In April 2003, Berlex Canada sent out a Dear Health Care Professional letter outlining recent published information on the risk of venous thromboembolism (VTE) with DIANE®-35 (cyproterone acetate and ethinyl estradiol). DIANE®-35, like all estrogen/progesterone combinations, is associated with an increased risk of VTE.
DIANE®-35 is indicated for the treatment of women with severe acne and its associated symptoms of androgenization, including seborrhea and mild hirsutism, that has been unresponsive to oral antibiotics and other available treatments. Based on an independent analysis that was commissioned by Berlex, cases of non-fatal VTE ranging in incidence from 1.2 to 9.9 events per 10,000 women-years have been observed in users of DIANE®-35. As context, the incidence of VTE in non-users of any oral contraceptive is estimated to be 0.5 to 1 event per 10,000 women-years, and increases to 4 events per 10,000 women-years in long-term users of low estrogen content (<50_g ethinyl estradiol) combination oral contraceptives. These event rates are rare, but still justify caution in the use of DIANE®-35.
Since its market introduction in 1998, Health Canada has received 11 reports of VTE equivalent to a reporting rate of 0.33 events per 10,000 women-years. One of these cases involved a death. It should be noted that reporting rates determined on the basis of spontaneously reported post-marketing adverse events are generally presumed to underestimate the risks associated with drug treatments.
Women with androgen-related conditions, e.g., severe acne or hirsutism, may have an inherently increased cardiovascular risk. The excess risk of VTE is highest during the rst year a woman ever uses a combination oral contraceptive.
Berlex summarized by saying that:
• DIANE®-35, as with all estrogen/progestogen combinations, is contraindicated in women with thrombophlebitis, thromboembolic disorders, or a history of these conditions.
• DIANE®-35 users appear to have an elevated risk of venous thromboembolic events compared to users of combination oral contraceptives in some published studies.
• DIANE®-35 should not be prescribed for the purpose of contraception alone.
• During treatment with DIANE®-35, other oral contraceptives should not be used.