Usage
- Brinzolamide is prescribed for lowering intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. It is used as monotherapy in adults who do not respond to beta-blockers or for whom beta-blockers are contraindicated. It is also used adjunctively with beta-blockers or prostaglandin analogs.
- Pharmacological Classification: Carbonic anhydrase inhibitor.
- Mechanism of Action: Brinzolamide inhibits carbonic anhydrase II (CA-II) in the ciliary processes of the eye. This inhibition reduces the formation of bicarbonate ions, which in turn decreases sodium and fluid transport into the aqueous humor, ultimately lowering IOP.
Alternate Names
- Brinzolamide ophthalmic suspension 1%.
- Brand Names: Azopt, Brinzolamide Indoco. Other combination products include SIMBRINZA (with brimonidine).
How It Works
- Pharmacodynamics: Brinzolamide lowers IOP by primarily suppressing the secretion of aqueous humor. Minimal effects on pupil size or accommodation are observed.
- Pharmacokinetics: Following topical administration, Brinzolamide is absorbed systemically. In the eye, Brinzolamide binds to CA-II within the ciliary processes. It is metabolized in the liver, primarily by CYP3A4, to N-desethylbrinzolamide and other metabolites. Excretion is primarily through the kidneys (approximately 60% as unchanged drug).
- Mode of Action: Brinzolamide binds reversibly to the active site of CA-II, inhibiting its catalytic activity. CA-II facilitates the conversion of carbon dioxide and water into bicarbonate ions and protons. The suppression of bicarbonate formation reduces fluid transport and ultimately lowers IOP.
- Elimination Pathways: Primarily renal excretion (about 60% as unchanged drug), with some hepatic metabolism followed by renal excretion of metabolites.
Dosage
Standard Dosage
Adults:
- One drop in the affected eye(s) two to three times daily.
Children:
- Not recommended for use in children under 18 years of age.
Special Cases:
- Elderly Patients: No dosage adjustment is generally needed.
- Patients with Renal Impairment: Contraindicated in severe renal impairment (CrCl <30 mL/min). No adjustment is required for moderate renal impairment.
- Patients with Hepatic Dysfunction: Not recommended due to a lack of studies in this population.
- Patients with Comorbid Conditions: Use with caution in patients with compromised corneas (e.g., low endothelial cell count), pseudoexfoliative glaucoma, or pigmentary glaucoma.
Clinical Use Cases
Brinzolamide is not systemically administered and therefore, these specific use cases are not applicable to Brinzolamide eye drops.
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations (e.g., status epilepticus, cardiac arrest)
Dosage Adjustments
- Dose adjustments may be necessary based on individual patient response and tolerability.
- No specific dose modifications for metabolic disorders or genetic polymorphisms are indicated.
Side Effects
Common Side Effects
- Blurred vision.
- Bitter or unusual taste in the mouth.
- Eye discomfort, burning, stinging, itching, dryness, foreign body sensation.
- Headache.
- Dry mouth.
Rare but Serious Side Effects
- Severe allergic reactions (skin rash, itching, hives, swelling of face, lips, tongue, or throat).
- Sudden vision loss or changes.
- Severe eye pain, redness, irritation, or discharge.
- Stevens-Johnson syndrome, toxic epidermal necrolysis.
Long-Term Effects
- Potential for corneal endothelial damage with prolonged use.
Adverse Drug Reactions (ADR)
Contraindications
- Hypersensitivity to brinzolamide, sulfonamides, or any component of the formulation.
- Severe renal impairment (CrCl <30 mL/min).
- Hyperchloremic acidosis.
Drug Interactions
- Other carbonic anhydrase inhibitors (e.g., acetazolamide, dorzolamide): Additive systemic effects; concomitant use is generally not recommended.
- High-dose salicylates: Potential for acid-base disturbances and drug interactions.
- Other medications: Review potential drug interactions as needed. CYP3A4 inducers/inhibitors may affect brinzolamide metabolism.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C.
- Fetal risk: Studies in animals have shown reproductive toxicity. Brinzolamide is not recommended during pregnancy unless the potential benefit outweighs the potential risk to the fetus.
- Breastfeeding: It is unknown if brinzolamide is excreted in human milk. A decision should be made whether to discontinue breastfeeding or discontinue the drug, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.
Drug Profile Summary
- Mechanism of Action: Carbonic anhydrase II inhibitor, decreases aqueous humor secretion.
- Side Effects: Blurred vision, bitter taste, eye irritation, headache, dry mouth. Rarely, severe allergic reactions or vision changes.
- Contraindications: Hypersensitivity to brinzolamide or sulfonamides, severe renal impairment, hyperchloremic acidosis.
- Drug Interactions: Other carbonic anhydrase inhibitors, high-dose salicylates.
- Pregnancy & Breastfeeding: Not recommended during pregnancy; unknown safety during breastfeeding.
- Dosage: 1 drop in affected eye(s) 2-3 times daily.
- Monitoring Parameters: Intraocular pressure.
Popular Combinations
- Brinzolamide and timolol (a beta-blocker).
- Brinzolamide and brimonidine (an alpha-2 adrenergic agonist). These provide additive IOP-lowering effects through different mechanisms.
Precautions
- General Precautions: Evaluate renal function, especially in elderly patients. Monitor for corneal changes with long-term use.
- Specific Populations: As noted above.
- Lifestyle Considerations: Blurred vision may temporarily occur after administration. Advise patients to avoid operating machinery or driving until vision clears.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Brinzolamide?
A: One drop in the affected eye(s) two to three times per day.
Q2: Can Brinzolamide be used in children?
A: No, brinzolamide is not recommended for use in children under 18 years of age due to a lack of safety and efficacy data.
Q3: What are the common side effects of Brinzolamide?
A: Common side effects include blurred vision, a bitter or unusual taste, eye irritation (burning, stinging, itching, dryness), headache, and dry mouth.
Q4: Is Brinzolamide safe to use during pregnancy?
A: Brinzolamide is generally not recommended for use during pregnancy. Animal studies have shown potential for reproductive toxicity. It should only be used if the potential benefit to the mother clearly outweighs the potential risk to the fetus.
Q5: Can Brinzolamide be used while breastfeeding?
A: It is unknown whether brinzolamide is excreted in human milk. A decision to use Brinzolamide during breastfeeding needs to consider the potential risk to the infant alongside the mother’s clinical need for the medication.
Q6: What should I do if I miss a dose of Brinzolamide?
A: If you miss a dose, instill the next dose as scheduled. Do not double the dose.
Q7: How does Brinzolamide interact with other medications?
A: Brinzolamide can have additive effects with other carbonic anhydrase inhibitors. It may also interact with high-dose salicylates. It is important to discuss all concomitant medications with your healthcare provider.
Q8: What are the contraindications to Brinzolamide use?
A: Brinzolamide is contraindicated in patients with hypersensitivity to Brinzolamide or sulfonamides, severe renal impairment, and hyperchloremic acidosis.
Q9: How should Brinzolamide be stored?
A: Brinzolamide ophthalmic suspension should be stored at room temperature, protected from light. Discard the bottle four weeks after opening, even if some suspension remains.
A: Remove contact lenses before instilling Brinzolamide. Wait at least 15 minutes after instilling the drops before reinserting lenses. The preservative in Brinzolamide (benzalkonium chloride) can be absorbed by soft contact lenses and discolor them. It can also cause eye irritation.
