Utrogestan, capsules 100 mg 28 pcs

Pharmacotherapeutic group: gestagen

ATX code: G03DA04

Pharmacological properties

Pharmacodynamics

The active ingredient of Utrogestan® is progesterone, identical to the natural ovarian corpus luteum hormone. Binding to receptors on the surface of target organ cells, it penetrates the nucleus where, by activating DNA, it stimulates RNA synthesis. It promotes the transition of the uterine mucosa from the phase of proliferation caused by the follicular hormone estradiol to the secretory phase, and after fertilization to the state necessary for the development of the fertilized egg. Reduces the excitability and contractility of the uterine muscles and fallopian tubes. Promotes the formation of the normal endometrium. Stimulates the development of mammary gland terminal elements and induces lactation.

Stimulating protein lipase increases fat stores; increases glucose utilization; by increasing basal and stimulated insulin concentrations, promotes glycogen accumulation in the liver; increases pituitary gonadotropic hormone production; reduces azotemia and increases renal excretion of nitrogen.

Pharmacokinetics

In oral administration

Intake

Micronized progesterone is well absorbed in the gastrointestinal tract (GIT). The plasma concentration of progesterone increases gradually during the first hour, the maximum plasma concentration (Cmax) is noted 1-3 hours after administration. Plasma progesterone concentration increases from 0.13 ng/ml to 4.25 ng/ml after 1 h, to 11.75 ng/ml after 2 h and is 8.37 ng/ml after 3 h, 2 ng/ml after 6 h and 1.64 ng/ml after 8 h after administration.

Metabolism

The main metabolites that are detected in plasma are 20-alpha-hydroxy-delta-4-alpha-pregnanolone and 5-alpha-dihydroprogesterone.

Excretion

Extracted by the kidneys as metabolites, 95% of which are glucuronconjugated metabolites, mainly 3-alpha, 5-beta-pregnandiol (pregnandione). These metabolites, which are determined in plasma and urine, are similar to substances produced during physiological corpus luteum secretion.

In vaginal administration

Absorption and distribution

Absorption is rapid, a high plasma concentration of progesterone is observed 1 hour after administration. Progesterone cmax in blood plasma is reached 2-6 hours after administration. When administered 100 mg twice daily, the average plasma concentration is maintained at 9.7 ng/ml for 24 hours. When administered in doses greater than 200 mg/day, the progesterone concentration corresponds to the first trimester of pregnancy. The binding to plasma proteins is 90%. Progesterone accumulates in the uterus.

Metabolism

Metabolized with the formation of mainly 3-alpha, 5-beta-pregnandiol. The concentration of 5-beta-pregnanolone in blood plasma is not increased.

Excretion

Extracted by the kidneys as metabolites, the main part is 3-alpha, 5-beta-pregnandiol (pregnandion). This is confirmed by a constant increase in its concentration (Cmax 142 ng/ml after 6 h).

Indications

Progesterone deficiency conditions in women:

For oral administration:

threatened abortion or prevention of habitual abortion due to

progesterone deficiency;

Active ingredient

Composition

The composition per 1 capsule:

The active ingredient: progesterone micronized 100 or 200 mg.

Excipients: sunflower oil 149 mg/298 mg, soy lecithin 1 mg/2 mg; capsule – gelatin 76.88 mg/153.76 mg, glycerin 31.45 mg/62.9 mg, titanium dioxide 1.67 mg/3.34 mg.

How to take, the dosage

The oral route of administration

The drug is taken orally in the evening before bedtime with water.

In most cases of progesterone deficiency, the daily dose of Utrogestan ® is 200-300 mg divided into 2 doses (200 mg in the evening before bedtime and 100 mg in the morning, if necessary).

In case of threatened abortion or to prevent habitual abortion due to progesterone insufficiency, 200-600 mg/day daily in I and II trimesters of pregnancy are prescribed. The further use of Utrogestan® is possible according to the prescription of the attending physician on the basis of the evaluation of the clinical data of a pregnant woman.

In case of luteal phase failure (premenstrual syndrome, cystic fibrosis, dysmenorrhea, menopausal transition) the daily dose of the drug is 200 or 400 mg for 10 days (usually from the 17th to the 26th day of the cycle).

In perimenopausal MHT in combination with estrogen, Utrogestan® is given for 200 mg daily for 12 days.

In postmenopausal MHT in a continuous regimen, Utrogestan® is administered in a dose of 100-200 mg from the first day of estrogen therapy. The dose is adjusted individually.

The vaginal route of administration

The capsules are placed deep in the vagina.

