December 7, 2011: Evidence of Greater Risk of Drospirenone-Containing Oral Contraceptives (YAZ and Yasmin)

Seven independent studies show that the hormone drospirenone (DRSP) contained in YAZ and Yasmin has a greater risk of venous thromboembolism (VTE, i.e. blood clots) than other oral contraceptives. The studies are:

1. Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. “Hormonal contraception and risk of venous thromboembolism: national follow-up study.” BMJ. 2009 Aug 13; 339. (Denmark)
2. Lidegaard Ø, Nielsen LH, Skovlund CW, Skjeldestad FE, Løkkegaard E. “Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9.” BMJ. 2011 Oct 25; 343. (Denmark)
3. Jick SS, Hernandez RK. "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." BMJ. 2011 Apr 21; 342. (U.S.)
4. Parkin L, Sharples K, Hernandez RK, Jick SS. "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 Apr 21; 342. (U.K.)
5. FDA-Funded Study Entitled “Combined Hormonal Contraceptives (CHCs) and the Risk of Cardiovascular Disease Endpoints” (Final Report, Nov. 3, 2011) (U.S. - Kaiser database)
6. Gronich N, Lavi I, Rennert G. "Higher risk of venous thrombosis associated with drospirenone-containing oral contraceptives: a population-based cohort study." CMAJ. 2011 Nov 7. (Israel)
7. van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, Doggen CJ, Rosendaal FR. "The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study." BMJ. 2009 Aug 13; 339. (Holland)
   

EU and UK Scientific Reviews Found Greater VTE Risk of DRSP-OCs

• VTE risk of DRSP-OCs with “is higher than the risk associated with combined pills containing levonorgestrel;” (U.K. Pharmocovigilance Expert Advisory Group May 10, 2011.)
• “Yasmin: risk of venous thromboembolism higher than levonorgestrel-containing pills.” (U.K. Medicinal products Regulatory Health Agency (MHRA), June 6, 2011.)
• Risk of VTE for DRSP-OCs is “higher than for levonorgestrel-containing” OCs. (E.U. Pharmacovigilance Working Party, May 26, 2011.)
• Evidence of higher risk stronger now; three additional studies (Lidegaard 2011, FDA/Kaiser and Gronich/Israeli study).
  

In sum,

• Seven consecutive independent studies unanimously showed higher risk of DRSP.
• E.U and U.K expert panels agree with findings by the independent studies.
• Only Bayer-sponsored studies failed to show higher risk of DRSP.
  

December 5, 2011: Recently Unsealed Court Documents Show that Bayer Withheld Important Safety Data from the FDA Concerning Its Birth Control Pills Yasmin and YAZ

On December 5, 2011 a federal court unsealed reports by several expert witnesses hired by plaintiffs in the YAZ/Yasmin litigation. Bayer is currently facing thousands of lawsuits nationwide filed by users of its popular birth control pills Yasmin and YAZ. The plaintiffs in the case allege that YAZ and Yasmin caused them to suffer serious injuries including serious and life-threatening blood clots.

Bayer’s contraceptives generated $1.58 billion in sales last year. Yasmin and YAZ contain a hormone called drospirenone which has been the subject of safety concerns. A number of independent studies have been published showing an increase of blood clots among women taking drospirenone-containing contraceptives compared to other types of oral contraceptives. In October 2011, the FDA published an analysis which warned that women taking YAZ and Yasmin were 74 percent more likely to suffer blood clots than women on other low-dose estrogen contraceptives.
 
The newly released expert witness reports found that Bayer withheld important safety information from the FDA regarding its products YAZ and Yasmin. Some of the reports also conclude that Bayer engaged in the practice of selling YAZ and Yasmin for off-label uses (uses unapproved by the FDA), such as for the treatment of premenstrual syndrome (PMS).  The reports also reference numerous internal Bayer documents, including emails, memos and presentations in support of the experts’ opinions.

