Bayer Affirms Benefit-Risk Profile of Its Oral Contraceptives

WAYNE, N.J., April 21, 2011 /PRNewswire/ -- Bayer HealthCare Pharmaceuticals, Inc. is aware of two studies published today in The British Medical Journal, ONLINE FIRST.  These papers 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" by Lianne Parkin et al(1); 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" by Susan S. Jick et al(2).  

Bayer's assessment, based on its review to date, is that the manner in which the authors applied the study methodology reported in these two publications and the databases used provide less reliable conclusions than are available from existing scientific evidence around the risk of developing venous thromboembolism (VTE), or blood clots, with combination oral contraceptives (COCs).  Given the already large and robust scientific body of evidence, in Bayer's opinion, these studies do not change the overall assessment about the safety of Bayer's oral contraceptives.  Bayer re-affirms that the overall body of available scientific evidence continues to provide support that the risk of developing venous thromboembolism (VTE), or blood clots, in women using drospirenone-containing combination oral contraceptives (COCs) is comparable to other combination birth control pills studied.

"Bayer has sponsored several independently-conducted, large-scale, prospective, observational safety studies on the use of combined oral contraceptives (COCs), including the EURAS(3) Study and LASS(4) follow up study, the Ingenix(5) Study and the INAS(6) Study" said Leo Plouffe, MD, Vice President, US Medical Affairs, Women's HealthCare, Bayer HealthCare Pharmaceuticals.  "Bayer's assessment that its drospirenone-containing COCs are safe and effective when taken as directed according to prescribing information is supported by consistent clinical findings over a 15 year period and up to 10 years of post-marketing study results which support that the risk of VTE is similar with any COC studied, regardless of the progestin."

Combination oral contraceptives are among the most systematically studied and widely-used medicines available today.  Bayer's combined oral contraceptives have been and continue to be extensively studied worldwide.  

The above referenced study protocols have been reviewed by regulatory authorities in both Europe (EMA) and the USA (FDA).  They have also been acknowledged by many experts in the field as among the most comprehensive and best-designed studies of their kind. These studies continue to build on a large established body of well-grounded data about the safety of oral contraceptives with study designs that allow for control of key confounding factors and minimize the risk of bias.  Importantly, data from these studies have consistently shown that the risk of VTE with drospirenone is comparable to that seen with other progestins, including levonorgestrel.  

"The EURAS and Ingenix studies are already reflected in an April 2010 FDA-approved US label update for YAZ® (3 mg drospirenone / 0.02 mg ethinyl estradiol) and Yasmin® (3 mg drospirenone/ 0.03 mg ethinyl estradiol)," Dr. Plouffe continued. "As science has developed, so too has the need and demand for more detailed information and methods that help us control for confounders.  With the EURAS and INAS Studies, we had the right mechanism in place to observe the risk of VTE in a controlled environment, thus affirming that VTE risk is comparable across any combined oral contraceptives studied, with similar dosages of a progestin."

All birth control pills, including Bayer's, carry an increased risk of blood clots, stroke and heart attack.  These serious side effects are rare.  Oral contraceptives increase the tendency to develop strokes (stoppage or rupture of blood vessels in the brain) and heart attacks (blockage of blood vessels in the heart). Blood clots (venous thrombosis) and blockage of blood vessels are a serious side effect of taking oral contraceptives.  VTE is an uncommon event among women using combined oral contraceptives, and pregnancy increases the risk of VTE as much or more than the use of COCs.

Women should not use YAZ or Yasmin if they smoke and are over age 35.  Smoking increases the risk of serious side effects from the Pill, which can be life-threatening, including blood clots, stroke or heart attack.  This risk increases with age and number of cigarettes smoked.

Women should not use YAZ or Yasmin if they have kidney, liver, or adrenal disease because this could cause serious heart and health problems, or if they have or have had blood clots, certain cancers, history of heart attack or stroke, or if they are or may be pregnant.  YAZ and Yasmin increase the risk of serious conditions including blood clots, stroke and heart attack.  Smoking increases these risks, especially in women over 35.  The risk of blood clots is highest during the first year of use.  