Prevention (prevention) of preterm birth in women at risk (with shortening of the cervix and/or with the presence of history of preterm birth and/or premature rupture of membranes): the usual dose is 200 mg before bedtime, from the 22nd to the 34th week of pregnancy.

The complete absence of progesterone in women with non-functioning (absent) ovaries (egg donation): against the background of estrogen therapy, 100 mg/day on days 13 and 14 of the cycle, then – 100 mg twice a day from day 15 to 25 of the cycle, from day 26 and in case of pregnancy determination, the dose increases by 100 mg/day each week, reaching a maximum of 600 mg/day, divided into 3 doses. This dose is usually used for 60 days.

Luteal phase support during an in vitro fertilization cycle: 200 to 600 mg/day starting on the day of chorionic gonadotropin injection during the first and second trimesters of pregnancy is recommended.

Luteal phase support in spontaneous or induced menstrual cycle, in infertility associated with impaired corpus luteum function: it is recommended to use 200-300 mg/day starting on day 17 of the cycle for 10 days, in case of delayed menstruation and pregnancy diagnosis the treatment should be continued.

In cases of threatened abortion or to prevent habitual abortion arising against a background of progesterone insufficiency: 200-400 mg/d in 2 doses daily in I and II trimesters of pregnancy.

Interaction

In oral administration

Progesterone increases the effect of diuretics, hypotensive drugs, immunosuppressants, anticoagulants.

Decreases the lactogenic effect of oxytocin.

Concomitant use with agents inducers of microsomal liver enzymes CYP3A4, such as barbiturates, antiepileptic drugs (phenytoin), rifampicin, phenylbutazone, spironolactone, griseofulvin is accompanied by acceleration of progesterone metabolism in the liver.

The simultaneous administration of progesterone with some antibiotics (penicillins, tetracyclines) may lead to a decrease in its effectiveness due to impaired intestinal hepatic recirculation of sex hormones due to changes in intestinal microflora.

The severity of these interactions may vary from patient to patient; therefore, it is difficult to predict the clinical effects of these interactions.

Ketoconazole may increase the bioavailability of progesterone.

Progesterone may increase the concentration of ketoconazole and cyclosporine.

Progesterone may decrease the effectiveness of bromocriptine.

Progesterone may cause a decrease in glucose tolerance, which may increase the need for insulin or other hypoglycemic drugs in diabetic patients.

The bioavailability of progesterone may be reduced in female patients who smoke or drink too much alcohol.

In intravaginal use

The interaction of progesterone with other drugs in intravaginal use has not been evaluated. Concomitant use of other drugs used intravaginally should be avoided to avoid impairing the release and absorption of progesterone.

Special Instructions

The drug Utrogestan® should not be used for contraceptive purposes.

The drug should not be taken with food because food increases the bioavailability of progesterone.

The product Utrogestan® should be used with caution in patients with diseases and conditions which may be exacerbated by fluid retention (hypertension, cardiovascular disease, chronic renal failure, epilepsy, migraine, bronchial asthma); In patients with diabetes; mild to moderate liver function abnormalities; photosensitivity.

Patients with a history of depression should be monitored, and if severe depression develops, the drug should be stopped.

The product Utrogestan ® contains soy lecithin, which may cause hypersensitivity reactions (hives and anaphylactic shock).

Patients with a history or history of associated cardiovascular disease should also be monitored periodically by a physician.

The use of Utrogestan® after the first trimester of pregnancy can cause cholestasis.

Long-term treatment with progesterone requires regular medical monitoring (including liver function tests); treatment should be discontinued if liver function tests are abnormal or if there is cholestatic jaundice.

Progesterone use may decrease glucose tolerance and increase the need for insulin and other hypoglycemic agents in diabetic patients.

If amenorrhea occurs during treatment it is necessary to rule out the presence of pregnancy.

If the treatment course is started too early at the beginning of menstrual cycle, especially before the 15th day of the cycle, shortening of the cycle and/or acyclic bleeding are possible. In case of acyclic bleeding the drug should not be used until the cause of the bleeding has been clarified, including an endometrial histological examination.

If patients have a history of or are prone to chloasma, it is recommended that UV radiation be avoided.

In over 50% of cases of spontaneous abortions in early pregnancy are caused by genetic disorders. In addition, the cause of spontaneous abortions in early pregnancy may be infectious processes and mechanical damage. Administration of Utrogestan® in these cases may result only in delayed rejection and evacuation of a non-viable fetal egg.

The use of Utrogestan® to prevent threatened abortion is justified only in cases of progesterone deficiency.

In cases of perimenopausal MHT with estrogens, the use of Utrogestan® for at least 12 days of the menstrual cycle is recommended.

