Active ingredients: Ulipristal acetate
EllaOne 30 mg tablet
Indications Why is Ellaone used? What is it for?
ellaOne is an emergency contraceptive
ellaOne is a contraceptive intended to prevent pregnancy after unprotected sexual intercourse or following the failure of a contraceptive method. Eg:
- if you have had unprotected sex;
- if your or your partner's condom has broken or slipped off, or if you have forgotten to use it;
- if you have not taken the birth control pill according to the instructions.
You must take ellaOne as soon as possible after intercourse, and in any case within a maximum of 5 days (120 hours).
Sperm can survive up to 5 days inside the body after intercourse
ellaOne is suitable for any woman of childbearing age, including teenagers.
The use of ellaOne is possible at any time during the menstrual cycle.
ellaOne does not work if you are pregnant already.
In case of delayed menstruation, there is a possibility of pregnancy. If you are late in menstruation or if you have pregnancy symptoms (heavy breasts, morning sickness), you should consult a doctor or healthcare professional before taking ellaOne.
If you have unprotected sex after taking ellaOne, the medicine will not prevent pregnancy.
Unprotected intercourse at any point in your cycle can cause pregnancy.
ellaOne should not be used as a regular contraceptive
If you are not using a regular method of birth control, talk to a doctor or healthcare professional to choose one that is right for you.
How ellaOne works
ellaOne contains the substance ulipristal acetate, which works by modifying the activity of the natural hormone progesterone, which is necessary for ovulation to occur. As a result, ellaOne works by delaying ovulation. Emergency contraception is not effective in all cases. Out of 100 women who take ellaOne, about 2 become pregnant.
ellaOne is a contraceptive used to prevent pregnancy. If you are already pregnant, ellaOne will not terminate the existing pregnancy.
Emergency contraception does not protect against sexually transmitted infections.
Only the use of condoms guarantees protection from sexually transmitted infections. EllaOne does not offer protection from HIV infection or other sexually transmitted diseases (for example, Chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B and syphilis ). If you are concerned about this, please contact a healthcare professional.
At the end of this leaflet you will find more information on contraception.
Contraindications When Ellaone should not be used
Do not take ellaOne
- If you are allergic to ulipristal acetate or any of the other ingredients of this medicine
Precautions for use What you need to know before taking Ellaone
Talk to your pharmacist, doctor or other healthcare professional before taking ellaOne
- if your period is late or if you have pregnancy symptoms (heavy breasts, morning sickness), as you may already be pregnant (see section "Pregnancy, breast-feeding and fertility");
- if you suffer from severe asthma;
- if you have severe liver disease.
In all women, emergency contraception should be taken as soon as possible after unprotected intercourse. According to some data, ellaOne may be less effective with increasing body weight or body mass index (BMI), but these data are limited and inconclusive. Therefore, ellaOne is recommended for all women regardless of weight or BMI.
If you are concerned that you have any problems related to taking emergency contraception, talk to a healthcare professional.
If you become pregnant despite taking ellaOne, it is important that you see your doctor. See the "Pregnancy, breast-feeding and fertility" section for more information.
Interactions Which drugs or foods can change the effect of Ellaone
Other contraceptives and ellaOne
Using ellaOne may temporarily reduce the effectiveness of regular hormonal contraceptives, such as pills and patches. If you are taking a hormonal contraceptive, continue to use it regularly after taking ellaOne, but use a condom every time you have intercourse, until your next period.
Do not use ellaOne together with another emergency contraceptive pill containing levonorgestrel. Taking the two medicines together could reduce the effectiveness of ellaOne.
Other medicines and ellaOne
Tell your pharmacist, doctor or other healthcare professional if you are taking, have recently taken or might take any other medicines.
This is especially important if you are taking any of the medicines listed below as they may make ellaOne less effective:
- Phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, oxcarbazepine (used in the treatment of epilepsy)
- Ritonavir, efavirenz, nevirapine (used in the treatment of HIV infection)
- Rifampicin, rifabutin (used in the treatment of tuberculosis)
- St John's wort (Hypericum perforatum) or herbal medicines that contain it (used to treat depression or anxiety).
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
Pregnancy
Before taking ellaOne, if your period is late, tell your pharmacist, doctor or other healthcare professional, or do a pregnancy test to make sure you are not already pregnant (see section "Warnings and precautions").
ellaOne is a contraceptive used to prevent pregnancy. If she is already pregnant, she will not terminate an existing pregnancy.