In addition, YAZ and Yasmin contain drospirenone, a different kind of hormone that for some may increase potassium too much. Therefore, women should not take YAZ or Yasmin if they have kidney, liver, or adrenal disease because this could cause serious heart and health problems.  Women who are on daily, long-term treatment for a chronic condition with medications that may also increase potassium (see below), should consult with their healthcare provider as they should have a blood test to check their potassium level during the first month of taking YAZ or Yasmin.

Important Safety Information About YAZ®

What is YAZ® prescribed for?

For women who choose the Pill for birth control, YAZ is approved to:

• Prevent pregnancy -  99% effective when taken as directed
• Treat premenstrual dysphoric disorder (PMDD)
  • YAZ is not approved to treat Premenstrual Syndrome (PMS), a less serious set of symptoms occurring before your period
• Treat moderate acne in women at least 14 years of age

Who should not take YAZ?

Women should not use YAZ if they smoke and are over age 35. Smoking increases the risk of serious side effects from the Pill, which can be life-threatening, including blood clots, stroke or heart attack. This risk increases with age and number of cigarettes smoked.

Women should not use YAZ if they have kidney, liver, or adrenal disease because this could cause serious heart and health problems, or if they have or have had blood clots, certain cancers, history of heart attack or stroke, or if they are or may be pregnant.

What are the most serious risks of taking YAZ?

YAZ increases the risk of serious conditions including blood clots, stroke, and heart attack. The risk of blood clots is highest during the first year of use.  This risk is greatest when first starting the Pill and when restarting the same or a different Pill after a 4 week or greater break.

In addition, YAZ contains drospirenone, a different kind of hormone that for some may increase potassium too much. Women should consult their healthcare provider if they are on daily long-term treatment for a chronic condition with medications that may also increase potassium (see below), as they should have a blood test to check their potassium level during the first month of taking YAZ.

What medications may increase potassium?

NSAIDs—ibuprofen (Motrin®, Advil®), naproxen (Aleve® and others) when taken long-term and daily for arthritis or other problems, potassium-sparing diuretics (spironolactone and others), potassium supplementation, ACE inhibitors (Capoten®, Vasotec®, Zestril®, and others), angiotensin-II receptor antagonists (Cozaar®, Diovan®, Avapro®, and others), aldosterone antagonists, and heparin.

What are the most common side effects?

In the contraception and moderate acne clinical trials, the most common side effects were headache/migraine, menstrual irregularities, nausea/vomiting, breast pain/tenderness, and mood changes.

In the PMDD clinical trials, the most common side effects were menstrual irregularities, nausea, headache, breast tenderness, fatigue, irritability, decreased libido, weight gain, and mood changes.

YAZ does not protect against HIV infection (AIDS) or other STDs.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see full Prescribing Information about YAZ, including boxed warning, available at http://yaz-us.com/.

Important Safety Information about SAFYRAL™ and YASMIN®

SAFYRAL (drospirenone/ethinyl estradiol/levomefolate calcium tablets and levomefolate calcium tablets) and YASMIN (drospirenone 3 mg /ethinyl estradiol 0.03 mg) are associated with increased risks of several serious side effects, including blood clots, stroke, and heart attack. Women, especially those 35 and over, are strongly advised not to smoke because it increases these risks. In addition, SAFYRAL and YASMIN contain drospirenone, a different kind of hormone that for some may increase potassium too much.

What are SAFYRAL™ and YASMIN® prescribed for?

Available by prescription only, for women who choose the Pill for birth control, SAFYRAL and YASMIN are approved to:

• Prevent pregnancy — 99% effective when taken as directed

SAFYRAL is also approved for women who choose the Pill for birth control to:

• Provide a daily dose of folate supplementation, which is recommended for women in their reproductive years. Folate lowers the risk of having rare neural tube birth defects in a pregnancy occurring during use or shortly after stopping.

