Brinzolamide

S01E - Antiglaucoma preparations and miotics ATC S01EC04 Small molecule approved 1998 Topical Natural product

JFDA label: Azopt Eye Drops

Mechanism of Action

Inhibitor of Carbonic anhydrase 2 — Carbonic anhydrase II inhibitor

Target	Action	Gene / class
Carbonic anhydrase 2 efficacy	INHIBITOR	CA2

Indications

Approved

Elevated intraocular pressure

Contraindications

Source: Lexicomp

Additional contraindications (not in US labeling): Hypersensitivity to sulfonamide Absolute
Hypersensitivity to brinzolamide or any component of the formulation Absolute
severe renal impairment (CrCl Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Common Hyperemia

Nervous system disorders (2)

Common Foreign body sensation of eye · headache

Gastrointestinal disorders (1)

Common Dysgeusia

Skin and subcutaneous tissue disorders (1)

Common Dermatitis

Eye disorders (8)

Common blepharitis · Blurred vision · eye discharge · eye discomfort · eye pain · eye pruritus · keratitis · xerophthalmia

Respiratory, thoracic and mediastinal disorders (1)

Common Rhinitis

Dosing

Source: Lexicomp

Elevated intraocular pressure: Ophthalmic: Instill 1 drop in affected eye(s) 3 times daily

Refer to adult dosing.

CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling. CrCl

There are no dosage adjustments provided in the manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

Ophthalmic effects

Vision may be temporarily blurred, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

Sulfonamide (“sulfa”) allergy

The FDA-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, 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. Disease-related concerns:

Acute angle-closure glaucoma

Use has not been studied in acute angle-closure glaucoma.

Corneal endothelium

Use with caution in patients with low endothelial cell counts; may be at increased risk of corneal edema.

Renal impairment

Use is not recommended in patients with severe renal impairment (has not been studied). 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. Special populations:

Contact lens wearers

Product may contain benzalkonium chloride which may be absorbed by soft contact lenses; remove lens prior to administration and wait 15 minutes before reinserting.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events have been observed in animal reproduction studies.

Lactation

Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.

Monitoring

Clinical pearl	Ophthalmic exams and intraocular pressure

Chemistry & Properties

Formula	C12H21N3O5S3
Molecular weight	383.52 g/mol
IUPAC name	(4R)-4-(ethylamino)-2-(3-methoxypropyl)-1,1-dioxo-3,4-dihydrothieno[3,2-e]thiazine-6-sulfonamide
CAS	138890-62-7
PubChem CID	68844
InChIKey	`HCRKCZRJWPKOAR-JTQLQIEISA-N`
logP	0.09 (XLogP -0.3)
Polar surface area	118.8 Å²
H-bond acceptors / donors	7 / 2
Drug-likeness (QED)	0.64
Lipinski violations	0

SMILES

CCN[C@H]1CN(CCCOC)S(=O)(=O)c2sc(S(N)(=O)=O)cc21

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C9	Substrate	—
CYP3A4	Substrate	—

Receptor binding (top 4)

Target	Action	Affinity
carbonic anhydrase 7 (CA7)	Inhibitor	pKi 8.6
Carbonic Anhydrase Isozymes, CA II	Binding	pKi 8.5
carbonic anhydrase 12 (CA12)	Inhibitor	pKi 8.5
Carbonic Anhydrase Isozymes, CA IX	Binding	pKi 7.4

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Azopt Eye Drops	Ophthalmic Solution 10 mg/ml	5 ml	The Jordan Drugstore Co	4.110
Azarga	Injection 10 mg/ml, 5 mg/ml	5 ml	The Jordan Drugstore Co	8.830
Simbrinza Eye drops, suspension	Suspension 10 mg/1 ml, 2 mg/1 mg	5 ml	The Jordan Drugstore Co	11.130