One of the expert witness reports, written by the former commissioner of the FDA, states “Bayer presented a selective view of the data, and that presentation obscured the potential risks associated with Yasmin.” The report also states that Bayer failed to include an analysis that “demonstrated an increase in the U.S. reporting rate” for venous thromboembolism (VTE) or blood clots in a 2004 safety review of Yasmin provided to the FDA. The report further points out that an earlier draft of that 2004 review submitted to the FDA included an opinion by company researchers that the “spontaneous reporting data do signal a difference in the VTE rates for Yasmin.” However, this statement was not included in the final version submitted to the FDA.
 
The report also finds that the company withheld important safety information concerning the risk of blood clots before Yasmin was approved.  In his report, the former head of the FDA, states that, “These facts would impact the agency’s risk-benefit equation about the drug and whether it could be approved.” He concludes, “Had I, or a medical review officer, known these facts prior to approval, further investigation would have been warranted before a decision on Yasmin’s NDA [New Drug Application] could be made.”
In addition, the report criticizes the way the company evaluated and handled spontaneous adverse event reports. The former head of the FDA states in the report, “Bayer’s spontaneous reporting analysis demonstrated a safety signal about Yasmin and VTE risk,” and further, “Bayer had a duty to present a full and balanced view of all the data and analysis concerning Yasmin to the FDA and health-care professional and failed to do so.”

The expert witness reports also find that Bayer promoted YAZ and Yasmin for “off-label” uses such as treatment of premenstrual syndrome (PMS) or symptoms of PMS. Such “off-label” promotion violates FDA regulations. One of the expert witness reports cites to internal Bayer documents showing that the company hired a Los Angeles based gynecologist to help promote their products citing an internal company email in which a Bayer representative noted that the physician would “mention off-label benefits of our products.” As part of her promotion efforts, the gynecologist wrote a book which contained “off-label” claims about Yasmin, including statements that Yasmin could help women with PMS-related symptoms such as fluid retention, bloating, and depression. Cited documents in the report show that Bayer also planned to purchase 10, 000 copies of the book as part of a “strategy to have the book appear on the New York Times bestseller list.”  Other documents cited in the expert witness report show that the company secured story placements in women’s magazines such as Allure, which touted ”off-label” benefits of YAZ for treating PMS.

According to an attorney representing the Plaintiffs, the newly unsealed documents were provided to the FDA because “they contain relevant information obtained from Bayer that has not been previously provided to the FDA and will assist the committee and the FDA in its own evaluation of the benefits and risks of drospirenone-containing oral contraceptives.”

The FDA has set a December 8, 2011 hearing to discuss the findings and determine if the YAZ and/or Yasmin labels should carry additional warnings or if other actions are warranted. Materials from both Plaintiffs and Defendants have been submitted to the FDA for consideration at the hearing. The recently unsealed expert witness reports were submitted to the FDA after the submission deadline for written materials, so it is uncertain whether such documents will be considered by the FDA prior to the hearing.

October 14, 2011: ABC Nightline’s Chris Cuomo presented an investigation of DRSP (DROSPIRENONE) containing birth control pills. Click HERE to watch the “ABC NEWS YAZ Bitter Pill Investigation”.

The story also aired on Good Morning America on October 15, 2011. It featured the case of C. Ubersox, a 24 year-old woman who, after seeing YAZ commercials featuring healthy and fit women, decided to use YAZ to lose weight in preparation for her upcoming wedding.  While on YAZ, however, she suffered bilateral pulmonary emboli.  Her heart stopped en route to the hospital.  She fell into a coma and when she awoke, she was blind.  She explained to ABC Nightline and Good Morning America how she lost her career, her fiancé, and her eyesight, all results of injuries suffered while taking YAZ. BAYER declined to participate in the ABC interview. The print story “New Studies Find YAZ More Risky Than Other Leading Birth Control Pills: ABC News Investigates” is available at http://abcnews.go.com/TheLaw/studies-find-yaz-risky-leading-birth-control-pills/t/story?id=14741760

On September 26, 2011, the FDA announced that it is convening an advisory panel in December 2011 to review and evaluate emerging science and data regarding the risks of “VTEs”, or blood clots, associated with using DRSP (drospirenone) birth control pills such as YAZ and Yasmin. The FDA has acknowledged that 'concern' exists over the risks associated with YAZ and Yasmin.

