Article date: June 2013
Cyproterone with ethinylestradiol (co-cyprindiol, brand leader Dianette) is licensed as a second-line treatment for women with severe acne or moderately severe hirsutism. A review of the benefits and risks of co-cyprindiol was initiated in January 2013 following concerns in France about the risk of venous thromboembolism (VTE) and off-label use as a contraceptive. The review has concluded that the balance of benefits and risks of co-cyprindiol remains positive; however, some important changes to product information for prescribers and women have been made to further improve this balance.
New information wording
Indication for use
The review considered the available data on the safety and efficacy of co-cyprindiol and concluded that it should be used in women of reproductive age for the treatment of:
- skin conditions related to androgen sensitivity, such as severe acne with or without seborrhoea
Co-cyprindiol should only be used when treatment with topical therapy or systemic antibiotics has failed.
Co-cyprindiol provides effective contraception in women who require it to treat androgen-sensitive conditions, but it should not be used solely as a contraceptive.
Review of postmarketing data for adverse drug reactions has suggested that some women are using Dianette as well as a combined hormonal contraceptive. This exposes them to twice the dose of oestrogen and substantially increases their risk of VTE. Use of an additional hormonal contraceptive with co-cyprindiol is therefore contraindicated.
Rare risk of VTE
The risk of VTE with co-cyprindiol is rare and similar to that associated with the hormonal contraceptive pills. The available observational data have limitations, but taken together their findings provide sufficient evidence that co-cyprindiol has a 1.5–2 times statistically significant increase in VTE risk (deep vein thrombosis, DVT, or pulmonary embolism, PE) compared with levonorgestrel-containing pills. Although more limited, the available evidence also suggests that the VTE risk with Dianette is likely to be similar to that with contraceptives that contain desogestrel, gestodene, or drospirenone.
Duration of treatment
In 2008 we published updated advice on the recommended duration of use of co-cyprindiol. The recent review has confirmed that acne is a chronic condition that requires at least 3 months of treatment with Dianette to relieve symptoms, and that prolonged treatment might be needed. The need to continue treatment should be evaluated periodically by the treating physician.
Advice for healthcare professionals:
- the benefits of co-cyprindiol outweigh the risks in women of reproductive age for the treatment of:
- skin conditions related to androgen sensitivity (eg, severe acne with or without seborrhoea)
- co-cyprindiol provides effective contraception in these women - an additional hormonal contraceptive should not be used in combination with co-cyprindiol
- the need to continue treatment should be evaluated periodically by the treating physician
- the risk of VTE is rare but this remains an important side effect, and healthcare professionals should themselves be vigilant for signs and counsel patients to remain vigilant for signs and symptoms. These include:
- DVT—unusual leg pain (usually in the calf), which may be accompanied by tenderness or swelling in the leg; increased warmth, redness, or discolouration of skin
- PE—sudden sharp chest pains (which may increase with breathing in); shortness of breath (which can come on suddenly or gradually); sudden coughing for no apparent reason; severe light-headedness, dizziness or fainting
Remember that suspected adverse reactions to co-cyprindiol should be reported to us on a Yellow Card.
European Medicines Agency statement
BNF section 13.6.2 Oral preparations for acne
Article citation: Drug Safety Update June 2013 vol 6, issue 11: A3.