Depo Provera Fractures - Unexplained Fractures while on Depo Provera
September 12, 2006 11:50

We have been contacted by many women who have suffered fractures that could not be explained. The common thread — they were all taking Dep Provera.As a result, we have done a lot of research on this topic, searching the web for information to determine... (Read Article)

Many woen have been using the Depo-Provera shot for years. There are now side effects associated with this injection, inculding Loss of Height and Shrinking. Fractures. Loss in Bone Density. Women are now considering other methods of birth control.

The Food and Drug Administration today approved updated labeling for the Ortho Evra contraceptive patch to warn healthcare providers and patients that this product exposes women to higher levels of estrogen than most birth control pills. Ortho Evra was the first skin patch approved for birth control.

It is a weekly prescription patch that releases ethinyl estradiol (an estrogen hormone) and norelgestromin (a progestin hormone) through the skin into the blood stream. FDA advises women to talk to their doctor or healthcare provider about whether the patch is the right method of birth control for them.

Furthermore, women taking or considering using this product should work with their health care providers to balance the potential risks related to increased estrogen exposure against the risk of pregnancy if they do not follow the daily regimen associated with typical birth control pills. Because Ortho Evra is a patch that is changed once a week, it decreases the chance associated with typical birth control pills that a woman might miss one or more daily doses.

The addition of this new warning is a result of FDA's and the manufacturer's analysis directly comparing the levels for estrogen and progestin hormones in users of Ortho Evra with those in a typical birth control pill. In general, increased estrogen exposure may increase the risk of blood clots. However, it is not known whether women using Ortho Evra are at a greater risk of experiencing these serious adverse events.

The new bolded warning specifically states that women who use Ortho Evra are exposed to about 60 percent more total estrogen in their blood than if they were taking a typical birth control pill containing 35 micrograms of estrogen. However, the maximal blood level of estrogen (peak blood levels) is about 25% lower with Ortho Evra than with typical birth control pills. While the estrogen level with the patch remains constant for one week until the patch is removed, the peak blood levels with a daily birth control pill rapidly declines to levels that are lower than on the Orthro Evra.

FDA is continuing to monitor safety reports for the Ortho Evra patch. The manufacturer, Ortho McNeil Pharmaceuticals is conducting additional studies to compare the risk of developing serious blood clots in women using Ortho Evra to the risk in women using typical birth control pills that contain 35 micrograms of estrogen.

The new labeling information is available along with additional information for healthcare providers and consumers online at: www.fda.gov/cder/drug/infopage/orthoevra/default.htm.

FDA notified healthcare professionals and patients of revisions to the label for Ortho Evra, a skin patch approved for birth control, that includes a bolded warning about higher exposure to estrogen for women using the weekly patch compared to taking a daily birth control pill containing 35 micrograms of estrogen. A woman on Ortho Evra may be exposed to approximately 60% more estrogen than if she were taking a typical 35 microgram estrogen birth control pill. Estrogen use is linked to blood clots in the legs and lungs and other clotting problems such as strokes and heart attacks. It is not known if women using Ortho Evra have a higher risk of serious side effects than women taking the typical 35 microgram estrogen pills.

From Joan Claybrook & Frank Clemente
FOR IMMEDIATE RELEASE

Statement of Dr. Sidney Wolfe, Director of Public Citizen?s Health Research Group

Washington, DC--More than two months ago, we warned readers of our online Web site, www.WorstPills.org, and the 180,000 readers of our Worst Pills, Best Pills newsletter not to use the dangerous new birth control patch, Ortho Evra (Ortho-McNeil), because of the increased risk of life-threatening blood clots in people using this product. (For the full text of this warning, go to www.WorstPills.org.)

The new warning by the U.S. Food and Drug Administration (FDA) belatedly acknowledges the increased dangers of using the drug. These dangers were noted by the FDA physician who reviewed the drug before the agency approved it. Despite the fact that the agency has now admitted that ?women who use Ortho Evra are exposed to about 60 percent more estrogen than if they were taking a typical birth control pill - important because increased estrogen means increased risks - the agency still allowed the drug on the market and is stubbornly unwilling to ban it.

Contraceptives are prescribed to younger, mainly healthy women and should be associated with the lowest possible risk of serious adverse drug reactions. Blood clots in the lungs were seen in two women given Ortho Evra in clinical trials conducted before the drug was approved (in addition to an increasing number of similar cases in women after the drug was marketed), and there is no evidence that the patch is a more effective contraceptive compared to older, second-generation birth control pills.

The FDA medical officer who reviewed the drug before approval, in addition to differing with the company about the evidence for increased blood clots, also expressed concern that 211 of 3,088 women (6.8 percent) in pre-approval clinical trials gained 10 or more pounds. He also noted that the contraceptive effectiveness of Ortho Evra was reduced in women weighing more than 198 pounds.

