Utrogestan capsules 100mg, 28pcs

Composition

for 1 capsule:  

Active ingredient:

micronized progesterone 100 or 200 mg.

Auxiliary substances:

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.

Description:

100 mg capsules are round,

200 mg capsules are oval, soft shiny yellowish gelatin capsules containing an oily whitish homogeneous suspension (without visible phase separation).

Pharmacological action

Pharmacotherapeutic group: progestogen

ATX Code: G03DA04

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics

The Active ingredient of Utrozhestan® is progesterone, which is identical to the natural hormone of the ovarian corpus luteum. Binding to receptors on the surface of target organ cells, it penetrates into the nucleus, where it activates DNA and stimulates RNA synthesis. Promotes the transition of the uterine mucosa from the proliferation phase caused by the follicular hormone estradiol to the secretory phase, and after fertilization – to the state necessary for the development of a fertilized egg. Reduces excitability and contractility of the uterine and fallopian tube muscles. Promotes the formation of a normal endometrium. It stimulates the development of the terminal elements of the breast and induces lactation.

Stimulating protein lipase, increases fat reserves; increases glucose utilization; increases the concentration of basal and stimulated insulin, promotes the accumulation of glycogen in the liver; increases the production of pituitary gonadotropins; reduces azotemia, increases the excretion of nitrogen by the kidneys.

Pharmacokinetics

When taken orally

Suction

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

Metabolism

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

Deduction

It is excreted by the kidneys in the form of metabolites,95% of which are glucuronconjugated metabolites, mainly 3-alpha,5-beta-pregnanediol (pregnandion). These metabolites, which are detected in blood plasma and urine, are similar to substances formed during physiological secretion of the corpus luteum.

When administered vaginally

Suction and distribution

Absorption is rapid, and a high concentration of progesterone in the blood plasma is observed 1 hour after use. Cmax of progesterone in blood plasma is reached 2-6 hours after use. When 100 mg is administered twice a day, the average plasma concentration remains at the level of 9.7 ng/ml for 24 hours. When administered in doses of more than 200 mg/day, the progesterone concentration corresponds to the first trimester of pregnancy. Plasma protein binding is 90%. Progesterone accumulates in the uterus.

Metabolism

It is metabolized to form mainly 3-alpha,5-beta-pregnanediol. The concentration of 5-beta-pregnanolone in the blood plasma does not increase.

Deduction

It is excreted by the kidneys in the form of metabolites, the main part is 3-alpha,5-beta-pregnanediol (pregnandion). This is confirmed by a constant increase in its concentration (Cmax 142 ng / ml after 6 hours).

Indications

Progesterone deficiency conditions in women: For oral use:

• threatened abortion or prevention of habitual abortion due to;
• progesterone deficiency;
• infertility due to luteal insufficiency;
• premenstrual syndrome;
• menstrual disorders due to ovulation or anovulation disorders;
• fibrocystic mastopathy;
• menopausal transition;
• menopausal (hormone replacement) therapy (MHT) in peri-and postmenopausal (in combination with estrogen-containing drugs).

For intravaginal use:

• MGT in the case of progesterone deficiency with non-functioning (missing) ovaries (egg donation);
• prevention (prophylaxis) of preterm birth in women at-risk (with a short cervix and/or the presence of anamnestic data of preterm birth and/or premature rupture of membranes);
• support the luteal phase in preparation for in vitro fertilization;
• support the luteal phase in spontaneous or induced menstrual cycle;
• premature menopause;
• MGT (in combination with èstrogensoderžaŝimi drugs);
• infertility due to luteal insufficiency;
• threatening abortion or the prevention of habitual abortion due to lack of progesterone.

Use during pregnancy and lactation

Utrozhestan is indicated for use in the first and second trimesters of pregnancy.

Use with caution in the third trimester of pregnancy (due to the risk of liver function disorders) and during lactation.

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 the presence of these conditions/ diseases in the anamnesis; 

– vaginal bleeding of unknown origin;

– incomplete abortion;

– porphyria;

– known or suspected malignancies of the breast and genital organs;

– severe liver disease (including cholestatic jaundice, hepatitis, syndrome Dubin-Johnson, Rotor, malignant liver tumors) in the present or in the anamnesis;

– children’s age up to 18 years (efficacy and safety not established);

– the period of breastfeeding.

WITH CAUTION

, Diseases of the cardiovascular system, arterial hypertension, chronic renal failure, diabetes mellitus, bronchial asthma, epilepsy, migraine, depression, hyperlipoproteinemia, liver function disorders of mild and moderate severity; photosensitivity.

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

Side effects

Listed below adverse events, observed in the oral mode of application of the drug, divided by frequency of occurrence in accordance with the following gradation: often (>1/100, <1/10); infrequently (>1/1000, <1/100); rare (>1/10000, <1/1000); very rare (<1/10000).