Important Safety Information About SAFYRAL and YASMIN, Including Boxed Warning

Who should not take SAFYRAL or YASMIN?

Do not use SAFYRAL or YASMIN if you smoke and are over age 35. Smoking increases your risk of serious side effects from the Pill, which can be life-threatening, including blood clots, stroke or heart attack. This risk increases with age and the number of cigarettes smoked.

Do not use SAFYRAL or YASMIN if you have kidney, liver or adrenal disease because this could cause serious heart and health problems, or if you have or have had blood clots, certain cancers, a history of heart attack or stroke, or if you are or may be pregnant.

What are the most serious risks of taking SAFYRAL and YASMIN?

SAFYRAL and YASMIN increase the risk of serious conditions, including blood clots, stroke and heart attack. The risk of blood clots is highest during the first year of use.

In addition, SAFYRAL and YASMIN each contain drospirenone, a different kind of hormone that for some may increase potassium too much. Consult your healthcare provider if you are on daily, long-term treatment for a chronic condition with medications that may also increase potassium (see below), as you should have a blood test to check your potassium level during the first month of taking SAFYRAL or YASMIN.

What medications may increase potassium?

NSAIDs — ibuprofen (Motrin®, Advil®), naproxen (Aleve® and others) when taken long-term and daily for arthritis or other problems, potassium-sparing diuretics (spironolactone and others), potassium supplementation, ACE inhibitors (Capoten®, Vasotec®, Zestril®, and others), angiotensin-II receptor antagonists (Cozaar®, Diovan®, Avapro®, and others), aldosterone antagonists, and heparin.

What are the most common side effects?

In contraception and folate clinical trials, the most common side effects were premenstrual syndrome, headache/migraine, breast pain/tenderness/discomfort, nausea/vomiting and abdominal pain/discomfort/tenderness.

SAFYRAL and YASMIN do not protect against HIV infection (AIDS) or other STDs.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see full prescribing information about SAFYRAL, including boxed warning.

Please see full prescribing information about YASMIN, including boxed warning.

About Bayer HealthCare Pharmaceuticals Inc.

Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals business of Bayer HealthCare LLC, a subsidiary of Bayer AG. Bayer HealthCare is one of the world's leading, innovative companies in the healthcare and medical products industry, and combines the activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions.  As a specialty pharmaceutical company, Bayer HealthCare Pharmaceuticals provides products for Diagnostic Imaging, General Medicine, Hematology, Neurology, Oncology and Women's Healthcare.  The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.

BAYER (reg'd), the Bayer Cross (reg'd), YAZ (reg'd) and YASMIN (reg'd), and SAFYRAL™ are trademarks of Bayer HealthCare Pharmaceuticals.

Forward-Looking Statements

This news release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

(1) Lianne Parkin senior lecturer in epidemiology and Katrina Sharples, senior lecturer in biostatistics of the Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, New Zealand; and Rohini K. Hernandez, epidemiologist and Susan S. Jick, director, Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, Massachusetts, USA

(2) Susan S. Jick, director and Rohini K. Hernandez, epidemiologist, Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, Massachusetts, USA

(3) Dinger, Jurgen et al.: The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance study on Oral Contraceptives based on 142,475 women-years of observation. In: Contraception, 75, 2007, 344– 354.

(4)  Long-Term Active Surveillance Study for Oral Contraceptives (LASS) clinicaltrials.gov ; http://clinicaltrials.gov/ct2/show/NCT00676065?term=LASS&rank=1  

(5) Seeger, John et al.: Risk of Thromboembolism in Women Taking Ethinylestradiol/Drospirenone and Other Oral Contraceptives. In: Obstetrics & Gynecology, Vol. 110, No. 3, September 2007, 587 – 893.

(6)  Dinger, Jurgen et al.: The risk of venous thromboembolism in users of a drospirenone -containing oral contraceptive with a 24-day regimen - results from the INAS-OC study.  In:  Fertility and Sterility, Vol 94, Issue 4, Supplement 1, September 2010, S3.

SOURCE Bayer HealthCare Pharmaceuticals, Inc.