Gynecology Xagena

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Xagena Newsletter

Risk of venous thromboembolism: benefits of combined hormonal contraceptives continue to outweigh risks

The European Medicines Agency ( EMA ) has now completed the review of combined hormonal contraceptives ( CHCs ), particularly of the risk of venous thromboembolism ( VTE or blood clots in veins ) associated with their use. The European Medicines Agency’s Committee for Medicinal Products for Human Use ( CHMP ) has concluded that the benefits of CHCs in preventing unwanted pregnancies continue to outweigh their risks, and that the well-known risk of VTE with all CHCs is small.

The product information of CHCs will be updated to help women make informed decisions about their choice of contraception together with their healthcare professional. It is important that women are made aware of the risk of VTE and its signs and symptoms, and that doctors take into consideration a woman’s individual risk factors when prescribing a contraceptive. Doctors should also consider how the risk of VTE with a particular CHC compares with other CHCs.

The review also looked at the risk of arterial thromboembolism ( ATE, blood clots in arteries, which can potentially cause a stroke or heart attack ). This risk is very low and there is no evidence for a difference in the level of risk between products depending on the type of Progestogen.

Information to healthcare professionals

The EU-wide review of combined hormonal contraceptives has confirmed that the known risk of venous thromboembolism with all low-dose CHCs ( Ethinylestradiol less than 50 mcg ) is small.

Differences exist between CHCs in their risk of VTE depending on the type of Progestogen they contain. Currently available data indicate that CHCs containing the progestogens Levonorgestrel, Norethisterone or Norgestimate have the lowest risk of VTE.

When prescribing a CHC, careful consideration should be given to the individual woman’s current risk factors, particularly those for VTE, and the difference in risk of VTE between products. CHCs are contraindicated if a woman has one serious or multiple risk factors that put her at high risk of blood clots.

There is no evidence for differences between low-dose CHCs in their risk of arterial thromboembolism ( ATE ).

Because a woman’s individual risk factors will change over time, there is a need to regularly re-assess the suitability of her contraceptive.
It is also important to raise awareness of the signs and symptoms of VTE and ATE when prescribing a CHC. Healthcare professionals should always consider the possibility of a CHC-associated thromboembolism when presented with a woman who has symptoms.

Risk of developing a blood clot in a year:
a) Women not using a combined hormonal pill / patch / ring and are not pregnant: about 2 out of 10,000 women;

b) Women using a CHC containing Levonorgestrel, Norethisterone or Norgestimate: about 5-7 out of 10,000 women;

c) Women using a CHC containing Etonogestrel or Norelgestromin: about 6-12 out of 10,000 women;

d) Women using a CHC containing Drospirenone, Gestodene or Desogestrel: about 9-12 out of 10,000 women;

e) Women using a CHC containing Chlormadinone, Dienogest or Nomegestrol: not yet known;

CHCs contain two types of hormones, an oestrogen and a progestogen. The review included all contraceptives containing low-dose oestrogen and the following progestogens: Chlormadinone, Desogestrel, Dienogest, Drospirenone, Etonogestrel, Gestodene, Nomegestrol, Norelgestromin and Norgestimate. These are sometimes referred to as third generation or fourth generation contraceptives and are available as pills, skin patches and vaginal rings. During the review, the risk of VTE with these medicines was compared with that of CHCs containing Levonorgestrel and Norethisterone ( also known as second generation contraceptives ).

The classification as second, third or fourth generation is however not science-based and not standardised, and may differ between institutions and publications.

With the exception of Zoely ( Nomegestrol acetate / Estradiol ), Ioa ( Nomegestrol acetate / Estradiol ) and Evra ( Norelgestromin / Ethinylestradiol ), which have been authorised centrally through the EMA, all other combined contraceptives in the EU ( European Union ) have been authorised via national procedures. ( Xagena )

Source: European Medicines Agency, 2013