If you become pregnant despite taking ellaOne, there is no evidence that ellaOne is adversely affecting your pregnancy. It is however important that you see your doctor. As with any pregnancy, the doctor may decide to check that the pregnancy does not occur outside the uterus (ectopic). This check is especially important in case of severe abdominal pain (stomach ache) or bleeding, or if in the past you have have already had an ectopic pregnancy, have had tubal surgery or have a "long-lasting (chronic)" genital infection.
If you become pregnant despite taking ellaOne, ask your doctor to enter your pregnancy details in an official registry. You can also report this information directly on www.hra-pregnancy-registry.com. Your details will remain anonymous - no one will know that the information is about you Sharing your information can help other women in the future to understand the safety or risks of ellaOne during pregnancy.
Feeding time
If you take ellaOne while breastfeeding, do not breastfeed for one week after taking ellaOne. During this period it is recommended to pump the milk to stimulate and preserve its production, but to throw it away. The effects of breastfeeding in the week following ellaOne are unknown.
Fertility
ellaOne will not adversely affect your subsequent fertility. If you have unprotected sex after taking ellaOne, the medicine will not prevent pregnancy. It is therefore important to use a condom until your next period. If you want to start or continue using a regular method of birth control after using ellaOne, you can, but you must also use a condom until your next period.
Driving and using machines
Some women report dizziness, sleepiness, blurred vision and / or loss of concentration after taking ellaOne (see section 4 "Possible side effects"). If you experience these symptoms, do not drive or use machines.
ellaOne contains lactose
If you have been told by your doctor or other healthcare professional that you have an "intolerance to some sugars, please inform your pharmacist before taking this medicine.
Dose, Method and Time of Administration How to use Ellaone: Posology
Always use this medicine exactly as described in this leaflet or as instructed by your pharmacist, doctor or other healthcare professional. If in doubt, consult your pharmacist or doctor.
How to take the ellaOne tablet
- Take one tablet by mouth as soon as possible and in any case no later than 5 days (120 hours) after unprotected sex or contraceptive failure. Do not wait to take the tablet.
- The use of ellaOne is possible at any time during the menstrual cycle.
- ellaOne can be taken at any time of the day, before, during or after a meal.
If you vomit after taking ellaOne
If you vomit (throw up) within 3 hours of taking the tablet, take another one as soon as possible.
If you have another sexual relationship after taking ellaOne
If you have unprotected sex after taking ellaOne, the medicine will not prevent pregnancy. After taking ellaOne and until your next period, you should always use a condom for every sexual intercourse.
If your next period is late after taking ellaOne
After taking ellaOne it is normal for your next period to be delayed by a few days. However, if you do not have a period after more than 7 days or if your bleeding is unusually light or unusually heavy or if you experience symptoms such as abdominal pain (tummy ache), breast pain, vomiting or nausea, you may be pregnant. She needs to take a pregnancy test right away. If you become pregnant it is important that you see your doctor (see section "Pregnancy, breast-feeding and fertility").
Overdose What to do if you have taken too much Ellaone
If you take more ellaOne than you should
No harmful effects have been reported when taking a higher dose of this medicine than recommended. However, ask your pharmacist, doctor or other healthcare professional for advice.
If you have any further questions on the use of this medicine, ask your pharmacist, doctor or other healthcare professional.
Side Effects What are the side effects of Ellaone
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some symptoms, such as breast pain and abdominal pain (tummy pain), vomiting and malaise (nausea) are also possible signs of pregnancy. If you miss a period and experience these symptoms after taking ellaOne, you must have a pregnancy test (see section "Pregnancy, breast-feeding and fertility").
Common side effects (which may affect up to 1 in 10 people)
- nausea, abdominal pain (abdominal pain) or discomfort, vomiting
- painful menstruation, pelvic pain, breast pain
- headache, dizziness, mood swings
- muscle aches, back pain, fatigue
Uncommon side effects (which may affect up to 1 in 100 people)
- diarrhea, heartburn, flatulence, dry mouth
- unusual or irregular vaginal bleeding, heavy / prolonged periods, PMS, vaginal irritation or discharge, decreased or increased libido
- hot flashes
- changes in appetite, emotional disturbances, anxiety, agitation, difficulty falling asleep, drowsiness, migraine, visual disturbances
- influence
- acne, skin lesions, itching
- fever, chills, malaise
Rare side effects (which may affect up to 1 in 1,000 people)
- genital pain or itching, pain during intercourse, ruptured ovarian cyst, unusually low menstruation
- loss of concentration, dizziness, tremors, disorientation, fainting
- abnormal ocular sensation, redness of the eyes, sensitivity to light
- dry throat, taste disturbances
- hives (itchy rash), feeling thirsty
Reporting of side effects
If you get any side effects, talk to your pharmacist, doctor or other healthcare professional. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and blister after "EXP." The expiry date refers to the last day of that month.
