Mifepristone

Pharmacological properties

mifepristone is a synthetic steroidal antigestagenic agent (blocks the action of progesterone at the receptor level), does not reveal gestagenic activity. there is antagonism with corticosteroids (due to competition at the level of binding to receptors).

It enhances the contractility of the myometrium, stimulating the release of interleukin-8 in choriodecidual cells, increasing the sensitivity of the myometrium to prostaglandins.

Depending on the phase of the menstrual cycle, it delays ovulation, changes in the endometrium and prevents the implantation of a fertilized egg.

Pharmacokinetics After a single dose of 600 mg C_max in blood plasma 1.98 mg / l is achieved after 1.3 hours. Absolute bioavailability is 69%. In blood plasma, mifepristone is 98% bound to proteins: albumin and acid alpha-1 glycoprotein.

After the distribution phase, excretion initially takes place slowly, the concentration decreases by 2 times between 12–72 hours, then much faster. T_½ is 18 hours

Indications

Immediate (postcoital) contraception (after unprotected intercourse or if the method of contraception used cannot be considered reliable).

Application

Inside, within 72 hours after unprotected contraception, 1 tablet of ginepriston 10 mg once.

To maintain the effect of contraception, one should refrain from eating 2 hours before and within 2 hours after using the drug.

Ginepriston can be used in any phase of the menstrual cycle.

Contraindications

A history of hypersensitivity to mifepristone, adrenal insufficiency and prolonged corticosteroids therapy, acute or chronic renal and / or liver failure, porphyria, uterine fibroids, scarring in the uterus, anemia, hemostasis disorders (including previous treatment with anticoagulants), inflammatory diseases of the female genital organs, the presence of severe extragenital pathology. severe form of ba.

Side effects

From the genitourinary system: spotting from the genital tract, menstrual irregularities, endometritis.

From the nervous system: headache, dizziness.

From the gastrointestinal tract: nausea, vomiting, diarrhea, abdominal cramps.

On the part of the skin and subcutaneous tissue: urticaria, skin rashes.

From the immune system: hypersensitivity reactions.

Others: a feeling of discomfort in the lower abdomen, weakness, malaise, chills, hyperthermia, toxic shock syndrome, tenderness of the mammary glands.

special instructions

To prescribe with caution in case of hemostasis violation (including previous treatment with anticoagulants), chronic obstructive pulmonary diseases (including BA), severe arrhythmias, cardiac arrhythmias and heart failure, patients who have had a history of prosthetic heart valves, infectious endocarditis.

Due to the anticorticosteroid activity of mifepristone, the effectiveness of long-term corticosteroid therapy, including inhaled corticosteroids in patients with AD, can be reduced within 3-4 days after the use of mifepristone. In these cases, a dose adjustment of GCS may be required.

The drug is not recommended for regular use with the goal of planned continuous contraception. The drug does not protect against sexually transmitted diseases and AIDS.

The patient should be informed in advance about possible adverse reactions. If menstruation is delayed for more than 5 days or appears on time, but its course differs from normal, or for some reason there is a suspicion of pregnancy, the possibility of pregnancy should be excluded.

Use during pregnancy and lactation. The drug can not be used during pregnancy. Breastfeeding should be stopped for 14 days after taking the drug.

Children.It is advisable to use immediate contraception as a means of protection against unwanted pregnancy for adolescents only in emergency cases in people who have been raped, taking into account all the possible consequences.

The ability to influence the reaction rate when driving vehicles or working with mechanisms. There is no information on the effect of the drug on the ability to drive vehicles or work with complex mechanisms, but the possibility of developing adverse reactions from the nervous system (dizziness, weakness) should be considered.

Interactions

The simultaneous use of NSAIDs should be avoided, the combined use of NSAIDs is not recommended for 8-12 days after the use of the drug. rifampicin, dexamethasone, some anticonvulsants (phenytoin, phenobarbital, carbamazepine) can stimulate the metabolism of mifepristone (reduce its concentration in blood plasma).

Despite the fact that the metabolism of mifepristone occurs with the participation of the CYP 3A4 enzyme of the cytochrome P450 system, while taking the drug with inhibitors of this enzyme (ketoconazole, itraconazole, erythromycin, grapefruit juice), it is possible to inhibit the metabolism of mifepristone and increase its level in blood plasma.

According to in vitro studies, the simultaneous use of mifepristone with drugs that are substrates of CYP 3A4 can lead to an increase in the level of these drugs in blood plasma. Due to the slow removal of mifepristone from the body, this interaction can be observed for a long time after its use. Caution should be exercised while using mifepristone with drugs that are substrates for CYP 3A4, have a narrow therapeutic range, including some drugs that are used during general anesthesia.

Concurrent use with NSAIDs should be avoided.

Overdose

The use of ginepriston in a dose of up to 2 g does not cause adverse reactions. in case of an overdose of the drug, adrenal insufficiency is possible. symptomatic therapy.

Storage conditions

At a temperature not exceeding 30 ° C.