Drug Safety Update

Volume 4, Issue 11 June 2011

Latest advice for medicines users

Yasmin: risk of venous thromboembolism higher than levonorgestrel-containing pills

Article date: June 2011
Summary
Epidemiological studies have shown that the risk of venous thromboembolism (VTE) for drospirenone-containing combined oral contraceptives (COCs), including Yasmin, is higher than for levonorgestrel-containing COCs (so-called ‘second generation’ pills) and may be similar to the risk for COCs that contain desogestrel or gestodene (so-called ‘third generation’ pills). The risk of VTE with Yasmin remains very small and, like other oral contraceptives, is less than that associated with pregnancy. Prescribers should be aware of the updated information when discussing the most suitable type of contraceptive for any woman who wants to start or switch contraception

Venous thromboembolism (VTE) in association with use of combined oral contraceptives (COCs) is not a new issue. For a given dose of oestrogen, the absolute incidence of VTE varies according to the type of progestogen in the pill but is, for all COCs, very small.

The incidence of VTE in association with the use of levonorgestrel-containing, desogestrel-containing, or gestodene-containing pills has been studied extensively. Overall, these studies have shown that women who use pills that contain desogestrel or gestodene have a slightly higher risk of developing VTE than do those who use levonorgestrel-containing pills. The excess risk of VTE is highest during the first year a woman ever starts or switches their COC.

Yasmin contains drospirenone, a relatively new progestogen, and was first licensed in 2000. Evidence of the level of VTE risk associated with Yasmin has been accruing since then. The results of two early prospective cohort studies suggested no difference in risk of VTE between Yasmin and levonorgestrel-containing pillsDinger JC, et al. Contraception 2007; 75: 344–54. or ‘other’ COCs.Seeger JD, et al. Obstet Gynecol 2007; 110: 587–93. However, in 2009, a Danish cohort studyLidegaard Ø, et al. BMJ 2009; 339: b2890. and a Dutch case-control studyvan Hylckama Vlieg A, et al. BMJ 2009; 339: b2921. of the risk of VTE in association with a number of COCs found the risk with drospirenone-containing pills to be higher than the risk associated with levonorgestrel-containing pills. Two further studies were recently published: one using the US PharMetrics databaseJick SS and Hernandez RK, BMJ; 2011; 340: d2151. and the other using the UK General Practice Research Database.Parkin L et al. BMJ 2011; 340: d2139. Both corroborated the findings of the Danish3 and Dutch4 studies of an increased risk of VTE in association with use of drospirenone-containing pills relative to levonorgestrel-containing pills.

Recent unpublished re-analyses of data from the Danish study3 directly compared VTE risk for drospirenone-containing pills, levonorgestrel-containing pills, and desogestrel/gestodene-containing pills. These data strengthen and confirm the original findings, and have enabled firmer conclusions about the relative risk associated with drospirenone-containing pills.

All epidemiological studies have some limitations in their methods; however, the totality of the available evidence now clearly shows that the risk of VTE for drospirenone-containing COCs, including Yasmin, is higher than the risk for levonorgestrel-containing second-generation COCs. Furthermore, it suggests that the level of the risk may be similar to that for third-generation COCs that contain desogestrel or gestodene.

Product information for Yasmin, as for all COCs, already contains extensive warnings about the risk of VTE and these have been updated to reflect the totality of the evidence.

Advice for healthcare professionals:

  • The risk of VTE in association with drospirenone-containing pills, including Yasmin, is higher than that for levonorgestrel-containing ‘second generation’ pills and may be similar to the risk for ‘third-generation’ pills that contain desogestrel or gestodene
  • Levonorgestrel-containing pills have the lowest thrombotic risk and are the safest pill for a woman who wants to start or switch contraception. Prescribers should be aware of the updated information when discussing the most suitable type of contraceptive for a woman who wants to start or switch contraception
  • Any prescribing decision should take into account each woman’s personal risk factors and any contraindications, including her experience with other contraceptive formulations
  • All COCs, including Yasmin, should be prescribed with caution to obese women (BMI >30), or those with a higher baseline risk of VTE for other reasons
  • Estimates are not precise, but for women who do not use a contraceptive pill about one case of VTE per 10 000 is expected each year. By comparison, about six cases of VTE are expected to occur in every 10 000 pregnancies. In healthy women who take Yasmin, between three and four cases of VTE are expected to occur in every 10 000 women each year. The previous estimate was between two and four cases in every 10 000 women each year. All these estimates relate to women who are otherwise in good health
  • There is no reason for women to stop taking drospirenone-containing COCs or any other COC on the basis of these findings

Advice for women:

  • All hormonal contraceptives are highly effective and safe. They have important health benefits, including those from avoiding unplanned pregnancy. If you take Yasmin, there is no need to stop doing so on the basis of these findings. When used appropriately, the benefits of all combined oral contraceptives, including Yasmin, far outweigh the risk of VTE, which is rare
  • If you have any concerns about your contraception, you should discuss them with your contraceptive provider, but keep taking your contraceptive pill until you have done so. If you stop taking your pill, you will need to use another method of contraception, such as a condom, from then on because you otherwise risk becoming pregnant
  • A number of combined oral contraceptives and other contraceptive choices are available. Your contraceptive provider will discuss the most suitable choice of contraceptive for you, taking into consideration your medical history and any contraindications
  • Venous thromboembolism (VTE) associated with use of combined oral contraceptives is not a new issue. The risk of a VTE for any combined oral contraceptive, including Yasmin, is very small and smaller than the risk of VTE associated with pregnancy
  • The combined pill contains an oestrogen (ethinylestradiol) and a progestogen, and the level of risk of VTE varies slightly according to the type of progestogen.  Evidence now shows that the risk is lowest with pills that contain the progestogen levonorgestrel and is slightly higher in pills that contain the progestogens drospirenone (such as Yasmin), desogestrel, or gestodene

Further information:

MHRA safety summary of hormonal contraceptives

BNF section 7.3.1 Combined hormonal contraceptives

See also the European Pharmacovigilance Working Party (PhVWP) monthly report for May 2011

 

Article citation: Drug Safety Update June 2011, vol 4 issue 11: A2.

References

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Page last modified: 06 June 2011