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.

FULL CMI

EllaOne®

Active ingredient: ulipristal acetate 30 mg

Consumer Medicine Information (CMI)

This leaflet provides important information about using EllaOne. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using EllaOne.

Where to find information in this leaflet:

1. Why am I using EllaOne?
2. What should I know before I use EllaOne?
3. What if I am taking other medicines?
4. How do I use EllaOne?
5. What should I know while using EllaOne?
6. Are there any side effects?
7. Product details

1. Why am I using EllaOne?

EllaOne contains the active ingredient ulipristal acetate. EllaOne is an oral emergency contraceptive, 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.

EllaOne is used to prevent pregnancy after unprotected sex or if your contraceptive method has failed. For example:

  • if you had sex without protection.
  • if you forgot to take your contraceptive pill.
  • if your or your partner's condom tore, slipped or came off, or if you forgot to use one.

2. What should I know before I use EllaOne?

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

Warnings

Do not use EllaOne if:

  • you know or suspect you are pregnant as EllaOne does not work if you are already pregnant.
  • you are allergic to ulipristal acetate, or any of the ingredients listed at the end of this leaflet.
    Always check the ingredients to make sure you can use this medicine.

Check with your doctor or pharmacist if:

  • your period is late or you have symptoms of pregnancy (heavy breasts, morning sickness) as you may already be pregnant.
  • If you have severe asthma.
  • If you suffer from severe liver disease
  • If you have intolerance to some sugars as EllaOne contains lactose
  • take any medicines for any other condition

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor or pharmacist if you are pregnant or intend to become pregnant.

EllaOne is a contraceptive used to prevent a pregnancy from starting.

If you are already pregnant it will not interrupt and existing pregnancy.

Talk to your doctor or pharmacist if you are breastfeeding or intend to breastfeed. If you are breastfeeding, do not breast feed your baby for one week after taking EllaOne. During this time, it is recommended you use a breast pump to maintain milk production and that you discard any expressed 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

3. What if I am taking other medicines?

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

Medicines that may reduce the effect of EllaOne include:

  • Medicines used to treat epilepsy: phenytoin, fosphenytoin, phenobarbital primidone, carbamazepine, oxcarbazepine.
  • Medicines used to treat HIV infection: ritonavir, efavirenz, nevirapine.
  • Medicines used to treat certain bacterial infections: rifampicin, rifabutin.
  • Herbal remedies used for depression and anxiety containing St John's wort (Hypericum perforatum).

Ask your pharmacist or doctor if EllaOne is right for you if you have used any of the medicines listed above in the last few weeks.

Using EllaOne® with regular hormonal contraceptives could reduce contraceptive action of both medicines.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect EllaOne.

4. How do I use EllaOne?

How much to take

  • Take one tablet by mouth.
  • Follow the instructions provided with the medicine.
  • Do not exceed the recommended dosage.

When to take EllaOne

  • Take as soon as possible and no later than 120 hours (5 days) after you have had unprotected sex or contraceptive failure. If you miss taking EllaOne within 5 days after sex, it cannot be relied upon to work as a contraceptive, and it is important you contact your doctor.
  • 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, consult your pharmacist, doctor or healthcare provider. You may need to take another tablet.

If you take too much EllaOne

If you think that you have used too much EllaOne you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning. There has been no report of harmful effects from taking higher dose than recommended of this medicine.

5. What should I know while using EllaOne?

Things you should know

  • EllaOne does not work if you are already pregnant
  • Emergency contraception is not effective in every case: of 100 women who take EllaOne, approximately 2 will become pregnant.
  • EllaOne is for occasional use only and should not be used as a regular contraceptive method.
    Emergency contraception is a backup method for preventing pregnancy and should only be used occasionally.

Things you should do after using EllaOne

If you want to have sex, you should use a reliable barrier contraceptive method, such as a condom until your next period. This is because EllaOne will not work if you have unprotected sex again.

If you wish to start using regular hormonal contraception such as birth control pills, you should do so no sooner than 5 days after taking EllaOne. You should still 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 it had failed to work, you should continue taking the hormonal contraceptive on the same day as taking EllaOne.

Most women have a normal period at the expected time. But some may have their period later or earlier than normal. 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 become pregnant or think you are 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.

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

Remind any doctor or pharmacist you visit that you are using EllaOne.

Things you should not do

  • Do not take EllaOne if you are, or think that you are pregnant.
  • Do not use EllaOne as a regular method of contraception.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how EllaOne affects you.

After taking EllaOne some women experience dizziness, drowsiness, blurred vision and/or loss of concentration in some women. If this happens, do not drive or operate machinery.

Looking after your medicine

  • Store below 25°C.
  • Store in the original packaging in a cool dry place away from moisture, heat or sunlight; for example, do not store it:
    - in the bathroom or near a sink, or
    - in the car or on windowsills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention. See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions.

Common side effects

Common side effectsWhat to do
Stomach and intestinal-related:
  • feeling sick
  • belly pain or discomfort
  • vomiting
Head, neurology, and behavior related:
  • headache
  • dizziness
  • tiredness
  • mood swings
Reproductive system related:
  • painful period
  • lower abdominal pain
  • breast tenderness
Muscle related:
  • muscle pain
  • back pain
Speak to your doctor or pharmacist if you have any of these less serious side effects and they worry you.

Uncommon side effects

Rare side effectsWhat to do
Stomach and intestinal related:
  • diarrhoea
  • heartburn
  • intestinal gases
  • dry mouth
  • appetite changes
Reproductive system related:
  • abnormal vaginal bleeding and menstrual disorder (heavy/ prolonged periods, premenstrual syndrome)
  • vaginal inflammation
  • vaginal discharge
  • hot flushes
General disorders:
  • influenza
  • fever
  • chills
Neurology and behavior related:
  • emotional disorders
  • anxiety
  • agitation
  • trouble sleeping
  • sleepiness
  • migraine
  • visual disturbances
Skin related:
  • acne
  • skin lesions
  • itching
Tell your pharmacist or doctor if you notice anything that is making you feel generally unwell.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

7. Product details

This medicine is available over-the-counter without a doctor's prescription.

What EllaOne contains

Active ingredient
(main ingredient)		Ulipristal acetate 30 mg
Other ingredients
(inactive ingredients)		Lactose monohydrate
Povidone
Croscarmellose sodium
Magnesium stearate
Potential allergensLactose

Do not take this medicine if you are allergic to any of these ingredients.

What EllaOne looks like

EllaOne is a white to marble creamy, round curved tablet engraved on both faces with the code “ella”, packed in a blister pack of 1 tablet (Aust R 219535).

Who distributes EllaOne

Perrigo Australia
25 – 29 Delawney Street
Balcatta WA 6021 – Australia
Tel: 1800 805 546
E-mail: [email protected]

EllaOne® is a registered trademark and product of:
Laboratoire HRA Pharma,
200 avenue de Paris
92320 CHATILLON – France

This leaflet was prepared in April 2024

Published by MIMS July 2024

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