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FDA: Birth Control Pills Containing Drospirenone:
Possible Increased Risk of Blood Clots
 
 
  "danger of potential blood clots.......recent research has suggested that drospirenone may somewhat increase the risk of blood clots.......The agency's analysis suggests the real chance of a woman having a clot remains small, Barbieri said. a study of 1.3 million Danish women published in October in the journal BMJ found that women taking Yaz or Yasmin had double the risk of blood clots, compared with women taking the older contraceptives........According to the report, 10 in 10,000 women on the new drugs experience a clot compared with about 7 in 10,000 on the older pills. To prevent just one clot, 2,000 women would have to switch from Yasmin, Yaz or their generic versions, Barbieri said.......Studies have shown conflicting evidence about whether women who take the pills have a higher risk of blood clots than if they take older birth control pills that don't contain drospirenone......women's health advocates such as Cynthia Pearson, executive director of the National Women's Health Network in Washington, who said pills such as Yasmin should be taken of the market because there are safer options available....."

FDA: Birth Control Pills Containing Drospirenone: Possible Increased Risk of Blood Clots

[10/27/2011 - Report: Combined Hormonal Contraceptives (CHCs) and the Risk of Cardiovascular Disease Endpoints -

FDA] [09/26/2011 - Drug Safety Communication- FDA]

[UPDATED 10-27-2011] FDA notified healthcare professionals of release of the final report of the FDA-funded study that evaluated the risk of blood clots in users of several different hormonal contraceptives. The link is provided below. FDA's review of the results of this study, specifically those results related to drospirenone-containing birth control pills, will be presented and discussed at the joint meeting of the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee on December 8, 2011.

[UPDATED 09/26/2011] FDA has not yet reached a conclusion, but remains concerned, about the potential increased risk of blood clots with the use of drospirenone-containing birth control pills. FDA has completed its review of the two 2011 studies that evaluated the risk of blood clots for women who use drospirenone-containing birth control pills. FDA is continuing its review of a separate FDA-funded study that evaluated the risk of blood clots in users of several different hormonal birth control products (contraceptives). Preliminary results of the FDA-funded study 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.

Given the conflicting nature of the findings from six published studies evaluating this risk, as well as the preliminary data from the FDA-funded study FDA has scheduled a joint meeting of the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee on December 8, 2011 to discuss the risks and benefits and specifically the risk of blood clots of drospirenone-containing birth control pills.

[Posted 05/31/2011]

AUDIENCE: OBGYN, Family Practice, Patient

ISSUE: FDA is aware of two newly published studies that evaluated the risk of venous thromboembolism (VTE) in women who use birth control pills that contain drospirenone. The two recently published studies looked at whether there is a higher risk of blood clots in women taking birth control pills containing the progestin drospirenone when compared to similar women taking birth control pills containing a different progestin called levonorgestrel. These two new studies reported that there is a greater risk of VTE associated with birth control pills that contain drospirenone. This risk is reported to be up to 2 to 3 times greater than the risk of VTE associated with using levonorgestrel-containing pills. Other studies have not reported an increase in risk. The FDA is currently evaluating the conflicting results from these studies and will look at all currently available information to fully assess the risks and benefits of drospirenone-containing birth control pills. FDA will continue to communicate any new safety information to the public as it becomes available. Read the drug safety communication for more information on these studies.

BACKGROUND: Drospirenone is a type of female sex hormone called a progestin. Most birth control pills contain two types of hormones--estrogen and progestin. Birth control pills work by preventing the release of eggs from the ovaries (ovulation) and changing the cervical mucus and the lining of the uterus to prevent pregnancy. Brand names of drospirenone-containing products include Yaz (generics Gianvi and Loryna), Yasmin (generics Ocella, Syeda, and Zarah), Beyaz, and Safyral.

RECOMMENDATION: If your birth control pill contains drospirenone, do not stop taking it without first talking to your healthcare professional. Contact your healthcare professional immediately if you develop any symptoms of blood clots, including persistent leg pain, severe chest pain, or sudden shortness of breath. If you smoke and are over 35 years of age, you should not take combination oral contraceptives because they increase the risk that you could experience serious cardiovascular events, including blood clots.

