FDA approves smaller levonorgestrel intrauterine system— a 'mini Mirena'

Smaller size makes Skyla IUS good choice for nulliparous women

The Food and Drug Administration has given approval to Skyla, a new intrauterine system (IUS) from Bayer HealthCare Pharmaceuticals of Wayne, NJ. Available by prescription in February 2013, Skyla is the first new intrauterine contraceptive to receive U.S. approval in more than a decade.

Skyla is Bayer's second intrauterine contraceptive; its Mirena IUS was approved for U.S. contraceptive use in 2000. Skyla's small, flexible plastic T-shaped device measures 28 mm by 30 mm, as compared to Mirena's 32 mm by 32 mm dimensions. Skyla contains 13.5 mg levonorgestrel. The drug is released at an average in vivo rate of approximately 6 mcg/day over three years. Mirena contains 52 mg of levonorgestrel. Its drug is released at a rate of approximately 20 mcg per day, which decreases progressively to half that value after five years.

Skyla's labeled approval is for up to three years of contraceptive use. In comparison, Mirena is labeled for up to five years of birth control.

How does the addition of a new intrauterine device bode for the growth of long-acting reversible contraceptive (LARC) methods of family planning? "It is clear that LARC methods are more popular that ever, as there is an overall recognition that LARC methods are the best way for many women to prevent an unintended pregnancy," says Susan Wysocki, WHNP-BC, FAANP, president & chief executive officer of iWomansHealth in Washington, DC, which focuses on information on women's health issues for clinicians and consumers. "The addition of Skyla will give women another excellent option for preventing pregnancy."

Skyla is an excellent contraceptive option for women looking for long-acting reversible contraception, agrees Beth Jordan Mynett, MD, medical director, Association of Reproductive Health Professionals (ARHP) in Washington, DC. Its lower hormonal dose and smaller device size make it a method that may appeal to nulliparous women, especially younger women, notes Mynett. ARHP offers an online educational program on new developments in contraception such as Skyla to help providers be aware of what is in the development pipeline and to help their patients choose the best available contraceptive method. (To access the ARHP New Developments in Contraception webinar, visit www.arhp.org. Select "Professional Education," then "New Developments in Contraception.")

Who's a good candidate?

Which women will be good candidates for the long-acting reversible contraceptive? Anita Nelson, MD, professor in the Obstetrics and Gynecology Department at the David Geffen School of Medicine at the University of California in Los Angeles, sees three potential categories:

  • nulliparous women and those who have delivered only by Caesarean section;
  • women who desire shorter-term contraception;
  • women who want the lowest hormone levels.

The availability of a smaller progestin-releasing intrauterine system will provide additional choices for women and their clinicians, says Andrew Kaunitz, MD, professor and associate chair in the Obstetrics and Gynecology Department at the University of Florida College of Medicine — Jacksonville. A smaller IUS may be advantageous, particularly for nulliparous women, he states. Nelson says she hopes that "by introducing an IUS specifically indicated for nulliparous women, we can erase remaining clinician opposition to the use of this important option to more women."

Labeling should help clinicians determine which intrauterine system is best for a particular woman. The product labeling for Skyla specifically states that it can be used whether or not a woman has had a child, whereas the labeling for Mirena states it is recommended for women who have had at least one child, Wysocki points out.

"Although Skyla has a shorter duration of use than Mirena, for many women, the three years of duration is a perfect length of time, whether they are interested in child spacing or accomplishing a life goal, such as graduate school," Wysocki states. "The smaller amount of progestin may also be an advantage for some women."

Skyla has a smaller inserter diameter. It is 3.8 mm in diameter compared to Mirena's 4.75 mm diameter. Although developed for use by young women, clinicians may find it much easier to insert in perimenopausal women as a progestin for hormone therapy use, says James Trussell, PhD, professor of economics and public affairs and director of the Office of Population Research at Princeton (NJ) University. While not specifically labeled for this indication, such use might prove beneficial, Trussell notes.

Is it effective?

