Consumer medicine information

EllaOne

Ulipristal acetate

BRAND INFORMATION

Brand name

EllaOne

Active ingredient

Ulipristal acetate

Schedule

S3

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using EllaOne.

What is in this leaflet

This leaflet answers some common questions about EllaOne®. It does not contain all the available information. It does not take the place of talking to your pharmacist or doctor.

All medicines have risks and benefits. Your pharmacist or doctor has weighed the risks of you being given EllaOne® against the expected benefits it will have for you.

If you have any concerns about being given this medicine, ask your pharmacist or doctor.

Keep this leaflet. You may need to read it again.

What EllaOne® is used for

EllaOne® is an oral emergency contraceptive intended to prevent pregnancy after unprotected sex or if your contraceptive method has failed, for example:

  • if you had sex without protection;
  • if your or your partner’s condom tore, slipped or came off, or if you forgot to use one;
  • if you did not take your birth control pill as recommended.

You should take EllaOne® as soon as possible after sex, and within a maximum of 5 days (120 hours). This is because the sperm can survive up to 5 days in your body after intercourse.

EllaOne® is suitable for any woman of child bearing age, including adolescents.

You can take EllaOne® at any time in the menstrual cycle.

EllaOne® contains the substance ulipristal acetate, which acts by modifying the activity of the natural hormone progesterone which is necessary for ovulation to occur. As a result, EllaOne® works by postponing ovulation.

Emergency contraception is not effective in every case: of 100 women who take EllaOne®, approximately 2 will become pregnant.

EllaOne® does not work if you are already pregnant.

EllaOne® is not suitable as a regular method of contraception.

After using EllaOne®, if you want to have sex, you should use a reliable barrier contraceptive method such as condom. This is because EllaOne® will not work if you have unprotected sex again.

EllaOne® does not protect against HIV infection (AIDS) or any other sexually transmitted diseases (such as chlamydia, genital herpes, genital warts, gonorrhoea, hepatitis B and syphilis). Only condoms can protect you from these diseases.

Ask your pharmacist or doctor if you have any questions about why this medicine has been recommended for you.

Before you take EllaOne®

When you must not take it

  • if you know or suspect that you are pregnant.
  • if you are allergic to ulipristal acetate, or to any of the other ingredients listed under “Product description”.

You should not use this medicine after the expiry date printed on the EllaOne® pack or if the packaging is torn or shows signs of tampering.

After using EllaOne®, if you want to have sex, you should use a reliable barrier contraceptive method such as condom. This is because EllaOne® will not work if you have unprotected sex again.

Emergency contraception is a backup method for preventing pregnancy and should only be used occasionally. Your pharmacist, doctor or healthcare provider can tell you about long-term methods of contraception that may be appropriate for you.

Before you start to take EllaOne®

Tell your pharmacist or doctor if you have allergies to any other medicines, foods, preservatives or dyes.

EllaOne® contains lactose. Tell your pharmacist, doctor or healthcare provider if you have intolerance to some sugars.

Tell your pharmacist, doctor, or healthcare provider:

  • if your period is late or you have symptoms of pregnancy (heavy breasts, morning sickness), as you may already be pregnant
  • if you suffer from severe asthma.
  • if you suffer from severe liver disease.

If you have not told your pharmacist or doctor about any of the above, tell him/her before you take EllaOne®.

Pregnancy
EllaOne® is a contraceptive used to prevent a pregnancy from starting. If you are already pregnant it will not interrupt an existing pregnancy.

If you are breast-feeding
Do not breast-feed your baby for one week after taking EllaOne®. During this time, it is recommended to use a breast pump in order to maintain milk production but throw away your breast milk. The effect of breastfeeding your baby in the week after taking EllaOne® is not known.

Fertility
EllaOne® will not affect your future fertility. If you have unprotected sex after taking EllaOne®, it will not stop you from becoming pregnant. Therefore it is important you use condoms until your next period. After using EllaOne®, if you wish to start using regular hormonal contraception such as birth control pills, you should do so no sooner than 5 days after the intake of EllaOne®. Be sure to also use a reliable barrier contraceptive method such as condoms until your next period.

Taking other medicines

Tell your pharmacist or doctor if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket, health food shop, naturopath, herbalist or internet.

