Ella (Page 3 of 6)

8.3 Females and Males of Reproductive Potential

Contraception

Progestin-containing contraceptives may impair the ability of ella to delay ovulation. Advise females to use a reliable barrier method for subsequent acts of intercourse until her next menstrual period.

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 of contraception 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 [see Dosage and Administration (2.2), Warnings and Precautions (5.5), Drug Interactions (7), and Clinical Pharmacology (12.2, 12.3)].

8.4 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.

8.5 Geriatric Use

This product is not intended for use in postmenopausal women.

8.6 Race

While no formal studies have evaluated the effect of race, a cross-study comparison of two pharmacokinetic studies indicated that exposure in South Asians may exceed that in Caucasians and African Americans. However, no difference in efficacy and safety was observed for women of different races in clinical studies.

8.7 Hepatic Impairment

No studies have been conducted to evaluate the effect of hepatic disease on the disposition of ella.

8.8 Renal Impairment

No studies have been conducted to evaluate the effect of renal disease on the disposition of ella.

10 OVERDOSAGE

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.

11 DESCRIPTION

The ella (ulipristal acetate) tablet for oral use contains 30 mg of a single active steroid ingredient, ulipristal acetate [17α-acetoxy-11β-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione], a synthetic progesterone agonist/antagonist. The inactive ingredients are lactose monohydrate, povidone K-30, croscarmellose sodium and magnesium stearate.

Ulipristal acetate is a white to yellow crystalline powder which has a molecular weight of 475.6. The structural formula is:

Ulipristal acetate structural formula
(click image for full-size original)

C30 H37 NO4

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

When taken immediately before ovulation is to occur, ella postpones follicular rupture. The likely primary mechanism of action of ulipristal acetate for emergency contraception is therefore inhibition or delay of ovulation; however, alterations to the endometrium that may affect implantation may also contribute to efficacy.

12.2 Pharmacodynamics

Ulipristal acetate is a selective progesterone receptor modulator with antagonistic and partial agonistic effects (a progesterone agonist/antagonist) at the progesterone receptor. It binds the human progesterone receptor and prevents progesterone from occupying its receptor.

The pharmacodynamics of ulipristal acetate depend on the timing of administration in the menstrual cycle. Administration in the mid-follicular phase causes inhibition of folliculogenesis and reduction of estradiol concentration.

Pharmacodynamic data showed that administration of ella to 34 women in the late follicular phase postponed follicular rupture for at least 5 days in all (100%) of 8 subjects who took ella before the luteinizing hormone (LH) surge and 11 (79%) of 14 subjects who took ella immediately before ovulation (when LH has already started to rise). However, treatment was not effective in postponing follicular rupture when administered on the day of LH peak.

Dosing in the early luteal phase does not significantly delay endometrial maturation but decreases endometrial thickness by 0.6 ± 2.2 mm (mean ± SD).

Hormonal Contraceptives after ella intake:

In women initiating hormonal contraception (quickstart scenario):

When a combined oral contraceptive pill (COC) containing ethinyl estradiol 30 µg + levonorgestrel 150 µg was started the day after ella intake during the follicular phase, ella did not interfere with the COC’s ability to suppress ovarian activity, as assessed by measurement of follicle size via transvaginal ultrasound, combined with serum progesterone and estradiol levels: ovarian activity was suppressed in 61.5% (24/39) of subjects receiving ella plus COC and 62.2% (23/37) of subjects receiving a placebo plus the COC. The incidence of ovulation was similar between the group that received ella plus the COC [33.3% (13/39)] and the group that received a placebo plus the COC [32.4% (12/37)]. [see Dosage and Administration (2.2), Warnings and Precautions (5.5) and Drug Interactions (7.3)].

The initiation of a desogestrel 75 µg progestin-only pill (POP) the day after ella intake during the follicular phase was associated with a higher incidence of ovulation in the six days following ella intake compared to an ella -only treatment group, and a relatively slower onset (3 to 4 days) of thickened cervical mucus compared to a group given desogestrel without prior ella intake (2 days), suggesting an effect of prior use of ella on the ability of desogestrel to inhibit mucus permeability. [See Dosage and Administration (2.2), Warnings and Precautions (5.5) and Drug Interactions (7.1; 7.3)].

When a COC containing ethinyl estradiol 30 µg + levonorgestrel 150 µg was started 2 days after ella intake, ella ‘s ability to delay ovulation, as assessed by transvaginal ultrasound, was reduced: follicular rupture occurred in 9/33 subjects (27%) in less than 5 days, compared to 1/33 subjects after ella alone (3%). [See Dosage and Administration (2.2), Warnings and Precautions (5.5) and Drug Interactions (7.1)].

In women resuming combined hormonal contraception (missed pills scenario):

The effects on ovarian activity of delaying versus immediately resuming COCs after ella intake were investigated in 49 women who had been using COCs containing ethinyl estradiol 30 µg + levonorgestrel 150 µg once daily for 21 days followed by 7 days of placebo pills for at least one cycle. All subjects missed three consecutive pills (Days 5-7) during the first week of pills in the subsequent cycle and took ella on the following day (Day 8). These subjects were randomized to resume their COCs either on the same day as ella intake versus five days later. No ovulations with potential risk of pregnancy occurred in either group in the five days following ella intake. However, in the group that waited five days to resume taking COCs, 4/23 (17.4%) women did ovulate later in the cycle (Days 18-26) whereas no ovulations (0/26) occurred in the group that resumed COC intake on the same day as ella intake. Whether similar results can be expected with other COC products containing different progestins or missed active pills during different weeks in a treatment cycle is unknown.

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