This document posted October 2009 Recommendations and Reasons Committee to Evaluate Drugs (CED) Dorzolamide / – new preservative-free formulation

Product: Highlights of Recommendation: Background: DORZOLAMIDE / TIMOLOL (Cosopt® Preservative Free) 2%/0.5% ♦ Cosopt is an combining two Cosopt is an eye drop combining two drug ophthalmic solution (new formulation) drug ingredients, dorzolamide and ingredients, dorzolamide and timolol, used timolol, used to treat increased to treat increased intraocular pressure Class of drugs: intraocular pressure (pressure in the (pressure in the eye) associated with Carbonic anhydrase inhibitor / eye) associated with ocular hypertension ocular hypertension or . beta-blocker combination or glaucoma. Increased intraocular pressure over time ♦ Cosopt (with benzalkonium chloride as a leads to progressive damage to the optic nerve and can result in vision loss and Indication: preservative) is already available in a blindness. These medications work by Treatment of ocular hypertension and multi-use bottle and is listed on the Ontario Drug Benefit Formulary as a reducing the production of fluid in the open-angle glaucoma eye, thereby lowering the pressure in the Limited Use benefit. Cosopt Preservative Free is a new formulation that does not eye. Manufacturer: contain benzalkonium and comes in Merck Frosst Canada Ltd. individual, single-use packages. Cosopt (with preservative) is listed on the

♦ The Committee reviewed a study Ontario Drug Benefit Formulary as a comparing the efficacy and safety of the Limited Use benefit according to the CED Recommendation new preservative-free dorzolamide/ following criteria: timolol (Cosopt Preservative Free) with The CED recommended that the original preservative-containing As second-line therapy for patients who preservative-free dorzolamide/timolol formulation. Both preparations were do not have an adequate intraocular (Cosopt Preservative Free) not be found to be equally effective in lowering pressure lowering response to single- funded on the basis that it has not been intraocular pressure, and there were no drug therapy with ophthalmic beta- shown to improve tolerability or provide significant differences in tolerability blocking agents. any other clinical advantage; therefore, between the two formulations. OR For use as initial therapy in an urgent the significant price premium could not ♦ The Committee acknowledged that some be justified. patients may experience minor irritation situation (e.g., patients with a high baseline intraocular pressure) where with the use of preservative-containing single-drug therapy is unlikely to be eye drops but questioned the incidence effective. of true allergic reactions to benzalkonium chloride that can only be managed with the use of a preservative- Executive Officer Decision free preparation. It was noted that studies demonstrating intolerance to benzalkonium chloride were conducted Based on the CED’s recommendation, by administering high concentrations of the Executive Officer decided not to the preservative directly into the eyes of fund preservative-free dorzolamide/ animals. timolol (Cosopt Preservative Free). ♦ Preservative-free dorzolamide/ timolol (Cosopt Preservative Free) costs $56.85 per 60-unit package (one month of treatment). This is more than three times the cost of the preservative- containing formulation. ♦ Overall, the Committee noted that evidence of improved tolerability Status with preservative-free dorzolamide/ timolol (Cosopt Funding not available through the Preservative Free) is lacking. Ontario Public Drug Programs. Moreover, the incidence of true allergic reaction to benzalkonium is unknown. For these reasons, the continued... Committee indicated that the significant price premium for the

preservative-free preparation could

not be justified.

Detailed Discussion: CEDAC Recommendation:

No additional details. The full CED discussion (http://www.cadth.ca/index.php/en/cdr/ is as outlined in the Highlights of recommendations) Recommendation section. The Canadian Expert Drug Advisory Committee (CEDAC) did not review dorzolamide/timolol (Cosopt Preservative Free).

Ministry of Health and Long-Term Care

Ontario Public Drug Programs

For more information, please contact:

Ministry of Health and Long-Term Care Ontario Public Drug Programs Hepburn Block, 9th Floor

80 Grosvenor Street, Queen’s Park

Toronto, Ontario M7A 1R3 or click: (http://www.health.gov.on.ca/english/ providers/program/drugs/ced_rec_table.html)