There is no medical reason for women to use the more dangerous Ortho Evra rather than one of the older, better understood, and equally effective oral contraceptives.

###

Public Citizen is a national, nonprofit consumer advocacy organization based in Washington, D.C. For more information, please visit www.citizen.org.

What needs to be disclosed, and what has been disclosed by Pfizer are two different things.

While Pfizer now will admit that Depo Provera shots can be very dangerous especially with long term use, resulting in fractures and Osteoporosis, they won't show the test results that lead to that conclusion.

In 1992, there were to be studies done of the long term side effects with respect to bone density.

The FDA, on 10/29/1992, in Press Release P92-31, Depo Provera, said, "Recent data have also demonstrated that long-term use may contribute to osteoporosis. The manufacturer will conduct additional research to study this potential effect. "

Where is the "additional research"? It was conducted. Dr. Diane F. Merritt for Upjohn (Pfizer) according to her CV. Her CV states that she received RESEARCH SUPPORT as "Principal Investigator. Upjohn "Assessment of Bone Mineral Density in Women Receiving Depo-Provera Contraception Injection. (1995-2002)"

Again, there is no evidence of publication of Dr. Merritt's 7 years of research. However now Pfizer says, "Women who use Depo-Provera Contraceptive Injection may lose significant bone mineral density. Bone loss is greater with increasing duration of use and may not be completely reversible. It is unknown if use of Depo-Provera Contraceptive Injection during adolescence or early adulthood, a critical period of bone accretion, will reduce peak bone mass and increase the risk of osteoporotic fracture in later life."

And the package insert refers to a 7 year study that showed bone loss that was not reversible.

Pfizer says, "Since the U.S. approval of DEPO-PROVERA in 1992, the prescribing information has included a warning that use of the product may be considered among the risk factors for development of osteoporosis. Additional clinical research was initiated in the 1990s to clarify the effects of DEPO-PROVERA on bone mineral density in women aged 25 to 35 and in adolescents. The results of these studies were recently submitted to the FDA and are reflected in the revised labeling for DEPO-PROVERA."

But I wonder... why now? Why does the disclosure/label change come in November 2004? The following questions and research results from this inquiry:

• When was the drug going to become generic? 3 months after they changed the label. Does that mean that Pfizer waited until the market share was going to drop anyway before they warned? Or is this merely a coincidence?
  
• When was research to be done? Some of it was completed in 2002. Does that mean that the studies were never published, even though they were finished in 2002?
  
• How many studies sites were there It appears that there were 15 sites for one study. And there was more than one study being done. For example: March, 1998: Cromer BA (contractual, principal consultant): Evaluation of bone mineral density and total body calcium in adolescent DP150CI (Depo-Provera) users and matched controls. Pharmacia & Upjohn Co.; $409,500 over 5 years as site 1 and $460,000 for site 2 (of a total of 15 sites). See: http://www.metrohealthresearch.org/pdf/Cromer_cv.pdf
  
• How many doctors studied the BMD effects? We have already found at least 6 doctors who list having done these studies between starting on or after 1994 and finishing on or before 2005. Some were completed in 2002.
  
• How long did the studies last? Some lasted as long as 8+ years. Others 7 years. Others 5 years. There are many studies that were done to measure the long term effects of Depo Provera on BMD.
  
• How much was spent on studies of BMD?: There appears to be over $5,000,000 that went into these sorts of studies.
  

I am trying to contact any women who participated in a clinical trial or study of the side effects of Depo Provera. In particular, the studies I am interested in are:

Doctor Study Name Start End

Diane F. Merritt, M.D. "Assessment of Bone Mineral Density in Women Receiving Depo-Provera Contraception Injection." 1995 2002

Diane F. Merritt, M.D. Cyclo-Provera Contraceptive Injection: A Comparative Study of Safety, Patient Acceptability and Efficacy to Ortho-Novum 7/7/7, 28 Tablets 1997 1999

Melanie Ariane Gold, D.O. Evaluation of Bone Mineral Density and Total Body Calcium in Adolescent Depo-Provera Users and Matched Controls 1998 2005

Melanie Ariane Gold, D.O. Cyclo-Provera and Depo-Provera versus Ortho-Novum 7/7/7: a comparative study of the safety and acceptability in adolescents 1999

Barbara A. Cromer, M.D. Evaluation of bone mineral density and total body calcium in adolescent DP150CI (Depo-Provera) users and matched controls. 1998

Barbara A. Cromer, M.D. Depo-Provera and Bone Mineral Density in Adolescents. National Institutes of Health 1999 2004

Dilip R. Patel, MD Cyclo-Provera Contraceptive Injection and Depo-Provera Contraceptive Injection versus Ortho-Novum 7/7/7, 28 tablets : A comparative study of safety and patient acceptability in adolescents ( 18 years or less ) who desire contraception 1999 2000 (cut short!)

