Mifepristone

Mifepristone is a drug that has an anti-gestagenic effect. It is a synthetic steroid that works by blocking progesterone receptors, which leads to changes in the endometrium and weakens the attachment of the embryo to the uterine wall.

The drug is widely used in medicine in several countries for the medical termination of early pregnancy (usually before 9 weeks of gestation). In combination with prostaglandins such as misoprostol, mifepristone can induce abortion (termination of pregnancy) by causing the uterus to contract and expel the fetal egg and developing fetus.

In addition, the drug is also used for other medical purposes such as induction of labor in cases of stillbirth or to manage hyperglycemia in Icenko-Cushing's syndrome.

Indications Mifepristone

1. Early termination of pregnancy: The drug is used to medically terminate a pregnancy in the first 9 weeks of pregnancy. Combined with prostaglandins such as misoprostol, mifepristone helps induce abortion by causing the uterus to contract and expel the fetal egg and developing fetus.
2. Induction of labor induction in stillbirth: Mifepristone may be used for induction of labor in cases of stillbirth, when the fetus has died in utero.
3. Managing hyperglycemia in Icenko-Cushing syndrome: Icenko-Cushing syndrome is characterized by an excess of cortisol in the body. The drug may be used to manage the hyperglycemia (high blood sugar) associated with this syndrome by blocking glucocorticoid receptors.

Release form

The drug is usually available in the form of tablets for oral administration. Dosage and dosage regimen may vary depending on the medical purpose.

Pharmacodynamics

Mifepristone is an antiprogesterone that acts on progesterone receptors by blocking them. Progesterone is a female sex hormone that plays a key role in regulating the menstrual cycle and maintaining pregnancy.

The mechanism of action varies depending on how it is used:

1. Abortifacient action: As an abortifacient, mifepristone is used to terminate pregnancy. It penetrates the placental barrier and binds to progesterone receptors in the endometrium (the inner layer of the uterus), leading to destruction of endometrial tissue and rupture of the placenta, resulting in termination of pregnancy.
2. Medical abortion: The drug can also be used in combination with prostaglandin (usually misoprostol) for medical termination of pregnancy in the first trimester. Prostaglandin helps to strengthen uterine contractions and facilitate expulsion of uterine contents.
3. Treatment of gynecologic conditions: In addition to its abortifacient action, mifepristone can be used to treat some gynecologic conditions such as endometriosis and submucosal myomas. In this case, by blocking progesterone receptors, the drug can induce changes in the endometrium and reduce the size of myomas.

Pharmacokinetics

1. Absorption: Mifepristone is usually well absorbed in the intestine after oral administration. It may be administered orally as tablets.
2. Metabolism: The drug undergoes extensive metabolism in the liver. The major metabolite, desmethylmifepristone, also has pharmacologic activity. This process usually involves cytochrome P450 enzymes.
3. Excretion: Mifepristone and its metabolites are usually excreted with urine and feces, mainly as metabolites.
4. Semi-disposition: The drug's elimination half-life is about 18-87 hours.
5. Protein binding: Mifepristone binds strongly to plasma proteins, mainly albumin.

Dosing and administration

The drug is usually used in combination with another drug, such as misoprostol, for medical abortion therapy. Here is the general route of administration and doses for this purpose:

1. Dosage: Usually administered in a dose of 200 mg. Occasionally a dose of 600 mg may be prescribed, but this depends on physician recommendations and specific clinical circumstances.
2. How to use: Mifepristone is usually taken orally as tablets. In most cases, it is taken in the presence of medical personnel monitoring the patient.
3. Time of administration: Mifepristone is usually taken at the beginning of a medical abortion procedure, usually at a clinic or health facility. Then, after a certain number of hours or days (depending on the protocol), another drug, such as misoprostol, may be taken to complete the abortion process.
4. Follow-up: It is important that the patient be under medical supervision throughout the abortion process and afterwards to monitor their health and provide the necessary support.

Use Mifepristone during pregnancy

The use of mifepristone (or any other drug) during pregnancy should only be used under strict medical supervision and in accordance with a doctor's recommendations. Mifepristone is usually used exclusively for early medical abortion (usually before 9 weeks' gestation) when there is a medical indication for abortion.

However, it is important to realize that the use of the drug during pregnancy may be associated with risks to the mother and child. Therefore, the decision to use it should be carefully weighed by a doctor, taking into account the circumstances of a particular pregnancy, potential side effects and risks.

It is also important to note that mifepristone is a drug whose use may result in termination of pregnancy, so its use during pregnancy may result in abortion if it is not anticipated or desired.

Contraindications

1. Allergic reaction to the drug itself or to any of its components.
2. Unidentified ectopic pregnancy.
3. Anemia (reduced red blood cells in the blood) or other serious blood disorders.
4. Diseases that require treatment with anticoagulants (blood thinners).
5. Adrenal diseases.
6. Renal or liver failure.
7. Taking anticoagulants (blood thinners) when they cannot be stopped temporarily.

Side effects Mifepristone

1. Medical abortion:

   • Bleeding: It can be heavy and last for several weeks.
   • Pain and cramps: In the lower abdomen and lower back.
   • Headaches.
   • Nausea and vomiting.
   • Diarrhea or liquid stools.
   • Possible increase in body temperature or fever.

2. Treatment of gynecologic conditions:

   • Menstrual disorders: Unusual menstrual bleeding or changes in the menstrual cycle.
   • Headaches.
   • Possible nausea and vomiting.
   • Fatigue or weakness.

3. Common side effects:

   • Allergic reactions: For example, skin rash, itching, or swelling.
   • Changes in blood counts: For example, changes in hemoglobin or platelet levels.

Overdose

Information on overdose in the medical literature is limited due to the relatively low toxicity of this drug. However, in case of overdose, undesirable side effects such as heavy bleeding, lower abdominal pain, dizziness, nausea and vomiting may occur.

Interactions with other drugs

Mifepristone may interact with other medicines, altering their efficacy, safety or causing undesirable side effects. Interactions may occur when different medicines are taken at the same time. Some of the possible interactions may include the following:

1. Antihistamines: The drug may increase the sedative effect of antihistamines such as diphenhydramine.
2. Drugs affecting the liver system: Mifepristone is metabolized in the liver, therefore drugs affecting liver function may alter its metabolism. For example, cytochrome P450 inhibitors or inducers (e.g., ketoconazole, rifampicin) may alter mifepristone levels in the body.
3. Drugs that reduce bleeding: Concurrent use with anticoagulants (e.g. Warfarin) may cause bleeding problems.
4. Drugs that affect the reproductive system: Some drugs, such as progesterone and its derivatives, may alter the effectiveness of the drug.

Storage conditions

Storage conditions are usually specified in the instructions for use provided by the manufacturer. Here are the general recommendations:

1. Temperature: Mifepristone should generally be stored at room temperature, which is usually 15 to 30 degrees Celsius (59 to 86 degrees Fahrenheit).
2. Humidity: The drug should be stored in a dry place to avoid exposure to moisture. Storage in humid conditions or in the bathroom is not recommended.
3. Light: Mifepristone should be stored in the original package or in a dark container protected from direct exposure to light. This will help prevent the active substance from decomposing when exposed to light.
4. Other recommendations: It is important to follow the instructions on the package and your doctor's recommendations regarding storage of the drug. Some mifepristone preparations may have additional specific storage instructions, such as the need to store in the refrigerator.