Safety Information
Based on the data of Kuhnz et al. Bayer plc (the manufacturer of Primolut N®, a brand product containing norethisterone 5 mg), have decided to update the reference safety information in order to point out that 1 mg orally administered norethisterone/NETA metabolises to 4–6 μg EE. This is also valid for all generic norethisterone preparations manufactured and distributed by other worldwide pharmaceutical companies.
Therapeutic doses of norethisterone should now be seen as a combination-like product with estrogenic and progestogenic properties. Considering the known data for COCs, Bayer plc has adapted the reference safety information for Primolut N to provide similar 'contraindications' and 'warnings and precautions' sections as EE-containing COCs. Approval is currently being sought with the UK Medicines and Healthcare products Regulatory Authority to include these labelling changes in Primolut N's Summary of Product Characteristics.
This change in labelling should lead to safer prescribing of progestogens for women with dysfunctional uterine bleeding. Based on currently available data the updated reference safety information does not change the overall positive benefit/risk balance for prescribing therapeutic doses of norethisterone in those at low risk of VTE. However, health care professionals will need to reassess the need for such treatment in women at high risk of VTE. One very small study has suggested that 10 mg medroxyprogesterone acetate, administered three times a day, is as effective in reducing heavy menstrual bleeding as a daily dose of 15 mg norethisterone taken from Day 12 to Day 25. Therefore, where clinical indications remain in those who are obese, immobile, about to undergo surgery, carriers of a thrombophilia or have a personal or strong family history of VTE, medroxyprogesterone acetate is a suitable alternative.