U.S. FDA Approves Second Bayer Oral Contraceptive That Also Raises Folate Levels

WAYNE, N.J., Dec. 16, 2010 /PRNewswire/ -- Bayer HealthCare Pharmaceuticals, Inc. today announced the U.S. Food and Drug Administration (FDA) has approved a new oral contraceptive (OC), SAFYRAL™ (drospirenone 3 mg/ ethinyl estradiol 30 mcg/ levomefolate calcium 451 mcg tablets and levomefolate calcium 451 mcg tablets).  In women who choose an OC for birth control, SAFYRAL raises folate levels for the purpose of reducing the risk of rare neural tube defects (NTDs) in a pregnancy conceived while taking SAFYRAL or shortly after discontinuing it.  SAFYRAL provides the birth control YASMIN® (drospirenone 3 mg/ ethinyl estradiol 30 mcg) with 451 mcg levomefolate calcium, which is a B vitamin.

SAFYRAL is the second Bayer OC which contains folate.  In September, the FDA approved Beyaz™ (drospirenone 3 mg/ ethinyl estradiol 20 mcg/ levomefolate calcium 451 mcg tablets and levomefolate calcium  451 mcg tablets), the first OC approved by the FDA to raise folate levels in women who choose an OC for birth control.

"With the FDA approval of Safyral, Bayer now offers two oral contraceptives that contain folate," said Leslie North, Vice President of Marketing, Women's HealthCare, Bayer HealthCare Pharmaceuticals.  "SAFYRAL and Beyaz are part of Bayer's growing women's health franchise, and these new products reinforce our commitment to providing women various contraceptive options."

The Centers for Disease Control and Prevention, the U.S. Preventive Services Task Force, the March of Dimes and other leading health authorities recommend that all women of childbearing age supplement their diet with at least 400 mcg of folic acid daily.(1),(2),(3)  A well-established body of evidence supports folate supplementation as a means to reduce the incidence of neural tube defects  – rare birth defects of the brain and spinal cord.(2),(3),(4)  These rare birth defects happen in the first few weeks of pregnancy – often before a woman finds out she is pregnant.  As a result, daily folate supplementation is particularly important at least one month before and three months after conception.(2)

"Combining an oral contraceptive with folate is important, because women may become pregnant during OC use or shortly after discontinuation, possibly before seeking preconception counseling from their healthcare providers," said Dr. Anita Nelson, Professor of Obstetrics and Gynecology at the Harbor-UCLA Medical Center, Torrance, California.  "For women who already use YASMIN for contraception, SAFYRAL offers these women a new option to receive daily folate supplementation as part of their OC routine."

Women should not use SAFYRAL 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.

Patients are advised to alert their healthcare provider if they are taking folate supplements.  SAFYRAL is not indicated during pregnancy.  SAFYRAL has 99 percent contraceptive efficacy when used as directed.  If pregnancy occurs during treatment with SAFYRAL, further intake must be stopped.  If a woman discontinues use of SAFYRAL either with the intention of becoming pregnant or if she discontinues due to pregnancy while on the product, she is strongly encouraged to speak with her healthcare provider about taking a multivitamin with folic acid or another folate to maintain recommended folate intake.

SAFYRAL is in a 21/7 day regimen consisting of 21 days of drospirenone 3 mg/ethinyl estradiol 30 mcg with levomefolate calcium 451 mcg (Metafolin®*) followed by seven days of Metafolin only.  SAFYRAL is expected to be available in mid-January 2011 by prescription only.

Women should not use SAFYRAL 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.  SAFYRAL increases 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, SAFYRAL contains drospirenone, a different kind of hormone that for some may increase potassium too much.  Women should consult with their healthcare provider if they are on daily long-term treatment for a chronic condition with medications that may also increase potassium, as they should have a blood test to check their potassium level during the first month of taking SAFYRAL.

