Polihexanide Other names: Polyhexanide

Pharmacodynamics were not tested in the scope of clinical trials. Polihexanide acts on both the active trophozoite and dormant cystal forms of Acanthamoeba. Polihexanide is a polycationic polymer composed of hexamethylene biguanide units and has a dual-targeted mechanism of action that involves:

• Disruption of Acanthamoeba cell membranes. Polihexanide, positively charged, binds to the phospholipid bilayer of the trophozoites membrane, negatively charged, causing membrane damage, cell lysis and death due to leakage of essential cell components. Polihexanide is also able to penetrate the ostiole of the encysted Acanthamoeba to exert the same effect. This action only marginally affects the neutral phospholipids in mammalian cell membrane.
• DNA binding. Once polihexanide has passed through the cell membrane, it condenses and damages Acanthamoeba chromosomes. Polihexanide interacts extensively with the DNA phosphate backbone to block the Acanthamoeba DNA replication process. This mechanism is restricted to Acanthamoeba cells as polihexanide is unable to penetrate the nucleus of mammalian cells.

Pharmacokinetics were not studied.

Polihexanide is intended for topical ophthalmic application. The systemic absorption of polihexanide is expected to be negligible after topical administration to the eye.

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development.

A 26-week toxicity study using daily administration (16 times/day at approximately 1-hour intervals from day 1 to day 5, 8 times/day at approximately 2-hour intervals from day 6 to week 3 and 4 times/day at approximately 4-hour intervals from week 4 to week 26) of polihexanide 0.8 mg/mL eye drops was conducted in rabbits. The study did not indicate any local or systemic effects of the treatment. No indications of a systemic effect of polihexanide 0.8 mg/mL eye drops were observed during 26 weeks of treatment period. Post mortem macroscopic and histopathological examinations performed at the end of the study did not reveal treatment-related changes.

There was no evidence of genotoxicity in in vitro and in vivo studies.

There was no evidence of embryo-foetal toxicity in oral studies in the rat and the rabbit.