Utrogestan capsules 200 mg No. 14

Instructions for Utrozhestan capsules 200 mg No. 14

Composition

active ingredient: progesterone;

1 capsule contains 200 mg of micronized progesterone;

Excipients: sunflower oil, soy lecithin, gelatin, glycerin, titanium dioxide (E 171), purified water.

Dosage form

Capsules.

Main physicochemical properties:

200 mg capsules: oval, soft, gelatin capsules of a slightly yellowish color, containing a whitish oily suspension.

Pharmacotherapeutic group

Sex gland hormones. Progestogens. ATX code G03D A04.

Pharmacological properties

Pharmacodynamics

The pharmacological properties of the drug are due to progesterone - one of the hormones of the corpus luteum, which contributes to the formation of a normal secretory endometrium in women. It causes the transition of the uterine mucosa from the proliferation phase to the secretory phase, and after fertilization, it promotes its transition to the state necessary for the development of a fertilized egg. Reduces the excitability and contractility of the muscles of the uterus and fallopian tubes. It has no androgenic activity. It has a blocking effect on the secretion of hypothalamic LH and FSH releasing factors, inhibits the formation of gonadotropic hormones by the pituitary gland and ovulation.

Pharmacokinetics

Oral use

The level of progesterone in plasma is increased from the first hour after absorption of the drug in the digestive tract. The highest level of progesterone in blood plasma is observed 1-3 hours after taking the drug (after 1 hour - 4.25 ng/ml, after 2 hours - 11.75 ng/ml, after 4 hours - 8.37 ng/ml, after 6 hours - 2 ng/ml and 1.64 ng/ml after the 8th hour). The main metabolites of progesterone in plasma are 20α-hydroxy,δ4α-pregnanolone and 5α-dihydroprogesterone. The drug is excreted in the urine in the form of glucuronic metabolites, the main of which is 3α,5β-pregnanediol (pregnanediol). These metabolites are identical to those formed during physiological secretion of the corpus luteum.

Intravaginal use

After insertion into the vagina, progesterone is rapidly absorbed by the mucous membrane.

The increase in plasma progesterone levels begins within the first hour, with the highest plasma levels being reached 1-3 hours after administration.

At the average prescribed dose (100 mg of progesterone per night), Utrogestan allows achieving and maintaining a physiological and stable level of plasma progesterone (on average at the level of 9.7 ng/ml), similar to that in the luteal phase of the menstrual cycle with normal ovulation. Thus, Utrogestan stimulates adequate maturation of the endometrium, promotes embryo implantation.

At higher doses (above 200 mg per day), which are increased gradually, the vaginal route of administration allows achieving plasma progesterone levels similar to those during the first trimester of pregnancy.

Metabolism: The metabolites in plasma and urine are identical to those found during physiological secretion of the corpus luteum: in plasma, these are mainly 20α-hydroxy, δ4α-pregnanolone and 5α-dihydroprogesterone. Urinary excretion is 95% in the form of glucuronic metabolites, the main component of which is 3α, 5β-pregnanediol (pregnanediol).

Indication

Disorders associated with progesterone deficiency.

Oral use

Gynecological:

disorders associated with progesterone deficiency, namely: premenstrual syndrome, menstrual cycle disorders (dysovulation, anovulation), fibrocystic breast disease, premenopause; hormone replacement therapy in menopause (in combination with estrogen therapy); infertility in luteal insufficiency.

Obstetric:

prevention of habitual miscarriage or threatened miscarriage due to luteal insufficiency; threat of premature birth.

Intravaginal use

Reduced ability to fertilize in primary or secondary infertility with partial or complete luteal insufficiency (dysovulation, luteal phase support during preparation for in vitro fertilization, egg donation program). Prevention of habitual miscarriage or threatened spontaneous miscarriage in luteal insufficiency. Prevention of premature birth in women with a short cervix or in women with a history of premature spontaneous birth. Impossibility or limitation of oral use of the drug.

Contraindication

Hypersensitivity to any component of the drug. Severe liver dysfunction. Suspected or confirmed breast or genital neoplasia. Undiagnosed vaginal bleeding. Failed or incomplete abortion. Thrombophlebitis. Thromboembolic disorders. Cerebral hemorrhage. Porphyria.

Interaction with other medicinal products and other types of interactions

When using estrogen for menopausal hormone therapy, it is strongly recommended to administer progesterone no later than the 12th day of the cycle.

If Utrozhestan is combined with beta-adrenomimetics in the treatment of threatened preterm labor, the doses of the latter can be reduced.

Concomitant use of other drugs may alter progesterone metabolism, causing an increase or decrease in progesterone plasma concentrations and, consequently, altering the drug's action.

