Diane 35 safety concerns BY: MOHAMMED ALSAIDAN

Background Diane-35 contains Yasmin : Ethinylestradiol (35 μg) cyproterone acetate (2mg) Yasmin : Ethinylestradiol (30 μg) drospirenone (3 mg)

Background Cases of venous thromboembolism were first reported in the 1960s in women taking combination OCP Low-estrogen preparations are associated with lower rates of venous thrombosis. “third-generation progestagens” (e.g., desogestrel) are associated with about double the risk of venous thrombosis of either the first- (norethindrone) or second- generation (levonorgestrel) progestagens, although the association is controversial

Background Venous thrombosis develops usually within the first year after starting the drug Oral contraceptives users at increased risk of venous thromboembolism include those who are Obese prothrombotic mutations (factor V Leiden carriers ) Injury Immobility postoperative status postpartum status

Indications Diane-35 is approved only as therapy for androgen-sensitive skin conditions, including hirsutism severe acne unresponsive to oral antibiotic therapy seborrhea FPHL OCP ! Decrease uric acid level in obese patient with PCOs Pretreatment to improve the outcome of ovulation induction by clompiphene Cyproterone acetate has antiandrogen effects resulting from its blockade of androgen receptors

Background Diane-35 should be discontinued 3–4 menstrual cycles after a woman’s skin condition has resolved. Cyproterone acetate has antiandrogen effects resulting from its blockade of androgen receptors

Recommendation Diane-35 should be reserved for temporary use in the treatment of moderate to severe acne related to androgen sensitivity and/or hirsutism, in women of reproductive age, when alternative treatments such as topical therapy (applied to the skin) or antibiotics have failed and should not be used solely as an oral contraceptive All women taking combination OCP should be informed of this rare but potentially serious adverse effect, particularly if they are taking Diane- 35. Clearly caution, and not panic, is warranted.

Recommendation Switching 2220 women from Diane-35 to an oral levonorgestrel contraceptive for 1 year would prevent 1 case of nonfatal venous thromboembolism. Consider not prescribing Diane-35 for women at risk of venous thromboembolism (especially those who carry prothrombotic mutations), Most venous thrombotic events are truly idiopathic (i.e. the women have no clinically recognizable risk factors).

Recommendation The risk of VTE with these medicines is 1.5 to 2 times higher than for COCs containing levonorgestrel and may be similar to the risk with contraceptives containing gestodene, desogestrel or drospirenone. Furthermore the PRAC concluded that in the treatment of alopecia the benefits did not outweigh the risks.

Recommendation Concomitant use with another hormonal contraceptive would expose the woman to a higher dose of oestrogen and increase her risk of VTE. To raise the awareness amongst healthcare professionals and patients of the risk of thromboembolism, the company should carry out a study on the use of Diane 35 as well as a study on the effectiveness of the recommended risk minimisation measures. The next meeting of 27 to 29 May 2013. The CMDh will adopt a final decision

Thank you