When the Food and Drug Administration (FDA) approved Skyla, a 13.5-mg levonorgestrel-releasing intrauterine system (LNG-IUS), early this year, it increased the number of IUDs available in the United States by one-third. The new device joins the copper IUD (ParaGard) and the 52-mg LNG-IUS (Mirena) as options for women seeking long-acting intrauterine contraception. The new device and Mirena both are manufactured by Bayer HealthCare Pharmaceuticals.
Skyla releases 14 μg of levonorgestrel daily, an amount that decreases progressively to 5 μg/day after 3 years. The device comes packaged within a sterile inserter and is approved for 3 years of use.
Approval followed a multinational Phase 3 trial
The trial involved 1,432 women 18 to 35 years old, 556 (38.8%) of whom were nulliparous. The primary efficacy endpoint used to assess contraceptive reliability was the pregnancy rate, calculated as the Pearl Index (PI). The PI estimate for the first year of use, based on the five pregnancies that occurred after the onset of treatment and within 7 days after Skyla removal or expulsion, was 0.41, with a 95% upper confidence limit of 0.96. The cumulative 3-year pregnancy rate, based on 10 pregnancies and 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
As a point of reference, the 12-month pregnancy rate for Mirena was ≤0.2%, and it was 0.5% over 5 years.2 The one-year pregnancy rate for ParaGard is 0.6% with perfect use, 0.8% with typical use.3
Of the women using Skyla, 21.9% discontinued because of an adverse event. The most common adverse reactions (occurring in ≥10% of users) were:
- changes in bleeding patterns
- vulvovaginitis
- abdominal or pelvic pain
- acne or seborrhea
- ovarian cyst
- headache.1
“These adverse events include anything that occurs during study. For 20% of sexually active women to have at least one episode of vulvovaginitis over 3 years is not a problem”—nor is an occasional twinge of abdominal pain, he adds.
Insertion and removal
Skyla should be inserted during the first 7 days of the menstrual cycle or immediately after a first-trimester abortion. No back-up contraception is needed if it is inserted at these times.
Postpartum insertions should take place a minimum of 6 weeks after delivery or after a second-trimester abortion to allow for complete uterine involution.
Skyla should be removed after 3 years of use, preferably during the menstrual cycle to allow for immediate insertion of a new device or initiation of an alternate method of contraception.
Bleeding patterns may change during early use
During the first 3 to 6 months of use, women may experience irregular periods and an increase in the number of bleeding days. Women also may have frequent spotting or light bleeding. Some women may experience heavy bleeding during this interval. Over time, the number of bleeding and spotting days is likely to decline, and there is a small chance that periods may stop altogether. In clinical trials, 6% of Skyla users developed amenorrhea by the end of the first year.1 By comparison, 20% of Mirena users developed amenorrhea by the end of the first year.2
The only IUD for nulliparas?
Although Skyla is the only IUD studied in a significant number of nulliparous women during Phase 3 studies, and its labeling states specifically that it is appropriate for use in this population, the other two IUDs are also safe for nulliparas.
“The label for ParaGard includes nulliparous and parous women,” notes Dr. Creinin. “The label for Mirena does not exclude nulliparous women, and there are huge numbers of studies about its use in teens and nulliparas. The only issue for Skyla is that the data presented to the FDA included nulliparous women, so the label reflects this fact.”
What’s the bottom line?
Skyla is an option for women who may desire a smaller IUD with a shorter duration of use. Although placement of Skyla is enhanced by a new inserter, compared with Mirena and ParaGard, Dr. Creinin notes that all IUD insertions, regardless of brand, are fairly straightforward. For example, a randomized trial by Gemzell-Danielsson and colleagues found that IUD insertion was “very difficult” in only 2 of 239 (0.8%) women receiving a prototype of Skyla and 4 of 254 (1.6%) women receiving Mirena.4
The cost of Skyla is approximately $650 (for 3 years of use) versus roughly $850 for Mirena and ParaGard (for 5 and 10 years of use, respectively).