Drug related safety issues affecting pregnancy outcome and concerning risk minimisation measures. Emphasis on pregnancy prevention programmes

PhD ceremony: Ms. H.J.M.J. Crijns, 12.45 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Drug related safety issues affecting pregnancy outcome and concerning risk minimisation measures. Emphasis on pregnancy prevention programmes

Promotor(s): prof. L.T.W. de Jong van den Berg

Faculty: Mathematics and Natural Sciences

The thesis, Ineke Crijns will touch on some safety signals regarding congenital anomalies discussed post-authorisation. With emphasis on drugs with a known teratogenicity having a Pregnancy Prevention Plan (PPP) to avoid pregnancy exposure, but in particular the isotretinoin PPP.

The seven PPPs present in European Union (EU) authorised drugs showed that differences in the reason for this programme but also in the programme itself and also common elements. It was concluded that PPPs should only be imposed on drugs with a known high risk of human teratogenicity. Furthermore, PPPs should be harmonised to avoid confusion with the stakeholders.

Regarding the isotretinoin PPP, in the EU pregnancies were reported and therefore in several EU member states additional measures were taken due to discontent of national authorities.

In the Netherlands, surveys to pharmacists and dermatologists showed that their adherence to the programme is not adequate. A drug utilisation study showed that compliance with contraceptive use according to the isotretinoin PPP was higher than in the general population but only 52-64%. Seventeen pregnancies exposed to isotretinoin indicated that the reason for failure was the poor compliance with or absence of contraceptive use.

Inadequate compliance with contraceptives is one reason for failure of the PPP and correct conditions will have to be set up and it should be considered to involve all stakeholders in the development to gain a broader basis.