Store below 25 ° C. Store in the original package to protect from moisture. Keep the blister in the outer carton to protect from light.
Medicines should not be thrown down the drain. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What ellaOne contains
- The active ingredient is ulipristal acetate. One tablet contains 30 milligrams of ulipristal acetate.
- The other ingredients are lactose, povidone K30, croscarmellose sodium, magnesium stearate.
Description of what ellaOne looks like and contents of the pack
ellaOne is a white or off-white curved round tablet with the code "? ll?" embossed on both sides.
ellaOne is available in a cardboard box containing a blister with 1 tablet.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
ELLAONE 30 MG TABLET
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 30 mg of ulipristal acetate.
Excipients with known effects:
each tablet contains 237 mg of lactose (as monohydrate).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablet.
White to off-white, round, curved tablet with the code "she". embossed on both sides.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Emergency contraceptive to be taken within 120 hours (5 days) of unprotected sexual intercourse or failure of another contraceptive method.
04.2 Posology and method of administration
Dosage
The treatment consists of one tablet to be taken by mouth as soon as possible and in any case no later than 120 hours (5 days) from unprotected sexual intercourse or the failure of another contraceptive method.
ellaOne can be taken at any time during the menstrual cycle.
If vomiting occurs within 3 hours of taking ellaOne, a second tablet should be taken.
In the event of delayed menstruation or symptoms of pregnancy, pregnancy must be ruled out prior to administration of ellaOne.
Special populations
Kidney failure
No dose adjustment is necessary.
Hepatic insufficiency
In the absence of specific studies, it is not possible to make alternative recommendations regarding the dose of ellaOne.
Severe hepatic insufficiency
In the absence of specific studies, the use of ellaOne is not recommended.
Pediatric population
There is no indication for a specific use of ellaOne in prepubertal children in the indication of emergency contraception.
Teenagers: ellaOne is suitable for any woman of childbearing age, including teenagers. No differences in safety or efficacy were observed compared to adult women at least 18 years of age (see section 5.1).
Method of administration
Oral use.
The tablet can be taken with or without food.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
04.4 Special warnings and appropriate precautions for use
ellaOne is intended for occasional use only. ellaOne should never replace the use of a regular method of birth control. In any case, women should be advised to use a regular method of contraception.
ellaOne is not intended for use in pregnancy and must not be taken by women who are pregnant or suspected. However, ellaOne does not terminate an existing pregnancy (see section 4.6).
ellaOne does not prevent pregnancy in all cases.
If you are more than 7 days late in the onset of your next period, if your expected period bleeding is abnormal or if there are symptoms that indicate pregnancy or if you are in doubt, a pregnancy test should be performed. As with any pregnancy, the possibility of an ectopic pregnancy must be considered. It is important to know that the presence of uterine bleeding does not exclude the possibility of an ectopic pregnancy. Women who become pregnant after taking ellaOne should contact their doctor (see section 4.2).
ellaOne inhibits or delays ovulation (see section 5.1). If ovulation has already occurred, ellaOne is no longer effective. As it is not possible to predict the timing of ovulation, ellaOne should be taken as soon as possible after unprotected sexual intercourse.
There are no data available on the efficacy of ellaOne taken more than 120 hours (5 days) after unprotected intercourse.
Limited and inconclusive data suggest that ellaOne may be less effective with increasing body weight or body mass index (BMI) (see section 5.1). In all women, emergency contraception should be taken as soon as possible after unprotected intercourse, regardless of body weight or BMI.
After taking ellaOne, menstruation may occur a few days earlier or later than expected. In about 7% of women, menstruation occurred more than 7 days earlier than expected. In 18, 5% of women experienced a delay of more than 7 days, while in 4% of patients the delay exceeded 20 days.
Taking ulipristal acetate concomitantly with an emergency contraceptive containing levonorgestrel is not recommended (see section 4.5).
Contraception after taking ellaOne
ellaOne is an emergency contraceptive that reduces the risk of pregnancy after unprotected intercourse, but does not confer contraceptive protection in subsequent intercourse, so after the use of emergency contraception it is necessary to advise women to use a barrier method reliable until your next period.