LAURA BARCHRACH, MD Depo-Provera: Evaluation of Bone Mineral Density and Total Body Calcium in Adolescent DP 150CI Users and Matched Controls 1998 2004

Simon Kipersztok, M.D. - USA Cyclo Provera Contraceptive Injection: An Open-Label Continuation Protocol for Patients Successfully Completing M/5415/004 or M/5415/0009

Simon Kipersztok, M.D. - USA A comparative study of safety, patient acceptability and efficacy to Ortho-Novum 7/7/7, 28 tablets 1997 1999

Simon Kipersztok, M.D. - USA Assessment of Bone Mineral Density (BMD) in Women Receiving Depo-Provera Contraceptive Injection 1994 2002

If you have information on the above research, please contact me at: Michael Monheit, Esquire

Melanie Ariane Gold, D.O. was managing a study under a research grant from Pharmacia & Upjohn/Pfizer totalling $1,087,783.

The research, she directed on site was called, "Evaluation of Bone Mineral Density and Total Body Calcium in Adolescent Depo-Provera Users and Matched Controls" and took place from 1998-2005.

Where are the results of this research?

It seems like Depo Provera is becoming one of those classic what did they know and when did they know it stories. And the more I dig, the more disheartened I am to find that the "new" label is revealing things that are not so "new."

Let's look at the history of the drug to see what might really be going on.

April 16, 2003
Pfizer Inc and Pharmacia Corporation began operating as a unified company on April 16, 2003, forging one of the world's fastest-growing and most valuable companies. With a research and development budget of $7.1 billion in 2003, the new Pfizer is now the world's leading research-based pharmaceutical company.

March 23, 2000
Pharmacia Corporation's corporate and pharmaceutical business headquarters will be in Peapack, N.J. The agricultural business headquarters will be in St. Louis and will retain the Monsanto name. (In April 2000, Pharmacia & Upjohn completed a merger with Monsanto and Searle creating Pharmacia, a dynamic new competitor in the pharmaceutical industry.)

On December 19, 1999, Monsanto Company and Pharmacia & Upjohn announced a definitive agreement to merge. The new company, to be called Pharmacia Corporation, will be a dynamic and powerful new competitor in the global pharmaceutical industry. The merger is expected to close the second quarter of 2000.

In 1998, Pharmacia & Upjohn relocated its global headquarters from the United Kingdom to the United States.

In 1995
Pharmacia & Upjohn: have Corporate headquarters:
Somerset County, NJ

The Upjohn Company [Depo Provera's maker]
Kalamazoo, MI


+


Pharmacia AB
Stockholm (Pharmacia)

Pre-1995
The Upjohn Company
1992 - FDA advisory panel recommends approval for Depo-Provera.
PIP: The fertility and maternal health drugs advisory committee of the US Food and Drug Administration recently voted to recommended approval of the use of Depo-Provera, manufactured by Upjohn Co. in Kalamazoo, MI. Depo-Provera is a hormonal contraceptive which contains depot-medroxyprogesterone acetate to be injected intramuscular every 3 months. Currently, it is approved by the FDA only for treatment of endometrial or renal cancer. Experts agree that Depo-Provera is an excellent drug and FDA approval is expected by the end of the year. The FDA denied Upjohn's application for approval of Depo-Provera for contraception in 1978, but since then studies have refuted the link between cancer and Depo-Provera. The committee also recommended post marketing studies to assess the problem. The FDA is also reviewing new data from New Zealand showing a possible increased risk of osteoporosis associated with longterm use of the drug. The FDA advisory committee recommended an informed consent document for women who would use Depo-Provera to advise about the risk of bone loss. The FDA is also reviewing new data from Thailand showing a link between low birth weight babies and Depo-Provera uses during pregnancy that could necessity a warning label to rule out pregnancy before administering Depo-Provera.

http://my.webmd.com/content/article/4/1680_50968.htmThere is another strike against Depo-Provera. A July 1991 study published in the British Medical Journal found that bone density significantly decreased in thirty women who had been using Depo-Provera for at least five years. If you are already at risk for osteoporosis due to your family history or due to the fact that you smoke or are underweight, or if you are of European or Asian origin, you should look for another contraceptive. In response, the FDA has asked Upjohn to continue research on the connection between Depo-Provera and osteoporosis. An Emory University study showed that Depo-Provera can cause menopausal symptoms in young women because it greatly decreases estrogen levels. This could be why osteoporosis is a risk; estrogen loss leads to bone thinning.

So when did they know this was dangerous? Long before November 2004.

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Information for women suffering from Osteoporosis due to use of Depo Provera