As many as 100 deaths have been attributed to YAZ / Yasmin ® oral contraceptives to date. In 2003 and again in 2008 the Federal Food and Drug Administration (FDA) issued severe warnings in connection with the advertising claims made by the manufacturer, Bayer. Robinson Calcagnie Robinson Shapiro Davis, Inc. has filed cases against the manufacturers of Yasmin®, Yaz® and Ocella® for injuries suffered by women who took these oral contraceptives.

The Defective Pharmaceuticals & Medical Devices litigation group at Robinson Calcagnie Robinson Shapiro Davis, Inc. has experienced trial lawyers who focus on representing plaintiffs in oral contraceptive litigation. If you, or a family member, have suffered serious injury, coma or death stemming from the use of Yaz®, Yasmin® or Ocella®, contact the personal injury attorneys at Robinson Calcagnie Robinson Shapiro Davis, Inc. today to schedule an appointment.

Click Here for a YAZ / Yasmin Lawsuit Evaluation.

The oral contraceptives YAZ®, Yasmin® and its generic equivalent Ocella® have been linked to serious circulatory and gallbladder diseases. A key ingredient in these drugs is believed to raise blood potassium levels to a dangerous level resulting in several potential injuries, including:

• Heart attacks
• Strokes
• Blood clots
  • Pulmonary embolism (PE)
  • Deep vein thrombosis (DVT)
• Liver tumors
• Death
• Heart attacks (and other cardiac events, such as arrhythmias)
• Strokes and TIA
• Kidney (renal) disease
• Gallbladder removal
• Pancreatitis
• Myocardial infarctions
• Other thrombosis events
  

In addition certain women may be at elevated risk of injury when using these contraceptives, including women with high blood pressure, high levels of blood potassium, kidney or liver impairment, adrenal gland abnormalities or women who are obese or diabetic.

Symptoms of blood clots require immediate medical attention and may include:

• Sudden severe headaches
• Unusual swelling or pain in extremities
• Sharp or crushing chest pain
• Coughing up blood
• Eye problems such as blurred / double vision or complete loss of vision
• Pain in the back of the lower leg

Click Here for a YAZ / Yasmin Lawsuit Evaluation.

Yasmin®, YAZ® and Ocella® are the first, and only, birth control medications on the market which utilize the fourth generation formulation of synthetic progesterone called drospirenone, coupled with a type of estrogen called ethinylestradiol. This unique formulation has a diuretic effect which can increase the blood potassium levels in users, resulting in development of blood clots, gallbladder damage and other injuries. Untreated, these symptoms may result in severe injury and even death.

Yasmin® was approved by the FDA in 2001 for both birth control and treatment of Premenstrual Dysphoric Disorder (PMDD) and later YAZ was also approved for treatment of severe acne. The highly popular oral contraceptive Yasmin® and its descendants YAZ® and Ocella® have increased risk of blood clots, heart attacks and strokes similar to those linked with other birth control medications and devices like the Nuvaring ®and Ortho Evra® patch, however, Yasmin® and its descendants have added the serious risk of severe gallbladder disease. Often surgical removal of the gallbladder is the only option for treatment.

Bayer, the manufacturer of both YAZ and YASMIN received warnings in 2003 for YASMIN® and 2008 for YAZ® from the Federal Food and Drug Administration (FDA) for both overstating the benefits and minimizing the serious safety risks of the oral contraceptive drugs. Under a federal law that prohibits promotion of drugs for uses not approved by the Federal Food and Drug Administration (FDA) Bayer was required to mount a $20 million advertising campaign to correct its previous misleading YAZ advertisements.

YAZ® lawsuits are lengthy and difficult endeavors that require a tremendous amount of investigation and work. A law firm must navigate several strict filing rules, including state or federal deadlines, in addition to determining which pharmaceutical companies, patch manufacturers, healthcare providers or companies in the distribution chain should bear responsibility for contributing to the death or injury. Robinson Calcagnie Robinson Shapiro Davis, Inc. evaluates every lawsuit on an individual basis before determining whether the firm will represent a plaintiff. This evaluation may include reviewing medical records from prescribing doctors, hospitals, pharmacies and the Offices of the City or County Medical Examiner, and speaking with key witnesses near the victim at or near the time of their death or injury. Upon a favorable review of this information by our team of medical experts and attorneys, clients will be retained and a product liability lawsuit will be filed against all defendants responsible for the client’s damages.