Although continued use of a regular hormonal contraceptive is not contraindicated when taking ellaOne, it may reduce its contraceptive efficacy (see section 4.5). Consequently, if a patient wishes to initiate or continue the use of ellaOne. a hormonal contraceptive can do this after taking ellaOne, however women should be advised to use a reliable barrier method of contraception until the next menstruation starts.
Specific populations
Concomitant use of ellaOne with CYP3A4 inducing drugs is not recommended due to their interaction (eg rifampicin, phenytoin, phenobarbital, carbamazepine, efavirenz, fosphenytoin, nevirapine, oxcarbazepine, primidone, rifabutin, St. John's wort /Hypericum perforatumand long-term use of ritonavir).
The use of ellaOne in women with severe asthma being treated with oral glucocorticoids is not recommended.
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this drug.
04.5 Interactions with other medicinal products and other forms of interaction
Potential for other drugs to interfere with ulipristal acetate
Ulipristal acetate is metabolised by CYP3A4 in vitro.
- CYP3A4 inducers
According to results in vivo, administration of ulipristal acetate with a strong CYP3A4 inducer such as rifampicin significantly reduces Cmax and AUC of ulipristal acetate by at least 90% and decreases the half-life of ulipristal acetate by 2.2-fold, with a corresponding reduction in exposure to ulipristal acetate about 10 times. Concomitant use of ellaOne with CYP3A4 inducers (eg rifampicin, phenytoin, phenobarbital, carbamazepine, efavirenz, fosphenytoin, nevirapine, oxcarbazepine, primidone, rifabutin, St. John's wort /Hypericum perforatum) therefore reduces the plasma concentrations of ulipristal acetate, with a consequent possible reduction in the efficacy of ellaOne, and is therefore not recommended (see section 4.4).
- CYP3A4 inhibitors
Results in vivo demonstrated that concomitant administration of ulipristal acetate with a strong inhibitor and a moderate inhibitor of CYP3A4 increases Cmax and AUC of ulipristal acetate up to a maximum of 2 and 5.9-fold, respectively. The effects of CYP3A4 inhibitors are unlikely to have clinical consequences.
The CYP3A4 inhibitor ritonavir may also have an inducing effect on CYP3A4 if used for a prolonged period. In such cases, ritonavir may reduce the plasma concentrations of ulipristal acetate. Concomitant use of these medicinal products is therefore not recommended (see paragraph 4.4). The induction of the enzyme wears off slowly and the effects on the plasma concentration of ulipristal acetate may occur even if the woman has stopped taking an enzyme inducer for 2-3 weeks.
Medicines affecting gastric pH
Concomitant administration of ulipristal acetate (10 mg tablet) with the proton pump inhibitor esomeprazole (20 mg daily for 6 days) resulted in a mean reduction in Cmax of approximately 65%, a delay in Tmax (from a median of 0.75 hours to 1.0 hours) and an increase in the mean area under the curve (AUC) of 13%. The clinical relevance of this interaction for the administration of a single dose of ulipristal acetate as emergency contraception is unknown.
Potential for ulipristal acetate to interfere with other medicinal products
Hormonal contraceptives
Since ulipristal acetate binds with great affinity to the progesterone receptor, it may interfere with the action of progestogen-containing medicines.
- The contraceptive action of combined hormonal contraceptives and progestogen-only contraceptives may be reduced.
- The concomitant use of ulipristal acetate and an emergency contraceptive method containing levonorgestrel is not recommended (see section 4.4).
The data in vitro 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 administration of a single dose, induction of CYP1A2 and CYP3A4 by ulipristal acetate or its active metabolite is unlikely to occur. Therefore administration of ulipristal acetate is unlikely to alter the clearance of medicinal products metabolised by these enzymes. .
P-gp substrates (P-glycoprotein)
The data in vitro indicate that ulipristal acetate may be a P-gp inhibitor at clinically relevant concentrations. The results in vivo with the P-gp substrate fexofenadine did not provide definitive results. The effects of P-gp substrates are unlikely to have clinical consequences.
04.6 Pregnancy and lactation
Pregnancy
ellaOne is not intended for use during pregnancy and should not be taken by women who are actually or suspected to be pregnant (see section 4.2).
ellaOne does not terminate an existing pregnancy.
Pregnancy may occasionally occur after ellaOne intake. Although no teratogenic potential has been identified, the results obtained in animal species are insufficient for an assessment of reproductive toxicity (see section 5.3). Limited data on exposure in human pregnancy to ellaOne does not suggest safety concerns, but it is important that any pregnancies of women who have taken ellaOne are reported at www.hra- pregnancy-registry.com. The purpose of this web log is to collect safety information from women who have taken ellaOne during pregnancy or who have become pregnant after taking ellaOne. All collected patient data will remain anonymous.
