Product Overview
Structure
for 1 capsule:
Active substance:
micronized progesterone 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.
Description:
capsules 100 mg - round, capsules 200 mg - oval, soft shiny yellowish gelatin capsules containing an oily whitish homogeneous suspension (without visible phase separation).
pharmachologic effect
Pharmacotherapeutic group: gestagen
ATX code: G03DA04
PHARMACOLOGICAL PROPERTIES
Pharmacodynamics
The active substance of the drug Utrozhestan® is progesterone, which is identical to the natural hormone of the corpus luteum of the ovary. By binding to receptors on the surface of cells of target organs, it penetrates into the nucleus, where, by activating DNA, it stimulates RNA synthesis. Promotes the transition of the uterine mucosa from the proliferation phase, caused by the follicular hormone estradiol, into the secretory phase, and after fertilization - into the state necessary for the development of a fertilized egg. Reduces the excitability and contractility of the muscles of the uterus and fallopian tubes. Promotes the formation of a normal endometrium. Stimulates the development of breast end elements and induces lactation.By stimulating protein lipase, it increases fat stores; increases glucose utilization; by increasing the concentration of basal and stimulated insulin, it promotes the accumulation of glycogen in the liver; increases the production of pituitary gonadotropic hormones; reduces azotemia, increases the excretion of nitrogen by the kidneys.
Pharmacokinetics
IngestionSuction
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 observed 1-3 hours after administration. 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 administration.
Metabolism
The main metabolites that are detected in blood plasma are 20-alpha-hydroxy-delta-4-alpha-pregnanolone and 5-alpha-dihydroprogesterone.
Withdrawal
It is excreted by the kidneys in the form of metabolites, 95% of them are glucuron-conjugated metabolites, mainly 3-alpha, 5-beta-pregnandiol (pregnandione). These metabolites, which are determined in blood plasma and urine, are similar to substances formed during the physiological secretion of the corpus luteum.
With vaginal administration
Absorption and distribution
Absorption occurs quickly, a high concentration of progesterone in the blood plasma is observed 1 hour after administration. Cmax of progesterone in blood plasma is achieved 2-6 hours after administration. With the introduction of 100 mg 2 times a day, the average concentration in the blood plasma remains at the level of 9.7 ng / ml for 24 hours. When administered in doses of more than 200 mg / day, the concentration of progesterone corresponds to the first trimester of pregnancy. Communication with plasma proteins - 90%. Progesterone builds up in the uterus.
Metabolism
Metabolized with the formation of predominantly 3-alpha, 5-beta-pregnanediol. The concentration of 5-beta-pregnanolone in blood plasma does not increase.
Withdrawal
It is excreted by the kidneys in the form of metabolites, the main part is 3-alpha, 5-beta-pregnandiol (pregnandione). This is confirmed by a constant increase in its concentration (Cmax 142 ng / ml after 6 hours).
Indications
For oral administration:
- threatening abortion or prevention of habitual abortion due to progesterone deficiency;
- infertility due to luteal insufficiency;
- premenstrual syndrome;
- menstrual irregularities due to disturbed ovulation or anovulation;
- fibrocystic breast disease;
- the period of the menopausal transition;
- menopausal (replacement) hormone therapy (MHT) in peri- and postmenopausal women (in combination with estrogen-containing drugs).
For intravaginal use: - MHT in case of progesterone deficiency with non-functioning (absent) ovaries (egg donation);
- support of the luteal phase during preparation for in vitro fertilization;
- support of the luteal phase in the spontaneous or induced menstrual cycle;
premature menopause;
- MHT (in combination with estrogen-containing drugs);
- infertility due to luteal insufficiency;
- threatening abortion or prevention of habitual abortion due to progesterone deficiency.
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 a history of these conditions / diseases; vaginal bleeding of unknown origin; incomplete abortion; porphyria; established or suspected malignant neoplasms of the breast and genitals; severe liver disease (including cholestatic jaundice, hepatitis, Dubin-Johnson, Rotor syndromes, malignant liver tumors) currently or in history; children under 18 years of age (efficacy and safety have not been established); period of breastfeeding.
Carefully:
Diseases of the cardiovascular system, arterial hypertension, chronic renal failure, diabetes mellitus, bronchial asthma, epilepsy, migraine, depression, hyperlipoproteinemia, liver dysfunctions of mild and moderate severity; photosensitivity.
The drug should be used with caution in the II and III trimesters of pregnancy.
