3 years
Not applicable.
Sucrose
Saccharin sodium
Potassium sorbate
Polysorbate 20
Aniseed oil
Peppermint oil
Purified water
Hydrochloric acid (for pH adjustment)
On repeated oral and parenteral administration of tramadol for 6 - 26 weeks in rats and dogs and oral administration for 12 months in dogs haematological, clinico-chemical and histological investigations showed no evidence of any substance-related changes. Central nervous manifestations only occurred after high doses considerably above the therapeutic range: restlessness, salivation, convulsions, and reduced weight gain. Rats and dogs tolerated oral doses of 20 mg/kg and 10 mg/kg body weight respectively, and dogs rectal doses of 20 mg/kg body weight without any reactions.
In rats tramadol dosages from 50 mg/kg/day upwards caused toxic effects in dams and raised neonate mortality. In the offspring retardation occurred in the form of ossification disorders and delayed vaginal and eye opening. Male fertility was not affected. After higher doses (from 50 mg/kg/day upwards) females exhibited a reduced pregnancy rate. In rabbits there were toxic effects in dams from 125 mg/kg upwards and skeletal anomalies in the offspring.
In some in-vitro test systems there was evidence of mutagenic effects. In-vivo studies showed no such effects. According to knowledge gained so far, tramadol can be classified as non-mutagenic.
Studies on the tumorigenic potential of tramadol hydrochloride have been carried out in rats and mice. The study in rats showed no evidence of any substance-related increase in the incidence of tumours. In the study in mice there was an increased incidence of liver cell adenomas in male animals (a dose-dependent, non-significant increase from 15 mg/kg upwards) and an increase in pulmonary tumours in females of all dosage groups (significant, but not dose-dependent).
11/11/2015
Mercury Pharmaceuticals Ltd
Capital House, 85 King William Street,
London EC4N 7BL, UK
Store in the original package in order to protect from light.
Dropper container consisting of a 10 ml amber glass bottle with inserted dropper applicator and sealed with a child safe screw cap.
Packed with 1, 3 or 5 bottles.
Not all pack sizes may be marketed.
PL 12762/0453
No special requirements.
Any unused product or waste material should be disposed of in accordance with local requirements.
17/03/2011
