The most commonly reported adverse reactions were headache, nausea, abdominal pain and dysmenorrhea.
Safety of ulipristal acetate has been evaluated in 4,718 women during the clinical development program.
The adverse reactions reported in the phase III program of 2,637 women are stated as follows. The vast majority of adverse reactions were mild or moderate and resolved spontaneously.
Adverse reactions are classified as: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000) and system organ class. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Infections and Infestations:
Uncommon: Vaginitis, nasopharyngitis, influenza, urinary tract infection. Rare: Infective conjunctivitis, hordeolum, pelvic inflammatory disease.
Metabolism and Nutrition Disorders:
Uncommon: Appetite disorders. Rare: Dehydration.
Common: Mood disorders. Uncommon: Emotional disorder, anxiety, insomnia, hyperactivity disorder, libido changes. Rare: Disorientation.
Nervous System Disorders:
Common: Headache, dizziness. Uncommon: Somnolence, migraine. Rare: Tremor, disturbance in attention, dysguesia, poor quality of sleep, parosmia, syncope.
Uncommon: Visual disturbance. Rare: Abnormal sensation in eye, ocular hyperemia, photophobia.
Ear and Labyrinth Disorders:
Uncommon: Hot flush. Rare: Haemorrhage.
Respiratory, Thoracic and Mediastinal Disorders:
Rare: Upper respiratory tract, congestion, cough, dry throat, epistaxis.
Common: Nausea, abdominal pain (NOS), upper abdominal pain, abdominal discomfort, vomiting. Uncommon: Lower abdominal pain, diarrhea, dry mouth, constipation, dyspepsia, flatulence. Rare: Gastro-esophageal reflux disease, toothache.
Skin and Subcutaneous Tissue Disorders:
Uncommon: Acne, skin lession, pruritus. Rare: Urticaria, genital pruritus.
Musculoskeletal and Connective Tissue Disorders:
Common: Myalgia, back pain. Rare: Pain in extremity, arthralgia.
Renal and Urinary Disorders:
Rare: Urinary tract disorder, chromaturia, nephrolithiasis, renal pain, bladder pain.
Reproductive System and Breast Disorders:
Common: Dysmenorrhea, pelvic pain, breast tenderness. Uncommon: Menorrhagia, vaginal discharge, menstrual disorder, metrorrhagia, vaginal haemorrhage, hot flush, premenstrual syndrome. Rare: Genital pruritus, dysfunctional uterine bleeding, dyspareunia,
ruptured ovarian cyst, vulvovaginal pain, menstrual discomfort, hypomenorrhea.
General Disorders and Administration Site Conditions:
Common: Fatigue. Uncommon: Pain, irritability, chills, malaise, pyrexia. Rare: Chest discomfort, inflammation, thrist.
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 >7 days earlier than expected and 18.5% had a delay of >7 days beyond the anticipated onset of menses. The delay was >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 ella 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 >1 dose of ella (73 women enrolled twice and 9 enrolled 3 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.