Side effects
The following undesirable effects noted with the oral route of administration of the drug are distributed according to the frequency of occurrence in accordance with the following gradation: often> 1/100, <1/10; infrequently> 1/1000, <1/100; rarely> 1/10000, <1/1000; very rarely <1/10000.
From the genitals and mammary gland: often - menstrual irregularities, amenorrhea, acyclic bleeding; infrequently - mastodynia.
From the side of the psyche: very rarely - depression.
From the nervous system: often - headache; infrequently - drowsiness, transient dizziness.
From the gastrointestinal tract: often - bloating; infrequently - vomiting, diarrhea, constipation; rarely - nausea.
From the liver and biliary tract: infrequently - cholestatic jaundice.
From the immune system: very rarely - urticaria.
On the part of the skin and subcutaneous tissues: infrequently - itching, acne; very rarely - chloasma.
Drowsiness, transient dizziness are possible, as a rule, 1-3 hours after taking the drug. These side effects can be reduced by lowering the dose, using the drug at bedtime, or switching to the vaginal route of administration.
These unwanted effects are usually the first signs of an overdose. Drowsiness and / or transient dizziness are observed, in particular, in the case of concomitant hypoestrogenism. Reducing the dose or restoring a higher estrogenation immediately eliminates these phenomena without diminishing the therapeutic effect of progesterone.
If the course of treatment starts 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.
Registered changes in the menstrual cycle, amenorrhea or acyclic bleeding are characteristic of all progestogens.
Application in clinical practice
With post-marketing use, the following adverse events were noted with oral administration of progesterone: insomnia; premenstrual syndrome; tension in the mammary glands; vaginal discharge; joint pain; hyperthermia; increased sweating at night; fluid retention; change in body weight; acute pancreatitis; alopecia, hirsutism; changes in libido; thrombosis and thromboembolic complications (when HRT is performed in combination with estrogen-containing drugs); increased blood pressure.
The preparation contains soy lecithin, which can cause hypersensitivity reactions (urticaria and anaphylactic shock).
Vaginal method of administration. It was reported about individual cases of the development of reactions of local intolerance to the components of the drug (in particular, soy lecithin) in the form of hyperemia of the vaginal mucosa, burning, itching, oily discharge.
Systemic side effects with intravaginal use of the drug in recommended doses, in particular drowsiness or dizziness (observed with oral administration of the drug), were not observed.
Interaction
Progesterone enhances the effect of diuretics, antihypertensive drugs, immunosuppressants, anticoagulants. Reduces the lactogenic effect of oxytocin.
Simultaneous use with drugs-inducers of 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.
The simultaneous administration of progesterone with some 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 in different patients, therefore, it is difficult to predict the clinical effects of these interactions.
Ketoconazole may increase the bioavailability of progesterone. Progesterone can increase the concentration of ketoconazole and cyclosporine.
Progesterone can decrease the effectiveness of bromocriptine.
Progesterone can cause a decrease in glucose tolerance, as a result of which - an increase in the need for insulin or other hypoglycemic drugs in patients with diabetes mellitus.
The bioavailability of progesterone can be reduced in patients who smoke and with excessive alcohol consumption.
For intravaginal use
The interaction of progesterone with other drugs with intravaginal use has not been evaluated. The simultaneous use of other drugs used intravaginally should be avoided in order to avoid impaired release and absorption of progesterone.
How to take, course and dosage
Orally
The drug is taken orally in the evening before bedtime with water.
In most cases, with 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 the drug Utrozhestan® is possible as prescribed by the attending physician based on an assessment of the clinical data of a pregnant woman.
In case of insufficiency of the luteal phase (premenstrual syndrome, fibrocystic breast disease, dysmenorrhea, the period of the 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).
With MHT in perimenopause while taking estrogens, the drug Utrozhestan® is used at 200 mg per day for 12 days. With MHT in postmenopausal women in a continuous mode, the drug Utrozhestan® is used at a dose of 100-200 mg from the first day of taking estrogen-containing drugs. Dose selection is carried out individually.
Intravaginally
The capsules are inserted deep into the vagina.
Prevention (prophylaxis) of premature birth in women at risk (with shortening of the cervix and / or the presence of anamnestic data of premature birth and / or premature rupture of membranes): the usual dose is 200 mg at bedtime, from 22nd to 34th weeks 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 days 13 and 14 of the cycle, then 100 mg 2 times a day from 15 to 25 day of the cycle, from the 26th day, and if pregnancy is determined, the dose increases by 100 mg per day every week, reaching a maximum of 600 mg per day, divided into 3 doses. The indicated dose can be applied for 60 days.