Feeding time
Ulipristal acetate is excreted in breast milk (see section 5.2). The effect on newborns / infants has not been studied. A risk to the breastfed child cannot be excluded. Breastfeeding is not recommended for one week after ellaOne intake. During this period, the mother is recommended to take milk from the breast and discard it to keep milk production active.
Fertility
A rapid return to fertility is expected after treatment with ellaOne as an emergency contraceptive. Women should therefore be advised to use a reliable barrier method for all subsequent sexual intercourse until the next menstruation.
04.7 Effects on ability to drive and use machines
ellaOne may have a negligible or moderate influence on the ability to drive or use machines: mild to moderate dizziness is common after taking the medicine; drowsiness and blurred vision are uncommon episodes; disturbances have rarely been reported attention. The patient should be advised that she should not drive or operate machinery if she experiences such symptoms (see section 4.8).
04.8 Undesirable effects
Summary of the safety profile
The most frequently reported adverse reactions were headache, nausea, abdominal pain and dysmenorrhea.
The safety of ulipristal acetate was evaluated in 4,718 women during the clinical development program.
Table of adverse reactions
The table below shows the adverse reactions recorded in the phase III program in 2,637 women.
The adverse reactions listed below are classified by frequency and by system organ class. Within each frequency class, adverse reactions are listed in order of decreasing frequency.
The table lists adverse reactions by system organ class and frequency: very common (≥1 / 10), common (≥ 1/100 to
* Symptom that can also be related to an undiagnosed pregnancy (or related complications)
Adolescents: The safety profile observed in women under 18 years of age in studies and post-marketing experience is similar to that observed in adult women during the phase III program (section 4.2).
Post-marketing: Adverse reactions reported spontaneously in the post-marketing phase were similar in nature and frequency to the safety profile described during the phase III program.
Description of some adverse reactions
The majority of women (74.6%) in the phase III studies had menstruation after the expected date or within ± 7 days, while in 6.8% of them, menstruation appeared more than 7 days earlier than expected and on 18 , 5% reported a delay of more than 7 days on the expected date of the start of menstruation. The delay was greater than 20 days in 4% of women.
A minority (8.7%) of women reported intermenstrual bleeding for an average duration of 2.4 days. In the majority of cases (88.2%) the bleeding was described as spotting. Of the women who took ellaOne in phase III studies, only 0.4% reported profuse intermenstrual bleeding.
In the phase III studies, 82 women were enrolled more than once and therefore received more than one dose of ellaOne (73 women were enrolled twice and 9 women were enrolled three times). No differences were noted in the safety of these subjects in terms of the incidence and severity of adverse events, changes in the duration or volume of menstruation, or the incidence of intermenstrual bleeding.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. in "Annex V.
04.9 Overdose
There is little experience of overdose with ulipristal acetate. Single doses of the drug up to 200 mg were administered to women without safety concerns. These high doses were well tolerated, but the women had a shorter menstrual cycle (the uterine bleeding occurred 2-3 days earlier than expected) and in some of them the bleeding duration was prolonged, although not in excessive amounts (spotting) There is no antidote and subsequent treatment should be symptomatic.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: sex hormones and modulators of the genital system, emergency contraceptives.
ATC code: G03AD02.
Ulipristal acetate is an orally active synthetic selective progesterone receptor modulator which acts by binding with high affinity to the human progesterone receptor. When used for emergency contraception, the mechanism of action is to inhibit or delay ovulation by suppressing the rise of luteinizing hormone (LH). Pharmacodynamic data show that, even when taken immediately before the time it is predicted ovulation (when LH has already started to rise), ulipristal acetate is able to postpone the follicular rupture for at least 5 days in 78.6% of cases (p
1: Brache et al, Contraception 2013
§: defined as the presence of an intact dominant follicle five days after treatment in the late follicular phase
*: compared to levonorgestrel
NS: not statistically significant
†: compared to placebo
Ulipristal acetate also exhibits great affinity for the glucocorticoid receptor, and antiglucocorticoid effects have been recorded in animals. in vivo. However, such effects have not been observed in humans, even after repeated administration at the daily dose of 10 mg. Ulipristal acetate shows minimal affinity for the androgen receptor and no affinity for human estrogen or mineralocorticoid receptors.
