New Progestin-Only Pill Receives FDA Approval
EXECUTIVE SUMMARY
Women who are seeking an estrogen-free form of contraception now have a new option: Slynd, a drospirenone progestin-only pill. The pill is scheduled to be stocked on pharmacy shelves in fall 2019.
- Each package contains 24 tablets of 4 mg drospirenone and four inert tablets. Tablets must be taken every day at about the same time of the day so that the interval between two tablets is always 24 hours.
- Women who frequently miss their progestin-only pills should consider an alternative contraceptive method, such as an intrauterine device, implant, or injectable that is less user-dependent for effectiveness.
Women who are seeking an estrogen-free form of contraception now have a new option: Slynd, a drospirenone progestin-only pill (POP). The pill is scheduled for release in fall 2019.
Each package contains 24 tablets of 4 mg drospirenone and four inert tablets. Currently marketed ethinyl estradiol/drospirenone pills contain 3 mg of drospirenone, while norethindrone POPs contain 0.35 mg of norethindrone. Combination pills often contain 1 mg of norethindrone or norethindrone acetate, a dose that is three times higher than that found in the norethindrone progestin-only pills.
In clinical trials, Slynd showed no instances of thromboembolic events in clinical trials. Its use is contraindicated in females with renal impairment; adrenal insufficiency; presence or history of cervical cancer or progestin-sensitive cancers; liver tumors, benign or malignant, or hepatic impairment; and undiagnosed abnormal uterine bleeding.
Women with conditions that predispose to hyperkalemia should not use Slynd due to its antimineralocorticoid activity.
Information on the 13-cycle registration clinical trial for Slynd is contained in its package labeling, In an efficacy analysis based on 953 participants — all 35 years of age or younger — researchers determined a Pearl Index of 4.0, comparable to the failure rate observed in recent U.S. clinical trials of short-acting estrogen-progestin contraceptives.
Data analysis shows the percentage of participants with scheduled bleeding or spotting fell from 81% in Cycle 1 to 26% in Cycle 13, while the overall percentage of women with unscheduled bleeding or spotting decreased from 61% in Cycle 1 to 40% in Cycle 13.
These observations suggest that while scheduled withdrawal bleeding and spotting decreases with increasing duration of use, unscheduled bleeding/spotting remains relatively common in users of the new POP, says Andrew Kaunitz, MD, associate chair of the department of obstetrics and gynecology at the University of Florida College of Medicine—Jacksonville, and medical director of the UF Health Women’s Specialists—Emerson.
The safety profile for the new pill was demonstrated for all patients, including higher-risk populations like smokers, older women, and subjects with a body mass index (BMI) below 30 kg/m2, notes Enrico Colli, MD, chief scientific officer at Exeltis.
Who Is Eligible for POP?
Progestin-only contraceptives are appropriate for women for whom use of estrogen-progestin contraceptives is associated with elevated cardiovascular risks, including smokers age 35 and older, high blood pressure, those with migraines with aura, women with a history of thrombosis, and those with multiple cardiovascular risk factors, notes Kaunitz.
However, due to the low dose and corresponding concerns regarding possible low contraceptive efficacy, some clinicians are reluctant to use the norethindrone POP in fully fertile women, such as those who are not breastfeeding.
Since the Slynd package label indicates that “negligible” levels of progestin are excreted in breast milk, the pill should be appropriate for postpartum/lactating women, as well as those with cardiovascular risk factors who should avoid combination hormonal methods, says Kaunitz. “The availability of a second, and presumably more effective, POP for our patients represents good news for U.S. women,” he states.
Counsel women who use Slynd to take one tablet daily for 28 consecutive days; one white active tablet daily during the first 24 days and one green inert tablet daily during the four following days. Tablets must be taken every day at about the same time of the day so that the interval between two tablets always is 24 hours.
According to the U.S. Selected Practice Recommendations for Contraceptive Use, unlike combined pills, progestin-only pills inhibit ovulation in about half of cycles, although this rate can vary in individuals.1
Peak serum steroid levels are reached about two hours after administration, followed by rapid distribution and elimination, with serum steroid levels near baseline 24 hours after administration.2 This rapid distribution and elimination underscores the importance of taking POPs at approximately the same time each day.
Research indicates that an estimated 48 hours of POP use is necessary to achieve contraceptive effects on cervical mucus.2 Women who frequently miss their progestin-only pills should consider an alternative contraceptive method, such as an intrauterine device, implant, or injectable that is less user-dependent for effectiveness.
According to the package insert, the most common side effects for Slynd are acne, headache, breast pain and tenderness, weight gain, menstrual cramps, nausea, severe vaginal bleeding, and less sexual desire. Women who cannot tolerate irregular bleeding or amenorrhea may not find progestin-only pills a good fit, Contraceptive Technology authors recommend.3
Robert Hatcher, MD, MPH, professor emeritus of gynecology and obstetrics at Emory University School of Medicine, notes that the authors of a European study suggests that POPs containing desogestrel 75 mcg may inhibit ovulation reliably even when pills are taken 12 hours late.4
In a study of the 4 mg drospirenone formulation, findings suggest the pill inhibited ovulation in nearly all women, despite intentional 24-hour delays in pill intake and a four-day hormone break.5
“It appears that highly effective progestin-only pills which do not require strict adherence to taking pills 24 hours apart may be viable,” says Hatcher.
REFERENCES
- Curtis KM, Jatlaoui TC, Tepper NK, et al. U.S. Selected Practice Recommendations for Contraceptive Use, 2016. MMWR Recomm Rep 2016; 65(4):1-66.
- McCann MF, Potter LS. Progestin-only oral contraception: A comprehensive review. Contraception 1994;50(Suppl 1):S1-195.
- Raymond EG, Grossman D. Progestin-only pills. In: Hatcher RA, Trussell J, Nelson AL, et al. Contraceptive Technology: 21st revised edition. New York: Ayer Company Publishers, 2018.
- Korver T, Klipping C, Heger-Mahn D, et al. Maintenance of ovulation inhibition with the 75-microg desogestrel-only contraceptive pill (Cerazette) after scheduled 12-h delays in tablet intake. Contraception 2005;71:8-13.
- Duijkers IJM, Heger-Mahn D, Drouin D, et al. Maintenance of ovulation inhibition with a new progestogen-only pill containing drospirenone after scheduled 24-h delays in pill intake. Contraception 2016; 93:303-309.
Women who are seeking an estrogen-free form of contraception now have a new option: Slynd, a drospirenone progestin-only pill. The pill is scheduled for release in fall 2019.
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