Support of the luteal phase during the cycle of in vitro fertilization: it is recommended to use from 200 to 600 mg per day, starting from the day of injection of chorionic gonadotropin during the I and II trimester of pregnancy.
Support of the luteal phase in a spontaneous or induced menstrual cycle in infertility associated with dysfunction of the corpus luteum: 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 diagnosis of pregnancy, treatment should be continued.
In cases of threatened abortion or in order to prevent habitual abortion arising against the background of progesterone deficiency: 200-400 mg per day in 2 doses daily in the first and second trimesters of pregnancy.
Overdose
In some patients, the average therapeutic dose may be excessive due to the existing or emerging unstable endogenous secretion of progesterone, special sensitivity to the drug, or too low a concentration of estradiol.
Treatment:in case of drowsiness or dizziness, it is necessary to reduce the daily dose or prescribe the drug before bedtime for 10 days of the menstrual cycle; in case of shortening of the menstrual cycle or "smearing" bleeding, it is recommended to postpone the start of treatment to a later day of the cycle (for example, on the 19th instead of the 17th); in perimenopause and in postmenopausal MHT, it is necessary to ensure that the concentration of estradiol is optimal.
In case of an overdose, symptomatic treatment is carried out if necessary.
Special instructions
The drug should not be taken with food, as food intake increases the bioavailability of progesterone.
The drug Utrozhestan® should be taken with caution in patients with diseases and conditions that can be aggravated by fluid retention (arterial hypertension, cardiovascular diseases, chronic renal failure, epilepsy, migraine, bronchial asthma); in patients with diabetes mellitus; impaired liver function of mild to moderate severity; photosensitivity.
Patients with a history of depression should be monitored and discontinued if severe depression develops.
The composition of the drug 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 monitored periodically by a doctor.
The use of the drug Utrozhestan® after the first trimester of pregnancy can cause the development of cholestasis.
Long-term progesterone treatment requires regular medical examinations (including liver function tests); treatment should be canceled in case of deviations from the normal parameters of liver function tests or cholestatic jaundice.
With the use of progesterone, a decrease in glucose tolerance and an increase in the need for insulin and other hypoglycemic drugs in patients with diabetes mellitus are possible.
If amenorrhea appears 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, shortening of the cycle and / or acyclic bleeding are possible. In the case of acyclic bleeding, the drug should not be used until their cause is clarified, 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 exposure.
More than 50% of spontaneous abortions in early pregnancy are due to genetic disorders. In addition, infectious processes and mechanical damage can be the cause of spontaneous abortions in early pregnancy. The use of the drug Utrozhestan® in these cases can only lead to a delay in the rejection and evacuation of a non-viable ovum.
The use of the drug Utrozhestan® in order to prevent threatening abortion is justified only in cases of progesterone deficiency.
When carrying out MHT with estrogens during perimenopause, it is recommended to use the drug Utrozhestan® for at least 12 days of the menstrual cycle.
With a continuous mode of MHT in postmenopausal women, it is recommended to use the drug from the first day of estrogen intake.
During MHT, the risk of developing venous thromboembolism (deep vein thrombosis or pulmonary embolism), the risk of ischemic stroke, coronary heart disease increases.
Due to the risk of thromboembolic complications, the drug should be discontinued in the event of: visual disturbances such as loss of vision, exophthalmos, double vision, vascular retinal 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 the drug Utrozhestan® with estrogen-containing drugs, refer to the instructions for their use regarding the risks of venous thromboembolism.
The results of the Women Health Initiative Study (WHI) clinical study indicate a slight increase in the risk of breast cancer with prolonged, more than 5 years, the 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 when MHT is administered with estrogen-containing drugs in combination with progesterone.
The WHI study also found an increased risk of dementia when starting MHT over the age of 65.
Before starting MHT and regularly during its implementation, a woman should be examined to identify contraindications to its implementation. In the presence of clinical indications, an examination of the mammary glands and a gynecological examination should be carried out.
The use of progesterone can affect the results of some laboratory tests, including indicators of liver function, thyroid gland; coagulation parameters; concentration of pregnandiol.
Influence on the ability to drive vehicles and mechanisms
When using the drug orally, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.
Storage conditions
Store at a temperature not exceeding 25 ° C.
Keep out of the reach of children.