In a continuous regimen of MHT in the postmenopause, use of the drug from the first day of estrogen administration is recommended.

MHT increases the risk of venous thromboembolism (deep vein thrombosis or pulmonary embolism), risk of ischemic stroke, CHD.

Because of the risk of thromboembolic complications, the drug should be discontinued if the following conditions occur: visual disturbances, such as vision loss, exophthalmus, double vision, retinal vascular lesions; migraine; venous thromboembolism or thrombotic complications, regardless of their location.

If there is a history of thrombophlebitis, the patient should be closely monitored.

When using Utrogestan® with estrogen-containing medications, the instructions for their use must be consulted with regard to the risks of venous thromboembolism.

The results of the Women Health Initiative Study (WHI) clinical trial suggest a small increase in breast cancer risk when estrogen-containing drugs are used together with synthetic gestagens for longer than 5 years. It is not known whether there is an increased risk of breast cancer in postmenopausal women when MHT is given with estrogen-containing drugs in combination with progesterone.

The WHI study also found an increased risk of dementia when starting MHT over age 65.

Before starting MHT and regularly during it, women should be screened for contraindications to MHT. If clinically indicated, a breast exam and gynecologic exam should be performed.

The use of progesterone may affect several laboratory tests, including liver function, thyroid function, coagulation parameters, and pregnandiol concentration.

Influence on driving and operating ability

When using the drug orally, caution should be exercised while driving vehicles and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Contraindications

Hypersensitivity to progesterone or any of the excipients of the drug; deep vein thrombosis, thrombophlebitis; thromboembolic disorders (pulmonary embolism, myocardial infarction, stroke), intracranial hemorrhage or history of these conditions/diseases; vaginal bleeding of unclear genesis; incomplete abortion; porphyria; established or suspected malignancies of the breast or genital organs; severe liver disease (including cholestatic jaundice, hepatitis, Dubin-Johnson syndrome, Rotor, malignant liver tumors) at present or in anamnesis; children under 18 years of age (effectiveness and safety not established); breastfeeding period.

WARNING

Cardiovascular disease, arterial hypertension, chronic renal failure, diabetes, bronchial asthma, epilepsy, migraine, depression, hyperlipoproteinemia, mild to moderate liver function impairment; photosensitivity.

The drug should be used with caution during the second and third trimesters of pregnancy.

Side effects

The following adverse events noted with oral administration are graded according to the following frequency of occurrence: frequently (>1/100, <1/10); infrequently (>1/1000, <1/100); rarely (>1/10000, <1/1000); very rarely (<1/10000).

Drowsiness, transient dizziness are usually possible 1-3 h after taking the drug. These adverse reactions may be reduced by reducing the dose, using the drug before bedtime, or switching to the vaginal route of administration.

These adverse effects are usually the first signs of an overdose.

Drowsiness and/or transient dizziness have been observed particularly in cases of concomitant hypoestrogenism. Reducing the dose or restoring higher estrogenicity immediately eliminates these phenomena without reducing the therapeutic effect of progesterone.

If treatment begins too early (in the first half of the menstrual cycle, especially before day 15), menstrual cycle shortening or acyclic bleeding may occur.

Recorded menstrual cycle changes, amenorrhea or acyclic bleeding are common with all progestagens.

Application in clinical practice

The following adverse events with oral progesterone have been noted in clinical practice: Insomnia, premenstrual syndrome, breast tension, vaginal discharge, joint pain, hyperthermia, increased sweating at night, fluid retention, body weight changes, acute pancreatitis, alopecia, hirsutism, libido changes, thrombosis and thromboembolic complications (when MHT is combined with estrogen-containing drugs), increased BP.

The drug contains soy lecithin, which may cause hypersensitivity reactions (urticaria and anaphylactic shock).

In the vaginal route of administration

I have reported individual cases of local intolerance reactions of the drug components (in particular, soy lecithin) in the form of hyperemia of the vaginal mucosa, burning, itching, oily discharge.

Systemic adverse effects have not been noted with intravaginal administration at the recommended doses, such as drowsiness or dizziness (seen with oral administration of the drug).

Overdose

Symptoms: drowsiness, transient dizziness, euphoria, shortened menstrual cycle, dysmenorrhea.

In some patients, the average therapeutic dose may be excessive because of an existing or emerging unstable endogenous progesterone secretion, a particular sensitivity to the drug, or too low a concentration of estradiol.

Treatment:

In case of overdose, symptomatic treatment is given if necessary.

Pregnancy use

The drug should be used with caution in the second and third trimesters of pregnancy because of the risk of cholestasis.

Progesterone penetrates into breast milk, so the use of the drug is contraindicated during breastfeeding.

Similarities