EXECUTIVE SUMMARY
Another choice has been added to the expanding list of long-acting reversible contraceptive options with the September 2016 FDA approval of the Kyleena 19.5 mg levonorgestrel IUD from Bayer HealthCare Pharmaceuticals. The new IUD is available as of October 2016 by prescription only.
- Kyleena joins five other long-acting reversible contraception devices available in the United States. They are the single-rod etonogestrel implant, Nexplanon; three levonorgestrel IUDs: Mirena, Liletta, and Skyla; and the ParaGard copper-T IUD.
- Kyleena is similar in size to skyla and measures 28 mm horizontally and 30 mm vertically. It is approved for five years of effective use.
(Editor’s note: News of the approval was published first at reliasmedia.com, the web page of Contraceptive Technology Update’s publisher. To keep up with breaking healthcare news as it occurs, go online to reliasmedia.com.)
Family planning clinicians are adding another choice to the expanding list of long-acting reversible contraceptive options with the September 2016 FDA approval of the Kyleena 19.5 mg levonorgestrel IUD from Whippany, NJ-based Bayer HealthCare Pharmaceuticals. The new IUD is available as of October 2016 by prescription only.
Data show that the use of effective, long-acting birth control methods, including IUDs, have helped to reduce unintended pregnancies in the United States.1 However, there still is progress to be made, notes Anita Nelson, MD, professor and chair of the obstetrics and gynecology department at Western University of Health Sciences in Pomona, CA. Kyleena may be an appropriate choice for women who want a low-dose, non-daily birth control method, says Nelson, who was part of the research team.
“This is the low-dose version we tested in comparison to Skyla [another Bayer IUD], but with slightly more levonorgestrel, allowing five years of effective life,” observes Nelson.
The device offers less amenorrhea than the Mirena, which was the first IUD from Bayer, but it is indicated for five years, says Nelson. It may fill the needs of another group of women, she states.
An IUD that is approved for up to five years of use, yet is based on a smaller frame, represents an appealing option for many women and clinicians, notes Andrew Kaunitz, MD, University of Florida Research Foundation professor and associate chairman of the department of obstetrics and gynecology at the University of Florida College of Medicine–Jacksonville. “With smaller frame IUDs, insertion may be less uncomfortable for the woman, easier from the clinician’s perspective, and less likely to require cervical dilation,” states Kaunitz.
The use of long-acting reversible contraception (LARC) has increased in recent years, from 2.4% of all women using contraception in 2002 to 11.6% in 2013.2,3 Kyleena joins four other LARC devices available in the United States: one single-rod etonogestrel implant (Nexplanon, Merck, Whitehouse Station, NJ) and four brands of IUDs. These include three levonorgestrel IUDs:
- the 52 mg Mirena (Bayer), approved for the treatment of heavy menstrual bleeding in IUD users and for five years of contraceptive use;
- the 52 mg Liletta (Medicines360, San Francisco, and Actavis, Dublin, Ireland), approved for three years of contraceptive use;
- the 13.5 mg Skyla (Bayer), approved for three years of contraceptive use.
The ParaGard copper-T IUD (Teva Women’s Health, Sellersville, PA) is approved for 10 years of contraceptive use. Kyleena measures 28 mm horizontally and 30 mm vertically, similar to Skyla. Mirena and Liletta measure 32 mm horizontally and vertically. The ParaGard measures 32 mm horizontally and 36 mm vertically.
As noted in A Clinical Guide for Contraception,4 the copper-T IUD is approved for use in the United States for 10 years; however, the IUD has been demonstrated to provide efficacy for at least 12 years of use.5 Based on a small number of long-time users, using the copper-T IUD for 20 years carries a very small risk of pregnancy.6 The levonorgestrel IUD can be used for at least seven years and probably for 10 years.7,8 (Editor’s note: The Mirena IUD was the only levonorgestrel IUD available when A Clinical Guide for Contraception was written.)
Intrauterine contraceptives and the contraceptive implant offer top-tier pregnancy prevention, and their use is supported by the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics. Both organizations have issued policy statements affirming that LARC methods are safe, effective, and appropriate options for teens.9,10 (Contraceptive Technology Update reported on the subject. See the January 2014 article, “LARC methods: 7 things you need to know,” which is available at http://bit.ly/1T73i2V.)
Examine the Data
Researchers evaluated the contraceptive efficacy of Kyleena in a multicenter, multinational, randomized, open-label study conducted in 11 countries in Europe, Latin America, the United States, and Canada. Women less than six weeks postpartum, with a history of ectopic pregnancy, with clinically significant ovarian cysts, who are HIV-positive, or at high risk for STIs were excluded from the study. Women enrolled in the trial ranged in age from 18 to 35, of whom 1,452 received Kyleena. Of these, 40% (574) were nulliparous women. A total of 870 women (60%) completed three years of the study, 707 (49%) elected to enroll in an extension phase up to a total of five years, and 550 (38%) completed five years of use. Of Kyleena-treated women, 22% discontinued the study treatment due to an adverse reaction, 5.0% were lost to follow-up, 2.3% withdrew for unspecified reasons, 1.2% discontinued due to a protocol deviation, 0.9% discontinued due to pregnancy, and 20% discontinued due to other reasons.