Some medicines may make EllaOne® less effective. Ask your pharmacist or doctor if EllaOne® is right for you if you have used any of the medicines listed below in the last few weeks:

  • Phenytoin, fosphenytoine, phenobarbital, primidone, carbamazepine, oxcarbazepine (used to treat epilepsy)
  • Ritonavir,efavirenz, nevirapine (used to treat HIV infection)
  • Rifampicin, rifabutin (used to treat certain bacterial infections)
  • Herbal remedies containing St John's wort (Hypericum perforatum) (used for depression or anxiety)

Using EllaOne® with regular hormonal contraceptives could reduce contraceptive action of both drugs. After using EllaOne®, if you wish to start using regular hormonal contraception such as birth control pills, you should do so no sooner than 5 days after the intake of EllaOne®.

Be sure to also use a reliable barrier contraceptive method such as condoms until your next period.

If you have already been using a hormonal contraceptive but took EllaOne® because you thought that it had failed to work, you should continue using the hormonal contraceptive on the same day as taking EllaOne®.

Your pharmacist or doctor may have more information on medicines to be careful with or avoid while being treated with EllaOne®.

How to take EllaOne®

How much to take

Your pharmacist or doctor will tell you how and when to take EllaOne®.

The recommended dose of EllaOne® is one tablet.

EllaOne® is for occasional use only and should not be used to as regular contraceptive method.

How to take EllaOne®

The EllaOne® tablet should be taken orally.

When to take EllaOne®

  • Take one tablet by mouth as soon as possible and no later than 120 hours (5 days) after you have had unprotected sex or contraceptive failure. Take the tablet without delay.
  • You can take EllaOne® at any time in your cycle.
  • You can take EllaOne® either before, during or after a meal.
  • If you vomit within 3 hours of taking an EllaOne® tablet, you should consult your pharmacist, doctor or healthcare provider in order to take another tablet.

If you forget to take it

If you miss taking EllaOne® within 5 days (120 hours) after sex, it cannot be relied upon to work as a contraceptive. It is important to contact your doctor.

If you take too much (overdose)

There has been no report of harmful effects from taking higher dose than recommended of this medicine.

However, telephone your pharmacist, doctor, or the Poisons Information Centre (13 11 26) if you take too many EllaOne® tablets.

Side effects

Tell your pharmacist or doctor as soon as possible if you do not feel well while you are taking EllaOne®.

Do not be alarmed by the following list of side effects, you may not experience any of them.

Tell your pharmacist or doctor if you notice any of the following common side effects and they worry you:

  • nausea, abdominal pain, abdominal discomfort, vomiting
  • headache, dizziness
  • painful menses, pelvic pain, breast tenderness
  • tiredness
  • mood swings
  • muscle pain, back pain

Other uncommon side effects include:

  • diarrhoea, dry mouth, heartburn, intestinal gases
  • abnormal vaginal bleeding and menstrual disorder (heavy/prolonged periods, premenstrual syndrome)
  • vaginal inflammation, vaginal discharge
  • hot flushes
  • influenza, fever, chills
  • feeling sick
  • appetite changes, emotional disorders, anxiety, agitation, trouble sleeping, sleepiness, decreased / increased libido
  • acne, skin lesion, itching
  • migraine
  • visual disturbances

Tell your pharmacist or doctor if you notice anything that is making you feel generally unwell.

Other side effects not listed above are rare and may also occur in some people.

After taking EllaOne®, some women experience dizziness, drowsiness, blurred vision and/or loss of concentration. If you experience such symptoms, do not drive or use machines.

After taking EllaOne®

After using EllaOne®, if you want to have sex, you should use a reliable barrier contraceptive method such as condom. This is because EllaOne® will not work if you have unprotected sex again.

After using EllaOne®, if you wish to start hormonal contraception such as birth control pills in the same cycle, you should do so no sooner than 5 days after taking EllaOne®, and you should still use a reliable barrier contraceptive method such as condoms until your next period.

After taking EllaOne®, most women have a normal period at the expected time. But some may have their period later or earlier than normal (see “Side effects”). If your period is more than 7 days late or is unusually light or unusually heavy or if you experience symptoms such as abdominal pain, nausea, vomiting or breast pain or if you have any doubt about being pregnant, you should perform a pregnancy test to make sure you are not pregnant.

