Ulipristal is contraindicated in pregnancy. Data on the use in pregnant ulipristala absent or limited. Despite the fact that in the course of research on animals is not teratogenic potential found, data relating to the reproductive toxicity insufficient. Breastfeeding in animal studies demonstrated that ulipristal passes into breast milk. It is not known whether ulipristal in human breast milk, so it is impossible eliminate the risk for children during breastfeeding. Ulipristal is contraindicated during breastfeeding.
Dosing and Administration:
Inside one tablet 1 time per day regardless of the meal for no more than 3 months. Treatment should begin during the first week of the menstrual cycle. There are no data on treatment for more than 3 months, or repeated courses of therapy, so duration of treatment should not exceed 3 months. When you miss a pill should be taken as a pill drug can Esmiya® faster. If the receipt is missing for more than 12 hours, the missed pills not
accepted, and should simply resume normal reception.
Special groups of patients:
Renal failure: In patients with mild or moderate renal insufficiency correction doses are not required. Esmiya® drug is not recommended for use in patients with severe renal failure when it is impossible for ongoing monitoring (see "Special Instructions").
Liver failure: In patients with mild hepatic insufficiency dose adjustment is required. Esmiya® drug is not recommended for use in patients with moderate or severe hepatic impairment when it is impossible for ongoing monitoring
(See. Section "Special Instructions").
Children: Use of the drug Esmiya® relevant indications in children is not provided. Safety and efficacy ulipristala set only for women 18 years and older.
Profile Security: Safety was evaluated in ulipristala 393 women with uterine fibroids treated with 5 mg or 10 mg ulipristala during Phase III studies. The most frequently observed phenomenon in clinical trials was amenorrhea (82.2%), which is considered the desired outcome.
The most common adverse reaction was the emergence of "hot flashes." Overwhelming most adverse events were mild or lungs (94.9%) did not lead to cessation of treatment (99.3%) and resolved on their own.
The list of adverse reactions:
In two studies of phase III in patients with uterine fibroids treated with the drug in within 3 months, reported the following adverse reactions. Adverse adverse reactions are presented by system-organ class in accordance with the
MedDRAi classification with the frequency of occurrence: very common (> 1/10); often (from > 1/100 to <1/10); infrequently (from> 1/1000 to <1/100); rarely (from> 1/10000 to <1/1000); very much rare (<1/10000); not known (can not be estimated from the available data).
Within each frequency band side reactions are presented in order of decreasing seriousness.
Frequent: emotional disorders.
Disorders of the nervous system
Common: headache * (* - see. See "Description of the individual adverse reactions").
Violations by metabolism and nutrition
Uncommon: weight gain
Violations by the organ of hearing and labyrinthine disorders
Violations of the respiratory system, the chest and mediastinum
Disorders of the gastrointestinal tract
Common: abdominal pain, nausea.
Uncommon: dyspepsia, dry mouth, flatulence, constipation.
Violations of the skin and subcutaneous tissue
Common: acne, increased sweating.
Infrequent: skin lesions.
Violations by mygiechnoy skeletal system and connective tissue
Common: pain in the bones and muscles.
Uncommon: back pain.
Violations by the kidneys and urinary tract
Infrequent: urinary incontinence.
Violations by the genital and breast cancer
Very Frequent: amenorrhea, endometrial thickening *"tides"*.
Frequent: * metrorrhagia, ovarian cyst *, tension / breast tenderness, pelvic pain.
Infrequents: metrorrhagia, ovarian cyst rupture, vaginal discharge, and an increase in discomfort in the mammary glands.
General disorders and at the injection site: Frequent: edema, fatigue.
Changes in laboratory and instrumental studies:
Frequent: increase in the concentration of cholesterol in the blood.
Infrequent: increased concentration of triglycerides in the blood.
Description of the individual adverse events
Thickening of the endometrium:
In 10-15% of patients receiving ulipristal may be thickening of the endometrium (> 16 mm by ultrasound or MRI at the end of treatment). This effect is reversible after treatment and resuming the menstrual cycle. Moreover, reversible changes in the endometrium, as denoted PAEC differ from endometrial hyperplasia. The pathologist should be informed of admission ulipristala patient during histological examination at hysterectomy or endometrial biopsy.
