Brimonidine Tartrate

Class: alpha-Adrenergic Agonists
ATC Class: S01EA05
VA Class: OP109
Chemical Name: [S-(R*,R*,)]-2,3-Dihydroxybutanedioate-5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine
Molecular Formula: C11H10BrN5•C4H6O6
CAS Number: 79570-19-7
Brands: Alphagan P

Introduction

Relatively selective α2-adrenergic agonist.1 3 11 19

Uses for Brimonidine Tartrate

Ocular Hypertension and Glaucoma

Reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.1 3 13 19

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Brimonidine Tartrate Dosage and Administration

General

  • IOP should be determined after about 4 weeks of therapy with the drug; thereafter, IOP should be determined as necessary.17

Administration

Topical Administration

Apply topically to the affected eye(s).1 19

If more than one topical ophthalmic drug is used, administer the drugs at least 5 minutes apart.1 11 19

Dosage

Pediatric Patients

Ocular Hypertension and Glaucoma
Ophthalmic

The manufacturer makes no specific dosage recommendations for children ≥2 years of age.17

Adults

Ocular Hypertension and Glaucoma
Ophthalmic

One drop in the affected eye(s) 3 times daily, approximately 8 hours apart.1 11 19

Cautions for Brimonidine Tartrate

Contraindications

  • Concomitant use with an MAO inhibitor.1 19

  • Known hypersensitivity to brimonidine or any ingredient in the formulation.1 19

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Ocular hypersensitivity reactions (e.g., allergic conjunctivitis, conjunctival hyperemia, ocular pruritus) reported.1 If sensitivity reaction occurs, discontinue brimonidine.17

Possible partial cross-sensitivity between brimonidine and apraclonidine;18 use with caution in patients with a history of hypersensitivity to apraclonidine.17

General Precautions

Systemic Effects

Minimal effects on blood pressure in clinical studies; use with caution in patients with severe cardiovascular conditions, depression, orthostatic hypotension, cerebral or coronary insufficiency, Raynaud’s phenomenon, or thromboangiitis obliterans.1 19

IOP Monitoring

IOP-lowering effect of 0.2% brimonidine tartrate ophthalmic solution may diminish over time; routinely monitor IOP.19

Specific Populations

Pregnancy

Category B.1 19

Lactation

Distributed into milk in rats;1 17 discontinue nursing or the drug.1 19

Pediatric Use

Potentially serious adverse CNS effects, including apnea8 19 and lethargy reported in infants;8 19 not recommended for children < 2 years of age.1 6 19

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1 19

Common Adverse Effects

With brimonidine tartrate 0.15% ophthalmic solution in adults, allergic conjunctivitis,1 conjunctival hyperemia,1 ocular pruritus,1 burning sensation,1 conjunctival folliculosis,1 hypertension,1 xerostomia,1 and visual disturbances.1

With brimonidine tartrate 0.2% ophthalmic solution in adults, oral dryness, ocular hyperemia, burning and stinging, headache, blurring, foreign body sensation, fatigue/drowsiness, conjunctival follicles, ocular allergic reactions, ocular pruritus.19

Age- and weight-related somnolence and decreased mental alertness reported in children 2–7 years of age with glaucoma receiving brimonidine tartrate 0.2% ophthalmic solution.1 6 19

Interactions for Brimonidine Tartrate

No formal drug interaction studies have been performed.1 19

Specific Drugs

Drug

Interaction

Comment

β-Adrenergic blocking agents (topical or systemic)

Additive IOP-lowering and cardiovascular effects3 4 11

Use with caution1 19

Cardiac glycosides

Additive cardiovascular effects11

Use with caution1 19

CNS depressants (e.g., alcohol, barbiturates, general anesthetics, opiates, sedatives)

Additive CNS depressant effects1 19

Hypotensive agents

Additive IOP-lowering and cardiovascular effects3 4 11

Use with caution1 19

MAO inhibitors

Concomitant use contraindicated1 19

Antidepressants, tricyclics (TCAs)

TCAs that affect the metabolism and uptake of circulating amines may interfere with IOP-lowering effect of brimonidine1 19

Use with caution1 19

Brimonidine Tartrate Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations occurred within 0.5–4 hours after ocular administration of brimonidine tartrate 0.1 or 0.2% ophthalmic solution.1 19

Onset

Peak ocular hypotensive effects occur 2–3 hours following topical administration of brimonidine.1 3 19

Distribution

Extent

Distributed into milk in animals; not known whether the drug distributes into milk in humans.1 19

Elimination

Metabolism

Extensively metabolized in the liver.1 19

Elimination Route

Brimonidine and its metabolites are excreted principally in urine.1 19

Half-life

2–3 hours.1 19

Stability

Storage

Ophthalmic

Solution

15–25°C.1 19

Actions

  • Reduces IOP by decreasing aqueous humor production and increasing uveoscleral outflow.1 3 4 11 19

  • Selectivity for α2- versus α1-adrenergic receptors at least 10 or 28 times greater than that of clonidine or apraclonidine, respectively;3 9 11 may result in reduction in adverse pulmonary and cardiovascular effects.1 11

Advice to Patients

  • Importance of advising patients that brimonidine tartrate may cause fatigue and/or drowsiness and to exercise caution when engaged in hazardous activities requiring mental alertness.1 19

  • Importance of informing patients to administer other ophthalmic drugs at least 5 minutes apart.1 19

  • Importance of delaying insertion of soft contact lenses for at least 15 minutes after 0.2% brimonidine tartrate instillation, since benzalkonium chloride preservative in the solution may be absorbed by soft lenses.19

  • Importance of learning and adhering to proper administration techniques to avoid contamination of the solution container.17