If you do become pregnant after taking EllaOne®, it is important to contact your doctor. As for any pregnancy, your doctor may want to check that the pregnancy is not outside the womb. This is especially important if you have severe abdominal (stomach) pain or bleeding or if you have previously had a pregnancy outside the womb, tubal surgery or long term (chronic) genital infection.

Storage

Store below 25°C. Store in the original packaging to protect from moisture. Keep the blister in the outer carton to protect from light.

Keep EllaOne® where children cannot reach it.

Disposal

Dispose of EllaOne® in a secure place such that children and others cannot access the disposed product.

Product description

What it looks like

The EllaOne® tablet is a white to marble creamy, round curved tablet engraved on both faces with the code “еllа”.

Each tablet contains 30 mg of ulipristal acetate.

EllaOne® is available in the following pack size: carton containing one blister of 1 tablet.

Ingredients

The EllaOne® tablet contains the active ingredient ulipristal acetate, plus the inactive ingredients lactose monohydrate, povidone, croscarmellose sodium and magnesium stearate.

Supplier

EllaOne® is supplied in Australia by:

Brand Solutions Australia,
Level 3, Suite 72, 574 Plummer St
Port Melbourne, VIC 3207, Australia.
Telephone 1800 978 628
Email: [email protected]

EllaOne® is a registered trademark and product of:

Laboratoire HRA Pharma,
200 avenue de Paris
92320 CHATILLON
France

Australian registration number: AUST R 219535

This leaflet was revised in August 2019.

Copyright 2016. All rights reserved.

Published by MIMS June 2021

BRAND INFORMATION

Brand name

EllaOne

Active ingredient

Ulipristal acetate

Schedule

S3

 

1 Name of Medicine

Ulipristal acetate.

2 Qualitative and Quantitative Composition

Each tablet contains 30 mg of ulipristal acetate.

List of excipients with known effect.

Contains sugars (as lactose).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

EllaOne is a white to marble creamy, round tablet engraved on both faces with the code "еllа".

4 Clinical Particulars

4.1 Therapeutic Indications

Emergency contraception within 120 hours (5 days) of unprotected sexual intercourse or contraceptive failure.

4.2 Dose and Method of Administration

Dosage.

The treatment consists of one tablet to be taken orally as soon as possible, but no later than 120 hours (5 days) after unprotected intercourse or contraceptive failure.
EllaOne can be taken at any time during the menstrual cycle.
If vomiting occurs within 3 hours of EllaOne intake, another tablet should be taken.
If a woman's menstrual period is late or in case of symptoms of pregnancy, pregnancy should be excluded before EllaOne is administered.
EllaOne is more effective if taken in the first 24 hours following unprotected intercourse.

Method of administration.

Oral use.

The tablet can be taken with or without food.

Dosage adjustment in special populations.

Renal impairment.

No dose adjustment is necessary.

Hepatic impairment.

EllaOne is not recommended in severe hepatic impairment. No alternate dose recommendations for EllaOne can be made for mild or moderate hepatic impairment in the absence of specific studies.

Paediatric population (adolescents).

Adolescents of childbearing age - no differences in safety or efficacy have been shown compared to adult women aged 18 and older.
There is no relevant use of ulipristal acetate for children of prepubertal age in emergency contraception.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the listed excipients.
EllaOne should not be given to pregnant women. If menstrual bleeding is overdue, if the last menstrual period was abnormal in timing or character or if pregnancy is suspected for any other reason, pregnancy should be excluded (by pregnancy testing or pelvic examination) before treatment is given.
If a woman has had unprotected intercourse more than 120 hours earlier in the same menstrual cycle, conception may have already occurred. Treatment with EllaOne following the second act of intercourse may therefore be ineffective in preventing pregnancy.

4.4 Special Warnings and Precautions for Use

EllaOne does not prevent pregnancy every time.

