ITAMI Medicated plaster Ref.[50023] Active ingredients: Diclofenac

Diclofenac is absorbed slowly and incompletely from cutaneous formulations. The plasma concentrations of diclofenac at steady state are characterised by continuous absorption of diclofenac from the plaster, regardless of whether the plaster is applied in the morning or in the evening. Following cutaneous application, diclofenac may be absorbed into a dermal depot, from where it is released slowly into the central compartment. The systemic absorption of topical products is about 2-10% of that obtained with same dose administered orally.

The observed therapeutic efficacy is mainly explained by therapeutically relevant drug tissue concentrations beneath the site of application. Penetration to the site of action may vary with the extent and nature of the condition and depending on the site of application and action.

Mean plateau concentrations are approximately 1 ng/ml. Plasma protein binding of diclofenac is high at 99%. Metabolism and elimination are similar after cutaneous and oral use. Following rapid hepatic metabolism (hydroxylation and binding to glucuronic acid), ⅔ of the active substance is eliminated renally and ⅓ by the biliary route.

Non-clinical data based on conventional studies of safety pharmacology, genotoxicity and carcinogenic potential reveal no special hazards for humans beyond those already outlined in other sections of the Summary of Product Characteristics. In animal studies, chronic toxicity of diclofenac following systemic administration mainly manifested as gastrointestinal lesions and ulcers. In a 2-year toxicity study, rats treated with diclofenac showed a dose-related increase in thrombotic occlusion of the cardiac vessels.

In animal studies on reproductive toxicity, systemically administered diclofenac caused inhibition of ovulation in rabbits and impairment of implantation and early embryonic development in rats. The gestational period and duration of parturition were prolonged by diclofenac. The embryotoxic potential of diclofenac was studied in three animal species (rat, mouse, rabbit). Foetal death and growth retardation occurred at maternotoxic dose levels. Based on the available non-clinical data, diclofenac is regarded as non-teratogenic. Doses below the maternotoxic threshold had no impact on the postnatal development of the offspring.

Conventional studies on local tolerability reveal no special hazards for humans. Scientific literature data have shown that the active ingredient diclofenac may pose an environmental risk to the aquatic compartment (to fish).