Results from two independent, randomized, controlled clinical trials (see Table) of women who presented for emergency contraception between 0 and 72 hours after unprotected intercourse or failure of other contraceptive means showed that the efficacy of ulipristal acetate is not inferior to that of levonorgestrel. When data from the two studies were combined meta-analytically, the risk of pregnancy was significantly reduced with ulipristal acetate compared to levonorgestrel (p = 0.046).
2: Glasier et al, Lancet 2010
Two studies provide data on the efficacy of ellaOne administered up to 120 hours after unprotected intercourse. In an open-label clinical study of women who presented for emergency contraception and were given ulipristal acetate between 48 and 120 hours after unprotected intercourse, a pregnancy rate of 2.1% was observed (26/1241). In addition, the second comparative study mentioned above also provides data on 100 women treated with ulipristal acetate 72 to 120 hours after unprotected sexual intercourse, in whom no pregnancies were found.
Limited and inconclusive data from clinical trials suggest a possible trend towards decreased contraceptive efficacy of ulipristal acetate in women with high body weight or BMI (see section 4.4). The meta-analysis of the four clinical studies conducted on ulipristal acetate presented by later excluded women who had further unprotected sex.
A post-marketing observational study evaluating the efficacy and safety of ellaOne in adolescents aged 17 years and younger showed no differences in the safety and efficacy profile compared to adult women aged 18 years or older.
05.2 "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 ng / ml approximately 1 hour (0.5-2.0 h) after administration, and an AUC0-∞ of 556 ± 260 ng.h / ml.
Administration of ulipristal acetate accompanied by a high-fat breakfast led to a reduction in mean Cmax of approximately 45%, a delay in Tmax (median 0.75 to 3 hours) and an increase in the mean value of AUC0- ∞ equal to 25%, compared to administration in the fasted state. Similar results were obtained for the mono-demethylated active metabolite.
Distribution
Ulipristal acetate binds strongly (> 98%) to plasma proteins, including albumin, alpha-1- acid glycoprotein and high density lipoprotein.
Ulipristal acetate is a lipophilic compound and is distributed in breast milk with an "average daily excretion of 13.35 mcg [0-24 hours], 2.16 mcg [24-48 hours], 1.06 mcg [48-72 hours] ], 0.58 mcg [72-96 hours] and 0.31 mcg [96-120 hours].
The data in vitro indicate that ulipristal acetate may be an inhibitor of BCRP (breast cancer resistance protein) transporters in the intestine. The effects of ulipristal acetate on BCRP are unlikely to have clinical consequences.
Ulipristal acetate is not a substrate of OATP1B1 or OATP1B3.
Biotransformation / elimination
Ulipristal acetate is extensively metabolised to mono-demethylated, di-demethylated and hydroxylated derivatives. The mono-demethyl metabolite is pharmacologically active. Data obtained in vitro indicate that the mainly involved enzymes are CYP3A4 and, to a lesser extent, CYP1A2 and CYP2A6. The terminal half-life of ulipristal acetate in plasma after administration of a single 30 mg dose is estimated at 32.4 ± 6.3 hours, with a mean oral clearance (CL / F) of 76.8 ± 64.0 L / h.
Special populations
Pharmacokinetic studies of ulipristal acetate have not been conducted in female subjects with impaired renal or hepatic function.
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.Most of the results obtained in general toxicity studies referred to the mechanism of action of ulipristal acetate as a modulator of progesterone and glucocorticoid receptors, exhibiting anti-progesterone activity at exposures similar to therapeutic levels.
Data from reproductive toxicity studies are limited due to the absence of exposure measurements in these same studies. Ulipristal acetate has an embryolethal effect in rats, rabbits (at repeated doses above 1 mg / kg) and monkeys. There is no safety data for the human embryo with these repeated doses. At doses low enough to maintain gestation in animal species, no teratogenic effects have been observed.
Carcinogenicity studies (in rats and mice) showed that ulipristal acetate is not carcinogenic.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Lactose monohydrate
Povidone K30
Croscarmellose sodium
Magnesium stearate
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Store below 25 ° C. Store in the original package to protect from moisture. Keep the blister in the outer carton to protect from light.
06.5 Nature of the immediate packaging and contents of the package
PVC / PE / PVDC / aluminum blister containing 1 tablet. The package contains a blister with one tablet.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Laboratoire HRA Pharma
15, rue Béranger F-75003 Paris France
08.0 MARKETING AUTHORIZATION NUMBER
EU / 1/09/522/001
039366012
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 15 May 2009
Date of most recent renewal: May 20, 2014