EllaOne inhibits or postpones ovulation. If ovulation has already occurred, EllaOne is no longer effective. The timing of ovulation cannot be predicted and therefore EllaOne should be taken as soon as possible after unprotected intercourse.
No data are available on the efficacy of EllaOne when taken more than 120 hours (5 days) after unprotected intercourse.
Women who become pregnant after taking EllaOne should contact their doctor. If the next menstrual period is more than 7 days late, if the menstrual period is abnormal in character or if there are symptoms suggestive of pregnancy or in case of doubt, a pregnancy test should be performed. As with any pregnancy, the possibility of an ectopic pregnancy should be considered. It is important to know that the occurrence of uterine bleeding does not rule out ectopic pregnancy.
After EllaOne intake menstrual periods can sometimes occur a few days earlier or later than expected. In approximately 7% of the women, menstrual periods occurred more than 7 days earlier than expected. In 18.5% of the women a delay of more than 7 days occurred, and in 4% the delay was greater than 20 days.
Exclude pregnancy if suspected clinically before EllaOne is administered.
Concomitant use of ulipristal acetate with an emergency contraceptive containing levonorgestrel is not recommended.
Repeated use of EllaOne in the same menstrual cycle is not recommended. Women who present for repeated courses of emergency contraception should be advised to consider a long-term method of contraception, as emergency contraception is not as effective as conventional regular methods of contraception.
Use in women with severe asthma treated with oral glucocorticoids is not recommended.

Contraception after EllaOne intake.

EllaOne is an emergency contraceptive that decreases pregnancy risk after unprotected intercourse but does not confer contraceptive protection for subsequent acts of intercourse. Therefore, after using emergency contraception, women should be advised to use a reliable barrier method until the next menstrual period.
EllaOne is for occasional use only. It should in no instance replace a regular contraceptive method. In any case, women should be advised to adopt a regular method of contraception.
Because EllaOne binds to the same progesterone receptor as regular hormonal contraception, using them together could reduce contraceptive action. After using EllaOne, if a woman wishes to initiate regular hormonal contraception, she should do so no sooner than 5 days after the intake of EllaOne, provided that she uses a reliable barrier method until the next menstrual period. If she used EllaOne due to a perceived failure of her combined hormonal contraceptive (e.g. pill, patch, ring), she should resume this contraceptive method following the intake of EllaOne (within the same day) while using a reliable barrier method until the next menstrual period.

Specific populations.

This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption, should not take this medicine.

Use in the elderly.

No data available.

Paediatric use.

Post-pubertal adolescents.

No differences in safety or efficacy have been shown compared to adult women aged 18 and older.

Effects on laboratory tests.

No laboratory test interactions were observed during clinical evaluations.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Potential for other medicines to affect ulipristal acetate.

Hormonal contraceptives. Pharmacodynamic data show that progestin containing contraceptives may impair the ability of EllaOne to delay ovulation. The initiation of a desogestrel only pill the day after EllaOne intake during the follicular phase was associated with a higher incidence of ovulation in the five days following EllaOne intake. Therefore, if a woman wishes to initiate progestin-containing regular contraceptives, she can do so no sooner than 5 days after the intake of EllaOne, provided that she uses a reliable barrier method until the next menstrual period. If she used EllaOne due to a perceived failure of her combined hormonal contraceptive (e.g. pill, patch, ring), she should resume this contraceptive method following the intake of EllaOne (within the same day) while using a reliable barrier method until the next menstrual period.
Concomitant use of ulipristal acetate emergency contraception and levonorgestrel emergency contraception is not recommended.
CYP3A4 inducers and inhibitors. Ulipristal acetate is metabolised by CYP3A4 in vitro.

CYP3A4 inducers.

In vivo results show that the administration of ulipristal acetate with a strong CYP3A4 inducer such as rifampicin markedly decreases Cmax and AUC of ulipristal acetate by 90% or more and decreases ulipristal acetate half-life by 2.2-fold corresponding to an approximately 10-fold decrease of ulipristal acetate exposure. Concomitant use of EllaOne with CYP3A4 inducers (e.g. rifampicin, phenytoin, phenobarbital, carbamazepine, efavirenz, fosphenytoin, nevirapine, oxcarbazepine, primidone, rifabutin, St John's wort/ Hypericum perforatum) therefore reduces plasma concentrations of ulipristal acetate and may result in a decreased efficacy of EllaOne and is not recommended.