Drowsiness, transient dizziness are possible, as a rule,1-3 hours after taking the drug. These adverse reactions can be reduced by reducing the dose, using the drug before bedtime, or switching to the vaginal route of use.

These undesirable effects are usually the first signs of overdose.

Drowsiness and / or transient dizziness are observed, in particular, in the case of concomitant hypoestrogenia.Reducing the dose or restoring higher estrogenation immediately eliminates these phenomena, without reducing the therapeutic effect of progesterone.

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

Reported changes in the menstrual cycle, amenorrhea, or acyclic bleeding are characteristic of all progestogens.

Application in clinical practice

When used in clinical practice is marked by the following adverse events when administered orally progesterone: insomnia, premenstrual syndrome, tension in the Breasts, vaginal discharge, pain in the joints, hyperthermia, sweating at night, fluid retention, changes in body weight, acute pancreatitis, alopecia, hirsutism, changes in libido, thrombosis and thromboembolic complications (during MGT combined with èstrogensoderžaŝimi drugs), increased blood pressure.

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

With the vaginal method of application

Isolated cases of local intolerance to the components of the drug (in particular, soy lecithin) in the form of hyperemia of the vaginal mucosa, burning, itching, and oily discharge have been reported.

Systemic side effects with intravaginal use of the drug at the recommended doses, in particular, drowsiness or dizziness (observed with oral use of the drug), were not observed.

Interaction

For oral use

Progesterone enhances the effect of diuretics, antihypertensive drugs, immunosuppressants, and anticoagulants. Reduces the lactogenic effect of oxytocin. Concomitant use with drugs that induce microsomal liver enzymes CYP3A4, such as barbiturates, antiepileptic drugs (phenytoin, carbamazepine), rifampicin, phenylbutazone, spironolactone, griseofulvin, is accompanied by an acceleration of progesterone metabolism in the liver.

Concomitant use of progesterone with certain antibiotics (penicillins, tetracyclines) can lead to a decrease in its effectiveness due to a violation of the intestinal-hepatic recirculation of sex hormones due to changes in the intestinal microflora.

The severity of these interactions may vary from patient to patient, so predicting the clinical effects of these interactions is difficult.

Ketoconazole may increase the bioavailability of progesterone. Progesterone can increase the concentration of ketoconazole and cyclosporine.

Progesterone may reduce the effectiveness of bromocriptine.

Progesterone can cause a decrease in glucose tolerance, resulting in an increased need for insulin or other hypoglycemic drugs in patients with diabetes mellitus.

The bioavailability of progesterone may be reduced in smoking patients and with excessive alcohol consumption.

For intravaginal use

The interaction of progesterone with other drugs during intravaginal use was not evaluated. Concomitant use of other intravaginally administered medications should be avoided to avoid disrupting progesterone release and absorption.

How to take, course of use and dosage

By mouth

The drug is taken orally in the evening before going to bed, washed down with water.

In most cases of progesterone deficiency, the daily dose of Utrozhestan ® 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 deficiency: 200-600 mg per day daily in the first and second trimesters of pregnancy. Further use of Utrozhestan® is possible as prescribed by the attending physician based on an assessment of the clinical data of a pregnant woman.

If the luteal phase is insufficient (premenstrual syndrome, fibrocystic mastopathy, dysmenorrhea, menopausal transition), the daily dose is 200 or 400 mg, taken for 10 days (usually from the 17th to the 26th day of the cycle).

In perimenopausal MHT with estrogen supplementation, Utrozhestan® is used 200 mg per day for 12 days.

In postmenopausal MHT, Utrozhestan® is used continuously at a dose of 100-200 mg from the first day of taking estrogen-containing drugs. The dose is selected individually.

Intravaginally

Capsules are inserted deep into the vagina.

Prevention of preterm labor in women at risk (with shortening of the cervix and/or the presence of anamnestic data of preterm labor and/or premature rupture of the fetal membranes): the usual dose is 200 mg at bedtime, from the 22nd to 34th weeks of pregnancy.

Complete absence of progesterone in women with non-functioning (absent) ovaries (egg donation): against the background of estrogen therapy,100 mg per day on the 13th and 14th days of the cycle, then 100 mg 2 times a day from the 15th to the 25th day of the cycle, from the 26th day, and in case of pregnancy, the dose increases by 100 mg per day each week, reaching a maximum of 600 mg per day, divided into 3 doses. The indicated dose can be used for 60 days.

Support of the luteal phase during the in vitro fertilization cycle: it is recommended to use from 200 to 600 mg per day, starting from the day of injection of chorionic gonadotropin during the first and second trimester of pregnancy.

