Friday, December 9, 2011

Gynecologists Unfazed as Birth Control Clot Concerns Resurface at FDA

Share this history on :
By Elizabeth Lopatto and Robert Langreth - Dec 9, 2011 6:33 AM GMT+0700

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. (TEVA) 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 (WCRX)’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. (WPI)’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 (JNJ)’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.

To contact the reporter on this story: Elizabeth Lopatto in New York at Robert Langreth in New York at

To contact the editor responsible for this story: Reg Gale at

No comments: