Diane 35 safety concerns

BY: MOHAMMED ALSAIDAN

Background

• Diane-35 contains • 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

Background

• Diane-35 should be discontinued 3–4 menstrual cycles after a woman’s skin condition has resolved.

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