SIMBRINZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SIMBRINZA (SIMBRINZA).
SIMBRINZA is a fixed-dose combination of brinzolamide, a carbonic anhydrase inhibitor, and brimonidine, an alpha-2 adrenergic receptor agonist. Brinzolamide decreases aqueous humor secretion by inhibiting carbonic anhydrase in the ciliary processes. Brimonidine reduces aqueous humor production and increases uveoscleral outflow by activating alpha-2 adrenergic receptors.
| Metabolism | Brinzolamide is primarily metabolized via hepatic CYP3A4 isoenzyme, with some contribution from CYP2A6, CYP2B6, CYP2C8, CYP2C9, and CYP2C19. Brimonidine is extensively metabolized in the liver primarily by aldehyde oxidase and to a lesser extent by CYP450 enzymes. |
| Excretion | Brinzolamide: 60% renal as unchanged drug; 20% as N-desethyl brinzolamide metabolite. Brimonidine: ~87% renal within 120 hours (unchanged and metabolites). Both primarily excreted renally. |
| Half-life | Brinzolamide: 111 hours (multiple dosing) due to RBC binding. Brimonidine: ~3 hours (plasma); clinical IOP-lowering effect persists longer due to ocular tissue binding. |
| Protein binding | Brinzolamide: ~60% bound to plasma proteins (primarily albumin). Brimonidine: ~29% bound. |
| Volume of Distribution | Brinzolamide: 0.168 L/kg (high RBC distribution); brimonidine: not reported in adults (pediatric Vd ~1.2 L/kg, indicating extensive tissue distribution). Clinical meaning: brinzolamide accumulates in RBCs, extending its presence. |
| Bioavailability | Topical ophthalmic: systemic absorption is low; peak plasma concentrations are <1% of the administered dose for both agents. |
| Onset of Action | Topical ophthalmic: IOP reduction begins within 1 hour after instillation. |
| Duration of Action | Topical ophthalmic: IOP reduction maintained for at least 12 hours (twice-daily dosing). |
One drop of the suspension in the affected eye(s) twice daily.
| Dosage form | SUSPENSION/DROPS |
| Renal impairment | Not recommended in patients with severe renal impairment (CrCl <30 mL/min) due to risk of metabolic acidosis. No adjustment for mild to moderate impairment. |
| Liver impairment | No specific adjustment provided; however, caution is advised in severe hepatic impairment due to potential for increased systemic effects. |
| Pediatric use | Safety and efficacy not established; use not recommended in pediatric patients. |
| Geriatric use | No specific dose adjustment; use with caution due to increased prevalence of renal impairment and systemic comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SIMBRINZA (SIMBRINZA).
| Breastfeeding | Unknown. Brinzolamide excreted in rat milk; not known if excreted in human milk. Brimonidine may be excreted in milk. Caution advised. M/P ratio not available. Consider developmental benefits of breastfeeding vs mother's clinical need for Simbrinza. |
| Teratogenic Risk | Pregnancy Category C. No adequate well-controlled studies in pregnant women. In animal reproduction studies, no teratogenic effects were observed at oral doses up to 10 mg/kg/day brinzolamide and 5 mg/kg/day brimonidine. However, potential risks include fetal acidosis due to carbonic anhydrase inhibition (brinzolamide) and alpha-2 adrenergic effects (brimonidine) particularly in third trimester. Use only if potential benefit justifies potential risk to fetus. |
■ FDA Black Box Warning
None
| Common Effects | Application site reactions burning irritation itching and redness Blurred vision |
| Serious Effects |
["Hypersensitivity to brinzolamide, brimonidine, or any component of the formulation","Neonates and infants under 2 years of age (for brimonidine component: risk of apnea and bradycardia)","Concomitant use with monoamine oxidase inhibitors (MAOIs) or use within 14 days of MAOI discontinuation (due to brimonidine)","Severe renal impairment (CrCl <30 mL/min)","Hyperchloremic acidosis (due to carbonic anhydrase inhibition)"]
| Precautions | ["Sulfonamide hypersensitivity: Serious adverse reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with oral carbonic anhydrase inhibitors; caution in patients with known sulfonamide allergy.","Corneal endothelial effects: May cause corneal edema due to carbonic anhydrase inhibition; caution in patients with compromised corneas.","Inflammatory ocular conditions: Use with caution in patients with active ocular inflammation (e.g., uveitis) as it may exacerbate inflammation.","Contamination: Patients should be instructed to avoid touching the dropper tip to any surface to prevent contamination.","Concomitant use with other drugs: Caution with carbonic anhydrase inhibitors or alpha-adrenergic agonists.","Renal impairment: Not recommended in patients with severe renal impairment (CrCl <30 mL/min) due to potential acidosis.","Hepatic impairment: Use with caution in patients with severe hepatic disease."] |
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| Fetal Monitoring | Monitor intraocular pressure and corneal health. No specific fetal monitoring required but consider fetal ultrasound if used chronically high doses due to carbonic anhydrase inhibitor effects. |
| Fertility Effects | No human studies. Animal studies: no impairment of fertility at oral doses up to 10 mg/kg/day brinzolamide and 5 mg/kg/day brimonidine (approx 100 and 120 times human exposure). Clinical relevance unknown. |