About the Clinical Development Program for SAFYRAL

The FDA approval of SAFYRAL to raise folate levels in women who choose an OC for contraception is based on two clinical trials. The first trial was a pivotal 24-week clinical trial involving 379 healthy women aged 18-40 years, which found that YAZ® (drospirenone 3 mg/ ethinyl estradiol 20 mcg) in combination with 451 mcg of Metafolin increased folate levels from baseline.  This multicenter, randomized, double-blind, parallel group study conducted in a U.S. population with folate fortified food evaluated the effect of YAZ in combination with 451 mcg of Metafolin on red blood cell (RBC) folate and plasma folate levels compared to YAZ alone during 24 weeks of treatment. At week 24, the mean changes from baseline were significantly (p<0.0001) higher for women who took YAZ in combination with 451 mcg of Metafolin, as compared to women who took YAZ alone, for RBC folate (420 +/- 347 nmol/L vs. 34.3 +/- 171 nmol/L, respectively) and plasma folate (15.8 +/- 20.4 nmol/L vs. -2.2 +/- 14.6 nmol/L, respectively) levels.

In the U.S. folate study, the most common side effects were headache/migraine, menstrual irregularities, nausea/vomiting and breast pain/tenderness.  

The addition of folate to an OC was further evaluated in a separate European study, which looked at YASMIN in combination with either 451 mcg of Metafolin or 400 mcg of folic acid for 24 weeks, followed by 20 weeks of treatment with YASMIN only (no folate intake).  This study found that the Metafolin treatment produced maximum mean increases in plasma folate (33.5 +/- 14.5 nmol/L) and in RBC folate (782 +/- 260 nmol/L) levels at 24 weeks.  Upon discontinuation of folate intake, the average RBC and plasma folate levels gradually decreased to starting levels (or baseline) over 20 weeks.

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

Important Safety Information

What are Beyaz,™ YAZ® SAFYRAL™ and YASMIN® prescribed for?

For women who choose the Pill for birth control, Beyaz, YAZ, SAFYRAL and YASMIN are approved to:

• Prevent pregnancy

Beyaz and SAFYRAL are 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.

In addition, Beyaz and YAZ are also approved for women who choose the Pill for birth control to:

• Treat premenstrual dysphoric disorder (PMDD)
  • Beyaz and YAZ are 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 Beyaz, YAZ, SAFYRAL or YASMIN?

Do not use Beyaz, YAZ, 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, history of heart attack or stroke, or if you are or may be pregnant.

What are the most serious risks of taking Beyaz, YAZ, SAFYRAL or YASMIN?

Beyaz, YAZ, 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, Beyaz, YAZ, 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 Beyaz, YAZ, 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 Beyaz and YAZ clinical trials?

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

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.

What are the most common side effects in SAFYRAL and YASMIN clinical trials?

In the 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.

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

For SAFYRAL, Beyaz, YAZ and YASMIN full prescribing Information, including boxed warning, please visit www.SAFYRAL.com, www.beyaz.com, www.YAZ-us.com and www.yasmin-us.com, respectively.

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.

About Bayer HealthCare Pharmaceuticals Inc.

Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals operation of Bayer HealthCare LLC, a division of Bayer AG. One of the world's leading, innovative companies in the healthcare and medical products industry.  Bayer HealthCare combines the global activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. In the United States, Bayer HealthCare Pharmaceuticals comprises the following business units: Women's Healthcare, Diagnostic Imaging, General Medicine, Hematology/Neurology, and Oncology. The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.

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.

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

(1) Centers for Disease Control and Prevention. Folic Acid: Recommendations. Available at: http://www.cdc.gov/ncbddd/folicacid/recommendations.html. Accessed on 9/22/2010.

(2) U.S. Preventive Services Task Force. Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009;150:626-31.

(3) The March of Dimes. Pregnancy and Newborn Health Education Center: Folic Acid. Available at: http://www.marchofdimes.com/hbhb_syndication/173_769.asp. Accessed on 9/22/2010.

(4) Centers for Disease Control and Prevention. Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR 1992;41(No.RR-14): 1-6.

*Levomefolate calcium (Metafolin®) is licensed and supplied by Merck & Cie, Switzerland. Metafolin® is a registered trademark of Merck KGaA, Germany.

SOURCE Bayer HealthCare Pharmaceuticals, Inc.