TRAUMON Gel Ref.[51169] Active ingredients: Etofenamate

Plasma level

When subjects were given 300 mg etofenamate in the form of Traumon Gel 10%, maximum flufenamic acid plasma levels were measured between 12 and 24 hours after application (21-28 ng/ml).

Protein binding

Protein binding is between 98% - 99%.

Metabolism and elimination

Etofenamate elimination occurs renally in the form of numerous metabolites of flufenamic acid (hydroxylation, ether and ester cleavage) and their conjugates, 55%.

Enterohepatic circulation is likely.

After topical application, an elimination half-life of approximately 3.3 hours was observed.

Etofenamate is excreted in breast milk in low concentrations as flufenamic acid.

Bioavailability

The bioavailability of preparations containing etofenamate is subject to both high interindividual and intraindividual fluctuations, which are essentially due to the application site, skin moisture and other factors. After cutaneous application, the relative bioavailability, that is the systemically available portion of the dose, in the order of magnitude of other etofenamate preparations (up to 20%).

In case of topical application of etofenamate, the absorption rate must be taken into account when evaluating the toxicological data (see pharmacokinetics).

Acute toxicity

Studies on the acute toxicity of etofenamate were carried out on rats, mice, guinea pigs and rabbits with different applications. Oral application indicated higher toxicity as compared to cutaneous application. The intoxication chart characteristics are concentrated in the gastrointestinal tract, with diarrhoea and weight loss. These symptoms usually only appear a few days after application. Fatalities occurred between the 2nd and 14th day. After administering sub-lethal doses, the animals recovered within 14 days. The autopsy revealed peritonitis and ascites.

Sub-chronic and chronic toxicity

Sub-chronic toxicity tests were carried out on various animal species. Studies of one year duration and oral use were carried out in rats (7, 27, 100 mg/kg body weight/day) and monkeys (7, 26, 100 mg/kg body weight/day). In rats below 100 mg/kg body weight/day, bleeding and ulcers developed in the gastrointestinal area, with subsequent peritonitis and increased mortality.

The high dose led to a reduction in body weight, thymus weight and haemoglobin in monkeys.

Mutagenic and tumorigenic potential

The in vitro and in vivo studies on the induction of gene and chromosome mutations were negative. A mutagenic effect appears to be sufficiently excluded. In long-term studies with oral use in rats (7, 21, 63 mg/kg body weight/day) and mice (15, 45, 140 mg/kg body weight/day), there was no evidence of etofenamate’s tumorigenic potential.

Local tolerance

See point 4.8. "Side effects"

Reproductive toxicity

Etofenamate crosses the placenta.

There is no experience regarding human application. In animal experiments, the embryotoxic dose was below the maternally toxic one. From a dose of 21 mg/kg body weight orally (days 6-15 p.c.), the rat showed increased dilatation of the renal pelvis and an increased incidence of 14 rib pairs from 7 mg/kg body weight orally (days 6-15 p.c.) in young animals of treated mother animals.

Etofenamate is excreted in breast milk as flufenamic acid. The concentrations in breast milk are low, so that short-term and small-scale dermal treatment of the mother with etofenamate should not be regarded as an obstacle to breastfeeding.