Brimonidine Tartrate

BRIMONIDINE TARTRATE : 

BRIMONIDINE TARTRATE *KAMAL SINGH RATHORE, Dr. R.K.NEMA, Dr. S.S.SISODIA *B.N.GIRLS COLLEGE OF PHARMACY, UDAIPUR-313002 RAJ. kamalsrathore@gmail.com +919828325713(M)

Brimonidine Tartrate structure and IUPSC name : 

Brimonidine Tartrate structure and IUPSC name 5-Bromo-N-(4, 5-dihydro-1H-imidazol-2-yl) quinoxalin-6-amine

Introduction of BT : 

Introduction of BT Brimonidine is a α2-adrenergic receptor agonist. Alpha 2 agonists, through the activation of the Gi GPCR, inhibit the production of acetylcholine. This reduces cAMP and hence Aqueous Humor production by the ciliary body. Description:    Brimonidine Tartrate Ophthalmic Solution 0.2% is a relatively selective alpha-2 adrenergic agonist for ophthalmic use. In solution, brimonidine tartrate ophthalmic solution 0.2% has a clear, greenish-yellow color. It has an osmolality of 280-330 mOsml/kg and a pH of 5.6-6.6

Physico-chemical properties : 

Physico-chemical properties Chemical data Formula: C11H10BrN5.C4H6O6 Mol. Mass: 292.135 g/mol (442.24 as the tartrate salt) Physical properties Appearance, color and odor: cream-light yellow powder, or off- white, odorless, crystalline solid. Melting point: 207-208 C Solubility: the solubility of brimonidine tartrate in a variety of solvents at room temperature (≈25C) Soluble in water, slightly soluble in methanol

Clinical uses : 

Clinical uses Brimonidine is indicated for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Mechanism of Action:    Brimonidine tartrate ophthalmic solution 0.2% is an alpha adrenergic receptor agonist. It has a peak ocular hypotensive effect occurring at two hours post-dosing. Fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow.

Clinical Evaluations : 

Clinical Evaluations Elevated IOP presents a major risk factor in glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss. Brimonidine tartrate has the action of lowering intraocular pressure with minimal effect on cardiovascular and pulmonary parameters.

Pharmacodynamics/Kinetics : 

Pharmacodynamics/Kinetics Onset of action: Peak effect: 2 hours Metabolism: Hepatic Half-life elimination: 2-3 hours Time to peak, plasma: Alphagan®: 1-4 hours; Alphagan® P: 0.5-2.5 hours Excretion: Urine (74%)

Dosage and Dosage Forms : 

Dosage and Dosage Forms Ophthalmic: Children 2 years of age and Adults: Glaucoma: Instill 1 drop in affected eye(s) 3 times/day (approximately every 8 hours), Remove contact lenses prior to administration; wait 15 minutes before reinserting Solution, ophthalmic, as tartrate: Alphagan® P: 0.15% (5 mL, 10 mL, 15 mL) [contains Purite® 0.005% as preservative]

Contraindications : 

Contraindications Brimonidine tartrate ophthalmic solution 0.2% is contraindicated in patients with hypersensitivity to brimonidine tartrate or any component of this medication. It is also contraindicated in patients receiving monoamine oxidase (MAO) inhibitor therapy. Overdose If overdose is suspected, contact your local poison control center or emergency room immediately. This medicine may be harmful if swallowed.

Drug interactions : 

Drug interactions Possible potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthesia) or with sleeping pills, other antihistamines and pain relievers which can cause excessive drowsiness. Beta-blockers either ophthalmic and systemic (may further slow down heart beat) and antihypertensive and/or cardiac glycosides (can further lower the blood pressure); tricyclic antidepressants. Do not use this ophthalmic solution if you have taken a monoamine oxidase (MAO) inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl), or tranylcypromine (Parnate) in the last 14 days. There may be other drugs not listed that can affect brimonidine. Tell your doctor about all the prescription and over-the-counter medications (e.g. minerals, vitamins, herbal products) that you use.

