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Observational studies find increased VTE risk with Yasmin
Drug interactions with hormonal contraception — key changes to advice
Observational studies find increased VTE risk with Yasmin
Two observational studies (UK study1 and US study2) found a two to three-fold increased relative risk of venous thromboembolism (VTE) associated with the use of combined oral contraceptives (COCs) containing drospirenone (e.g. Yasmin), compared with COCs containing levonorgestrel. In these studies, the incidence of VTE was about 20 to 30 cases per 100,000 women-years of use with COCs containing drospirenone and about 10 cases per 100,000 women-years of use with COCs containing levonorgestrel. However, this risk of VTE with COCs is less than that associated with pregnancy (about 60 cases per 100,000 pregnancies).3
Action
Health professionals should review their prescribing of oral contraceptives to ensure it reflects updated MHRA advice.3 The VTE risk with COCs containing drospirenone (e.g. Yasmin) is higher than with second generation COCs containing levonorgestrel, and may be similar to that of third generation COCs containing desogestrel or gestodene. Although patient choice is an important factor in selecting a suitable contraceptive, a COC containing levonorgestrel is a sensible choice for a woman who decides to start, or switch contraception, because of levonorgestrel’s well known safety profile. However, there is no reason for women to stop taking COCs containing drospirenone, or indeed any other COC, on the basis of these findings.
What is the background to this?
In April 2010, the MHRA advised prescribers4 that the VTE risk associated with Yasmin may be slightly higher than previously estimated. Two further observational studies looking at the VTE risk associated with COCs containing drospirenone compared with COCs containing levonorgestrel have now been published.1, 2
What do the studies claim?
In the UK study,1 current use of a COC containing drospirenone was associated with a three-fold higher risk of VTE compared with current use of a COC containing levonorgestrel; odds ratio (OR) adjusted for body mass index 3.3 (95% confidence interval [CI] 1.4 to 7.6). The crude incidence rate for VTE was 23.0 (95%CI 13.4 to 36.9) per 100,000 woman-years among current users of a COC containing drospirenone and 9.1 (95%CI 6.6 to 12.2) per 100,000 woman-years among current users of a COC containing levonorgestrel, giving an age adjusted incidence rate ratio of 2.7 (95%CI 1.5 to 4.7).
In the US study,2 current use of a COC containing drospirenone was associated with a two-fold higher risk of VTE compared with current use of a COC containing levonorgestrel; unadjusted OR 2.3 (95%CI 1.6 to 3.2). Incidence rates for VTE were 30.8 (95%CI 25.6 to 36.8) per 100,000 woman-years among users of a COC containing drospirenone and 12.5 (95% CI 9.61 to 15.9) per 100,000 woman-years among users of a COC containing levonorgestrel, giving an age adjusted incidence rate ratio of 2.8 (95%CI 2.1 to 3.8).
So what?
In light of these new observational data,1, 2 the MHRA has updated its previous advice.3 They advise that COCs containing levonorgestrel have the lowest thrombotic risk and are the safest COC for a woman who wants to start or switch contraception. However, there is no reason for women to stop taking COCs containing drospirenone or any other COC on the basis of these findings.3
There is no conclusive evidence that Yasmin is clinically superior to other COCs with regard to non-contraceptive effects (e.g. fluid retention, weight gain, skin condition or premenstrual symptoms).5 Yasmin is relatively expensive compared with other COCs, at £63.70 for one year’s supply, compared with £6.46 to £27.95 for other COCs (excluding Qlaira▼).6 In the quarter to December 2010, approximately 17% of all standard strength COC prescription items dispensed were for Yasmin. This represented about 45% of the total cost of standard strength COCs — about £18m of the £40m annual spend in England (see Figure 1). Click here for a larger image.
| Figure 1. Trends in spending on standard strength COCs in general practice in England |
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© NHS Business Services Authority 2011
See MeReC Rapid Review No. 3549 for further study details. More information can be found in the NPC e-learning materials on contraception.
- Parkin L, et al. BMJ 2011;340:d2139
- Jick SS, Hernandez RK. BMJ 2011;340:d2151
- MHRA. Drug Safety Update. June 2011;4(11):A2
- MHRA. Drug Safety Update. April 2010;3(9):2–3
- NPC. Contraception — current issues. MeReC Bulletin 2006;17(2)
- Regional Drug and Therapeutics Centre (Newcastle). Cost comparison charts April 2011
Drug interactions with hormonal contraception — key changes to advice
New guidance from the Faculty of Sexual and Reproductive Healthcare on drug interactions with hormonal contraception advises that women taking COCs no longer require additional contraceptive precautions during or after a course of antibacterials for three weeks or less, with the exception of rifabutin and rifampicin.1
Action
Health professionals involved in prescribing or issuing COCs should familiarise themselves with the key messages of this guidance. Overall, the available evidence does not generally support the possibility that non-enzyme-inducing antibacterials reduce COC efficacy. In line with WHO and US guidance, additional contraceptive precautions are now recommended only when prescribing:
- rifampicin and rifabutin (as these induce liver enzymes)
- other antibacterials if diarrhoea and vomiting occur, either as a result of the antibacterial, or the illness itself.
Patient information leaflets (and Summaries of Product Characteristics, SPCs) may not have been updated to reflect the new guidance, so this should be explained clearly to patients when prescribing or dispensing COCs, or when prescribing an antibacterial for a patient who is using a COC. A summary of some of the important changes to this guidance is given below.
Interaction between antibacterials and COCs
Additional precautions are no longer required to maintain contraceptive efficacy when using antibacterials that are not enzyme inducers with COCs for durations of three weeks or less, unless diarrhoea and vomiting occur. However, it is still accepted that additional contraceptive precautions should be advised with enzyme inducers. Rifampicin-like drugs (e.g. rifampicin, rifabutin) are the only antibiotics that are enzyme inducers and that have consistently been shown to reduce serum levels of ethinylestradiol.
Other enzyme-inducing drugs
All women starting enzyme-inducing drugs should be advised to use a reliable contraceptive method unaffected by enzyme inducers (e.g. progestogen-only injectable, copper-bearing intrauterine device or levonorgestrel-releasing intrauterine system).
Coumarin anticoagulants (e.g. warfarin)
Use of oestrogens and/or progestogens has been associated with both increased and decreased anticoagulant effect of coumarin anticoagulants. Given the lack of consistent evidence a true interaction is unlikely.
Lamotrigine▼
New evidence suggests that COCs should not usually be recommended in women on lamotrigine monotherapy due to the risk of reduced seizure control while taking a COC and the potential lamotrigine toxicity in the COC-free week. The clinical significance of this interaction is unknown and further evidence would be required to alter existing recommendations.
Ulipristal acetate▼
There is a theoretical reduction in the efficacy of progestogen-containing contraceptives with this emergency contraceptive. Additional precautions are required.
For more information on the recommendations see MeReC Rapid Review No. 2586.
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