United Kingdom. Further to safety concerns that have arisen in recent years about third- generation combined oral contraceptives containing desogestrel or gestodene, the Medicines Commission has further reviewed all currently available relevant data and has confirmed that the incidence of venous thromboembolism is about 25 per 100,000 women per year of use.

The incidence of venous thrombembolism in users of “second-generation” combined oral contraceptives (those containing levonorgestrel) is about 15 per 100,000 women per year of use. This indicates a small excess risk of about 10 cases of venous thromboembolism per 100,000 women years for women using third-generation combined oral contraceptives containing desogestrel or gestodene which has not been satisfactorily explained by bias or confounding. However, the absolute risk of venous thromboembolism in women taking combined oral contraceptives containing desogestrel or gestodene is very small and is much less than the risk of venous thromboembolism in pregnancy.

The Summaries of Product Characteristics (data sheets) and patient information leaflets for combined oral contraceptives containing desogestrel or gestodene will be updated to include the following statements:

Contraindications:

• History of confirmed venous thromboembolism (VTE). Family history of idiopathic VTE. Other known risk factors for VTE.

Warnings:

• An increased risk of venous thromboembolic disease (VTE) associated with the use of oral contraceptives is well established but is smaller than that associated with pregnancy, which has been estimated at 60 cases per 100,000 pregnancies. Some epidemiological studies have reported a greater risk of VTE for women using combined oral contraceptives containing desogestrel or gestodene (the so-called third generation pills) than for women using pills containing levonorgestrel (the so-called second generation pills). The spontaneous incidence of VTE in healthy non-pregnant women (not taking any oral contraceptive) is about 5 cases per 100,000 women per year. The incidence in users of second generation pills is about 15 per 100,000 women per year of use. The incidence in users of third generation pills is about 25 per 100,000 women per year of use: this excess incidence has not been satisfactorily explained by bias or confounding. The level of all of these risks of VTE increases with age and is likely to be increased in women with other known factors for VTE such as obesity.

Reference: Current Problems in Pharmacovigilance, Vol. 25, June 1999.