Drug Injury Watch

Bayer Affirms Safety Of YAZ / Yasmin And Refutes 2011 BMJ Articles About Risk Of Blood Clots

Just As It Did In 2010 Label Change, Bayer Contends New Medical Studies Are Less Reliable Than Other VTE Evidence

(Posted by Tom Lamb at DrugInjuryWatch.com)

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UPDATE:  New research suggests that women who use oral contraceptives (OCs) containing drospirenone (DRSP) have an increased risk of venous thromboembolism (VTE) compared with users of birth control pills containing levonorgestrel . These findings are from a Danish study published by the British medical journl BMJ online October 25, 2011:

Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-2009. Lidegaard Ø, Nielsen LH, Skovlund CW, et al. BMJ 2011; DOI: 10.1136/bmj.d6423. Full text available for FREE at BMJ web site.

(10/30/11)

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UPDATE:  FDA Drug Safety Communication: Safety Review of possible increased risk of blood clots with birth control pills containing drospirenone  [May 31, 2011]

... The European Medicines Agency (EMA) announced on May 27, 2011, that it is updating the product information on oral contraceptives containing drospirenone and ethinyl estradiol regarding the risk of venous thromboembolism after review of all available data, including the same newly published data FDA is reviewing.

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.

(6/2/11) 

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Women who use Bayer's YAZ and Yasmin birth control pills -- or other oral contraceptives containing the progesterone, or progestin, drospirenone (DRSP), e.g., Ocella, Gianvi, Zarah, Beyaz, and Safyral -- face a two-times to three-times higher risk for venous thromboembolism (VTE), or blood clots, than women using birth control products containing levonorgestrel, according to two case-control analyses published by The British Medical Journal (commonly called "BMJ") in April 2011.

As for Bayer's response to these two new BMJ articles about the safety of YAZ and Yasmin, it was more or less the same as the press release it issued back in April 2010 when Bayer refuted the reliability of two earlier BMJ articles which asserted that women using birth control pills with drospirenone, like YAZ and Yasmin, were at an increased risk of developing blood clot-related side effects such as pulmonary embolism (PE) or deep vein thrombosis (DVT).

The two BMJ articles in published in 2011 about DRSP birth control pills like YAZ and Yasmin are:

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

"Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data".

The earlier 2009 BMJ articles about two studies that Bayer characterizes as "unreliable" in its current package insert, or label, for YAZ and Yasmin (accessed 4/25/11) are:

"Hormonal contraception and risk of venous thromboembolism: national follow-up study"; and,

"The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study".

The corresponding press releases issued by Bayer about these two sets of YAZ / Yasmin drug safety articles published by BMJ, which were issued almost exactly a year apart (but are virtually the same as far as their "tune" goes), are:

"Bayer Affirms Benefit-Risk Profile of Its Oral Contraceptives -- Established body of well grounded data show VTE risk comparable in combined oral contraceptives studied" (April 22, 2011); and,

"BAYER UPDATES LABELS FOR YAZ and YASMIN -- Body of Evidence Affirms VTE Risk/Benefit Profile for YAZ and Yasmin Is Comparable to Other Combination Oral Contraceptives" (April 9, 2010).

In fact, one wonders whether the March 2011 label change for YAZ which we wrote about here -- "Another Rather "Odd" YAZ Label Change By Bayer: March 2011 -- Provides New Warnings About Certain Side Effects As Regards ALL Birth Control Pills (Not Specific To YAZ)"  -- was not made by Bayer in anticipation of more medical journal articles with findings about the increased blood clot risks, like those recently published by BMJ.

To summarize, several different medical researchers find a significant increased risk of developing blood clots when using YAZ or Yasmin and the medical journal BMJ accepts their articles for publication, but Bayer tells everyone to just ignore those findings because their safety evidence is better.

Hopefully the FDA will not follow Bayer's advice and, instead, take action based on these two sets of medical articles about the blood clot side effects linked to YAZ and Yasmin, as well as Ocella, Gianvi, Zarah, Beyaz, and Safyral -- birth control pills which contain the progestin drospirenone, or DRSP.