The contraceptive method has proven efficacy, as evidenced by results of a Phase III multicenter, multinational, randomized open-label trial. The study included 1,432 women ages 18-35 who received Skyla, of which 38.8% (556) had not yet had a child. The Pearl Index estimate for the first year of use based on the five pregnancies that occurred after the onset of treatment and within seven days after Skyla removal or expulsion was 0.41 with a 95% upper confidence limit of 0.96. The cumulative three-year pregnancy rate, based on 10 pregnancies, estimated by the Kaplan-Meier method was 0.9 per 100 women or 0.9%, with a 95% upper confidence limit of 1.7%.1

Most common adverse reactions noted in clinical trials included vulvovaginitis (20.2%), abdominal/pelvic pain (18.9%), acne/seborrhea (15.0%), ovarian cyst (13.2%), headache (12.4%), dysmenorrhea (8.6%), breast pain/discomfort (8.6%), increased bleeding (7.8%), and nausea (5.5%).

Rapid return to fertility is seen with the device. According to its product labeling, about three out of four women who want to become pregnant will become pregnant in the first year after Skyla is removed.

Counsel on changes

Changes in menstrual patterns are the most common side effect of intrauterine contraception.2 According to Skyla's prescribing information, women should be counseled that for the first three to six months, their periods might become irregular and their number of bleeding days might increase. Women also might have frequent spotting or light bleeding; some women have heavy bleeding during this time.

"After you have used Skyla for a while, the number of bleeding and spotting days is likely to lessen," the prescribing information reads. "There is a small chance that your periods will stop altogether."

Tell women to call the office, however, if bleeding remains heavier than usual or increases after it has been light for a while, the prescribing information advises.

Is it safe to breastfeed while using Skyla? Women may use Skyla when breastfeeding if more than six weeks have passed since the baby was born, the prescribing information states. If a woman is breastfeeding, Skyla is not likely to affect the quality or amount of her breast milk or the health of the nursing baby. However, isolated cases of decreased milk production have been reported among women using progestin-only birth control pills.3

Often, lesser is better, suggests Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at Emory University School of Medicine in Atlanta.

"The hope is, of course, that the smaller size of the 'mini-Mirena' IUS, Skyla, will be better tolerated by women with a smaller uterus, such as young teens and perimenopausal women, says Hatcher. "The hope also is the smaller size of the inserter will make this intrauterine device (IUD) easier to insert in some women."

However, in this case, lesser is worse when it comes to duration of contraceptive effectiveness, as women getting a Skyla device are only protected for three years, notes Hatcher. In their book, "A Clinical Guide For Contraception," Speroff and Darney say "the LNG IUD can be used for at least seven years and probably for 10 years," Hatcher says. They are, of course, referring to the Mirena IUS, he says.4 The Skyla IUS is approved for up to three years; this is not better, states Hatcher.

"In the not too distant future, a cheaper generic form of Mirena may be available; when this happens, it will be both less expensive and will be made effective for a longer period of time than the Skyla IUS," says Hatcher. "Therefore, a challenge for clinicians will be to decide who can use the slightly larger Mirena IUS that remains effective for so much longer than the Skyla [device]."

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References

  1. Nelson A, Apter D Hauck, B, et al. A global, randomized, Phase III, Pearl Index study comparing the efficacy and safety of two low-dose levonorgestrel-releasing intrauterine systems (LNG-IUSS) in nulliparous and parous women. Fertil Steril 2012; 98(6);S5.
  2. Dean G, Schwarz EB. Intrauterine contraceptives (IUCs). In: Hatcher RA, Trussell J, Nelson AL, et al. Contraceptive Technology: 20th revised edition. New York: Ardent Media; 2011.
  3. Truitt ST, Fraser AB, Grimes DA, et al. Hormonal contraception during lactation. systematic review of randomized controlled trials. Contraception 2003; 68(4):233-238.
  4. Speroff L, Darney PD. A Clinical Guide for Contraception. Philadelphia: Lippincott Williams & Wilkins; 2011.