Brinzolamide and Brimonidine
(brin ZOH la mide & bri MOE ni deen)
- Brimonidine and Brinzolamide
- Brinzolamide and Brimonidine Tartrate
- Brinzolamide/Brimonid Tartrate
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Simbrinza: Brinzolamide 1% and brimonidine tartrate 0.2% (8 mL) [contains benzalkonium chloride]
Brand Names: U.S.
- Alpha2 Agonist, Ophthalmic
- Carbonic Anhydrase Inhibitor (Ophthalmic)
- Ophthalmic Agent, Antiglaucoma
Brinzolamide inhibits carbonic anhydrase, leading to decreased aqueous humor secretion. This results in a reduction of intraocular pressure (IOP).
Brimonidine has selective agonism for alpha2-receptors and causes reduction of aqueous humor formation and increased uveoscleral outflow
Brinzolamide: Topical: Into systemic circulation
Brinzolamide: Accumulates extensively in red blood cells, binding to carbonic anhydrase (brinzolamide and metabolite)
Brimonidine: Extensively, hepatic
Brinzolamide: To N-desethyl brinzolamide
Brimonidine: Urine (74%)
Brinzolamide: Urine (predominantly as unchanged drug)
Time to Peak
Brimonidine: Within 0.5 to 4 hours
Brimonidine: 2 to 3 hours
Brinzolamide: 111 days
Use: Labeled Indications
Reduction of intraocular pressure: Treatment of elevated intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma
Hypersensitivity to brinzolamide, brimonidine, or any component of the formulation; children <2 years of age
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to sulfonamides; concurrent monoamine oxidase (MAO) inhibitor therapy or antidepressant therapy that affects noradrenergic transmission (eg, tricyclic antidepressants, mianserin); severe renal impairment; hyperchloremic acidosis
Reduction of intraocular pressure: Ophthalmic:
US labeling: Instill 1 drop in affected eye(s) 3 times daily
Canadian labeling: Instill 1 drop in affected eye(s) 2 times daily
Refer to adult dosing.
Children ≥2 years and Adolescents: Ophthalmic: Refer to adult dosing. Note: The Canadian labeling does not recommend use in patients <18 years.
Dosing: Renal Impairment
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling.
CrCl <30 mL/minute: Use is not recommended (has not been studied; brinzolamide and metabolite are excreted predominately by the kidney).
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
CrCl <30 mL/minute: Use is contraindicated.
Dosing: Hepatic Impairment
US labeling: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.
Canadian labeling: Use is not recommended.
Shake bottle well prior to administration. If using additional topical ophthalmic preparations, separate administration by at least 5 minutes. Remove contact lenses prior to administration and wait 15 minutes after administration before reinserting. 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.
Store at 2°C to 25°C (36°F to 77°F). After opening the bottle, the Canadian labeling recommends discarding the 10 mL bottle within 125 days and the 5 mL bottle within 32 days.
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy
Alpha-/Beta-Agonists (Indirect-Acting): Carbonic Anhydrase Inhibitors may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Monitor therapy
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Beta-Blockers: Alpha2-Agonists may enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. 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. Exceptions: Levobunolol; Metipranolol. Consider therapy modification
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of other 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. Avoid combination
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Brinzolamide. Monitor therapy
Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Iobenguane I 123: Alpha2-Agonists may diminish the therapeutic effect of Iobenguane I 123. Avoid combination
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
MAO Inhibitors: May enhance the adverse/toxic effect of Brimonidine (Ophthalmic). MAO Inhibitors may increase the serum concentration of Brimonidine (Ophthalmic). Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
Mianserin: May diminish the therapeutic effect of Alpha2-Agonists (Ophthalmic). Avoid combination
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirtazapine: May diminish the antihypertensive effect of Alpha2-Agonists. Management: Consider avoiding concurrent use. If the combination cannot be avoided, monitor for decreased effects of alpha2-agonists if mirtazapine is initiated/dose increased, or increased effects if mirtazapine is discontinued/dose decreased. Consider therapy modification
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: May diminish the antihypertensive effect of Alpha2-Agonists. Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Tricyclic Antidepressants: May diminish the therapeutic effect of Alpha2-Agonists (Ophthalmic). Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification
Percentages as reported with combination product. Also see individual agents.