Powerful inducers of liver enzymes, namely: barbiturates, antiepileptic drugs (phenytoin), rifampicin, phenylbutazone, spironolactone, griseofulvin, cause increased metabolism at the hepatic level.

Some antibiotics (ampicillins, tetracyclines) can cause changes in the intestinal microflora, resulting in a change in the enterohepatic steroid cycle.

It is known that such drug interactions are individual and may differ significantly in different patient groups, therefore it is not possible to predict any clinical manifestations of such interactions unequivocally. All progestins may reduce glucose tolerance, which may require an increase in the daily dose of insulin and other antidiabetic agents in patients with diabetes.

Progesterone bioavailability can be reduced by smoking and increased by alcohol.

Application features

Treatment at recommended doses has no contraceptive effect.

If treatment is started too early in the menstrual cycle, especially before day 15 of the cycle, a shortened cycle or bleeding may occur.

In case of uterine bleeding, do not prescribe the drug without clarifying the cause, in particular during endometrial examination.

It should be used with caution in patients with fluid retention (e.g., hypertension, cardiovascular disease, kidney disease, epilepsy, migraine, bronchial asthma), with a history of depression, diabetes mellitus, liver dysfunction, and photosensitivity.

Before prescribing the drug, patients with a family history of neoplasms and patients with recurrent cholestasis or persistent itching during pregnancy, impaired liver function, heart or kidney failure, fibrocystic mastopathy, epilepsy, asthma, otosclerosis, diabetes mellitus, multiple sclerosis, systemic lupus erythematosus should be carefully examined.

Due to the thromboembolic and metabolic risk, which cannot be completely ruled out, the drug should be discontinued in the event of:

visual disturbances, such as loss of vision, double vision, retinal vascular lesions, proptosis, optic disc edema; thromboembolic venous or thrombotic complications, regardless of the site of the lesion; severe headache, migraine.

If amenorrhea occurs during treatment, pregnancy, which may be the cause of amenorrhea, should be confirmed or ruled out.
When using the drug vaginally, oily discharge is possible, which is associated with the dosage form of the drug.

More than half of early spontaneous abortions are caused by genetic complications. In addition, infectious manifestations and mechanical disorders can be the cause of early abortions; the only justification for the appointment of progesterone would then be to delay the expulsion of a dead egg. Therefore, the appointment of progesterone on the recommendation of a doctor should be provided for cases where progesterone secretion is insufficient.

Before starting treatment, the patient should undergo a thorough medical and accurate gynecological examination, including intravaginal and mammological examination, Papanicolaou smear, taking into account the anamnesis, contraindications and precautions for use. Regular check-ups with a doctor are recommended during treatment. Women receiving hormone replacement therapy should carefully assess all the risks/benefits associated with therapy.

In patients with postmenopausal symptoms who are receiving or have received hormone replacement therapy (HRT), there is a slight to moderate increase in the likelihood of being diagnosed with breast cancer. This may be due to early diagnosis of patients or the actual benefit of HRT, as well as a combination of both. The risk of being diagnosed with breast cancer increases with increasing duration of treatment and returns to baseline values five years after stopping HRT. Breast cancer diagnosed in patients who are receiving or have recently received HRT is less invasive than that occurring in women who have not received HRT. The doctor should discuss the higher risk of developing breast cancer with patients who will receive long-term hormone therapy when assessing the benefits of HRT.

The drug should not be taken with food, but should be taken at bedtime. Simultaneous food intake increases the bioavailability of the drug.

Ability to influence reaction speed when driving vehicles or other mechanisms

For drivers and machine operators: drowsiness and dizziness are possible when taking the drug internally.

Taking the capsules before bedtime helps to avoid these unpleasant consequences.

Cases of drowsiness and dizziness were observed only during oral administration of the drug.

Use during pregnancy or breastfeeding

The use of Utrogestan is not contraindicated during pregnancy, including the first weeks (see the section "Indications" (Obstetric indications)).

During the period of use of the drug, no case of adverse effects of the drug on the fetus was observed.

When using the drug in the second and third trimesters of pregnancy, monitoring of liver function is required.

There is evidence of the possible development of hypospadias when progestogens are used during pregnancy to prevent spontaneous abortion or threatened abortion due to luteal insufficiency, which the patient should be informed about.

Method of administration and doses

The duration of treatment depends on the nature of the disease.

Oral use

In most cases, the average daily dose is 200-300 mg in 1 or 2 doses (200 mg in the evening, before bedtime, and 100 mg in the morning, if necessary).

In case of luteal phase insufficiency (premenstrual syndrome, menstrual cycle disorders, premenopause, fibrocystic breast disease): take for 10 days (usually from the 17th to the 26th day of the cycle, inclusive).