Slide 11: 

Pregnancy Teratogenic Effects: Pregnancy Category B. Brimonidine should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the foetus. Lactation It is not known whether brimonidine is excreted in human milk, although in animal studies, brimonidine tartrate has been shown to be excreted in breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Paediatric Use The safety and effectiveness have not been studied in paediatric patients below the age of 2 years. Brimonidine tartrate ophthalmic solution, 0.2% is not recommended for use in paediatric patients under the age of 2 years. Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

Adverse Reactions : 

Adverse Reactions Adverse events occurring in approximately 10-30% of the subjects, in descending order of incidence, included- burning and stinging, blurring, headache, fatigue/drowsiness, foreign body sensation, oral dryness, ocular hyperemia, conjunctival follicles, ocular allergic reactions, and ocular pruritus.

Dosage and Administration : 

Dosage and Administration The recommended dose is one drop of brimonidine tartrate ophthalmic solution 0.2% in the affected eye(s) three times daily, approximately 8 hours apart. Brimonidine tartrate ophthalmic solution 0.2% may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic product is being used, the products should be administered at least 5 minutes apart.

BRIMONIDINE Eye Drops : 

BRIMONIDINE Eye Drops COMPOSITION Each ml contains: Brimonidine tartrate .......... …..2 mg (equivalent to 1.32 mg as Brimonidine base) Benzalkonium chloride NF (as preservative)..... ………… 0.005% w/v Sterile aqueous vehicle ......... q.s.

International Brand Names : 

International Brand Names Alphagan® (Allergen) Alphagan™ (Allergen) Alphagan® (Allergen) Agglad ofteno® Brimodin-P (Cipla) Brimosun-P (Sun) Oftalmotonil® PMS-Brimonidine Tartrate ratio-Brimonidine Sandoz-Brimonidine Apo-Brimonidine®

How Supplied : 

How Supplied Brimonidine Tartrate Ophthalmic Solution 0.1%,0.15% and 0.2% are supplied sterile in a plastic bottle with a controlled drop tip in the following sizes: 5 mL bottles 10 mL bottles 15 mL bottles Storage Store between 15° - 25°C (59° - 77°F). KEEP OUT OF THE REACH OF CHILDREN. DO NOT USE IF IMPRINTED "Protective Seal" WITH YELLOW IS NOT INTACT.

UV scan of brimonidine tartrate : 

UV scan of brimonidine tartrate

Composition of stimulated tear fluid (Artificial lachrymal fluid) : 

Composition of stimulated tear fluid (Artificial lachrymal fluid)

Patient EducationFor use in eyes only. Wash hands before instilling. Remove contacts prior to administration and wait 15 minutes before reinserting. Sit or lie down to instill. Open eye, look at ceiling, and instill prescribed amount of solution. Apply gentle pressure to inner corner of eye. Do not let tip of applicator touch eyes; do not contaminate tip of applicator (may cause eye infection, eye damage, or vision loss). Brimonidine tartrate may cause fatigue or drowsiness in some patients. Avoid engaging in hazardous activities due to potential for decreased mental alertness. Wait at least 15 minutes after instilling brimonidine tartrate before reinserting soft contact lenses. Breast-feeding precaution: Do not breast-feed. : 

Patient EducationFor use in eyes only. Wash hands before instilling. Remove contacts prior to administration and wait 15 minutes before reinserting. Sit or lie down to instill. Open eye, look at ceiling, and instill prescribed amount of solution. Apply gentle pressure to inner corner of eye. Do not let tip of applicator touch eyes; do not contaminate tip of applicator (may cause eye infection, eye damage, or vision loss). Brimonidine tartrate may cause fatigue or drowsiness in some patients. Avoid engaging in hazardous activities due to potential for decreased mental alertness. Wait at least 15 minutes after instilling brimonidine tartrate before reinserting soft contact lenses. Breast-feeding precaution: Do not breast-feed.

References : 

References Byles DB, Frith P, and Salmon JF, “Anterior Uveitis as a Side Effect of Topical Brimonidine,” Am J Ophthalmol, 2000, 130(3):287-91. Levy Y and Zadok D, “Systemic Side Effects of Ophthalmic Drops,” Clin Pediatr (Phila), 2004, 43(1):99-101.

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