Pragisan, capsules 100 mg 30 pcs

Pragisan is a gestagen, a corpus luteum hormone. It binds to receptors on the surface of target organ cells and penetrates the nucleus where, by activating DNA, it stimulates RNA synthesis.

It promotes the transition of the uterine mucosa from the follicular hormone-induced proliferation phase to the secretory phase and, after fertilization, to the state necessary for the development of the fertilized egg. < br>

It reduces the excitability and contractility of the uterine and fallopian tube muscles and stimulates the development of mammary gland terminal elements.

Stimulating protein lipase, increases fat stores, increases glucose utilization by increasing basal and stimulated insulin concentrations, promotes glycogen accumulation in the liver, increases aldosterone production; in low doses accelerates and in high doses inhibits production of gonadotropic pituitary hormones; reduces azotemia, increases urinary nitrogen excretion. < br>

Activates the growth of the secretory division of the mammary gland acini and induces lactation. Promotes the development of normal endometrium.

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Indications

Disorders associated with progesterone deficiency.

Oral route of administration:
infertility due to luteal insufficiency;
premenstrual syndrome;
menstrual irregularities due to ovulation or anovulation disorders;
fibrocystic mastopathy;
premenopause;
hormone replacement therapy for peri- and postmenopause (in combination with estrogen-containing drugs).
Vaginal route of administration:
hormone replacement therapy in case of progesterone deficiency with non-functioning (absent) ovaries (egg donation);
prevention (prophylaxis) of premature birth in women at risk (with shortening of the cervix and/or anamnestic data of premature birth and/or premature rupture of membranes);
luteal phase support during preparation for in vitro fertilization;
luteal phase support in spontaneous or induced menstrual cycle;
premature menopause;
hormone replacement therapy (in combination with estrogen drugs);
infertility due to luteal insufficiency;
prevention of habitual and threatened abortion due to progestin deficiency.

Pharmacological effect

Pharmacotherapeutic group: Gestagen

Pharmacological action

Progestin, hormone of the corpus luteum. By binding to receptors on the surface of cells of target organs, it penetrates into the nucleus, where, activating DNA, it stimulates RNA synthesis. Promotes the transition of the uterine mucosa from the proliferation phase caused by follicular hormone to the secretory phase, and after fertilization – 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, stimulates the development of the end elements of the mammary gland.

By stimulating protein lipase, it increases fat reserves, increases glucose utilization, increasing the concentration of basal and stimulated insulin, promotes the accumulation of glycogen in the liver, increases the production of aldosterone: in small doses it accelerates, and in large doses it suppresses the production of pituitary gonadotropic hormones; reduces azotemia, increases nitrogen excretion in urine. Activates the growth of the secretory section of the acini of the mammary glands and induces lactation. Promotes the development of normal endometrium.

Pharmacokinetics

When taken orally

Suction

Micronized progesterone is well absorbed from the gastrointestinal tract. The concentration of progesterone in the blood plasma gradually increases during the first hour, Cmax is observed 1-3 hours after administration. After taking 200 mg, the concentration of progesterone in plasma increases from 0.13 ng/ml to 4.25 ng/ml after 1 hour and is 11.75 ng/ml after 2 hours, 8.37 ng/ml after 3 hours, 2 ng/ml after 6 hours, 1.64 ng/ml after 8 hours.

Metabolism

Metabolized in the liver with the participation of the CYP2C19 isoenzyme. The main metabolites that are detected in blood plasma are 20-alpha-hydroxy-delta-4-alpha-pregnanolone and 5-alpha-dihydroprogesterone.

Removal

Excreted by the kidneys in the form of metabolites. 95% of these are glucurone-conjugated metabolites, mainly 3-alpha, 5-beta-pregnanediol (pregnanediol). 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 insertion

Suction

Absorption occurs quickly; progesterone accumulates in the uterus; 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. When the drug is administered at a dose of 100 mg 3 times a day, the average concentration is maintained for 24 hours. When administered in doses of more than 200 mg/day, the concentration of progesterone corresponds to the first trimester of pregnancy.

Metabolism

Metabolized to form predominantly 3-alpha, 5-beta-pregnanediol. The concentration of 5-beta-pregnanediol in plasma does not increase.

Removal

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

Special instructions

Prajisan® should not be used for contraception.

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

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

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

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

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

During long-term treatment with progesterone, regular medical examinations (including liver function tests) are necessary; Treatment should be discontinued if abnormal liver function tests or cholestatic jaundice are present.

When using progesterone, a decrease in glucose tolerance and an increase in the need for insulin and other hypoglycemic drugs in patients with diabetes mellitus is possible.

If amenorrhea occurs during treatment, pregnancy must be excluded. If the course of treatment begins very early in the menstrual cycle, especially before the 15th day of the cycle, a shortening of the menstrual cycle and/or acyclic bleeding is possible. In 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 irradiation.

More than 50% of spontaneous abortions in early pregnancy are caused by genetic disorders. In addition, the cause of spontaneous abortions in early pregnancy can be infectious processes and mechanical damage. The use of the drug Prajisan® in these cases can only lead to a delay in rejection and evacuation of a non-viable ovum. Prescribing Prajisan® for the purpose of preventing and/or treating threatened miscarriage is justified only in cases of progesterone deficiency.

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

When carrying out HRT with estrogens during perimenopause, it is recommended to use Prajisan® for at least 12 days of the menstrual cycle. With a continuous HRT regimen in postmenopause, it is recommended to use the drug from the first day of taking estrogen.

