Regulatory Decision Summary for MONOPROST

Health Canada considers that the anticipated benefits of Monoprost outweigh its potential risks.

The benefit of Monoprost has been established by the marked reduction of intraocular pressure (IOP) following repeated once-daily ocular instillation. The reduction in IOP elicited by Monoprost was shown to be non-inferior to Xalatan. Latanoprost 0.005% - the active ingredient in both Monoprost and Xalatan - is a prostaglandin F2α analogue that is well established in the treatment of elevated IOP associated with glaucoma and ocular hypertension. Xalatan was first authorized for marketing in Canada in 1997. Unlike Xalatan, Monoprost does not contain the preservative benzalkonium chloride (BAK). While BAK is an effective preservative, it has been recently recognized that BAK may pose a risk of ocular surface disease - particularly following repeated exposure and subsequent accumulation.

Monoprost appears to be well tolerated following repeated dosing both in non-clinical (for example, conducted in rabbits) and clinical studies. Monoprost is associated with fewer observed ocular adverse events (AEs) compared to Xalatan, however, the frequency difference is relatively small and the clinical meaningfulness is unclear. Similarly, Monoprost is associated with statistically significantly fewer subjective symptoms relative to Xalatan, including: burning/stinging upon instillation, irritation/burning/stinging not upon instillation, and conjunctival hyperaemia. However, the relatively small frequency of symptoms and predominance of those reported as "present but not disturbing" makes robust conclusions regarding the clinical meaningfulness of these data challenging. Furthermore, the relative absence of reported AEs consistent with these symptoms further suggests a limited clinical relevance. The long-term ocular safety of the nonmedicinal ingredient macrogolglycerol hydroxystearate is uncertain, and is being monitored in the international post-market environment.

Overall, based on the data submitted, the benefits of Monoprost outweigh its potential risks under the conditions of use indicated in the Product Monograph at this time.