The data indicate that the new IUD is more than 98.5% effective in preventing pregnancy. The clinical trial’s primary outcome was the pregnancy rate, calculated as the Pearl Index, based on 28-day equivalent exposure cycles. Evaluable cycles excluded those in which backup contraception was used unless a pregnancy occurred in that cycle. The pregnancy rate (95% confidence interval) was: in year one, 0.16 (0.02, 0.58); year two, 0.38 (0.10, 0.96); year three, 0.45 (0.12,1.15); year four, 0.15 (0.00, 0.85); and year five, 0.37 (0.04, 1.33). The cumulative five-year Kaplan-Meier rate was 1.45 (0.82, 2.53).11
Check Side Effect Profile
How is Kyleena tolerated? The most common adverse reactions (occurring in 5% or more of users) reported during the clinical trial were vulvovaginitis (24%), ovarian cyst (22%), abdominal pain/pelvic pain (21%), headache/migraine (15%), acne/seborrhea (15%), dysmenorrhea/uterine spasm (10%), breast pain/breast discomfort (10%), and increased bleeding (8%). In combined studies of Kyleena and the 13.5 mg IUD, 22% discontinued prematurely due to an adverse reaction. The most common adverse reactions leading to discontinuation in the clinical trial were increased bleeding (4.5%), abdominal pain/pelvic pain (4.2%), device expulsion (3.1%), acne/seborrhea (2.3%), and dysmenorrhea/uterine spasm (1.3%). Serious adverse reactions occurring in more than a single subject in the clinical trial included: ectopic pregnancy/ruptured ectopic pregnancy (10 women); pelvic inflammatory disease (six women); missed abortion/incomplete spontaneous abortion/spontaneous abortion (four women); ovarian cyst (three women); abdominal pain (four women); depression/affective disorder (four women); and uterine perforation/embedded device, also known as myometrial perforation (three women).11,12
As with other levonorgestrel IUDs, clinicians should counsel that bleeding and spotting may increase in the first three to six months and remain irregular. Periods over time usually become shorter, lighter, or may stop.
In talking about this new option, clinicians can point out that it represents an excellent birth control choice for women who desire a highly effective and long-term (approved for five years), but reversible, method of contraception. Intrauterine contraception can be inserted anytime during the menstrual cycle when pregnancy can be excluded. Lack of estrogen makes intrauterine contraceptives appropriate for smokers older than age 35, postpartum women who are breastfeeding, and others with contraindications to estrogen.13
REFERENCES
- Finer LB, Zolna MR. Declines in unintended pregnancy in the United States, 2008-2011. N Engl J Med 2016; 374(9):843-852.
- Finer LB, Jerman J, Kavanaugh ML. Changes in use of long-acting contraceptive methods in the United States, 2007-2009. Fertil Steril 2012; 98:893-897.
- Daniels K, Daugherty J, Jones J. Current contraceptive status among women aged 15-44: United States, 2011–2013. NCHS Data Brief 2014; (173):1-8.
- Speroff L, Darney PD. A Clinical Guide for Contraception. Philadelphia: Lippincott Williams & Wilkins; 2011.
- Long-term reversible contraception. Twelve years of experience with the TCu380A and TCu220C. Contraception 1997; 56(6):341-352.
- Sivin I. Utility and drawbacks of continuous use of a copper T IUD for 20 years. Contraception 2007; 75(6 Suppl):S70-S75.
- Sivin I, Stern J, Coutinho E, et al. Prolonged intrauterine contraception: A seven-year randomized study of the levonorgestrel 20 mcg/day (LNg 20) and the Copper T380 Ag IUDS. Contraception 1991; 44(5):473-480.
- Hidalgo MM, Hidalgo-Regina C, Bahamondes MV, et al. Serum levonorgestrel levels and endometrial thickness during extended use of the levonorgestrel-releasing intrauterine system. Contraception 2009; 80(1):84-89.
- American College of Obstetricians and Gynecologists. Committee Opinion #539. Adolescents and long-acting reversible contraception: Implants and intrauterine devices. Obstet Gynecol 2012; 120(4):983-988.
- American Academy of Pediatrics, Committee on Adolescence. Policy statement: Contraception for adolescents. Pediatrics 2014; 134:e1244-e1256.
- Bayer HealthCare Pharmaceuticals. FDA approves Bayer’s Kyleena (levonorgestrel-releasing intrauterine system) 19.5 mg for prevention of pregnancy for up to five years. Press release. Accessed at http://prn.to/2cDbQgB.
- Nelson A, Apter D, Hauck B, et al. Two low-dose levonorgestrel intrauterine contraceptive systems: A randomized controlled trial. Obstet Gynecol 2013; 122(6):1205-1213.
- Association of Reproductive Health Professionals. Choosing a birth control method. Fact sheet. Accessed at http://bit.ly/1lyAN7s.