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

In cases of threatened abortion or in order to prevent habitual abortion that occur against the background of progesterone deficiency: 200-400 mg per day in 2 doses daily in the first and second trimesters of pregnancy.

Overdose

Symptoms: drowsiness, transient dizziness, euphoria, shortening of the menstrual cycle, dysmenorrhea.

In some patients, the average therapeutic dose may be excessive due to the presence or occurrence of unstable endogenous progesterone secretion, special sensitivity to the drug, or too low estradiol concentration.

Treatment:

– in case of drowsiness or dizziness you need to reduce the daily dose or prescribe the drug before bedtime for 10 days of the menstrual cycle;

in the case of shortening of menstrual cycle or “spotting” bleeding, initiation of treatment is recommended to defer to a later day of the cycle (e. g., on the 19th instead of the 17-th);

in the perimenopause and postmenopause MGT necessary to ensure that the concentration of estradiol is optimal.

In case of overdose, if necessary, symptomatic treatment is carried out.

Special instructions

Utrozhestan® should not be used for the purpose of contraception.

The drug should not be taken with food, as food intake increases the bioavailability of progesterone.

Utrozhestan® should be taken with caution in patients with diseases and conditions that may be aggravated by fluid retention (arterial hypertension, cardiovascular diseases, chronic renal failure, epilepsy, migraine, bronchial asthma); in patients with diabetes mellitus; mild to moderate hepatic impairment; photosensitivity.

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

Utrozhestan® contains soy lecithin, which can cause hypersensitivity reactions (urticaria and anaphylactic shock).

Patients with concomitant cardiovascular diseases or a history of them should also be periodically monitored by a doctor.

The use of Utrozhestan® after the first trimester of pregnancy may cause the development of cholestasis.

With long-term progesterone treatment, regular medical examinations (including liver function tests) should be performed; treatment should be discontinued if deviations from normal liver function tests or cholestatic jaundice occur.

When using progesterone, it is possible to reduce glucose tolerance and increase the need for insulin and other hypoglycemic drugs in patients with diabetes mellitus.

If amenorrhea occurs during treatment, it is necessary to exclude the presence of pregnancy.

If the course of treatment begins too early at the beginning of the menstrual cycle, especially before the 15th day of the cycle, cycle shortening and/or acyclic bleeding may occur. In the case of acyclic bleeding, the drug should not be used until the cause is determined, including a histological examination of the endometrium.

If there is a history of chloasma or a tendency to develop it, patients are advised to avoid UV radiation.

More than 50% of cases of spontaneous abortions in early pregnancy are caused by genetic disorders. In addition, the cause of spontaneous abortions in the early stages of pregnancy can be infectious processes and mechanical damage. The use of Utrozhestan® in these cases can only lead to a delay in rejection and evacuation of an unviable fetal egg. The use of Utrozhestan® for the prevention of threatened abortion is justified only in cases of progesterone deficiency.

When performing MHT with estrogens during perimenopause, it is recommended to use Utrozhestan® for at least 12 days of the menstrual cycle.

With a continuous MHT regimen in postmenopausal women, it is recommended to use the drug from the first day of taking estrogens.

When performing MHT, the risk of venous thromboembolism (deep vein thrombosis or pulmonary embolism), the risk of ischemic stroke, and coronary heart disease increases.

Due to the risk of developing thromboembolic complications, the drug should be discontinued in the event of: visual disturbances, such as vision loss, exophthalmos, double vision, retinal vascular lesions; migraines; venous thromboembolism or thrombotic complications, regardless of their location.

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

When using Utrozhestan® with estrogen-containing drugs, it is necessary to refer to the instructions for their use regarding the risks of venous thromboembolism.

The results of the Women’s Health Initiative Study (WHI) indicate a slight increase in the risk of breast cancer with long-term, more than 5 years, combined use of estrogen-containing drugs with synthetic progestogens. It is not known whether there is an increased risk of breast cancer in postmenopausal women during MHT with estrogen-containing drugs in combination with progesterone.

The results of the WHI study also revealed an increased risk of dementia at the onset of MHT over the age of 65.

Before starting MHT and regularly during its implementation, a woman should be examined for contraindications to its implementation. If there are clinical indications, a mammary gland examination and a gynecological examination should be performed.

Apply. progesterone intake may affect the results of some laboratory tests, including liver function, thyroid function, coagulation parameters, and pregnanediol concentrations.

Influence on the ability to drive vehicles and mechanisms

When using the drug orally, care should be taken when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Capsules.

Storage conditions

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

Shelf

life is 3 years. Do not use after the expiration date.

Active ingredient

Progesterone

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

For adults as prescribed by a doctor, For postmenopausal women, For Pregnant women as prescribed by a doctor

Indications

Menopause, Threatened Miscarriage, Threat of Premature birth, Mastopathy, Infertility Treatment, Premenstrual syndrome