1% to 10%:
Gastrointestinal: Dysgeusia (3% to 5%), xerostomia (3% to 5%)
Hypersensitivity: Local ocular hypersensitivity reaction (3% to 5%)
Ophthalmic: Blurred vision (3% to 5%), eye irritation (3% to 5%)
Concerns related to adverse events:
• Acid-base disturbances: Brinzolamide is absorbed systemically following topical administration; acid-base disturbances reported with oral carbonic anhydrase inhibitors may occur following topical application.
• Bacterial keratitis: Inadvertent contamination of multiple-dose ophthalmic solutions has caused bacterial keratitis.
• CNS effects: May cause CNS depression and/or blurred vision, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Sulfonamide (“sulfa”) allergy: The FDA-approved and Health Canada-approved product labelings 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, two 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/TEN), some clinicians choose to avoid exposure to these classes.
• Acute angle-closure (narrow-angle) glaucoma: Use has not been studied in patients with acute angle-closure glaucoma (Canadian labeling recommends avoiding use in these patients).
• Cardiovascular disease: Use with caution in patients with coronary insufficiency or severe or unstable cardiovascular disease.
• Cerebrovascular insufficiency: Use with caution in patients with cerebral insufficiency; may precipitate or aggravate symptoms.
• Corneal endothelium: Use with caution in patients with low endothelial cell counts; may be at increased risk of corneal edema.
• Depression: Use with caution in patients with depression; may precipitate or aggravate symptoms.
• Hepatic impairment: Use with caution in patients with hepatic impairment; has not been evaluated in this population. Due to lack of data, the Canadian labeling recommends avoiding use in hepatic impairment.
• Orthostatic hypotension: Use with caution in patients with orthostatic hypotension; may precipitate or aggravate symptoms.
• Renal impairment: Use is not recommended (US labeling) or contraindicated (Canadian labeling) in patients with severe renal impairment; use has not been evaluated in this population. Use caution in mild or moderate renal impairment due to possible risk of acid/base disturbances.
• Thromboangiitis obliterans: Use with caution in patients with thromboangiitis obliterans; may precipitate or aggravate symptoms.
• Vascular insufficiency: Use with caution in patients with vascular insufficiency, including Raynaud disease; may precipitate or aggravate symptoms.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Dosage form specific issues:
• Ophthalmic solution: May contain benzalkonium chloride which may be absorbed by contact lenses; remove lens prior to administration and wait 15 minutes before reinserting. Allow at least 5 minutes between applications with other eye drops. To avoid contamination, do not touch tip of container to any surface. Benzalkonium chloride may also cause punctate keratopathy or toxic ulcerative keratopathy. If use is frequent or prolonged, monitor closely.
Ophthalmic exams and IOP periodically
Pregnancy Risk Factor
Animal reproduction studies have not been conducted with this combination product; refer to individual monographs. The Canadian labeling recommends avoiding use of this combination product in women who are pregnant or of childbearing potential and not using contraception.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience blurred vision, change in taste, headache, dry mouth, burning, stinging, foreign body sensation in eye, or fatigue. Have patient report immediately to prescriber signs of a severe sulfonamide reaction (rash; red, swollen, blistered, or peeling skin; red or irritated eyes; mouth, throat, nose, or eye sores; fever, chills, or pharyngitis; cough that is new or worse; loss of strength and energy; any bruising or bleeding; or signs of liver problems like dark urine, fatigue, lack of appetite, nausea or abdominal pain, light-colored stools, vomiting, or jaundice), vision changes, or eye pain, or severe eye irritation (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
More about brimonidine/brinzolamide ophthalmic
- Other brands: Simbrinza