Agesta^® (Tablets) Instructions for Use

Marketing Authorization Holder

Promomed Rus LLC (Russia)

Manufactured By

Biokhimik, JSC (Russia)

ATC Code

G03XB01 (Mifepristone)

Active Substance

Mifepristone (Rec.INN registered by WHO)

Dosage Form

Agesta®

Tablets 10 mg: 1 or 2 pcs.

Dosage Form, Packaging, and Composition

Tablets light yellow with a greenish tint, flat-cylindrical in shape with a bevel; marbling is allowed.

Excipients: milk sugar (lactose), corn starch, colloidal silicon dioxide (aerosil), microcrystalline cellulose for medical purposes, calcium stearate.

1 pc. – contour cell packaging (1) – cardboard packs.
2 pcs. – contour cell packaging (1) – cardboard packs.
1 pc. – polymer jars (1) – cardboard packs.
2 pcs. – polymer jars (1) – cardboard packs.

Clinical-Pharmacological Group

Antigestagenic drug

Pharmacotherapeutic Group

Antigestagen

Pharmacological Action

Synthetic steroidal antigestagenic agent. It blocks the action of progesterone at the level of gestagen receptors. It does not possess gestagenic activity; antagonism with glucocorticosteroids is noted (due to competition at the level of receptor binding).

Depending on the phase of the menstrual cycle, it causes an increase in the contractile ability of the myometrium, stimulating the release of interleukin-8 in choriodecidual cells, increasing the sensitivity of the myometrium to prostaglandins (to enhance the effect, it is used in combination with a synthetic prostaglandin analogue), resulting in desquamation of the decidual membrane and expulsion of the ovum. It causes inhibition of ovulation, changes in the endometrium, and prevents implantation of a fertilized egg.

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

Pharmacokinetics

After a single dose, C_max of mifepristone in blood plasma is reached after 1.5 hours. The absolute bioavailability is 69%. The binding of mifepristone to blood plasma proteins (albumin and acidic α1-glycoprotein) is 98%. It undergoes the “first-pass” effect through the liver via N-demethylation and hydroxylation with the formation of three main metabolites.

After the distribution phase, elimination initially occurs slowly, the concentration decreases by half between 12-72 hours, then more rapidly. T_1/2 is 18 hours. It is not detected in blood plasma by day 11. Mifepristone is excreted mainly through the intestines.

Indications

Termination of intrauterine pregnancy in the early stages (up to 42 days of amenorrhea); induction of labor at full-term pregnancy; emergency postcoital contraception (after unprotected sexual intercourse or if the contraceptive method used cannot be considered reliable); uterine leiomyoma (size up to 12 weeks of pregnancy).

ICD codes

Dosage Regimen

Administer orally. The dose and regimen are determined individually, depending on the indication.

For medical termination of intrauterine pregnancy (up to 42 days amenorrhea): take a single dose of 600 mg (three 200 mg tablets) under physician supervision. Follow with a prostaglandin analogue 36-48 hours later.

For emergency postcoital contraception: take a single dose of 10 mg (one tablet) within 72 hours after unprotected intercourse.

For uterine leiomyoma (size up to 12 weeks pregnancy): take 50 mg once daily for three months.

For cervical ripening and labor induction at term: take a single dose of 200 mg under strict hospital conditions.

Take tablets with water. Do not break or chew. Avoid concomitant use of NSAIDs.

Adverse Reactions

From the digestive system nausea, vomiting, diarrhea.

From the CNS dizziness, headache.

From the reproductive system bloody discharge from the genital tract, menstrual cycle disorders, amenorrhea, exacerbation of inflammatory processes of the uterus and appendages, lochiometra, uterine subinvolution.

Allergic reactions urticaria.

Other feeling of discomfort and pain in the lower abdomen, weakness, hyperthermia.

Contraindications

General contraindications adrenal insufficiency, long-term use of glucocorticosteroids, acute or chronic renal failure, acute or chronic hepatic failure, porphyria, uterine fibroids, severe anemia, hemostasis disorders (including previous therapy with anticoagulants), inflammatory diseases of the female genital organs, severe extragenital pathology (without consultation with a physician), smoking women over 35 years of age, hypersensitivity to mifepristone (in history).

For medical termination of pregnancy suspicion of ectopic pregnancy, pregnancy not confirmed by clinical studies, pregnancy lasting more than 42 days of amenorrhea, pregnancy that occurred while using intrauterine contraception or after discontinuation of hormonal contraception.

For preparation and induction of labor severe preeclampsia, preeclampsia, eclampsia, preterm or postterm pregnancy, discrepancy between the size of the maternal pelvis and the fetal head, abnormal position of the fetus, bloody discharge during pregnancy from the genital tract of unspecified etiology.

For leiomyoma submucosal location of myomatous nodes, size of uterine leiomyoma exceeding 12 weeks of pregnancy, ovarian tumors, endometrial hyperplasia.

With caution should be prescribed for chronic obstructive pulmonary diseases, bronchial asthma, arterial hypertension, arrhythmias, chronic heart failure, heart rhythm disorders.

Use in Pregnancy and Lactation

If it is necessary to prescribe mifepristone, breastfeeding should be discontinued for 14 days.

The use of mifepristone for cervical ripening prior to childbirth does not affect subsequent lactation.

Use in Hepatic Impairment

Contraindicated in acute or chronic hepatic failure.

Use in Renal Impairment

Contraindicated in acute or chronic renal failure.

Special Precautions

Patients using Mifepristone for early termination of pregnancy should be informed that if there is no effect from its use on days 10-14 (incomplete abortion or ongoing pregnancy), the pregnancy must be terminated by another method due to the risk of congenital malformations in the fetus.

The use of mifepristone requires the prevention of Rh alloimmunization and other general measures accompanying abortion.

Patients with artificial heart valves or infectious endocarditis should receive prophylactic antibacterial therapy when using mifepristone.

Concomitant use of mifepristone with NSAIDs should be avoided.

The use of mifepristone for postcoital contraception does not protect against sexually transmitted diseases and AIDS.

It is not recommended for regular use as a planned permanent contraceptive.

Drug Interactions

With simultaneous use of mifepristone and glucocorticosteroids, it is necessary to increase the dose of the latter.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.