CYP3A4 inhibitors.

In vivo results show that administration of ulipristal acetate with a potent and a moderate CYP3A4 inhibitor increased Cmax and AUC of ulipristal acetate with a maximum of 2 and 5.9-fold, respectively. The effects of CYP3A4 inhibitors are unlikely to have any clinical consequences.
The CYP3A4 inhibitor ritonavir can also have an inducing effect on CYP3A4 when ritonavir is used for a longer period. In such cases ritonavir might reduce plasma concentrations of ulipristal acetate. Concomitant use is therefore not recommended. Enzyme induction wears off slowly and effects on the plasma concentrations of ulipristal acetate may occur even if a woman has stopped taking an enzyme inducer within the last 2-3 weeks.
Medicines affecting gastric pH. Administration of ulipristal acetate (10 mg tablet) together with the proton pump inhibitor esomeprazole (20 mg daily for 6 days) resulted in approximately 65% lower mean Cmax, a delayed Tmax (from a median of 0.75 hours to 1.0 hours) and 13% higher mean AUC. This interaction is not expected to have an impact on the efficacy of ulipristal acetate single dose for emergency contraception.

Potential for ulipristal acetate to affect other medicines.

Hormonal contraceptives. Pharmacodynamic data suggest that EllaOne may impact the effect of progestin containing hormonal contraceptives: the initiation of a desogestrel only pill the day after EllaOne intake during the follicular phase was associated with a higher incidence of ovulation in the five days following EllaOne intake and a slower onset of mucus blockage compared to desogestrel without prior EllaOne intake, suggesting an effect of prior use of EllaOne on the ability of desogestrel to inhibit mucus permeability. When a combined oral contraceptive pill (COCP) was started the day after EllaOne intake during the follicular phase, EllaOne did not interfere with COCP's ability to induce ovarian quiescence, but ovulation occurred later in the cycle in some women. Therefore, if a woman wishes to initiate or resume regular hormonal contraception after using EllaOne, it is recommended that for subsequent acts of intercourse she uses a reliable barrier method until the next menstrual period.
P-gp substrates. In vitro data indicate that ulipristal acetate may be an inhibitor of P-gp at clinically relevant concentrations. Results in vivo with the P-gp substrate fexofenadine were inconclusive. The effects of P-gp substrates are unlikely to have any clinical consequences.
BCRP substrates.

BCRP (breast cancer resistance protein) transporters.

In vitro data indicate that ulipristal acetate may be an inhibitor of BCRP at the intestinal level at clinically relevant concentrations. However, the effects of ulipristal acetate on BCRP are unlikely to have any clinical consequences given the pattern of clinical use of this product and the rapid absorption of ulipristal acetate from the GI tract.
Other medicines metabolised by CYP enzymes. In vitro data indicate that ulipristal acetate and its active metabolite do not significantly inhibit CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4, at clinically relevant concentrations. After single dose administration induction of CYP1A2 and CYP3A4 by ulipristal acetate or its active metabolite is not likely. Thus, administration of ulipristal acetate is unlikely to alter the clearance of medicines that are metabolised by these enzymes.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

A rapid return of fertility is likely following treatment with EllaOne for emergency contraception. Women should be advised to use a reliable barrier method for all subsequent acts of intercourse until the next menstrual period.
(Category D)
EllaOne should not be taken by any woman suspected or known to be pregnant.
Ulipristal acetate caused embryofetal lethality following repeated administration in the period following implantation in rats, rabbits and monkeys at subclinical doses (based on body surface area), occurring in the absence of maternotoxicity. In utero exposure to ulipristal acetate during gestation did not lead to increases in fetal malformations, skeletal anomalies or other developmental toxicity in surviving fetuses, including the fertility of surviving offspring. The clinical relevance of these findings is uncertain.
Limited human data regarding pregnancy exposure to EllaOne do not suggest any safety concern with use during early pregnancy.
 Ulipristal acetate is excreted in breast milk. The effect on newborn/ infants has not been studied. A risk to the breastfed child cannot be excluded. After intake of EllaOne, breastfeeding is not recommended for one week. During this time it is recommended to express and discard the breast milk in order to stimulate lactation.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effect on the ability to drive and use machines have been performed.
EllaOne may have minor or moderate influence on the ability to drive or use machines: mild to moderate dizziness is common after EllaOne intake; somnolence and blurred vision are uncommon; disturbance in attention has been rarely reported. The patient should be advised not to drive or use machines if they are experiencing such symptoms.