Click Here for a YAZ / Yasmin Lawsuit Evaluation.

Note: If you believe you have a potential Yasmin®, YAZ® or Ocella® lawsuit, keep any and all containers and boxes that are still in your possession. Do not return or destroy any remaining pills.

Publication Petition to the FDA to Ban Third Generation Oral Contraceptives Containing Desogestrel due to Increased Risk of Venous Thrombosis (HRG Publication #1799)

FDA Sanction Letters to Defendants Relating to YAZ/Yasmin

Below are a series of FDA letters relating to Drospirenone-containing oral contraceptives.
Since the introduction of YAZ, Yasmin and Ocella into the market, there have been a total of 4 FDA Warning Letters relating to Drospirenone-containing oral contraceptives.

7/10/03 FDA Letter #1 Requiring Discontinuation of Misleading Yasmin Ads

a.       Improperly Implied Superiority to Other Oral Contraceptives:  FDA found Yasmin ads “are misleading because they imply superiority to other COCs (and thus do not offer the same product benefits as Yasmin Tablets) when such has not been demonstrated by substantial evidence or substantial clinical experience.”
 
b.      Ads Minimized Health Risks of Yasmin:  “Thus, by failing to add the necessary context to clarify that increased blood potassium is a safety risk rather than a clinical benefit, the ad misleadingly represents or suggests that Yasmin is safer than has been demonstrated by substantial evidence or substantial clinical experience.  The TV ad not only misleads consumers about the efficacy of Yasmin, the ad also minimizes important context about the health risks of the drug.”
 
c.       Order to Discontinue Ads:  FDA ordered Defendants to immediately discontinue the TV ad and all other promotional materials and activities for Yasmin that contain the same or similar violative presentations.

10/3/08 FDA Letter #2 Requiring “Bayer to immediately cease dissemination” of its “Not Gonna Take It” and “Balloons” Ads

a.       Bayer’s "Not Gonna Take it" and "Balloons" Ads Are Misleading:  “FDA requires Defendants to cease “two 60-second direct-to-consumer (DTC) broadcast television advertisements (TV Ads) entitled ‘Not Gonna Take it’ (ZYRA-6323) and ‘Balloons’ (ZYRA-6567) for YAZ (drospirenone and ethinyl estradiol) Tablets (YAZ) submitted by Bayer HealthCare Pharmaceuticals, Inc. (Bayer) under cover of separate Forms FDA-2253 … are misleading because they broaden the drug's indication, overstate the efficacy of YAZ, and minimize serious risks associated with the use of the drug.  Thus, the TV Ads misbrand the drug in violation of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 352(n), 352(f)(1) & 321 (n), and FDA's implementing regulations. 21 CFR 201.1 OO(c)(1); 201.128; 202.1 (e)(5)(iii) & (e)(6)(i).”
 
b.      Misuse of Selective PMDD Symptoms to Suggest PMS Relief:  “The totality of the visual and audio presentations in both TV ads suggest that YAZ approved to treat women with any severity of the symptoms presented, including women with PMS, when this is not the case.“  “[G]iven the overlap in certain symptoms between premenstrual syndrome (PMS) and PMDD, and the material limitation on YAZ’s PMDD indication (that it has not been evaluated for the treatment of the less serious condition, PMS), the TV Ads misleadingly suggest that YAZ is appropriate for treating women with PMS, who may not be appropriate candidates for this drug.”
 
c.       Overstated Acne Benefits:  “[T]he TV Ads suggest that YAZ is approved for acne of all severities when this is not the case… These presentations fail to adequately convey that, as noted in the PI, ‘YAZ is indicated for the treatment of moderate acne vulgaris...’  The percentage of subjects assessed by the Investigator's Static Global Assessment (ISGA) with a 'clear' or 'almost clear' rating at day 15 of cycle 6 was 15% and 21% for subjects receiving YAZ versus 4% and 9% of placebo subjects in Studies 1 and 2, respectively. … [These studies] do not demonstrate that YAZ results in clear, acne-free skin for a typical woman; rather, these results demonstrate that it reduces the amount of acne lesions more than placebo but does not result in completely clear skin for these women. Thus, the TV Ads misleadingly overstate the efficacy of the drug.”
 