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 19

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.1 19

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Brimonidine Tartrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Solution

0.15%

Alphagan P

Allergan

0.2%*

Brimonidine Tartrate Ophthalmic Solution (with benzalkonium chloride)

Bausch & Lomb

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Alphagan P 0.1% Solution (ALLERGAN): 5/$78.99 or 15/$215.98

Alphagan P 0.1% Solution (ALLERGAN): 10/$154.95 or 30/$439.90

Alphagan P 0.1% Solution (ALLERGAN): 15/$232.95 or 45/$640.60

Alphagan P 0.15% Solution (ALLERGAN): 5/$88.55 or 15/$254.85

Alphagan P 0.15% Solution (ALLERGAN): 10/$168.99 or 30/$472.97

Alphagan P 0.15% Solution (ALLERGAN): 15/$259.99 or 45/$735.99

Brimonidine Tartrate 0.15% Solution (SANDOZ): 5/$72.99 or 15/$186.97

Brimonidine Tartrate 0.15% Solution (SANDOZ): 10/$134.99 or 30/$376.97

Brimonidine Tartrate 0.15% Solution (SANDOZ): 15/$185.99 or 45/$542.97

Brimonidine Tartrate 0.2% Solution (BAUSCH &amp; LOMB): 5/$19.99 or 15/$49.97

Brimonidine Tartrate 0.2% Solution (BAUSCH &amp; LOMB): 15/$52.99 or 45/$139.46

Brimonidine Tartrate 0.2% Solution (SANDOZ): 10/$51.99 or 30/$145.97

Combigan 0.2-0.5% Solution (ALLERGAN): 5/$90.85 or 15/$255.25

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Allergan, Inc. Alphagan P (brimonidine tartrate ophthalmic solution) prescribing information. Irvine, CA; 2001 Dec.

2. Allergan, Inc. Alphagan (brimonidine tartrate ophthalmic solution) prescribing information. Irvine, CA; 2001 Dec.

3. Cantor LB. The evolving pharmacotherapeutic profile of brimonidine, an α2-adrenergic agonist, after four years of continuous use. Expert Opin Pharmacother. 2000; 1:815-34. [PubMed 11249518]

4. Larsson LI. Aqueous humor flow in normal human eyes treated with brimonidine and timolol, alone and in combination. Arch Ophthalmol. 2001; 119:492-5. [IDIS 462462] [PubMed 11296014]

5. Schuman JS, Horwitz B, Choplin NT et al for the Chronic Brimonidine Study Group. A 1-year study of brimonidine twice daily in glaucoma and ocular hypertension. A controlled, randomized, multicenter clinical trial. Arch Ophthalmol. 1997; 115:847-52. [IDIS 389914] [PubMed 9230823]

6. Enyedi LB, Freedman SF. Safety and efficacy of brimonidine in children with glaucoma. J AAPOS. 2001; 5:281-4. [PubMed 11641636]

7. Serle JB for the Brimonidine Study Group III. A comparison of the safety and efficacy of twice daily brimonidine 0.2% versus betaxolol 0.25% in subjects with elevated intraocular pressure. Surv Ophthalmol. 1996; 41(Suppl 1):S39-47.

8. Carlsen JO, Zabriskie NA, Kwon YH et al. Apparent central nervous system depression in infants after the use of topical brimonidine. Am J Ophthalmol. 1999; 128:255-6. [IDIS 432058] [PubMed 10458196]

9. Walters TR. Development and use of brimonidine in treating acute and chronic elevations of intraocular pressure: a review of safety, efficacy, dose response, and dosing studies. Surv Ophthalmol. 1996; 41(Suppl 1):S19-26. [PubMed 8970246]

10. Melamed S, David R for the Brimonidine Study Group II. Ongoing clinical assessment of the safety profile and efficacy of brimonidine compared with timolol: year-three results. Clin Ther. 2000; 22:103-11. [IDIS 442936] [PubMed 10688394]

11. Maus TL, Nau C, Brubaker RF. Comparison of the early effects of brimonidine and apraclonidine as topical ocular hypotensive agents. Arch Ophthalmol. 1999; 117:586-91. [IDIS 428176] [PubMed 10326954]

12. Williams GC, Orengo-Nania S, Gross RL. Incidence of brimonidine allergy in patients previously allergic to apraclonidine. J Glaucoma. 2000; 9:235-8. [PubMed 10877374]

13. Lewis PR, Phillips TG, Sassani JW. Topical therapies for glaucoma: what family physicians need to know. Am Fam Physician. 1999; 59:1871-9. [PubMed 10208706]

14. Derick RJ, Robin AL, Walters TR et al. Brimonidine tartrate: a one-month dose response study. Ophthalmology. 1997; 104:131-6. [IDIS 381529] [PubMed 9022117]

15. Food and Drug Administration summary basis of approval on brimonidine tartrate 0.15% ophthalmic solution. NDA No. 21-262. Rockville, MD: undated. From the FDA website. Accessed March 25, 2002.

16. Katz LJ. Twelve-month evaluation of brimonidine-Purite versus brimonidine in patients with glaucoma or ocular hypertension. J Glaucoma. 2002; 11:119-26. [PubMed 11912359]

17. Allergan, Inc, Irvine, CA; Personal communication.

18. Williams GC, Orengo-Nania S, Gross RL. Incidence of brimonidine allergy in patients previously allergic to apraclonidine. J Glaucoma. 2000; 9:235-8. [PubMed 10877374]

19. Bausch & Lomb Pharmaceuticals, Inc. Brimonidine tartrate ophthalmic solution 0.2% prescribing information. Tampa, FL; 2003 May.

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