When carrying out hormone replacement therapy (HRT), the risk of developing venous thromboembolism (deep vein thrombosis or pulmonary embolism), the risk of developing ischemic stroke, and coronary heart disease increases.

Due to the risk of developing thromboembolic complications, the use of the drug should be discontinued if: visual disturbances such as loss of vision, exophthalmos, double vision, vascular lesions of the retina occur; 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 Prajisan® with estrogen-containing drugs, you must 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 long-term, more than 5 years, combined use of estrogen-containing drugs with synthetic gestagens. It is unknown whether there is an increased risk of breast cancer in postmenopausal women when undergoing HRT with estrogen-containing drugs in combination with progesterone.

The WHI study also found an increased risk of dementia when starting HRT after age 65.

Before starting HRT and regularly during it, a woman should be examined to identify contraindications to its implementation. If clinically indicated, a breast examination and gynecological examination should be performed.

The use of progesterone may affect the results of some laboratory tests, including liver and thyroid function tests; coagulation parameters; pregnanediol concentration.

Impact on the ability to drive vehicles and machinery

When taken orally, care must be taken when driving vehicles, using machinery and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Active ingredient

Progesterone

Composition

Active substance: progesterone

Excipients: peanut butter – 147.5 mg, soy lecithin – 2.5 mg.

Pregnancy

During pregnancy, the drug can only be used intravaginally.

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

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

Contraindications

For oral and vaginal use
deep vein thrombosis, thrombophlebitis;
thromboembolic disorders (pulmonary embolism, myocardial infarction, stroke), intracranial hemorrhage or a history of these conditions/diseases;
bleeding from the vagina of unknown origin;
incomplete abortion;
porphyria;
established or suspected malignant neoplasms of the mammary glands and genital organs;
age under 18 years (efficacy and safety have not been established);
lactation period (breastfeeding);
hypersensitivity to progesterone or any of the auxiliary components of the drug.
For oral use (optional)
severe liver diseases (including cholestatic jaundice, hepatitis, Dubin-Johnson syndrome, Rotor syndrome, malignant liver tumors) currently or in history;

The drug should be used with caution in diseases of the cardiovascular system, arterial hypertension, chronic renal failure, diabetes mellitus, bronchial asthma, epilepsy, migraine, depression, and in the second trimester of pregnancy.

Side Effects

By oral route

The following adverse events noted during oral administration of the drug are distributed according to the frequency of occurrence in accordance with the following gradation: often (>1/100, 1/1000, 1/10,000, <1/1000), very rare (<1/10,000).From the genital organs and mammary gland: often – amenorrhea, menstrual irregularities, acyclic bleeding; infrequently – mastodynia.From the mental side: very rarely – depression.From the nervous system: often – headache; infrequently – drowsiness, transient dizziness.From the gastrointestinal tract: often – bloating; uncommon – vomiting, diarrhea, constipation; rarely – nausea.From the liver and biliary tract: infrequently – cholestatic jaundice.From the immune system: very rarely – urticaria.From the skin and subcutaneous tissues: infrequently – itching, acne; very rarely – chloasma.Drowsiness and transient dizziness are possible, as a rule, 1-3 hours after taking the drug. These side effects can be reduced by reducing the dose, using the drug at bedtime, or switching to the intravaginal 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 higher estrogenization immediately eliminates these effects 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 of the cycle), a shortening of the menstrual cycle or acyclic bleeding is possible.Recorded changes in the menstrual cycle, amenorrhea or acyclic bleeding are characteristic of all progestogens.Application in clinical practiceDuring post-marketing use, the following adverse events were noted with oral use 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 carrying out HRT in combination with estrogen-containing drugs); increase in blood pressure.The drug contains soy lecithin, which can cause hypersensitivity reactions (urticaria and anaphylactic shock).For vaginal route of administrationIsolated 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, and oily discharge have been reported.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

For oral administration

Progesterone enhances the effect of diuretics, antihypertensive drugs, immunosuppressants, anticoagulants.

Reduces the lactogenic effect of oxytocin.

Concomitant use with drugs that induce 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 use of progesterone with some antibiotics (penicillins, tetracyclines) can lead to a decrease in its effectiveness due to disruption of the enterohepatic recirculation of sex hormones due to changes in the intestinal microflora.

The severity of these interactions may vary in different patients, so predicting the clinical effects of these interactions is difficult.

Ketoconazole may increase the bioavailability of progesterone. Progesterone may 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 increase in the need for insulin or other hypoglycemic drugs in patients with diabetes.

The bioavailability of progesterone may be reduced in patients who smoke and drink excessive alcohol.

For intravaginal use

Interactions with intravaginal use have not been assessed.

The simultaneous use of other intravaginal drugs should be avoided to avoid interfering with the release and absorption of progesterone.

Overdose

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

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

Treatment:
in case of drowsiness and dizziness, it is necessary to reduce the dose or prescribe the drug before bedtime for 10 days of the menstrual cycle;
in case of a shortening of the menstrual cycle or spotting, it is recommended to postpone the start of treatment to a later day of the cycle (for example, on the 19th day instead of the 17th);
in perimenopause and with HRT in postmenopause, it is necessary to ensure that the concentration of estradiol is optimal.
If necessary, carry out symptomatic treatment.

Storage conditions

The drug should be stored in a place protected from light, out of reach of children, at a temperature not exceeding 25°C.

Shelf life

2 years

Manufacturer

Sun Pharmaceutical Industries Ltd, India