Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel

Birth control pill (Photo credit: Wikipedia)

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Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database

BMJ 2011; 342 doi: http://dx.doi.org/10.1136/bmj.d2139 (Published 21 April 2011)

Cite this as: BMJ 2011;342:d2139

Objective To examine the risk of non-fatal idiopathic venous thromboembolism in current users of a combined oral contraceptive containing drospirenone, relative to current users of preparations containing levonorgestrel.

Design Nested case-control study.

Setting UK General Practice Research Database.

Participants Women aged 15-44 years without major risk factors for venous thromboembolism who started a new episode of use of an oral contraceptive containing 30 µg oestrogen in combination with either drospirenone or levonorgestrel between May 2002 and September 2009. Cases were women with a first diagnosis of venous thromboembolism; up to four controls, matched by age, duration of recorded information, and general practice, were randomly selected for each case.

Main outcome measures Odds ratios and 95% confidence intervals estimated with conditional logistic regression; age adjusted incidence rate ratio estimated with Poisson regression.

Results 61 cases of idiopathic venous thromboembolism and 215 matched controls were identified. In the case-control analysis, current use of the drospirenone contraceptive was associated with a threefold higher risk of non-fatal idiopathic venous thromboembolism compared with levonorgestrel use; the odds ratio adjusted for body mass index was 3.3 (95% confidence interval 1.4 to 7.6). Subanalyses suggested that referral, diagnostic, first time user, duration of use, and switching biases were unlikely explanations for this finding. The crude incidence rate was 23.0 (95% confidence interval 13.4 to 36.9) per 100 000 woman years in current users of drospirenone and 9.1 (6.6 to 12.2) per 100 000 woman years in current users of levonorgestrel oral contraceptives. The age adjusted incidence rate ratio was 2.7 (1.5 to 4.7).

Conclusions These findings contribute to emerging evidence that the combined oral contraceptive containing drospirenone carries a higher risk of venous thromboembolism than do formulations containing levonorgestrel.

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Drosperinone

English: Logo of the . (Photo credit: Wikipedia)

Birth Control Pills Containing Drospirenone: Label Change-Products may be associated with a higher risk for blood clots

AUDIENCE: OBGYN, Family Practice, Patient

ISSUE: FDA has completed its review of recent observational (epidemiologic) studies regarding the risk of blood clots in women taking drospirenone-containing birth control pills.Based on this review, FDA has concluded that drospirenone-containing birth control pills may be associated with a higher risk for blood clots than other progestin-containing pills.

BACKGROUND:  Drospirenone is a synthetic version of the female hormone, progesterone, also referred to as a progestin. FDA is adding information about the studies to the labels of drospirenone-containing birth control pills.

The revised drug labels will report that some epidemiologic studies reported as high as a three-fold increase in the risk of blood clots for drospirenone-containing products when compared to products containing levonorgestrel or some other progestins, whereas other epidemiological studies found no additional risk of blood clots with drospirenone-containing products.  The labels also will include a summary of the previously released results of an FDA-funded study of the blood clot risk.

RECOMMENDATION: Women should talk to their healthcare professional about their risk for blood clots before deciding which birth control method to use.

Healthcare professionals should consider the risks and benefits of drospirenone-containing birth control pills and a woman’s risk for developing a blood clot before prescribing these drugs.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.fda.gov/MedWatch/report.htm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[04/10/2012 - Drug Safety Communication - FDA]

Previous MedWatch Alert:

[10-27-2011]

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FDA Panel, Bayer Birth Control Pills & Blood Clots

By Ed Silverman in Pharmalot

Nearly six months after a pair of studies found that women taking birth control pills containing a hormone called drospirenone are more likely to develop blood clots than those who take an older oral contraceptive, the FDA has decided to hold an advisory panel meeting in December to review the risks and benefits.

Meanwhile, the agency is continuing to review a separate agency-funded study that evaluated the risk of blood clots in users of several different hormonal birth control products (contraceptives). Preliminary results suggest an approximately 1.5-fold increase in the risk of blood clots for women who use drospirenone-containing birth control pills compared to users of other hormonal contraceptives.

And so, the agency will convene the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee to examine the risk of blood clots of drospirenone-containing birth control pills. The most widely known oral contraceptives containing this hormone are the Yaz and Yasmin pills sold by Bayer.

The scrutiny is not good news for Bayer. Nearly 7,000 lawsuits are pending in the US over alleged injuries and deaths relating to Yaz and Yasmin, as well as generics. The lawsuits allege Yaz and Yasmin have risks beyond those of traditional birth control pills and Bayer too aggressively promoted the pills without disclosing higher risks. Bayer was warned by the FDA in 2008 that TV ads were misleading and did not disclose added risks (see here) and recently was chastised in the UK for running a Yasmin ad that boasted the pill could prove beneficial on the same problems it may cause (read this).

As to the data, the FDA says it reviewed six published epidemiologic studies that evaluated the risk of blood clots in women using birth control pills containing drospirenone, but generated conflicting findings. Two were postmarketing studies required by the FDA or European regulators, and did not report any difference in clot risk between the pills and products containing levonorgestrel or other progestins. But two studies in 2009 reported a 1.5- to 2-fold higher risk in women who use pills containing drospirenone as opposed to contraceptives containing levonorgestrel.

More recently, two articles published in 2011 in the British Medical Journal reported a 2- to 3-fold greater risk of clots in women using oral contraceptives containing drospirenone rather than levonorgestrel. However, the FDA notes these were epidemiological studies and, so far, has not reached a conclusion on the risk for blood clots, but remains concerned about a potential increased risk (here is the FDA statement).