OXYACT Film-coated tablet Ref.[27781] Active ingredients: Oxycodone

Absorption

Maximum oxycodone plasma concentrations are achieved after approximately 1 to 1.5 hours after the intake. Plasma concentrations are linear within a dose range of 5 to 20 mg.

Distribution

The absolute oral bioavailability of oxycodone is up to 87% with an elimination half-life of about 3 hours.

Biotransformation

Oxycodone is metabolised in the intestine and liver via the cytochrome P450 system to noroxycodone and oxymorphone as well as to several glucuronide conjugates. In vitro studies suggest that therapeutic doses of cimetidine probably have no relevant effect on the formation of noroxycodone. In man, quinidine reduces the production of oxymorphone while the pharmacodynamic properties of oxycodone remain largely unaffected. The contribution of the metabolites to the overall pharmacodynamic effect is irrelevant.

Elimination

Oxycodone and its metabolites are excreted via urine and faeces. Oxycodone crosses the placenta and is found in breast milk.

Linearity / non-linearity

The 5, 10 and 20 mg film-coated tablets are dose-proportional with regard to the amount of active substance absorbed as well as comparable with regard to the rate of absorption.

Non-clinical data based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity reveal no special hazards for humans beyond those already outlined in other sections of the SmPC.

Oxycodone showed no effect on fertility and early embryonic development in male and female rats in doses of up to 8 mg/kg body weight and induced no malformations in rats in doses of up to 8 mg/kg and and in rabbits in doses of 125 mg/kg bodyweight. However, in rabbits, when individual fetuses were used in statistical evaluation, a dose related increase in developmental variations was observed (increased incidences of 27 presacral vertebrae, extra pairs of ribs). When these parameters were statistically evaluated using litters, only the incidence of 27 presacral vertebrae was increased and only in the 125 mg/kg group, a dose level that produced severe pharmacotoxic effects in the pregnant animals.

In a study on peri- and postnatal development in rats, F1 body weights were lower at 6 mg/kg/d when compared to body weights of the control group at doses which reduced maternal weight and food intake (NOAEL 2 mg/kg body weight). There were neither effects on physical, reflexological, and sensory developmental parameters nor on behavioural and reproductive indices.

Long-term carcinogenicity studies with oxycodone have not been performed.