reactions to white birch allergen extract. Risk X: Avoid
According to the manufacturer, use is not recommended in women of childbearing potential not using contraception.
Adverse effects have been observed with brinzolamide in animal reproduction studies. Bradycardia and arrhythmia have been reported in an infant following ophthalmic administration of timolol during pregnancy. Refer to individual monographs for additional information.
Timolol is excreted in breast milk following oral and ophthalmic administration, though clinical beta blockade is not likely at recommended ophthalmologic doses. It is unknown whether brinzolamide is excreted in breast milk. Use of the combination product during lactation is not recommended. See individual agents.
Ophthalmic exams and IOP periodically; heart rate/signs of cardiac failure (patients with severe cardiac disease), hypersensitivity reactions, development of punctate and/or toxic ulcerative keratopathy with frequent or prolonged use
Brinzolamide inhibits carbonic anhydrase, leading to decreased aqueous humor secretion. This results in a reduction of intraocular pressure.
Timolol: Blocks both beta1- and beta2-adrenergic receptors, reduces intraocular pressure by reducing aqueous humor production or possibly outflow.
See individual agents.