Free Case Evaluation:  YAZ / Yasmin / Ocella / Gianvi / Zarah / Loryna / Syeda / Beyaz / Safyral
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Ortho Evra "Black-Box" Warning About Risks Of Blood Clots Added To Package Insert In March 2011

Warnings Increased About Risk Of Side Effects Like Pulmonary Embolism (PE) And Deep Vein Thrombosis (DVT)

(Posted by Tom Lamb at DrugInjuryWatch.com)

In March 2011 Ortho-McNeil-Janssen Pharmaceuticals, Inc. revised the Prescribing Information (more commonly called the "package insert" or "label") for its Ortho Evra (norelgestromin/ ethinyl estradiol) transdermal system to give a stronger warning about blood clot related side effects like pulmonary embolism (PE) and deep vein thrombosis (DVT).

Previously, the Boxed Warning, or "Black-Box" Warning, for the Ortho Evra skin patch birth control product only included a short paragraph titled "Cigarette Smoking and Serious Cardiovascular Risks". 

Now the Ortho Evra label (accessed 4/18/2011) has a Black Box warning which includes these two new paragraphs about a woman's risk of suffering adverse events while using the Ortho Evra patch:

Risk of Venous Thromboembolism

The risk of venous thromboembolism (VTE) among women aged 15-44 who used the
ORTHO EVRA® patch compared to women who used oral contraceptives containing
30-35 mcg of ethinyl estradiol (EE) and either levonorgestrel or norgestimate was
assessed in four U.S. case-control studies using electronic healthcare claims data. The
odds ratios ranged from 1.2 to 2.2; one of the studies found a statistically significant
increased risk of VTE for current users of ORTHO EVRA® (see WARNINGS -
Table 5).


Pharmacokinetic Profile of Ethinyl Estradiol

The pharmacokinetic (PK) profile for the ORTHO EVRA® patch is different from the
PK profile for oral contraceptives in that it has higher steady state concentrations and
lower peak concentrations. Area under the time-concentration curve (AUC) and
average concentration at steady state for ethinyl estradiol (EE) are approximately
60% higher in women using ORTHO EVRA® compared with women using an oral
contraceptive containing 35 mcg of EE. In contrast, peak concentrations for EE are
approximately 25% lower in women using ORTHO EVRA®. It is not known whether
there are changes in the risk of serious adverse events based on the differences in PK
profiles of EE in women using ORTHO EVRA® compared with women using oral
contraceptives containing 30-35 mcg of EE. Increased estrogen exposure may
increase the risk of adverse events, including venous thromboembolism. (See
WARNINGS and CLINICAL PHARMACOLOGY, Transdermal versus Oral
Contraceptives.)

Our March 2010 article about the safety profile of Ortho Evra, "Recent Report About Ortho Evra Safety Seems To Contradict Earlier Findings From Same Group", covered some of the developments which led to an April 2010 Ortho Evra label change.

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Reclast "Dear Doctor" Letter For Kidney Problems Should Be Sent By Novartis In U.S.

Public Citizen March 2011 Letter To FDA Points To Aclasta Safety Alert Material Sent In Canada During October 2010

(Posted by Tom Lamb at DrugInjuryWatch.com)

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UPDATE:  On September 1, 2011 the FDA announced that Reclast should not be used in patients with significant renal impairment, and physicians should screen patients for kidney dysfunction before starting them on the drug.

Further, the FDA ordered that Novartis put a new warning on the package insert, or label, for Reclast after receiving 20 reports of acute kidney failure resulting in death or requiring dialysis.

See: "FDA Drug Safety Communication: New contraindication and updated warning on kidney impairment for Reclast (zoledronic acid)"
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To start, Reclast is the U.S. name for the zoledronic acid medication sold by Novartis; it is identical to Aclasta, which Novartis sells in Canada.

By means of a March 10, 2011 letter, the consumer advocacy group Public Citizen is asking the FDA to require that Novartis warn doctors and patients in the U.S. about an apparent association between the osteoporosis drug Reclast and potentially serious kidney problems, "including acute renal failure requiring dialysis which in some cases resulted in death."

In more detail, Public Citizen wants Novartis to send a so-called "Dear Doctor" letter to physicians in the U.S., now, similar to the one the drug company sent out in Canada back on October 12, 2010.

From that October 2010 letter about Aclasta which Novartis sent to healthcare professionals in Canada:

The ACLASTA Product Monograph, has been revised to further emphasize precautions that should be taken into account to minimize the risk of renal adverse reactions:

• ACLASTA has been associated with renal dysfunction manifested as deterioration in renal function and in rare cases, acute renal failure.
• Renal impairment has been observed following the administration of ACLASTA*, occasionally after a single administration.
• Renal failure requiring dialysis or with a fatal outcome has occurred especially in patients with history of renal impairment or other risk factors. Risk factors include advanced age, concomitant nephrotoxic medicinal products, concomitant diuretic therapy or dehydration occurring after ACLASTA administration.

