generictimes productprofiles: Brimonidine Ophthalmic Solution 0.2%

Clinical Update

Glaucoma is the second leading causeof blindness in the United States. Specifically,open-angle glaucoma is progressiveand asymptomatic, with elevatedintraocular pressure causing a gradualincrease in cupping of the optic nervedisc. The effect of this cupping on the retinais the diminishment of the patient'svisual field.

There are several predisposing factors,including family history, concurrent diabetes,or severe myopia. Black patientsover the age of 40 and white patientsover the age of 65 also have an increasedrisk of developing open-angle glaucoma.

Although elevated intraocular pressureis considered a major risk factor, it isnot completely effective as a diagnostictool. Patients may have normal pressureswithin the eye and still have glaucoma.Visual field testing is the mainstayof glaucoma diagnosis and its progressivemanagement.

Without treatment, open-angle glaucomawill result in irreversible loss of vision.Before aggressive treatments involvinglasers or surgery are employed, therapyinvolves sterile ophthalmic solutions thataffect sympathetic receptors in the eye.Brimonidine, at a 0.2% concentration, createschanges at the alpha-receptor levelin order to reduce intraocular pressure.

Pharmacology

Reduction in intraocular pressure generallyis accomplished either by decreasingthe production of aqueous humorentering the eye or by increasing its outflowthrough the trabecular meshwork oruveoscleral pathways. Brimonidine is a relativelyselective alpha-2 receptor agonistand reduces intraocular pressure by bothdecreasing the production of aqueoushumor and increasing its outflow throughthe uveoscleral pathway. This alpha-2receptor agonist property reduces bothelevated and normal pressure in the eye,regardless of the presence of glaucoma.The maximum reduction in pressure isseen within 2 to 3 hours following theadministration of brimonidine. Overall, ophthalmicpressure is reduced by ~25%.

Administration and Dosing

The recommended dosing of brimonidinefor open-angle glaucoma is 1 drop inthe affected eye 3 times daily, spaced at8-hour intervals. Response to the initialtherapy should be checked after 4 weeksand then monitored periodically toobserve effectiveness and to look forpotential side effects.

As with any sterile ophthalmic preparation,care should be taken when handlingbrimonidine solution to preventcontamination. Patients should beadvised to wash their hands before andafter using this solution. In addition,when using multiple ophthalmic therapies,the patient needs to wait at least 5minutes before the administration ofother eyedrops.

Side Effects and Drug Interactions

Adverse effects occur frequently withbrimonidine (at a rate of 10-30%) andinclude localized burning, headache, thesensation of a foreign body in the eye,ocular pruritus, blepharitis, xerophthalmia,tearing, corneal staining, andblurred vision.

Although systemic effects of alpha-2agonists may result in vasoconstriction,the topical use of brimonidine amongadults appears to generate minimal concernamong clinicians regarding thiseffect. The manufacturers do recommendcaution, however, when using brimonidinein patients with severe cardiovascularconditions, orthostatic hypotension,cerebral or coronary insufficiency,or Raynaud's phenomenon.

Although concern over systemic effectsis slight among adults, it should benoted that ophthalmic use of brimonidineamong children under the age of 2 hasresulted in apnea and lethargy, and that,in early studies, treatment was discontinuedin 16% of children aged 2 to 7 due tosleepiness. Somnolence in these reportsappears to be age-and weight-related.Therefore, the use of brimonidine requirescautious monitoring in childrenunder the age of 7 and is actively discouragedin children under the age of 2.

In general, patients have allergic reactionsto brimonidine at a rate of 10% to20%. The high frequency of allergic reactionsto brimonidine appears to sensitizethe patient to subsequent drugs used totreat open-angle glaucoma. A special formulationusing a Purite product as a preservativehas been introduced to themarket in an effort to reduce the rate ofallergy. This form, however, is still underpatent protection.

Outlook

The consequences of untreated glaucomacan be devastating. Before today'scommonly available treatments, blindnessgenerally was inevitable. This progressivecondition can now be treatedwith several agents. Although patientswith glaucoma can experience anincreased quality of life with their use, thetreatments themselves possess sideeffects that require repeated assessment.Brimonidine is available as a 0.2% sterileophthalmic solution from Bausch andLomb, Allergan, and Falcon Pharmaceuticals.

Mr. Middleton is an instructor of pharmacologyat Kellogg CommunityCollege in Battle Creek, Mich.