Brimonidine
JFDA label: ALPHAGAN E/D
Mechanism of Action
12.1 Mechanism of Action The proposed mechanism of action of this fixed-dose combination of carbachol and brimonidine in presbyopia is pupillary constriction and the creation of a pinhole effect that improves near visual acuity and depth of focus. Carbachol is a cholinergic agent which produces constriction of the iris sphincter and ciliary body. Brimonidine tartrate, an alpha-adrenergic agonist, blocks contraction of the iris dilator muscle and relaxes tonic contraction of the ciliary muscle, enhancing selectivity for the pupil and increasing bioavailability of carbachol in the aqueous humor.
Indications
Approved
- Eye Manifestations — eye allergy
- Glaucoma — glaucoma
Off-label
- Diabetic Retinopathy
- Dry Eye Syndromes
- Glaucoma, Open-Angle
- Ocular Hypertension
- Rosacea
Contraindications
Source: openFDA
- is contraindicated in patients with known hypersensitivity to the active ingredients or to any of the excipients. Hypersensitivity. ( 4 ) Absolute
Adverse Reactions
Cardiac disorders (4)
Uncommon Arrhythmia · Bradycardia · Palpitations · Tachycardia
Vascular disorders (3)
Very Common Flushing
Rare Hypotension
Very Rare Hypertension
Nervous system disorders (9)
Very Common Dizziness · Headache · Somnolence
Uncommon Paraesthesia
Rare Coma · Developmental glaucoma · Glaucoma · Loss of consciousness · Syncope
Immune system disorders (1)
Very Common Hypersensitivity
Gastrointestinal disorders (3)
Very Common Dry mouth · Gastrointestinal disorder
Rare Nausea
Skin and subcutaneous tissue disorders (9)
Very Common Erythema · Eye pruritus · Pruritus
Common Erythema of eyelid
Uncommon Acne · Dermatitis · Dermatitis contact · Eyelids pruritus
Rare Rash
Musculoskeletal and connective tissue disorders (1)
Rare Muscle relaxant therapy
Psychiatric disorders (4)
Very Common Photophobia
Uncommon Depression
Rare Respiratory depression
Very Rare Insomnia
Eye disorders (14)
Very Common Conjunctivitis · Conjunctivitis allergic · Dry eye · Endophthalmitis · Eye discharge · Eye irritation · Eye pain · Eyelid oedema · Lacrimation increased · Ocular hyperaemia · Vision blurred · Visual impairment
Common Intraocular pressure increased
Uncommon Eye oedema
Infections and infestations (3)
Common Nasopharyngitis · Rhinitis
Uncommon Pharyngitis
Investigations (1)
Rare Body temperature decreased
General disorders and administration site conditions (26)
Very Common Asthenia · Blepharitis · Conjunctival follicles · Conjunctival hyperaemia · Conjunctival oedema · Fatigue · Hyperaemia · Oedema · Pain · Punctate keratitis · Sensation of foreign body
Common Rosacea · Skin burning sensation · Vital dye staining cornea present
Uncommon Dysgeusia · Hypertrophy · Iritis · Pain of skin · Skin warm
Rare Hypothermia · Hypotonia · Lethargy · Miosis · Pallor · Shock · Vasodilation procedure
Respiratory, thoracic and mediastinal disorders (5)
Uncommon Nasal congestion · Nasal dryness
Rare Apnoea · Dyspnoea · Pulmonary function test decreased
Injury, poisoning and procedural complications (1)
Rare Accidental exposure to product
Dosing
Source: openFDA
Warnings & Precautions
Source: openFDA
Warnings & Precautions
Blurred Vision : Advise patients not to drive or operate machinery if vision is not clear (e.g., blurred vision). Exercise caution in night driving and other hazardous activities in poor illumination. ( 5.1 ) Risk of Retinal Detachment : Rare cases of retinal tear and detachment have been reported with miotics. Individuals with preexisting retinal disease are at increased risk. Therefore, examination of the retina is advised in all patients prior to initiation of therapy. Patients should be advised to seek immediate medical care with sudden onset of flashes of lights, floaters, or vision loss. ( 5.2 ) Iritis : Caution is advised in patients with iritis. ( 5.3 ) Potentiation of Vascular Insufficiency : Use with caution in patients with depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension, or thromboangiitis obliterans. ( 5.4 )
Blurred Vision Miotics may cause accommodative spasm
Blurred Vision Miotics may cause accommodative spasm. Advise patients to not drive or operate machinery if vision is not clear (e.g., blurred vision). In addition, patients may experience temporary dim or dark vision with miotics. Advise patients to exercise caution in night driving and other hazardous activities in poor illumination.