In menopausal hormone replacement therapy: since estrogen therapy alone is not recommended, progesterone should be used as a supplement to it for the last 2 weeks of each therapeutic course, which follow a one-week maintenance of any replacement therapy, during which withdrawal bleeding may occur.

In case of threatened premature birth: take 400 mg of Utrogestan every 6-8 hours until the symptoms disappear. The effective dose and frequency of use are selected individually depending on the clinical manifestations of the threat of premature birth. After the symptoms disappear, the dose of Utrogestan is gradually reduced to a maintenance dose (for example, 200 mg 3 times a day). In this dose, the drug can be used up to 36 weeks of pregnancy.

The use of progesterone after 36 weeks of pregnancy is not recommended.

Intravaginal use

Insert the capsules deep into the vagina while lying on your back.

Before each use of the drug, it is necessary to wash your hands thoroughly so that no detergent remains on your hands.

The average dose is 200 mg of progesterone per day (1 capsule of 200 mg or 2 capsules of 100 mg, divided into 2 doses, morning and evening, which are inserted deep into the vagina, if necessary using an applicator). The dose can be increased depending on the patient's response.

In case of partial luteal phase insufficiency (dysovulation, menstrual cycle disorders), the daily dose is 200 mg for 10 days (usually from the 17th to the 26th day of the cycle).

In case of complete luteal phase deficiency [complete absence of progesterone in women with non-functioning (absent) ovaries (egg donation)]: the dose of progesterone is 100 mg on the 13th and 14th days of the transfer cycle. From the 15th to the 25th day of the cycle, the dose of progesterone is 200 mg, divided into two doses (morning and evening). Starting from the 26th day, in case of early diagnosis of pregnancy, the dose is increased gradually (every week) by 100 mg of progesterone per day, reaching a maximum of 600 mg of progesterone per day, divided into three doses. This dosage should be followed until the 60th day.

Luteal phase support during an in vitro fertilization cycle: treatment is carried out starting from the evening of the embryo transfer day, at the rate of 600 mg per day in 3 doses (200 mg once every 8 hours).

In case of threatened miscarriage or for the prevention of habitual miscarriages due to luteal insufficiency: 200-400 mg per day (100-200 mg per dose every 12 hours) up to 12 weeks of pregnancy.

Prevention of preterm birth in women with a short cervix or in women with a history of spontaneous preterm birth: the dose is 200 mg per day and is administered in the evening before bedtime from the 22nd to the 36th week of pregnancy.

Children

There are no clinical data on the use of the drug in children.

Overdose

Symptoms of overdose may manifest as symptoms of adverse reactions, including drowsiness, dizziness, euphoria, dysmenorrhea, decreased cycle length, and metrorrhagia.

In some individuals, the usual dose may be excessive due to existing or secondary unstable endogenous progesterone secretion, hypersensitivity to the drug, or very low concomitant blood estradiol levels.

In such cases, it is enough:

reduce the dose of progesterone or prescribe progesterone in the evening before bedtime for 10 days per cycle in case of drowsiness or transient dizziness; postpone the start of treatment to a later date in the cycle (for example, day 19 instead of day 17) in case of its shortening or bleeding; check whether the estradiol level is sufficient in a patient receiving hormone replacement therapy in premenopause.

Adverse reactions

The following phenomena were observed with oral administration:

Adverse reactions such as changes in libido, breast discomfort, premenstrual symptoms, hyperthermia, insomnia, alopecia, hirsutism, venous thromboembolism, pulmonary embolism, fluid retention, weight change, gastrointestinal disorders, and anaphylactic reactions may also occur.

Drowsiness and/or transient dizziness are observed especially in the case of concomitant hypoestrogenism. Reducing the dose of the drug or increasing the dose of estrogen immediately eliminates these phenomena without reducing the therapeutic effect.

If treatment is started too early in the menstrual cycle, especially before day 15, there may be a shortening of the cycle or spotting.

When using the drug vaginally, hypersensitivity reactions are possible, including burning, itching, hyperemia, and the appearance of oily discharge.

Expiration date

3 years.

Storage conditions

Store out of the reach of children at a temperature not exceeding 25 °C.

Packaging

Capsules 200 mg – 7 soft capsules in a blister; 2 blisters in a cardboard box.

Vacation category

According to the recipe.

Producer

Besins Manufacturing Belgium SA, Belgium; Cyndea Pharma, SL, Spain.

Location of the manufacturer and its business address

Groot Bijgaardenstraat 128, Drogenbos, B-1620, Belgium; Poligono Industrial Emiliano Revilla Sanz. Avenida de Agreda, 31, Olvega, 42110 (Soria), Spain.