4.8 Adverse Effects (Undesirable Effects)

Summary of the safety profile.

The safety of ulipristal acetate has been evaluated in 4,718 women during the clinical development program.
The most commonly reported adverse reactions were headache, nausea, abdominal pain and dysmenorrhea.

Tabulated list of adverse reactions.

The adverse reactions reported in the phase III program of 2,637 women are provided in Table 1. The vast majority of adverse reactions were mild or moderate and resolved spontaneously.
Adverse reactions listed in Table 1 are classified according to frequency and system organ class. Within each frequency grouping, adverse reactions are presented in order of decreasing frequency.
Table 1 lists adverse reactions according to system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) and rare (≥ 1/10,000 to < 1/1,000).

Adolescents.

The safety profile observed in women less than 18 years old in studies and postmarketing is similar to the safety profile in adults during the phase III program.

Postmarketing experience.

The adverse reactions spontaneously reported in postmarketing were similar in nature to the safety profile described during the phase III program.
Hypersensitivity reactions including rash, urticaria, swelling face, angioedema were also reported rarely. 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.

Description of selected adverse reactions.

The majority of women (74.6%) in the phase III studies had their next menstrual period at the expected time or within ± 7 days, while 6.8% experienced menses more than 7 days earlier than expected and 18.5% had a delay of more than 7 days beyond the anticipated onset of menses. The delay was greater than 20 days in 4% of the women.
A minority (8.7%) of women reported intermenstrual bleeding lasting an average of 2.4 days. In a majority of cases (88.2%), this bleeding was reported as spotting. Among the women who received EllaOne in the phase III studies, only 0.4% reported heavy intermenstrual bleeding.
In the phase III studies, 82 women entered a study more than once and therefore received more than one dose of EllaOne (73 women enrolled twice and 9 enrolled three times). There were no safety differences in these subjects in terms of incidence and severity of adverse events, change in duration or volume of menses or incidence of intermenstrual bleeding.
In a pharmacodynamic study, where 23 subjects had multiple intakes in the same cycle, EllaOne was well tolerated with a safety and bleeding profile similar to that observed for a single 30 mg dose.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Experience with ulipristal acetate overdose is limited. Single doses up to 200 mg have been used in women without safety concern. Such high doses were well tolerated; however, these women had a shortened menstrual cycle (uterine bleeding occurring within 2-3 days earlier than would be expected) and in some women, the duration of bleeding was prolonged, although not excessive in amount (spotting). There are no antidotes and further treatment should be symptomatic.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: sex hormones and modulators of the genital system, emergency contraceptives. ATC code: G03AD02.

Mechanism of action.

Ulipristal acetate is an orally active synthetic selective progesterone receptor modulator that acts via high affinity (nanomolar) binding to the human progesterone receptor. Its major metabolite, monodesmethyl ulipristal, has comparable affinity for the progesterone receptor. When used for emergency contraception the mechanism of action is inhibition or delay of ovulation via suppression of the luteinising hormone (LH) surge. Pharmacodynamic data show that even when taken immediately before ovulation is scheduled to occur (when LH has already started to rise), ulipristal acetate is able to postpone follicular rupture for at least 5 days in 78.6% of cases (p < 0.005 vs. levonorgestrel and vs. placebo) (see Table 2).
Ulipristal acetate also has high affinity for the glucocorticoid receptor and, antiglucocorticoid effects have been observed in vivo in animals. However, in humans, no such effect has been observed even after repeat administration at a daily dose of 10 mg. Ulipristal acetate has weak affinity for the androgen receptor and negligible affinity for the human oestrogen and mineralocorticoid receptors.

Clinical trials.