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

[10/27/2011 - Report: Combined Hormonal Contraceptives (CHCs) and the Risk of Cardiovascular Disease Endpoints - FDA]

[09/26/2011 - Drug Safety Communication- FDA]

[09/26/2011 - Questions and Answers -FDA]

[05/31/2011 - Drug Safety Communication - FDA]

[05/31/2011 - Questions and Answers - FDA]

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More Detail on Risk Urged for a Contraceptive Label

NY Times By PAM BELLUCK

Published: December 8, 2011

Labels on the popular birth control pills Yaz and Yasmin should be strengthened to include more information about the possibility that the pills could lead to greater risk of blood clots in women, an advisory committee to the Food and Drug Administration said on Thursday.

The panel, which voted 21 to 5 in favor of changing the labels, stopped short of recommending that they warn that the drugs are more likely than other contraceptive pills to cause blood clots. Instead, the experts suggested that the labels note that the evidence about blood clots is conflicting.

Currently, the labels suggest that these contraceptives have blood clot risks similar to those of other birth control pills that combine estrogens and progestins.

Morgan Liscinsky, an F.D.A. spokeswoman, said the panel "definitely felt that stronger labels were needed, that the labels need to be updated to reflect current data and acknowledge that it is conflicting."

The advisory committee also concluded, by a closer vote of 15 to 11, that the benefits of the pills still outweigh their risks. The F.D.A. does not have to follow the panel's recommendations, but the agency has indicated concern in recent months as some studies, including its own, have shown an elevated risk.

The question of whether these contraceptives, which use a newer synthetic form of progestin called drospirenone, can make women more prone to blood clots has been a subject of debate. Studies have shown differing results. Bayer, the German company that makes the drugs, has said that they pose no greater threat than other contraceptive pills, all of which somewhat elevate the risk of stroke and blood clots in the legs and lungs.

The company has said that studies that show otherwise contain methodological flaws that undercut the strength of their results.

But other recent research has suggested that drospirenone may somewhat increase the risk of blood clots. An F.D.A. analysis reported that about 10 in 10,000 women taking pills with drospirenone will experience a blood clot or venous thromboembolism in a year, compared with 6 in 10,000 women using other hormonal contraceptives.

And a study of 1.3 million Danish women published in October in the journal BMJ found that women taking Yaz or Yasmin had double the risk of blood clots, compared with women taking the older contraceptives.

Before Thursday's meeting, an F.D.A. briefing document acknowledged that studies had yielded conflicting results and said new studies were needed. But the scientists recommended that labels on the pills should be changed to inform the public of possible risks.

Although the agency could not determine whether the increased risk resulted from use of the drugs or some other cause, "we believe that, because of the consistency in recent reports for an increased risk, product labeling should reflect that very real possibility," the scientists wrote.

More than 10,000 lawsuits have been filed against Bayer claiming that women have been harmed by taking Yaz or Yasmin, including accusations of about 100 deaths linked to the contraceptives.

In documents released recently in those lawsuits, David Kessler, a former F.D.A. commissioner working as an expert witness for the plaintiffs, said that Bayer researchers found increased reports of blood clots in women using Yasmin in the United States, compared with those using three other pills, but did not provide that information to the F.D.A. in a 2004 safety review.

"Bayer presented a selective view of the data, and that presentation obscured the potential risks associated with Yasmin," Dr. Kessler testified. He also said the company promoted the pill for alleviating premenstrual syndrome, when it was not approved for that use.

Dr. Pamela A. Cyrus, a vice president for Bayer HealthCare Pharmaceuticals, said on Thursday that Bayer had consistently worked with the F.D.A. and other regulatory authorities around the world as new data have become available, had worked with the agencies to make label updates as appropriate and "will continue to do so."

Bayer said it would not comment on Dr. Kessler's testimony because it is part of continuing litigation.

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Bayer's Yaz Pill Backed by Panel Seeking Clarity on Risk

December 09, 2011, 3:36 AM EST

Dec. 9 (Bloomberg) -- Bayer AG's Yaz and its class of birth control pills containing the hormone drospirenone were backed in a close vote of U.S. advisers seeking clearer guidance for women about the danger of potential blood clots.

Studies have shown conflicting evidence about whether women who take the pills have a higher risk of blood clots than if they take older birth control pills that don't contain drospirenone. Those ambiguous results prompted the U.S. Food and Drug Administration to request yesterday's review.

The reproductive and drug safety advisory panels voted 15-11 that the benefits of the class of oral contraceptives including Yaz outweigh the risks. The advisers also voted 21-5 that information labels for the pills be changed to better reflect the potential for blood clots. The FDA isn't required to follow the panels' advice.

