Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction
Type of information:
experimental study
Adequacy of study:
other information

Data source

Reference
Reference Type:
other: EPAR - Scientific Discussion
Title:
Viread - EPAR - Scientific Discussion
Year:
2006
Bibliographic source:
European Medicines Agency

Materials and methods

GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Sex:
male/female

Administration / exposure

Doses / concentrations
Remarks:
Doses / Concentrations:
doses up to 600 mg/kg.
Basis:

Control animals:
not specified

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
It did not affect fertility and general reproductive performance of the male and female rats at doses up to 600 mg/kg. It was neither embryotoxic nor teratogenic in rats (doses up to 450 mg/kg/day) and in rabbits (doses up to 300 mg/kg/day).
The NOEL for maternal effects was 150 mg/kg/day in rats and 100 mg in rabbits respectively. In peri- and post natal toxicity study in rats, tenofovir DF significantly reduced pups survival and animal weights. The viability index in rats was reduced in the 450 mg/kg/dose group and significantly reduced in 600 mg/kg/day. Pup weights were also decreased in these groups and there was a slight delay of sexual maturation that did not affect
reproductive performance. The non effect dose was 150 mg/kg. In a non GLP study in rhesus macaques, there was evidence of reduced birth weight and several bone lengths at a dose of30 mg/kg/day, that correspond to 25-times the human exposure. Based on these results, tenofovir DF should be used in pregnant women only if the potential benefit outweighs the potential risks to the foetus as recommended in the Summary of Product Characteristics.
Reproductive NOEL in rats: 300 mg/kg/day