Two multicenter phase III clinical studies evaluated the efficacy and safety of EllaOne up to 120 hours after unprotected intercourse. A single blind comparative study (HRA2914-513 study) provided the primary data to support the efficacy and safety of ulipristal acetate for emergency contraception when taken 0 to 72 hours after unprotected intercourse and provided supportive data for ulipristal acetate for emergency contraception when taken > 72 to 120 hours after unprotected intercourse. An open label study (HRA2914-509 study) provided the primary data to support the efficacy and safety of ulipristal acetate for emergency contraception when taken 48 to 120 hours after unprotected intercourse. Additionally, one phase II study contributed to establishing efficacy of EllaOne compared to levonorgestrel within 72 hours of unprotected intercourse. The three studies are described below.
i) Single blind comparative study. This study was a multicentre, single blind, randomized comparison of the efficacy and safety of 30 mg ulipristal acetate (EllaOne) to levonorgestrel (another drug used for emergency contraception). Main inclusion criteria were women presenting for emergency contraception within 120 hours of unprotected intercourse, 16 years or more in UK (except Northern Ireland), 17 years or more in Northern Ireland (UK) and 18 years or more in Ireland and US, with regular cycle length (24 to 35 days).
In total, 2,221 healthy women with a mean age of 25 years who requested emergency contraception within 120 hours of unprotected intercourse were enrolled and randomly allocated to receive EllaOne (n = 1,104) or levonorgestrel 1.5 mg (n = 1,117).
The primary efficacy measurement was the pregnancy rate, calculated as the number of pregnancies after administration of emergency contraception, divided by the number of subjects administered emergency contraception.
In the EllaOne a group, 16 pregnancies occurred in 844 women aged 16 to 35 years when emergency contraception was taken 0 to 72 hours after unprotected intercourse. The number of pregnancies expected without emergency contraception was calculated based on the timing of intercourse with regard to each woman's menstrual cycle; EllaOne significantly reduced the pregnancy rate, from an expected 5.6% to an observed 1.9%, when taken within 72 hours after unprotected intercourse (p = 0.001). There were no pregnancies observed in the women who were administered EllaOne more than 72 hours after unprotected intercourse (10% of women who received EllaOne).
ii) Open label study. This study was a multicentre open label trial designed to support the efficacy and safety of ulipristal acetate for emergency contraception when taken 48 to 120 hours after unprotected intercourse. Main inclusion criteria were women, 18 or greater years of age, with regular cycle length (24 to 35 days) presenting for emergency contraception between 48 hours and 120 hours of unprotected intercourse. In total, 1,533 healthy women with a mean age of 24 years received a dose of 30 mg ulipristal acetate (EllaOne).
The primary efficacy measurement was the pregnancy rate, calculated as the number of pregnancies after administration of emergency contraception, divided by the number of subjects administered emergency contraception. Twenty-seven pregnancies occurred in 1,242 women aged 18 to 35 years evaluated for efficacy for a pregnancy rate of 2.1%. The number of pregnancies expected without emergency contraception was calculated based on the timing of intercourse with regard to each woman's menstrual cycle. EllaOne significantly reduced the pregnancy rate, from an expected rate of 5.5% to an observed rate of 2.2%, when taken 48 to 120 hours after unprotected intercourse (p < 0.001).
iii) Phase II comparative study. Study HRA2914-507 was a randomized double blind study conducted in healthy cycling women at least 18 years old and who requested emergency contraception at one of the participating clinical sites in the US within 72 hours (3 days) of unprotected intercourse. It was designed as a noninferiority trial to test the following hypothesis that 50 mg unmicronized ulipristal acetate had a pregnancy rate no worse than that of levonorgestrel with a noninferiority margin of 2%. The efficacy evaluable (EE) population included 1,546 women (773 the ulipristal acetate group and 773 in the levonorgestrel group).
The pregnancy rate and prevented fraction for the EE population administered ulipristal acetate were, respectively, 0.91% (0.365-1.857) and 85% (68-93).

Pooled analysis.