"All of these studies have significant strengths and weaknesses," said Julia Johnson, acting chairwoman of the panel and chair of the University of Massachusetts Medical School Department of Obstetrics and Gynecology.

Panel members were concerned the results may have been affected by factors that weren't studied such as women's body mass index, smoking habits, family history and ethnicity, Johnson said.

Difficult to Assess

"I think this makes it very difficult for us to determine any magnitude of increased risk, if there is any increased risk," said Paula Hillard, a panel member and chief of the Division of Gynecologic Specialties at Stanford University School of Medicine near Palo Alto, California.

While the birth-control pill's label now informs women of the conflicting studies, the language is confusing, said Elaine Morrato, an assistant professor in the University of Colorado, Denver, Department of Pediatrics. The results are mentioned in a complex paragraph and need to be more easily understood, possibly by using graphics, she said.

Bayer's Yaz and Yasmin brought in $1.5 billion in sales for the Leverkusen, Germany-based drugmaker last year as its second best-selling product, less than the $1.8 billion in 2009. Teva Pharmaceutical Industries Ltd., based in Petach Tikva, Israel, introduced a generic version of Yaz in May 2010. Bayer's stock dropped 0.7 percent to 46.13 euros at 9:10 a.m. in Frankfurt.

Women taking drospirenone were 74 percent more likely to experience clots than those on older hormonal contraceptives, the FDA found in a study published in October. Drospirenone is similar to the natural female hormone progesterone. Bayer conducted studies that found no increased risk.

Agency Report

The FDA pushed for more studies on birth control containing drospirenone after an agency staff report concluded on Dec. 6 that the health risks are unclear. A half-dozen studies in all have addressed clotting danger from the products.

The FDA has taken a similar position on Johnson & Johnson's Ortho Evra birth control patch, which studies have linked to increased chance of clotting.

The same panels evaluating Yaz will consider today how to best interpret studies on the J&J patch and vote on whether Ortho Evra's benefits outweigh the risks and whether its label accurately reflects potential hazards.

J&J, based in New Brunswick, New Jersey, doesn't release specific revenue numbers for the patch.

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Gynecologists Unfazed by Birth Control Clot Concerns

December 09, 2011, 4:08 AM EST

Dec. 8 (Bloomberg) -- Undeterred by evidence that newer birth control pills such as Bayer AG's Yasmin may carry more risk of dangerous blood clots, top doctors say they still plan to prescribe them.

Yasmin, introduced in 2001, and other contraceptives containing the hormone drospirenone have been the focus of lawsuits and studies that differ in conclusions about the risk. Advisers to the Food and Drug Administration meeting today to review the science, voted that the drugs' prescribing label be changed to better reflect the danger of getting a blood clot. The panel also said the pills' benefits outweigh the risks.

Many clinicians aren't convinced the newer pills pose more risk. Bloomberg News surveyed nine doctors at prominent medical centers and clinics and all said the evidence isn't conclusive or worrisome enough to stop using the pills.

So far, the clotting danger "is so rare it's clinically not that important," said Robert Barbieri, a professor of obstetrics, gynecology and reproductive biology at Harvard Medical School in Boston. Patients worry about the increase in risk as a result of news reports, he said; when he explains the numbers, they relax.

"A lot of people come in and say, 'I love this pill and would prefer not to come off it,'" Barbieri said by telephone. "They understand it's a slight risk but not a huge one."

Blood clots are a known side effect of all birth control pills since they hit the market 50 years ago. The newest generation may raise the risk, the FDA said in a study released October 27. That report and others, though, may not be conclusive, the FDA has said.

10 in 10,000

The agency's analysis suggests the real chance of a woman having a clot remains small, Barbieri said. According to the report, 10 in 10,000 women on the new drugs experience a clot compared with about 7 in 10,000 on the older pills. To prevent just one clot, 2,000 women would have to switch from Yasmin, Yaz or their generic versions, Barbieri said.

The FDA study didn't figure in the effects of other risk factors, including body weight and smoking, several doctors said.

A Dutch study published in 2009 found that birth control pills containing drospirenone was associated with a 6.3-fold higher risk of blood clots compared with a 3.6-fold jump linked to an older contraceptive. Two studies published this year also found an increased risk.

Those reports, though, contradict research funded by Leverkusen, Germany-based Bayer, which found no added risk from its products, the company has said.

$1.5 Billion in Sales

Bayer's Yaz and Yasmin generated $1.5 billion in sales for the drugmaker last year as its second-best selling product, less than the $1.8 billion it had in 2009. Teva Pharmaceutical Industries Ltd. introduced a generic version of Yaz in May 2010.

