Ella Drug Information

Ella is a progesterone agonist/antagonist emergency contraceptive indicated for prevention of pregnancy following unprotected intercourse or a known or suspected contraceptive failure . Ella is not intended for routine use as a contraceptive. Ella is a progesterone agonist/antagonist emergency contraceptive indicated for prevention of pregnancy following unprotected intercourse or a known or suspected contraceptive failure. Ella is not intended for routine use as a contraceptive.

Recommended Dosage and

Administration Take one tablet of ella orally as soon as possible within 120 hours (5 days) after unprotected intercourse or a known or suspected contraceptive failure. Take ella with or without food. Take ella at any time during the menstrual cycle.

Recommendations Regarding Use with Hormonal Contraception After ella use, initiate or resume

hormonal contraception no sooner than 5 days after the intake of ella and use a reliable barrier method until the next menstrual period. For known or suspected failure of hormonal contraception refer to the hormonal contraceptive’s prescribing information for instructions on what to do .

Recommendation in Case of Gastrointestinal Disturbances

If vomiting occurs within 3 hours of taking ella, consider repeating the dose.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Ella was studied in an open-label multicenter trial (Open-Label Study) and in a comparative, randomized, single-blind, multicenter trial (Single-Blind Comparative Study). In these studies, a total of 2,637 (1,533 + 1,104) women in the 30 mg ulipristal acetate groups were included in the safety analysis. The mean age of women who received ulipristal acetate was 24.5 years and the mean body mass index (BMI) was 25.3. The racial demographics of those enrolled were 67% Caucasian, 20% Black or African American, 2% Asian, and 12% other.

The most common adverse reactions (≥ 10%) in the clinical trials for women receiving ella were headache (18% overall), nausea (12% overall) and abdominal and upper abdominal pain (12% overall). Table 1 lists those adverse reactions that were reported in ≥ 5% of subjects in the clinical studies. Table 1: Adverse Reactions in ≥ 5% of Women (%) Receiving a Single Dose of ella (30 mg Ulipristal Acetate) Most Common Adverse Reactions Open-Label Study Single-Blind Comparative Study N = 1,533 N = 1,104 Headache 18 19 Nausea 12 13 Abdominal and upper abdominal pain 15 8 Dysmenorrhea 7 13 Fatigue 6 6 Dizziness 5 5

Postmarketing Experience Adolescents: the safety profile observed in adolescents aged 17 and

younger in studies and post-marketing is similar to the safety profile in adults . The following adverse reactions have been identified during post-approval use of ella : Skin and Subcutaneous Tissue Disorders: Acne Hypersensitivity reactions, including rash, urticaria, pruritis, and angioedema Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Changes in Emergency Contraceptive Effectiveness Associated with Co-Administration of Other Products

CYP3A inducers Drugs or herbal products that induce CYP3A4 decrease the plasma concentrations of ella, and may decrease its effectiveness . Avoid co-administration of ella and drugs or herbal products such as: barbiturates bosentan carbamazepine felbamate griseofulvin oxcarbazepine phenytoin rifampin St. John's Wort topiramate Hormonal contraceptives Progestin-containing contraceptives may impair the ability of ella to delay ovulation. After using ella, if a woman wishes to initiate or resume hormonal contraception, she can do so, no sooner than 5 days after the intake of ella and she should use a reliable barrier method until the next menstrual period.

If a woman used ella due to a known or suspected failure of her hormonal contraception refer to the hormonal contraceptive’s prescribing information for instructions on what to do .

Increase in Plasma Concentrations of ella Associated with Co-Administered Drugs

CYP3A4 inhibitors such as itraconazole or ketoconazole increase plasma concentrations of ella .

Effects of ella on Co-Administered Drugs Hormonal contraceptives: ella may impact the

effect of the progestin component of hormonal contraceptives. Therefore, if a woman wishes to use hormonal contraception after using ella, she should use a reliable barrier method for subsequent acts of intercourse until her next menstrual period .

Pregnancy Risk Summary Ella is contraindicated for use during an existing or suspected pregnancy. No signal of concern regarding pregnancy complications was found in postmarketing studies. Isolated cases of major malformations in ella- exposed pregnancies were identified; however, the data are not sufficient to determine a risk for birth defects with inadvertent use of ella during pregnancy.

Miscarriage was reported in 14% of the known pregnancy outcomes; a rate that is similar to the U.S. background rate for miscarriage. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. In animal reproduction studies, no malformations were observed during repeated administration of ulipristal acetate to pregnant rats, rabbits and monkeys at daily drug exposures ⅓, ½, and 3 times respectively, the human exposure at a dose of 30 mg . Data Human Data Ella pregnancy exposure data was collected in the U.S. and Europe from 1999 to 2015 and analyzed post-marketing using data from interventional clinical trials, observational studies and pharmacovigilance reports.

Known pregnancy outcomes were available for 462/784 pregnancies in which women received ella at doses of 30 mg or greater during the conception cycle or during pregnancy. Data of pregnancies with known outcome were analyzed prospectively for 272 cases and retrospectively for 190 cases. Pregnancy outcomes included 302 elective abortions (2 for fetal anomalies including 1 with trisomy 21), 63 spontaneous abortions, and 13 ectopic pregnancies.

No maternal or fetal deaths were reported. 84 pregnancies continued until birth, with congenital anomalies reported in 5 infants, including 4 major malformations (2/4 with genetic syndromes). Although these data do not allow estimation of the prevalence rate of congenital anomalies associated with inadvertent use of ella in pregnancy or determination of a causal relationship between reported anomalies and ella, they show that ella -exposed pregnancies were not associated with a pattern of increased risk of adverse outcomes. Animal Data Ulipristal acetate was administered repeatedly to pregnant rats and rabbits during the period of organogenesis. Embryofetal loss was noted in all pregnant rats and in half of the pregnant rabbits following 12 and 13 days of dosing, at daily drug exposures 1/3 and 1/2 the human exposure, respectively, based on body surface area (mg/m 2 ). There were no malformations of the surviving fetuses in these studies.

Adverse effects were not observed in the offspring of pregnant rats administered ulipristal acetate during the period of organogenesis through lactation at drug exposures 1/24 the human exposure based on AUC. Administration of ulipristal acetate to pregnant monkeys for 4 days during the first trimester caused pregnancy termination in 2/5 animals at daily drug exposures 3 times the human exposure based on body surface area.

Pediatric Use There is no relevant use of ulipristal acetate for children of prepubertal age in the indication emergency contraception. Adolescents: Safety and efficacy of ella have been established in women of reproductive age. The clinical trials of ella enrolled 41 females under age 18, and a post-marketing observational study evaluating effectiveness and safety of ella in adolescents enrolled 279 females under age 18, including 76 under age 16 years.

In these studies, the safety and efficacy profile observed in adolescents aged 17 and younger was similar to that in adults. Use of ella before menarche is not indicated.

Ella is contraindicated for use in the case of known or suspected pregnancy. Known or suspected pregnancy

Experience with ulipristal acetate overdose is limited. In a clinical study, single doses equivalent to up to 4 times ella were administered to a limited number of subjects without any adverse reactions.