4.2 Posology and method of administration
Children and adolescents: A limited number of women under 18 years were included in clinical trials of ellaOne.
(instead of women 18 years and older)
4.4 Special warnings and precautions
After ellaOne intake menstrual periods can sometimes occur earlier or later than expected by a few days. In approximately 7%(instead of 6%) of the women, menstrual periods occurred more than 7 days earlier than expected. In 18.5% (instead of 20%) of the women a delay of more than 7 days occurred, and in 4% (instead of 5.1%) the delay was greater than 20 days
4.8 Undesirable effects
Adverse events reported in more than 10 percent of subjects treated with ulipristal were headache, nausea and abdominal pain : this sentence has been added
Safety of ulipristal acetate has been evaluated in 4,718 (instead of 3391) women during the clinical development program.(instead of phase II and III studies only)
The adverse reactions reported in the phase III program of 2,637 (instead of 1533) women are provided in the table below. The vast majority of adverse reactions were mild or moderate and resolved spontaneously.
Adverse reactions listed below are classified according to frequency and system organ class. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness
MedDRA
|
Adverse reactions (frequency)
|
|
System Organ Class
|
Very common
≥1/10
|
Common
≥1/100 to <1/10
|
Uncommon
≥1/1,000 to <1/100
|
Rare
≥1/10,000 to <1/1,000
|
|
Infections and infestations
|
|
|
Vaginitis
Nasopharyngitis
Influenza
Urinary tract infection
|
Conjonctivitis infective Hordeolum
Pelvic inflammatory disease
|
|
Metabolism and nutrition disorders
|
|
|
Appetite disorders
|
Dehydration
|
|
Psychiatric disorders
|
|
Mood disorders
|
Emotional disorder
Anxiety
Insomnia
Hyperactivity disorder
Libido changes
|
Disorientation
|
|
Nervous system disorders
|
|
Headache
Dizziness
|
Somnolence
Migraine
|
Tremor
Disturbance in attention
Dysgueusia
Poor quality of sleep
Parosmia
Syncope
|
|
Eye disorders
|
|
|
Visual disturbance
|
Abnormal sensation in eye
Ocular hyperaemia
Photophobia
|
|
Ear and labyrinth disorders
|
|
|
|
Vertigo
|
|
Vascular disorders
|
|
|
Hot flush
|
Haemorrhage
|
|
Respiratory, thoracic and mediastinal disorders
|
|
|
|
Upper respiratory tract congestion
Cough
Dry throat
Epistaxis
|
|
Gastrointestinal disorders
|
|
Nausea
Abdominal pain (NOS)
Abdominal pain upper
Abdominal discomfort
Vomiting
|
Abdominal pain lower Diarrhoea
Dry mouth
Constipation
Dyspepsia
Flatulence
|
Gastro-oesophageal reflux disease
Toothache
|
|
Skin and subcutaneous tissue disorders
|
|
|
Acne
Skin lesion
Pruritus
|
Urticaria
Genital pruritus
|
|
Musculoskeletal and connective tissue disorders
|
|
Myalgia
Back pain
|
|
Pain in extremity
Arthralgia
|
|
Renal and urinary disorders
|
|
|
|
Urinary tract disorder Chromaturia
Nephrolithiasis
Renal Pain
Bladder pain
|
|
Reproductive system and breast disorders
|
|
Dysmenorrhea
Pelvic pain
Breast tenderness
|
Menorrhagia
Vaginal discharge
Menstrual disorder
Metrorrhagia
Vaginal haemorrhage
Hot flush
Premenstrual syndrome
|
Genital pruritus
Dysfunctional uterine bleeding
Dyspareunia
Ruptured ovarian cyst
Vulvovaginal pain
Menstrual discomfort
Hypomenorrhea
|
|
General disorders and administration site conditions
|
|
Fatigue
|
Pain
Irritability
Chills
Malaise
Pyrexia
|
Chest discomfort
Inflammation
Thirst
|
The changes are highlighted in yellow.
The majority of women (74.6%) (instead of 80.8%) in the phase III studies had their next menstrual period at the expected time or within ± 7 days, while 6.8% (instead of 6.1%) experienced menses more than 7 days earlier than expected and 18.5% (instead of 19.2%) had a delay of more than 7 days beyond the anticipated onset of menses. The delay was greater than 20 days in 4 % (instead of 5.1%) 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%), (instead of 91.8%) this bleeding was reported as spotting. Among the women who received ellaOne in the phase III studies, only 0.4% (instead of 0.3%) reported heavy intermenstrual bleeding.
In the phase III studies, 82 (instead of 75) women entered a study more than once and therefore received more than one dose of ellaOne (73 (instead of 66) 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
5.1. Pharmacodynamic properties
Pharmacotherapeutic group: Other sex hormones and modulators. ATC code: Not yet assigned.
Ulipristal acetate is an orally-active synthetic selective progesterone receptor modulator which acts via high-affinity binding to the human progesterone receptor. The primary mechanism of action is inhibition or delay of ovulation. Pharmacodynamic data show that even when taken immediately before ovulation is scheduled to occur, ulipristal acetate is able to postpone follicular rupture in some women.
Ulipristal acetate also has high affinity for the glucocorticoid receptor and in vivo, in animals, antiglucocorticoid effects have been observed. However, in humans, no such effect has been observed even after repeat administration at the daily dose of 10 mg. It has minimal affinity to the androgen receptor and no affinity for the human estrogen or mineralocorticoid receptors.
Results from two independent randomized controlled trials (see Table) showed the efficacy of ulipristal acetate to be non-inferior 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 meta-analysis, the risk of pregnancy with ulipristal acetate was significantly reduced compared to levonorgestrel (p=0.046).
|
Randomized controlled trial
|
Pregnancy rate (%)
within 72h of unprotected intercourse or contraceptive failure1
|
Odds ratio [95% CI] of pregnancy risk, ulipristal acetate vs levonorgestrel1
|
|
Ulipristal acetate
|
Levonorgestrel
|
|
HRA2914-507
|
0.91
(7/773)
|
1.68
(13/773)
|
0.50 [0.18-1.24]
|
|
HRA2914-513
|
1.78
(15/844)
|
2.59
(22/852)
|
0.68 [0.35-1.31]
|
|
Meta-analysis
|
1.36
(22/1617)
|
2.15
( 35/1625)
|
0.58 [0.33-0.99]
|
1 – Glasier et al, Lancet 2010
Two trials provide efficacy data on ellaOne used up to 120 hours after unprotected intercourse. In an open-label clinical trial, which enrolled women who presented for emergency contraception and were treated with ulipristal acetate between 48 and 120 hours after unprotected intercourse, a pregnancy rate of 2.1% (26/1241) was observed. In addition, the second comparative trial described above also provides data on 100 women treated with ulipristal acetate from 72 to 120 hours after unprotected intercourse, in whom no pregnancies were observed.
Date of revision of the text : 02/07/2010
Error of Typing : ellaOne (instead of Ellaone)
|