As of April 30, 2010 Novartis has received 265 spontaneous reports of renal impairment following administration of ACLASTA, corresponding to a reporting rate of approximately 20 cases per 100,000 patient-years of exposure.

Returning to the March 2011 Public Citizen letter about Reclast to the FDA:

Clearly, the current warnings and precautions in the FDA-approved label for Reclast [accessed March 10, 2011] about the risk of renal impairment are not sufficient for making physicians adequately aware of this serious, life-threatening renal toxicity associated with Reclast, the very reason that the Canadian government convinced the company to initiate the additional warnings. Many physicians in the U.S. fail to read the labels for drugs and thus are unaware of the renal toxic effects of Reclast and the precautions that must be taken to avoid such toxicity.

Public Citizen also suggested that the FDA should require Novartis to issue in the U.S. an item similar to its October 14, 2011 Public Communication, "Association of ACLASTA(zoledronic acid 5 mg/100 mL) solution for intravenous infusion with kidney dysfunction", which has been issued in Canada, only, thus far.

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Fosamax Litigation: Jaw Injury And Femur Fracture Cases, Federal And NJ Courts: April 2011 Update

Secrest MDL Trial Moved From March to September 2011; Hester v. Merck ONJ Trial Set For May 2011

(Posted by Tom Lamb at DrugInjuryWatch.com)

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UPDATE: On May 23, 2011 the U.S. Judicial Panel on Multidistrict Litigation (JPML) issued a Transfer Order such that, pursuant to 28 U.S.C. § 1407, all pending Fosamax femur fracture cases filed in the federal court system are transferred to the District of New Jersey and, with the consent of that court, assigned to the Honorable Garrett E. Brown, Jr., for coordinated or consolidated pretrial proceedings.

This second Fosamax multidistrict litigation (MDL) case, IN RE: FOSAMAX (ALENDRONATE SODIUM) PRODUCTS LIABILITY LITIGATION (NO. II) MDL No. 2243, is not same as the Fosamax MDL which Judge John Keenan has been presiding over in the U.S. District Court for the Southern District of New York, which is limited to jaw injury cases, such as osteonecrosis of the jaw (ONJ).

(6/6/11)______________________________________________________________________________

The following information about the ongoing Fosamax litigation comes from pages 128-129 of the Merck & Co., Inc. Form 10-K Annual Report For the Fiscal Year Ended December 31, 2010, which was filed with the Securities and Exchange Commission on February 28, 2011:

• As of December 31, 2010, approximately 1,295 cases, which include approximately 1,675 plaintiff groups, had been filed and were pending against [Merck & Co., Inc.] in either federal or state court....
• In these actions, plaintiffs allege, among other things, that they have suffered osteonecrosis of the jaw, generally subsequent to invasive dental procedures, such as tooth extraction or dental implants and/or delayed healing, in association with the use of Fosamax. In addition, plaintiffs in approximately 20% of these actions allege that they sustained stress and/or low energy femoral fractures in association with the use of Fosamax.
• The Fosamax MDL has been transferred to Judge John Keenan in the U.S. District Court for the Southern District of New York. As a result of the JPML order, approximately 870 of the cases are before Judge Keenan.
• As of December 31, 2010, approximately 385 cases were pending against [Merck] in Atlantic County, New Jersey.

Moving on, in the federal court Fosamax MDL the Secrest v. Merck trial had been scheduled to begin on March 14, 2011.  The Secrest trial has been rescheduled for September 7, 2011 by Judge Keenan.

The next osteonecrosis of the jaw (ONJ) Fosamax case scheduled for trial in the federal court MDL is Hester v. Merck; it is currently scheduled to begin May 9, 2011.

As reported previously, in February 2011 Judge Keenan announced that there will be two more bellwether trials conducted in the Fosamax MDL. As of April 1, 2011, these next two Fosamax trial cases had not been selected by Judge Keenan nor has he set the trial dates for those two additional bellwether cases.

We are actively involved in the Fosamax litigation in both the federal court MDL -- which is limited to jaw injury cases, such as osteonecrosis of the jaw (ONJ) -- as well as the New Jersey state court mass tort consolidation -- where most of the femur fracture Fosamax lawsuits are being filed.

Free Fosamax Case Evaluation 

Strictly Confidential, No Obligation.

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