Results from the two independent randomized controlled trials (studies HRA2914-507 and HRA2914-513, see Table 3) showed the efficacy of ulipristal acetate to be noninferior to that of levonorgestrel in women who presented for emergency contraception between 0 and 72 hours after unprotected intercourse or contraceptive failure. When the data from the two trials were combined via pooled analysis, the risk of pregnancy with ulipristal acetate was significantly reduced compared to levonorgestrel, regardless of whether treatment occurred within 24 (p = 0.035), 72 (p = 0.046) or 120 hours (p = 0.025) of intercourse (Glasier et al, Lancet 2010).
Data from the two phase III studies were pooled to provide a total efficacy population of women treated with ulipristal acetate up to 120 hours after unprotected intercourse (Table 4). Time trend analysis for the five 24 hour intervals from 0 to 120 hours between unprotected intercourse and treatment was conducted. There were no significant differences in the observed pregnancy rates across five time intervals.
A postmarketing observational study evaluating efficacy and safety of EllaOne in 279 adolescents aged 17 and younger showed no difference in the safety and efficacy profile compared to adult women aged 18 and older.

5.2 Pharmacokinetic Properties

Absorption.

Following oral administration of a single 30 mg dose, ulipristal acetate is rapidly absorbed, with a peak plasma concentration of 176 ± 89 nanogram/mL occurring approximately 1 hour (0.5-2.0 h) after ingestion, and with an AUC0-∞ of 556 ± 260 nanogram.h/mL.
The mean absolute bioavailability of ulipristal acetate is 27% [22.0 to 33.0%].
Administration of ulipristal acetate together with a high-fat breakfast resulted in approximately 45% lower mean Cmax, a delayed Tmax (from a median of 0.75 hours to 3 hours) and 25% higher mean AUC0-∞ compared with administration in the fasted state. Similar results were obtained for the active monodemethylated metabolite.

Distribution.

Ulipristal acetate is highly bound (> 98%) to plasma proteins, including albumin, alpha-1-acid glycoprotein, high density lipoprotein and low density lipoprotein.
Ulipristal acetate is a lipophilic compound and is distributed in breast milk, with a mean daily excretion of 13.35 microgram [0-24 hours], 2.16 microgram [24-48 hours], 1.06 microgram [48-72 hours], 0.58 microgram [72-96 hours], and 0.31 microgram [96-120 hours]. The average distribution volume is 3470 L.

Metabolism.

Ulipristal acetate is extensively metabolised to monodemethylated, di-demethylated and hydroxylated metabolites. The monodemethylated metabolite is pharmacologically active. In vitro data indicate that this is predominantly mediated by CYP3A4.

Excretion.

The main route of elimination is through faeces and less than 10% is excreted in the urine. The terminal half-life of ulipristal acetate in plasma following a single dose of 30 mg is to be about 32.4 ± 6.3 hours, with a mean oral clearance (CL/F) of about 76.8 ± 64.0 L/h.

Special populations.

No pharmacokinetic studies with ulipristal acetate have been performed in females with impaired renal or hepatic function.

5.3 Preclinical Safety Data

Genotoxicity.

In vitro tests for mutagenicity in bacterial and mammalian cells and for chromosomal damage in vitro and in vivo (mouse micronucleus test) revealed no genotoxic activity for ulipristal acetate.

Carcinogenicity.

Oral carcinogenicity studies were performed with ulipristal acetate in rats (2 years duration) and transgenic mice (6 months). No carcinogenic effect was observed with treatment at up to 10 mg/kg/day in rats (yielding 26 times the plasma AUC in patients after a 30 mg dose) or up to 130 mg/kg/day in mice (122 times the clinical AUC).

6 Pharmaceutical Particulars

6.1 List of Excipients

The tablet also contains the following inactive ingredients: lactose monohydrate, povidone, croscarmellose sodium and magnesium stearate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine. See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Store in the original packaging to protect from moisture. Keep the blister in the outer carton to protect from light.

6.5 Nature and Contents of Container

PVC-PVDC-Aluminium or PVC-PE-PVDC-Aluminium blister of 1 tablet.
The carton contains one blister of one tablet.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Ulipristal acetate is a white to yellowish crystalline powder. It is freely soluble in dichloromethane, soluble in methanol, acetone and ethanol and insoluble in water.
Chemical name: 17α-acetoxy-11β-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione.

Chemical structure.


CAS number.

126784-99-4.
Molecular formula: C30H37NO4. Molecular weight: 475.619.

7 Medicine Schedule (Poisons Standard)

Schedule 3 (Pharmacist Only Medicine).

Summary Table of Changes