Risk of Retinal Detachment Rare cases of retinal tear and detachment h
Risk of Retinal Detachment Rare cases of retinal tear and detachment have been reported with miotics. Individuals with pre-existing retinal disease are at increased risk. Examination of the retina is advised in all patients prior to the initiation of therapy. Advise patients to seek immediate medical care with sudden onset of flashes of lights, floaters, or vision loss.
Iritis Sequelae of ocular inflammation, i.e., adhesions (synechiae) be
Iritis Sequelae of ocular inflammation, i.e., adhesions (synechiae) between the iris and the lens, may be exacerbated with miotic use, therefore, YUVEZZI is not recommended to be used when iritis is present.
Potentiation of Vascular Insufficiency YUVEZZI may potentiate syndrome
Potentiation of Vascular Insufficiency YUVEZZI may potentiate syndromes associated with vascular insufficiency. YUVEZZI should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension, or thromboangiitis obliterans.
Potential for Eye Injury or Contamination To prevent eye injury or con
Potential for Eye Injury or Contamination To prevent eye injury or contamination, avoid touching the single-dose vial to the eye, eyelids, or to any other surface.
Pregnancy & Lactation
Pregnancy
Lactation
Until more data are available, an alternative topical agent might be preferred
Chemistry & Properties
| Formula | C11H10BrN5 |
|---|---|
| Molecular weight | 292.14 g/mol |
| IUPAC name | 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)quinoxalin-6-amine |
| CAS | 59803-98-4 |
| PubChem CID | 2435 |
| InChIKey | XYLJNLCSTIOKRM-UHFFFAOYSA-N |
| logP | 1.76 (XLogP 0.6) |
| Polar surface area | 62.2 Ų |
| H-bond acceptors / donors | 5 / 2 |
| Drug-likeness (QED) | 0.84 |
| Lipinski violations | 0 |
SMILES
Brc1c(NC2=NCCN2)ccc2nccnc12Biology & Pharmacokinetics
Pharmacokinetics
| BBB penetrant | Yes |
|---|
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP1A2 | Substrate | — |
| CYP2C9 | Substrate | — |
| CYP2D6 | Substrate | — |
| CYP3A4 | Substrate | — |
Receptor binding (top 5)
| Target | Action | Affinity |
|---|---|---|
| α2A-adrenoceptor (ADRA2A) | Agonist | pEC50 9.1 |
| α2A-adrenoceptor (ADRA2A) | Agonist | pIC50 8.9 |
| α2B-adrenoceptor (ADRA2B) | Agonist | pIC50 8.4 |
| α2C-adrenoceptor (ADRA2C) | Agonist | pEC50 8.2 |
| α2B-adrenoceptor (ADRA2B) | Agonist | pEC50 7.8 |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)
Registered Products (8)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| BRADO Plus Eye Drops | Ophthalmic Solution 0.2 g/100 ml, 0.68 g/100 ml | 5 ml | Amman Pharmaceutical Indusries | 6.110 |
| ALPHAGAN E/D | Ophthalmic Solution 0.2 % | 5 ml | Arab Company for Medical & Agricultural Products | 6.130 |
| Brimo | Solution 0.2 %w/v | 5 ml | شركة مستودع ادوية الايمان | 6.470 |
| Combigan | Solution 0.5 %, 0.2 % | 5 ml | Arab Company for Medical & Agricultural Products | 6.790 |
| BRADO Eye Drops | Ophthalmic Solution 0.2 % | 5 ml | Amman Pharmaceutical Industries Co | 7.460 |
| Alphagan P Ophth. Sol. | Solution 0.15 % | 5 ml | Arab Company for Medical & Agricultural Products | 8.220 |
| Lumify | Solution 0.025 % | 7.5 ml | Petra Drug Store | 8.220 |
| Simbrinza Eye drops, suspension | Suspension 10 mg/1 ml, 2 mg/1 mg | 5 ml | The Jordan Drugstore Co | 11.130 |