Reproductive toxicology

Retigabine had no effect on fertility or general reproductive performance.

In rats, retigabine and/or its metabolites crossed the placenta resulting in tissue concentrations that were similar in dams and foetuses.

There was no evidence of teratogenicity following administration of retigabine to pregnant animals during the period of organogenesis. In a study of peri- and post-natal development in rats, retigabine was associated with increased perinatal mortality following administration during pregnancy. In addition, there was a delay in auditory startle response development. These findings were apparent at exposure levels lower than those obtained with clinically recommended doses and were accompanied by maternal toxicities (including ataxia, hypokinesia, tremor and reduced body weight gain). The maternal toxicities interfered with higher dosing of the dams and hence deduction of safety margins with regard to human therapy.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

 Tablet core

Croscarmellose sodium

Hypromellose

Magnesium stearate

Microcrystalline cellulose.

Film-coating

50 and 400 mg tablets:

Polyvinyl alcohol

Macrogol 3350

Titanium dioxide (E171)

Talc (E553b)

Indigo carmine aluminium lake (E132)

Carmine (E120).

100 and 300 mg tablets:

Polyvinyl alcohol

Macrogol 3350

Titanium dioxide (E171)

Talc (E553b)

Indigo carmine aluminium lake (E132)

Iron oxide yellow (E172).

200 mg tablets:

Polyvinyl alcohol

Macrogol 3350

Titanium dioxide (E171)

Talc (E553b)

Iron oxide yellow (E172).

6.2 Incompatibilities

 Not applicable.

6.3 Shelf life

 18 months.

6.4 Special precautions for storage

 Do not store above 25°C.

6.5 Nature and contents of container

 50 mg tablets (maintenance packs):

Opaque PVDC/PE/PVC-aluminium foil blisters. Packs containing 21, 84 or 168 film-coated tablets.

100 mg tablets (maintenance packs):

Opaque PVDC/PE/PVC-aluminium foil blisters. Packs containing 21, 84 or 168 film-coated tablets.

200 mg tablets:

Opaque PVDC/PE/PVC-aluminium foil blisters. Pack containing 84 film-coated tablets; multi-pack comprising 168 (2 x 84) film-coated tablets.

300 mg tablets:

Opaque PVDC/PE/PVC-aluminium foil blisters. Pack containing 84 film-coated tablets; multi-pack comprising 168 (2 x 84) film-coated tablets.

400 mg tablets:

Opaque PVDC/PE/PVC-aluminium foil blisters. Pack containing 84 film-coated tablets; multi-pack comprising 168 (2 x 84) film-coated tablets.

Treatment initiation pack

Opaque PVDC/PE/PVC-aluminium foil blisters sealed into secondary heat-sealed card packaging. Pack containing 63 film-coated tablets (21 x 50 mg film-coated tablets and 42 x 100 mg film-coated tablets), presented as:

- one blister of 21 x 100 mg film-coated tablets

- one blister of 21 x 100 mg film-coated tablets and 21 x 50 mg film-coated tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

 No special requirements.

7. MARKETING AUTHORISATION HOLDER

 Glaxo Group Limited

Berkeley Avenue

Greenford

Middl