d.      Distracting Background and Action in Ads Minimize Risk:  “The audio communication of serious risk disclosures during the ‘major statement’ is minimized by distracting visuals, numerous scene changes, and other competing modalities such as the background music which combine to interfere with the presentation of the risk information. In ‘Not Gonna Take It’, the fast-paced visuals depict various women looking at pictures, trying on clothes, chatting at a cafe, stretching/exercising in a park, and walking down the street while the audio component describes the major risks associated with YAZ.  Similarly, in ‘Balloons,’ the background music plays as fast-paced visuals depict various women running in a park, sitting on a scenic waterfront, smiling, walking out of a coffee shop, driving and singing, walking out on a balcony, using an elevator, walking through the street to join friends, in addition, to a pigeon on a building ledge and balloons being released and floating away. These complex presentations distract from and make it difficult for viewers to process and comprehend the important risks being conveyed. This is particularly troubling as some of the risks being conveyed are serious, even life-threatening. The overall effect of the distracting visuals, graphics, concurrent supers and background music is to undermine the communication of important risk information, minimizing these risks and misleadingly suggesting that YAZ is safer than has been demonstrated by substantial evidence or substantial clinical experience.”
 
e.      Order for “Bayer to Immediately Cease Dissemination”:  “DDMAC asks Bayer to immediately cease dissemination of violative promotional materials for YAZ that are the same as or similar to those described above… Because the violations described above are serious, we request, further, that your submission include a comprehensive plan of action to disseminate truthful, non-misleading, and complete corrective messages about the issues discussed in this letter to the audience(s) that received the violative promotional materials.”

3/26/09 FDA Letter #3 Finding Bayer’s Yaz Internet Links “in violation of the Federal Food, Drug, and Cosmetic Act and FDA implementing regulations

8/5/09 FDA Letter #4 Finding Failed to Properly Test Yaz/Yasmin Ingredients Shipped to the United States

a.       “U.S. Food and Drug Administration (FDA) Investigator Jose Cruz and Chemist Miguel Martinez[‘s] inspection revealed significant deviations from U.S. current good manufacturing practices (CGMP) in the manufacture of non-sterile API’s [active pharmaceutical ingredients, for Yaz and Yasmin].”

i.      Bayer’s “Laboratory controls are deficient in that your firm has established procedures that allow for the averaging of out-of-specification (OOS) and within-specification analytical test results from separate samples. The use of these approved procedures resulted in API batches being released to the U.S. market based on passing averaged assay results.”

b.      “In all cases, your firm concluded that no analytical errors had been identified and that the values were true DOS results. Your firm concluded that these OOS results were within the accepted variation of the analytical method and that the quality of these batches was not affected. We disagree with your rationale and conclusion. An assay test is used to determine potency, not method variability. The validation of your analytical method should address robustness or variability, while system suitability is designed to address instrument variation performance, which was met in each of these instances. We believe that these results were true ODS values and that these batches should not have been released for distribution.”
 
c.       “You state that this is appropriate averaging and in line with the FDA OOS guidance document. We disagree with your rationale and interpretation of the FDA OOS guidance. Your firm prepares two to three separate samples, which are assayed individually. We expect you to treat each of these results independently, and not to average an OOS result with a passing individual result. The hiding of an OOS result in the average is an unacceptable practice.”
 
d.      “Until all corrections have been completed and FDA has confirmed corrections of the violations and your firm's compliance with CGMP, this office may recommend withholding approval of any new applications or supplements listing your firm as an API manufacturer. In addition, failure to correct these deficiencies may result in FDA denying entry of articles manufactured by your firm into the United States.”

Click here to view a recent BMJ Study showing that risk of blood clots in YAZ/Yazmin users is double the risk of most oral contraceptives on the market.

Click here to view the Dutch Warning for DSRP/ EE oral contraceptives.

April 2011 - British Medical Journal publishes Boston University study by Susan Jick showing women using YAZ and Yasmin have approximately twice the risk of nonfatal venous thromboembolism as those using 2nd Generation levonorgestrel contraceptives.