(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 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). 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients water for injection sodium acetate 6.2 Incompatibilities ZYDOL solution for injection has proved to be incompatible (immiscible) with solutions for injection of diazepam, diclofenac, indometacin, phenylbutazone, midazolam, piroxicam and isoxicam. 6.3 Shelf Life 5 years. Once opened, Zydol should be used immediately and any unused portions should be discarded. 6.4 Special precautions for storage Do not store above 30oC Store in the original container. 6.5 Nature and contents of container ZYDOL solution for injection is supplied in boxes of 5 clear Type I glass ampoules, each ampoule containing 2ml of tramadol hydrochloride. 6.6 Special precautions for disposal No special requirements for disposal. Any unused product or waste material should be disposed of in accordance with local requirements. Instructions for handling
(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 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). 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients water for injection sodium acetate 6.2 Incompatibilities ZYDOL solution for injection has proved to be incompatible (immiscible) with solutions for injection of diazepam, diclofenac, indometacin, phenylbutazone, midazolam, piroxicam and isoxicam. 6.3 Shelf Life 5 years. Once opened, Zydol should be used immediately and any unused portions should be discarded. 6.4 Special precautions for storage Do not store above 30oC Store in the original container. 6.5 Nature and contents of container ZYDOL solution for injection is supplied in boxes of 5 clear Type I glass ampoules, each ampoule containing 2ml of tramadol hydrochloride. 6.6 Special precautions for disposal No special requirements for disposal. Any unused product or waste material should be disposed of in accordance with local requirements. Instructions for handling
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