Annovera From TherapeuticsMD and Population Council

The FDA has approved Annovera (segesterone acetate and ethinyl estradiol vaginal system) from TherapeuticsMD and the Population Council for pregnancy prevention.¹ Annovera is the first long-acting prescription birth control that is patient controlled, procedure free, and reversible. It is a flexible, soft ring that can prevent ovulation for 1 year and can be used long term, including by those who are nulliparous.² The approval carries the limitation that Annovera has not been adequately evaluated in women with a body mass index (BMI) greater than 29 kg/m2.¹

PHARMACOLOGY AND PHARMACOKINETICS

Annovera is a combination hormonal contraceptive (CHC) that suppresses ovulation to reduce the chance of pregnancy.¹ The system releases an average continuous daily dose of 0.15 mg of segesterone acetate and 0.013 mg of ethinyl estradiol^.1,2

DOSING AND ADMINISTRATION

Annovera is supplied as a single silicone elastomer vaginal system with 103 mg of segesterone acetate and 17.4 mg of ethinyl estradiol. One system should be inserted vaginally and remain in place continuously for 21 days. It should then be removed for 7 days to allow a 1-week dose-free interval, at which point a withdrawal bleed may occur. After removal, it should be cleaned with mild soap and warm water, patted dry with a clean cloth or paper towel, and placed in its case for the dose-free interval. This schedule is repeated with the same ring every 4 weeks for 13 cycles.^1,3

CLINICAL TRIALS

The efficacy of Annovera was evaluated in 2 multicenter trials of 2111 women aged 18 to 40 years. The study participants were healthy and sexually active, with regular menstrual cycles. The mean age of participants was 26.7 years, and the mean BMI was 24.1 kg/m.² After 1 year, the pooled pregnancy rate was 2.98 per 100 woman-years of Annovera use. Return to fertility, which was determined by pregnancy or return of menses, was evaluated in 290 patients, who either discontinued use of Annovera or switched to a nonhormonal method of contraception at the study’s end. All 290 participants experienced a return to fertility within 6 months of stopping Annovera.¹

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Annovera carries a boxed warning that the risk of serious cardiovascular events is greatly increased in patients who smoke cigarettes while using CHC. Because this risk increases with age, Annovera should not be used in women over 35 who smoke.

Annovera is contraindicated in women with acute hepatitis, current or history of breast cancer or other estrogen- or progestin-sensitive cancer, high risk of arterial or venous thrombotic diseases, hypersensitivity to any of the components of Annovera, liver tumors, severe cirrhosis, or undiagnosed abnormal uterine bleeding. The use of Annovera in combination with hepatitis C medications containing ombitasvir/ paritaprevir/ritonavir, with or without dasabuvir, is also contraindicated. Women also must wait 2 weeks after the completion of treatment with ombitasvir/pari- taprevir/ritonavir before initiating Annovera.

Annovera should be stopped if a thromboembolic or thrombotic event occurs, as well as jaundice. It also should not be used in women with hypertension with vascular disease or uncontrolled hypertension. Cardiovascular risk factors should be considered in all women before using Annovera, especially in those over age 35 years.

Women should not use the system at least 4 weeks before and until 2 weeks after major surgery and no earlier than 4 weeks after delivery if they are not breastfeeding. Annovera should not be used during breastfeeding or pregnancy. Women with diabetes or prediabetes should have their blood glucose monitored while using Annovera. Women with uncontrolled dyslipidemias may require a different contraception method. Discontinuation of Annovera may be warranted if significant changes in headaches occur. Women using Annovera may experience amenorrhea or irregular bleeding. Concomitant use of substances that induce certain enzymes, including CYP3A4, may decrease the effectiveness of Annovera or increase breakthrough bleeding.

The most common adverse reactions (>5% incidence) are abdominal pain, bleeding irreg- ularities, breast tenderness/pain/discom- fort, diarrhea, dysmenorrhea, genital pruritus, headache, migraine, nausea, urinary tract infection, vaginal discharge, vomiting, and vulvovaginal mycotic infection/candidiasis.¹

References

• Annovera [prescribing information]. New York, NY: Population Council; 2018. annovera.com/pi.pdf.Accessed January 22, 2019.
• TherapeuticsMD announces FDA approval of Annovera (segesterone acetate/ethinyl estradiol vaginal system) for birth control [news release]. Boca Raton, FL: TherapeuticsMD; August 10, 2018. ir.therapeuticsmd.com/news-releases/news-release-details/therapeuticsmd-announces-fda-approval-annoveratm-segesterone#. Accessed January 22, 2019.
• FDA approves new vaginal ring for one year of birth control [news release]. Silver Spring, MD: FDA; August 10, 2018. fda.gov/newsevents/newsroom/pressannouncements/ucm616541.htm.Accessed January 22, 2019.

Monica Holmberg, PharmD, BCPS, earned her PharmD at the University of Connecticut in Storrs and completed an ambulatory care residency at the Phoenix VA Health Care System in Arizona. Her practice has also included pediatrics and inpatient mental health. She lives in Phoenix.