Combined hormonal contraceptives and venous thromboembolism: review confirms risk is small
- Medicines and Healthcare products Regulatory Agency
- 12 February 2014
- Therapeutic area:
- Obstetrics, gynaecology and fertility
A review of the latest evidence on the risk of thromboembolism advises to consider risk factors and remain vigilant for signs and symptoms. - the risk of blood clots with all low-dose CHCs is small - there is good evidence that the risk of venous thromboembolism (VTE) may vary between products, depending on the progestogen - CHCs that contain levonorgestrel, norethisterone, or norgestimate have the lowest risk of VTE - the benefits of any CHC far outweigh the risk of serious side effects - prescribers and women should be aware of the major risk factors for thromboembolism, and of the key signs and symptoms
Article date: February 2014
Risk of VTE
In January we sent a letter through the Central Alerting System to inform prescribers of the outcome of a European review of the latest evidence on the risk of thromboembolism with CHCs. The review confirmed our previous understanding that the level of risk of VTE with all low-dose CHCs (ethinylestradiol <50 micrograms) remains small and products with the lowest risk of VTE are those containing the progestogens levonorgestrel, norethisterone, and norgestimate. Progestogen-specific estimates of VTE incidence are provided in the table.
Table: Risk of VTE with CHCs
|Progestogen in CHC (combined with ethinylestradiol, unless stated)||Relative risk vs levonorgestrel||Estimated incidence (per 10 000 women per year of use)|
|Gestodene; desogestrel; drospirenone||1.5–2.0||9–12|
|Dienogest (combined with ethinylestradiol or estradiol)/ nomegestrel acetate (estradiol)||To be confirmed*||To be confirmed*|
*Further studies ongoing or planned to collect sufficient data to estimate risk for these products.
We have also taken this opportunity to update baseline VTE rates to reflect current evidence. Compared with previous rates, the increased values are likely to be due to improvements in VTE diagnosis and reporting, and due to an increase in obesity over time. The new rates will be included in updated product information (Summary of Product Characteristics and Patient Information Leaflet)
Our recent letter includes the following tools to help prescribers and women jointly make informed choices:
A prescribing checklist that may be used during a CHC consultation has also been made available (annex 2 of the letter). The checklist:
- specifies the conditions that contraindicate the use of a CHC
- lists the factors that increase a woman’s risk (such as older age, obesity, prolonged immobilisation, surgery, personal history of thromboembolism, smoking etc)
- reminds prescribers that the presence of more than one risk factor may constitute a contraindication
Information for women
A user card and information sheet have also been made available for women. One describes the signs and symptoms of deep vein thrombosis, pulmonary embolism, stroke, and heart attack and states when the risk of a thromboembolism may be particularly high (annex 3 of the letter). The other provides more detailed information on the risk of thromboembolism with CHCs in the form of questions and answers (annex 4 of the letter). You may wish to provide this information to women during their consultation.
Updated product information
The Summary of Product Characteristics for prescribers and the Patient Information Leaflet for women will be updated to reflect current understanding of the available evidence and to make information on the risk of thromboembolism as clear as possible.
Advice for healthcare professionals:
- There is no need for any woman to change her CHC on the basis of this review and the updated information
- Consider using the prescribing checklist to help CHC consultations
- Carefully consider: any contraindications for use; the difference in risk of VTE between products; and a woman’s current risk factors when prescribing a CHC
- Reassess a woman’s risk factors at routine appointments
- Discuss the risk of VTE with each woman, and raise awareness of the signs and symptoms of thromboembolism when prescribing a CHC; consider providing her with the further information mentioned above
- Always consider the possibility of a CHC-associated thromboembolism when presented with a woman who has relevant symptoms
- Ask all women with signs and symptoms of thromboembolism if they are “taking any medicines or if they are using a combined hormonal contraceptive”
Advice to give to women:
- Remind women to read the Patient Information Leaflet that accompanies each pack of CHCs and if you consider it helpful, recommend that they read the information provided in user card and information sheet
- Remind women to mention that they are using a CHC if asked whether they are taking any medicines
Prescribers should also be aware of current product information and clinical guidance (Medical Eligibility Criteria (MEC) and Faculty of Sexual Healthcare) when discussing the most suitable type of contraceptive for any woman.
Article citation: Drug Safety Update volume 7 issue 7, February 2014: A2.
Published: 12 February 2014
Therapeutic area: Obstetrics, gynaecology and fertility