"Tides": "Tides" were observed in 12.7% of patients, but their frequency varied in different studies. In a study with their active control rate was 24% (10,5% moderate or severe) for the group ulipristala and 60.4% (39.6% moderate or severe) for leuprorelin group. In placebo-controlled study, the incidence "Tide" amounted to 1.0% for ulipristala and 0% for placebo.
Headache: Headache mild or moderate degree was observed in 6.4% of patients.
Ovarian cyst: In 1.5% of patients during treatment were found functional ovarian cysts, which spontaneously disappeared within a few weeks.
Uterine bleeding: Patients with heavy menstrual bleeding due to uterine leiomyoma, are at risk of increased bleeding, which may require surgery. There have been several such messages in the course of therapy, and 2-3 months after treatment ulipristal th.
Data on overdose ulipristala limited. Single doses of 200 mg and 50 mg doses daily for 10 days designate a limited number of volunteers, with no marked or severe serious adverse reactions.
Interaction with other drugs:
The possible influence of other drugs on the action ulipristala
Ulipristal has steroidal structure and acts as a selective modulator predominantly progesterone receptor inhibitory effect on progesterone receptor. Thus, gestagens and hormonal contraceptives may reduce the effectiveness ulipristala by competitive effects on receptor progesterone. It is therefore not recommended simultaneous use of drugs, containing progestins.
Inhibitors of CYP3A4:
After applying a moderate inhibitor of CYP3A4 erythromycin propionate (500 mg, 2 times a day for 9 days) in healthy female volunteers figures and Stach AUCulipristala rose by 1.2 and 2.9 times, respectively; value AUCaktivnogo ulipristala metabolite increased 1.5 times, while sschah active metabolite decline (0.52 times). The combined use of powerful inhibitors of CYP3A4 (ketoconazole, ritonavir nefazodone) may lead a greater increase in the plasma concentration ulipristala blood. Dose adjustment when ulipristala application in patients receiving a weak inhibitor of isoenzyme CYP3A4, is not required. The combined use of moderate or potent inhibitors
CYP3A4 isoenzyme with ulipristalom not recommended.
Inducers of CYP3A4:
Patients receiving inductors isoenzyme CYP3A4, can be observed ulipristala decreased concentration in the blood plasma. The combined use of ulipristala and powerful inducers of isoenzyme CYP3A4 (rifampicin, carbamazepine, phenytoin, drugs Hypericum perforatum) is not recommended. Drugs affecting the pH of gastric juice application ulipristala (10 mg / day) together with a proton pump inhibitor esomeprazole (20 mg 1 time per day for 6 days) reduces the average whisk 65% elongation (median of 0.75 hours to 1.0 hours) and a higher average AUCna 13%. Such effects of drugs that increase the pH of gastric juice is not considered clinically significant for the daily use of pills ulipristala The possible impact on the action ulipristala drugihlekarstvennyh drugsHormonal contraceptives Ulipristal may interfere with the action of hormonal contraceptives (only gestagensoderzhaschih pills, progestogen-releasing systems or combined oral contraceptives) and progestogen drugs used for other indications. Therefore the concomitant administration of drugs containing the progestogen without recommended. Gestagensoderzhaschie drugs should not be used within 12 days.
Patients should be informed that the treatment is usually ulipristalom leads to a significant decrease in menstrual blood loss during or amenorrhea the first 10 days of treatment. With continuing excessive bleeding patient should seek medical advice. Typically, the menstrual cycle is resumed for 4 weeks after treatment.
The majority of women who took ulipristal at therapeutic doses, there was anovulation. However, long-term use fertility ulipristala not been studied. Effect on the ability to drive vehicles and mechanisms Ulipristal may have a minimal effect on the ability to drive vehicles and machinery, as after taking ulipristala can observed slight dizziness.
Tablets of 5 mg. 14 tablets in a blister of PVC / PE / PVDC film and orange aluminum foil. 2 or 6 blisters in a cardboard box with instructions application.
In the dark place at a temperature not exceeding 30° C. Keep out of reach of children!
2 years. Do not use the drug after the expiry date.
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