New year, new oral contraceptives: 2 new OCs join birth control options

Beyaz, Lo Loestrin Fe gain Food and Drug Administration approval

Add Beyaz and Lo Loestrin Fe to the list of birth control choices for U.S. women. Both oral contraceptives (OCs) received Food and Drug Administration (FDA) approval in late 2010.

Beyaz, manufactured by Bayer HealthCare Pharmaceuticals of Wayne, NJ, is now stocked on pharmacy shelves; Warner Chilcott LLC of Rockaway, NJ, says it anticipates the commercial launch of Lo Loestrin Fe in early 2011.

Beyaz is based on Bayer's approved product Yaz, which contains the same doses of estrogen and progestin: 3 mg of drospirenone and 0.02 mg of ethinyl estradiol. The combined oral contraceptive also contains a folate (0.451 mg of levomefolate calcium). Beyaz is approved for the previously approved indications for Yaz, which include pregnancy prevention; treatment of premenstrual dysphoric disorder symptoms in women who choose to use an oral contraceptive for contraception; and treatment of moderate acne vulgaris in women at least 14 years of age, only if the patient desires an oral contraceptive for birth control. Beyaz also is approved for the secondary indication in women who choose to use an oral contraceptive as their method of contraception, to raise folate levels for the purpose of reducing the risk of a neural tube defect in a pregnancy conceived while taking the OC or shortly after discontinuing the drug. Women need 400 mcg of folate each day to help prevent major birth defects in the brain and spine, according to the Centers for Disease Control and Prevention.1 The concept of adding folate to OCs is not new. It has been championed for several years by Godfrey Oakley, MD, MSPM, former director of the CDC's Division of Birth Defects and Developmental Disabilities.

To some clinicians, supplementing OCs with folate seems counterintuitive, or even a mixed message, says Andrew Kaunitz, MD, professor and associate chair in the Obstetrics and Gynecology Department at the University of Florida College of Medicine — Jacksonville. However, many reproductive-age patients are not consistently taking multivitamins with folate, Kaunitz notes. Birth control pills represent a popular contraceptive choice, albeit one with a relatively high failure rate, says Kaunitz.

"From this perspective, an OC that also contains folate replete has appeal, increasing the likelihood that women will be folate replete at the time of conception," Kaunitz states. "Given the potential individual and public health benefits, it is my hope that going forward, many OC formulations supplemented with folate will become available."

Research presented at the recent 66th Annual Meeting of the American Society for Reproductive Medicine (ASRM) suggests that addition of folate could indeed benefit women. Study results indicate that adding folic acid to oral contraceptives could reduce neural tube defects by between 24% and 31% a year.2 William Gibbons, MD, ASRM president, says, "Women currently using contraception, but who may soon wish to have a child, would seem a natural target for folic acid supplementation. Fortifying birth control pills could be a novel way to increase folic acid levels in women of child-bearing age."

Lo Loestrin Fe takes another tack in approaching contraception; its daily dosage of 10 mcg of ethinyl estradiol represents the lowest dosage of estrogen of any oral contraceptive available in the United States. Its 28-day dosing schedules includes 24 tablets, each containing 1 mg of the progestin norethindrone acetate and 10 mcg of ethinyl estradiol; two tablets each containing 10 mcg of ethinyl estradiol; and two tablets, each containing 75 mg of ferrous fumarate.

Check study results

For folate supplementation, the primary efficacy study using Beyaz was a multicenter, double-blind, randomized, active-controlled U.S. trial in 379 healthy women ages 18-40 who were treated with Beyaz or Yaz for up to 24 weeks. Results of the randomized, double-blind, parallel group study found that Beyaz treatment increased folate levels from baseline. The study evaluated the effect of Beyaz on red blood cell (RBC) folate and plasma folate levels compared to Yaz. At week 24, the mean changes from baseline were significantly higher (p < 0.0001) for women who took Beyaz as compared to women who took Yaz, for RBC folate (420 ± 347 nanomole/liter (nmol/L) versus 34.3 ± 171 nmol/L) and plasma folate (15.8 ± 20.4 nmol/L versus 2.2 ± 14.6 nmol/L) levels.

Adverse reactions seen across the three indications for Beyaz (contraception, acne, folate supplementation) overlapped and were reported using the frequencies from the pooled dataset. The most common treatment-emergent adverse reactions in 2% or more of users were headache/migraine (5.9%), menstrual irregularities (spotting, metrorrhagia, and menorrhagia) (4.1%), nausea/vomiting (3.5%), and breast pain/tenderness (3.2%).3

In a one-year (13 28-day cycles) multicenter open-label clinical trial, 1,270 women ages 18 to 35 were studied to assess the efficacy of Lo Loestrin Fe, completing the equivalent of 12,482 28-day evaluable cycles of exposure. The weight range for women treated was 89 to 260 pounds, with a mean weight of 150 pounds. Among the women in the study, 51% had not used hormonal contraception immediately prior to enrolling in the study. Of those women treated, 13.7% were lost to follow-up, 10.7% discontinued due to an adverse event, and 8.9% discontinued by withdrawing their consent.

The pregnancy rate (Pearl Index) in women ages 18-35 was 2.92 pregnancies per 100 women-years of use (95% confidence interval 1.94 – 4.21), based on 28 pregnancies that occurred after the onset of treatment and extending through the seven days following the last dose of Lo Loestrin Fe. Cycles in which conception did not occur, but which included the use of backup contraception, were not included in the calculation of the Pearl Index. The index calculation includes women who did not take the drug correctly.4

Common adverse reactions occurring in 2% or more of all women using the study drug include nausea/vomiting (7%), headache (7%), bleeding irregularities (including metrorrhagia, irregular menstruation, menorrhagia, vaginal hemorrhage, and dysfunctional uterine bleeding) (5%), dysmenorrhea (4%), weight fluctuation (4%), breast tenderness (4%), acne (3%), abdominal pain (3%), anxiety (2%), and depression (2%).4

References

  1. Centers for Disease Control and Prevention. Facts about Folic Acid. Accessed at http://www.cdc.gov/ncbddd/folicacid/about.html.
  2. Lynen R, Farkouh RA, Taylor TN, et al. Potential impact of using folate-fortified oral contraceptives on risk of neural tube defects in the United States. Presented at the 66th Annual Meeting of the American Society for Reproductive Medicine. Denver; October 2010.
  3. Bayer HealthCare Pharmaceuticals Inc. Beyaz prescribing information. Accessed at http://berlex.bayerhealthcare.com/html/products/pi/fhc/Beyaz_PI.pdf.
  4. Warner Chilcott LLC. Lo Loestrin Fe prescribing information. Accessed at http://www.wcrx.com/pdfs/pi/pi_loloestrinfe.pdf.