Ulipristal (Ulipristal)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Other hormones, their analogs and antagonists

Included in the formulation
  • Esmia®
    pills inwards 
    GEDEON RICHTER, OJSC     Hungary
    • АТХ:

    G.03.A.D.02   Ulipristal

    G.03.A.D   Preparations for emergency contraception

    Pharmacodynamics:

    Synthetic selective modulator of progesterone receptors, characterized by a tissue-specific partial antiprogestronic effect.

    Has a direct effect on the endometrium. The changes that occur in the endometrium are associated with an antagonistic effect on the progesterone receptors. Histological changes are represented by inactive and poorly proliferating epithelium, accompanied by asymmetric growth of stroma and epithelium, marked cystic enlargement of glands with mixed estrogenic (mitotic) and progestogen (secretory) effects on the epithelium. These changes are reversible and disappear after discontinuation of treatment, should not be taken for endometrial hyperplasia.

    It has a direct effect on leiomyomas, suppressing cell proliferation and inducing apoptosis, which leads to a decrease in their size.

    Pharmacokinetics:

    After a single oral dose of 5 mg or 10 mg whitewashed quickly absorbed, reaching about 1 hour after taking Cmax 23.5 ± 14.2 ng / ml and 50.0 ± 34.4 ng / ml, respectively. AUC 0-∞ is 61.3 ± 31.7 and 134.0 ± 83.8 ng × h / ml, respectively. Ulipristal is rapidly transformed into a pharmacologically active metabolite, with 9.0 ± 4.4 ng / ml and 20.6 ± 10.9 ng / ml, AUC 0 -∞ = 26.0 ± 12.0 and 63.6 ± 30.1 ng × h / ml, respectively, 1 h after administration of Cmax, respectively.Admission to a dose of 30 mg together with breakfast with a high fat content leads to a decrease in the average Cmax by about 45%, the extension of the time to reach Cmax (from a median of 0.75 h to 3 h) and a 25% increase in AUC0-∞, compared with fasting. The same results were obtained for the active mono-N-demethylated metabolite. Ulipristal to a high degree (> 98%) binds to plasma proteins, including albumin, α1-acid glycoprotein, HDL and LDL.

    Rapidly converted to mono-N-demethylated and then to di-N-demethylated metabolites. Data in vitro show that this process occurs with the participation of the CYP3A4 isoenzyme. Based on the fact that the metabolism of vypristopitala is mediated by cytochrome P450, the effect of hepatic insufficiency on the excretion of ulcer is expected, which will lead to an increase in its effect.

    The main way of excretion is through the intestine, less than 10% of the substance is excreted by the kidneys. Final half-life Upristupala after a single intake of 5 mg or 10 mg is approximately 38 hours, the average clearance of about 100 liters / h.

    Indications:

    Preoperative therapy of moderate and severe symptoms of uterine fibroids in adult women of reproductive age over 18 years with a duration of not more than 3 months.

    ICD-10

    II.D10-D36.D25.9   Leiomyoma of uterus, unspecified

    II.D10-D36.D25.2   Subserous leiomyoma of the uterus

    II.D10-D36.D25.1   Intramural uterine leiomyoma

    II.D10-D36.D25.0   Submucosal uterine leiomyoma

    II.D10-D36.D25   Leiomyoma of the uterus

    Contraindications:

    Hypersensitivity, bleeding from the vagina of an unknown etiology or for reasons not related to uterine myoma; cancer of the uterus, cervix, ovary or breast; duration of therapy over 3 months; bronchial asthma (severe form, not amenable to oral corticosteroids); pregnancy; lactation; children's age till 18 years.

    Carefully:

    Elderly age, renal and hepatic insufficiency.

    Pregnancy and lactation:

    Category of recommendations FDA H.

    Contraindicated in pregnancy and lactation.

    Dosing and Administration:

    Inside to 5 mg 1 time / day, regardless of food intake for not more than 3 months.

    Treatment should be started during the first week of the menstrual cycle.

    Side effects:

    From the psyche: often - emotional disorders; infrequently - anxiety.

    From the nervous system: often - headache; infrequently - dizziness.

    From the side of metabolism: infrequently - an increase in body weight.

    From the organ of hearing and balance: often - vertigo.

    From the respiratory system: infrequently - epistaxis.

    From the side of the digestive system: often - pain in the abdomen, nausea; infrequently - dyspepsia, dry mouth, flatulence, constipation.

    From the skin and subcutaneous tissue: often - acne, increased sweating; infrequently - skin lesions.

    From the osteomuscular system: often - pain in the bones and muscles; infrequently - back pain.

    From the urinary system: infrequently urinary incontinence.

    On the part of the reproductive system and mammary glands: very often - amenorrhea, thickening of the endometrium, tides; often - metrorrhagia, ovarian cyst, tension / tenderness of the mammary glands, pelvic pain; infrequently - rupture of ovarian cysts, vaginal discharge, an increase and discomfort in the mammary glands.

    On the part of the body as a whole: often - swelling, increased fatigue; infrequently, asthenia.

    On the part of laboratory indicators: often - increasing the concentration of cholesterol in the blood; infrequently, an increase in the concentration of triglycerides in the blood.

    Overdose:

    Pronounced symptoms of side effects. Treatment is symptomatic. Abolition of the drug.

    Interaction:

    Hormonal contraceptives and gestagens can reduce the effectiveness of vandalizing by competing with the progesterone receptor.

    May interfere with the action of hormonal contraceptives (only gestagen-containing tablets, gestagen releasing systems or combined oral contraceptives) and progestogen drugs used for other indications. Therefore, the concomitant use of medications containing gestagen is not recommended.

    Gestagen-containing drugs should not be used within 12 days after the cessation of treatment by illicit drug.

    After applying a moderate inhibitor of the isoenzyme CYP3A4 erythromycin propionate (500 mg 2 times / day for 9 days) in healthy female volunteers, the Cmax and AUC vypristupalas increased by 1.2 and 2.9 times, respectively; the AUC value of the active metabolite increased 1.5 times, while the Cmax of the active metabolite decreased (by 0.52 times). Combined use of powerful inhibitors of the isoenzyme CYP3A4 (ketoconazole, ritonavir, nefazodone) may lead to a greater increase in vigilance in the blood plasma. Dose adjustments in the use of vaginal discharge in patients receiving weak inhibitors of the CYP3A4 isoenzyme are not required.The combined use of moderate or potent inhibitors of the CYP3A4 isoenzyme with vulture is not recommended.

    Special instructions:

    There is no reason to believe that renal insufficiency can significantly affect the excretion of ulcers. There is no experience of therapeutic use of ulcers in patients with hepatic insufficiency. It is expected that liver failure may affect the excretion, which will lead to increased exposure to the drug. Typically, the menstrual cycle resumes within 4 weeks after the end of the course of treatment.

    Can have a minimal impact on the ability to drive vehicles and work with mechanisms, because after taking vaginal can be slightly dizzy.

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