Version May 2024
Intraocular pressure reduction (alternative): Ophthalmic: Instill 1 drop in affected eye(s) 3 times daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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).
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.
Refer to adult dosing.
(For additional information see "Brinzolamide and brimonidine: Pediatric drug information")
Intraocular pressure (IOP) reduction: Children ≥2 years and Adolescents: Ophthalmic: Instill 1 drop in affected eye(s) 3 times 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 renal impairment (CrCl ≥30 ml/minute): There are no dosage adjustment provided in the manufacturer's labeling; brinzolamide and metabolite are excreted predominately by the kidney; use with caution.
Severe renal impairment (CrCl <30 mL/minute): Use is not recommended (has not been studied); brinzolamide and metabolite are excreted predominately by the kidney.
There are no dosage adjustments provided in manufacturer's labeling (has not been studied); use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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%)
Hypersensitivity to brinzolamide, brimonidine, or any component of the formulation; neonates, infants, and children <2 years of age.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to sulfonamides (see Warnings/Precautions for additional details); concurrent monoamine oxidase inhibitor therapy or antidepressant therapy that affects noradrenergic transmission (eg, tricyclic antidepressants, mianserin); severe renal impairment (CrCl <30 mL/minute); hyperchloremic acidosis.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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: 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 that require mental alertness, especially when used in children.
• 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/toxic epidermal necrolysis), some clinicians choose to avoid exposure to these classes.
Disease-related concerns:
• Acute angle-closure (narrow-angle) glaucoma: Use has not been studied in patients with acute angle-closure glaucoma.
• 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.
• Hepatic impairment: Use with caution in patients with hepatic impairment; has not been evaluated in this population.
• Orthostatic hypotension: Use with caution in patients with orthostatic hypotension; may precipitate or aggravate symptoms.
• Renal impairment: Use is not recommended 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.
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.
May cause CNS depression, particularly in young children; contraindicated for use in infants or children <2 years. Brimonidine has been reported to cause somnolence (50% to 83%) and decreased alertness in children 2 to 6 years of age with pediatric glaucoma.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Ophthalmic:
Simbrinza: Brinzolamide 1% and brimonidine tartrate 0.2% (8 mL) [contains benzalkonium chloride, propylene glycol]
No
Suspension (Simbrinza Ophthalmic)
1-0.2% (per mL): $31.06
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Ophthalmic:
Simbrinza: Brinzolamide 1% and brimonidine tartrate 0.2% (10 mL) [contains benzalkonium chloride, propylene glycol]
For ophthalmic use only. 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.
To minimize systemic absorption, have patient block the drainage of the eyedrop from the conjunctival sac by pressing their inner ocular corner with the forefinger and then closing the eyelid (Ref).
Ophthalmic: 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. Apply gentle pressure to lacrimal sac immediately following instillation (1 minute) or instruct patient to gently close eyelid after administration to decrease systemic absorption of ophthalmic drops (Ref). 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 solution changes color or becomes cloudy, do not use. Vision may be temporarily blurred and drowsiness may occur; following administration, use caution when operating machinery, driving a motor vehicle, or performing other tasks that require concentration.
Reduction of intraocular pressure: Treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Alpha-/Beta-Agonists (Indirect-Acting): Carbonic Anhydrase Inhibitors may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Risk C: Monitor therapy
Amantadine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Amantadine. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: 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. Risk D: Consider therapy modification
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
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 at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: 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. Risk X: Avoid combination
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: 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 the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Mianserin: May diminish the therapeutic effect of Alpha2-Agonists (Ophthalmic). Risk X: Avoid combination
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: 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. Risk D: Consider therapy modification
Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Brimonidine (Ophthalmic). Monoamine Oxidase Inhibitors may increase the serum concentration of Brimonidine (Ophthalmic). Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: May diminish the therapeutic effect of Alpha2-Agonists. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Tricyclic Antidepressants: May diminish the therapeutic effect of Alpha2-Agonists (Ophthalmic). Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: 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. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Animal reproduction studies have not been conducted with this combination product; refer to individual monographs.
It is not known if brinzolamide or brimonidine are excreted into breast milk following ophthalmic application. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.
Ophthalmic exams and IOP periodically.
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
Absorption: Brinzolamide: Topical: Into systemic circulation; Brimonidine: Topical: Into systemic circulation. Systemic absorption variable and may be reduced by postadministration maneuvers to slow lacrimal drainage.
Distribution: Brinzolamide: Accumulates extensively in red blood cells, binding to carbonic anhydrase (brinzolamide and metabolite).
Protein binding: Brinzolamide: ~60%.
Metabolism:
Brimonidine: Extensively, hepatic.
Brinzolamide: To N-desethyl brinzolamide.
Half-life elimination:
Brimonidine: 2 to 3 hours.
Brinzolamide: 111 days.
Time to peak, serum concentration: Brimonidine: Within 1 to 4 hours.
Excretion:
Brimonidine: Urine (74%).
Brinzolamide: Urine (predominantly as unchanged drug and metabolites).
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