Gynestril^® (Tablets) Instructions for Use

Marketing Authorization Holder

Nizhpharm JSC (Russia)

Manufactured By

OHFK, JSC (Russia)

Contact Information

Nizhpharm group of companies (Russia)

ATC Code

G03XB01 (Mifepristone)

Active Substance

Mifepristone (Rec.INN registered by WHO)

Dosage Form

Gynestril®

Tablets 50 mg: 10, 20, 30, 40, or 60 pcs.

Dosage Form, Packaging, and Composition

Tablets from light yellow to light yellow with a greenish tint, flat-cylindrical in shape, with a bevel.

Excipients: microcrystalline cellulose, sodium carboxymethyl starch, talc, calcium stearate.

10 pcs. – contour cell packs (1) – cardboard packs.
10 pcs. – contour cell packs (2) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (4) – cardboard packs.
10 pcs. – contour cell packs (6) – cardboard packs.

Clinical-Pharmacological Group

Antigestagenic drug used for the treatment of uterine leiomyoma

Pharmacotherapeutic Group

Sex hormones and modulators of the genital system; other sex hormones and modulators of the genital system; progesterone receptor modulators

Pharmacological Action

Synthetic steroidal antigestagenic drug (blocks the action of progesterone at the receptor level), does not possess gestagenic activity. Antagonism with glucocorticoids has been noted (due to competition at the level of receptor binding).

Sex hormones, especially progesterone, play a key role in the pathogenesis of uterine leiomyoma. The use of mifepristone as a blocker of progesterone receptors may contribute to both inhibition of tumor growth and reduction in the size of myomatous nodes and the uterus.

Antagonism of mifepristone with glucocorticoids due to competition at the level of receptor binding has been noted.

Pharmacokinetics

Absorption

After administration, C_max is reached in 1.3 hours. Bioavailability is 69%.

Distribution and Metabolism

Binding of mifepristone to plasma proteins, albumin, and acidic alpha₁-glycoprotein, is 98%.

It is metabolized with the participation of the CYP3A4 isoenzyme by demethylation and hydroxylation to form three active metabolites.

Elimination

After the distribution phase, elimination initially occurs slowly, the concentration decreases by half between 12-72 hours, then more rapidly with a T_1/2 of 18 hours. The terminal T_1/2 (including for all active metabolites) reaches 90 hours. It is excreted mainly through the intestine (about 90%).

Indications

• Treatment of uterine leiomyoma (size up to 12 weeks of pregnancy).

ICD codes

Dosage Regimen

Take the drug orally at a dose of 50 mg (one tablet) once daily.

Administer the tablet with a sufficient amount of water.

Adhere to a continuous course of treatment for three months.

Initiate therapy only after confirming the diagnosis of uterine leiomyoma and excluding contraindications, such as pregnancy or submucosal node location.

Take the dose at approximately the same time each day to maintain stable plasma concentrations.

If a dose is missed and less than 12 hours have passed, take the missed tablet immediately.

If more than 12 hours have passed, skip the missed dose and continue the regular schedule; do not double the dose.

Monitor for potential adverse effects, including menstrual cycle disturbances, lower abdominal discomfort, or signs of adrenal insufficiency.

Discontinue use and seek medical advice if severe adverse reactions occur.

Do not use the drug for longer than the prescribed three-month course without re-evaluation by a physician.

Assess treatment efficacy via clinical and ultrasound examination upon completion of the course.

Adverse Reactions

In accordance with the grading of the frequency of adverse reactions according to WHO, “frequency unknown” – based on available data, it is not possible to determine the frequency of occurrence of an adverse reaction.

From the reproductive system frequency unknown – menstrual cycle disorders, amenorrhea, oligomenorrhea, discomfort and pain in the lower abdomen, simple endometrial hyperplasia (reversible after drug withdrawal).

From the digestive system frequency unknown – nausea, vomiting, diarrhea.

Allergic reactions frequency unknown – itching, urticaria.

Other frequency unknown – headache, dizziness, hyperthermia, weakness.

Contraindications

• Hypersensitivity to mifepristone or other components of the drug;
• Pregnancy;
• Breastfeeding period;
• Adrenal insufficiency;
• Long-term glucocorticoid therapy;
• Acute or chronic renal failure;
• Hepatic insufficiency;
• Porphyria;
• Hemostasis disorders (including previous treatment with anticoagulants);
• Inflammatory diseases of the female genital organs;
• Severe extragenital pathology;
• Submucosal location of myomatous nodes;
• Uterine leiomyoma exceeding 12 weeks of pregnancy in size;
• Ovarian tumors;
• Endometrial hyperplasia.

With caution

Chronic obstructive pulmonary diseases (including bronchial asthma), severe arterial hypertension, cardiac arrhythmias, chronic heart failure.

Use in Pregnancy and Lactation

The drug Gynestril^® is contraindicated for use during pregnancy and the breastfeeding period.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency.

Use in Renal Impairment

Contraindicated in acute or chronic renal failure.

Pediatric Use

No data.

Geriatric Use

No data.

Special Precautions

Patients with artificial heart valves or infectious endocarditis should receive prophylactic antibiotic treatment when using the drug Gynestril^®.

Effect on the ability to drive vehicles and mechanisms

There are no data indicating that the drug may affect the ability to drive a car and other mechanisms. However, when using mifepristone, dizziness may develop. In case of this side effect, you should refrain from driving vehicles and operating machinery.

Overdose

Taking mifepristone in doses up to 2 g does not cause adverse reactions.

Symptoms in cases of drug overdose, adrenal insufficiency may be observed.

Treatment symptomatic. If acute adrenal insufficiency is suspected, the administration of dexamethasone is recommended (1 mg of dexamethasone counteracts 400 mg of mifepristone).

Drug Interactions

Considering that the CYP3A4 isoenzyme is involved in the metabolism of mifepristone, it is possible that simultaneous use of inhibitors of this isoenzyme (ketoconazole, itraconazole, erythromycin, grapefruit juice) may increase, and inducers (rifampicin, dexamethasone, St. John’s wort preparations, phenytoin, phenobarbital, carbamazepine) may decrease the plasma concentration of mifepristone.

Caution should be exercised when mifepristone is used concomitantly with drugs that are substrates of CYP3A4 and have a narrow therapeutic range (including drugs for general anesthesia), due to a possible increase in the plasma concentration of these drugs.

With simultaneous use of mifepristone and NSAIDs, an increase in the plasma concentration of the latter is possible; if simultaneous use is necessary, NSAIDs should be used at the lowest recommended dose.

Mifepristone may reduce the effectiveness of long-term glucocorticoids, including inhaled glucocorticoids in patients with bronchial asthma, which may require dose adjustment.

Storage Conditions

The drug should be stored in the original packaging in a place inaccessible to children at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life – 5 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.