Yaz, approved for sale in the U.S. in 2006, has a lower dose of estradiol than Yasmin, cleared in 2001, and the pills are taken on a different schedule. They are among a group of pills introduced since 2001 that combine drospirenone, a synthetic version of the female hormone progesterone, with estradiol, a form of the hormone estrogen.

As the conflict over the worth of the research data plays out in the U.S., Bayer faces more than 10,000 lawsuits over injuries allegedly caused by the pills. Lawyers cite FDA reports on at least 50 deaths of those on the drugs from 2004 to 2008.

The first trials are scheduled for next month in federal court in Illinois and state court in Philadelphia.

Legal Costs

The financial impact from legal costs outweighs the potential loss of sales because most revenue from the Bayer products comes from outside the U.S., where the controversy has generated the most attention, said Peter Spengler, an analyst with DZ Bank AG Deutsche Zentral in Frankfurt.

"The legal costs and potential payments to patients or family members are much more severe or higher than the potential loss of sales in the U.S.," he said in a telephone interview. Of a projected 1.06 billion euros ($1.42 billion) in 2011 worldwide sales of Yaz and Yasmin, only 160 million euros of it come from the U.S., Spengler said.

The most widely used pill containing estrogen and a progestin is Dublin-based Warner Chilcott's Loestrin, according to data supplied by IMS Health Inc., a Norwalk, Connecticut- based industry research company. Loestrin, had 9.9 percent of that market share followed by Watson Pharmaceuticals Inc.'s Trinessa with 6.7 percent and Yaz with 6.5 percent.

Yaz and Yasmin copies from Israel-based Teva Pharmaceutical Industries Ltd. make up 6.2 and 3.7 of the market.

FDA advisers will assess risks and benefits of Johnson & Johnson's birth-control patch Ortho Evra on Dec. 9. An FDA staff report released this week also said that more research is needed to determine whether the product is linked to an increased risk of blood clots.

Patient Preferences

Doctors said some women prefer the new drugs over older pills because they help control acne and reduce premenstrual dysphoric disorder, a condition linked with emotional and physical disturbances. Some patients also find older contraceptives may cause weight gains and mood swings, said Sarah Pentlicky, a family planning fellow at the University of Pennsylvania in Philadelphia.

Changing the dose of hormones by switching to new- generation pills such as Yaz or Yasmin can help, she said.

Mixed results released over the last several years have made a lot of women confused, said Steven R. Goldstein, professor of obstetrics and gynecology at the New York University School of Medicine.

"Because of all the publicity, without reading the fine print, women who have been on this for two or three years successfully are now scared to death," Goldstein said in a telephone interview.

Discussing Risk

Goldstein now brings up the subject with women on the pills, explaining that all birth control pills carry some risk, and if the new ones do have an increased risk, it is a small increase, he said.

"People who have been on this successfully need not come off," he said. "We should not rush to any kind of judgment."

On the other side of the debate are women's health advocates such as Cynthia Pearson, executive director of the National Women's Health Network in Washington, who said pills such as Yasmin should be taken of the market because there are safer options available.

Birth control pills have generally gotten safer over the decades -- until now, she said.

"The drospirenone-containing group of pills are a step in the wrong direction," Pearson said in a telephone interview. "It is increasing the risk for no extra benefit."

Inconclusive Data

Michelle Fox, assistant professor of obstetrics and gynecology at Johns Hopkins University in Baltimore, said the picture isn't so clear. She advises women on the possibility of higher risk, and continues to prescribe the drugs, she said.

"The data's inconclusive," Fox said. "It shows a slight but persistent increase. There are a lot of problems with the literature."

Pregnancy also increases the risk of a blood clot, by about 10 times that of a birth control pill, she said.

The inconclusiveness of the data "is a topic that FDA will be discussing in detail with epidemiologists and clinical experts on the advisory committee," FDA spokeswoman Morgan Liscinsky said in an e-mailed statement.

Given the public's confusion, the questions the FDA is asking are "pretty logical," said Harvard's Barbieri.

Vanessa Cullins, vice president for external medical affairs at Planned Parenthood Federation of America, said that all of the contraceptives should remain available so women can make their own choices.

"The important issue is making sure providers and women are aware of the increase in risk and are able to use this to make an informed decision," Cullins said in a telephone interview.

 
 
 
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