Levonova, Mirena, Norplant.

Composition and form of release

Levonorgestrel. Implant capsules (1 capsule - 36 mg); intrauterine device (in 1 IUD - 52-52 mg).

Pharmachologic effect.

Synthetic progestin. Contraceptive. It has an effect on the gonadotropic function of the pituitary gland, which leads to a slight decrease in the peak of FSH and LH. It causes changes in the endometrium, which lead to a disruption in the process of implantation of the embryo. Promotes an increase in the viscosity of cervical mucus, which prevents the advancement of sperm. After subcutaneous implantation of 6 capsules, the contraceptive effect is achieved after 24 hours.

Levonorgestrel as part of an intrauterine device has a direct local effect on the endometrium (reducing its implantation function), fallopian tubes, the viscosity of the mucus of the cervical canal, which increases the effectiveness and duration of IUD use, without suppressing ovulation.

Pharmacokinetics

Diffusion from the vertical rod of the T-shaped device occurs continuously at a rate of 20 μg / day. After several weeks of installation, the plasma concentration is 0.4-0.6 nmol / l. After long-term presence of the device (24, 60 months) in the uterine cavity, the concentration of levonorgestrel in blood plasma was 192 and 159 pg / ml, respectively. The indicated concentrations are low and the systemic effect of the drug is minimal. The capsules are implanted under the skin in the inner area of ​​the shoulder for a period of 5 years. The contraceptive effect is achieved after 24 hours.

When it enters the bloodstream, levonorgestrel binds to blood plasma proteins - 97% (with SHBG and albumin) and only 2.5% is in free form. Vd - 137 liters. T1 / 2 -14-20 hours. Metabolized with the formation of glucuronide conjugates. It is excreted in the urine 60% and in the feces 40% in the form of metabolites.

Indications

Implant capsules:
long-term hormonal contraception in cases where intrauterine and estrogen-containing contraceptives cannot be used; if necessary, immediate contraception after an abortion.
Intrauterine device: .

Application

Capsules - 6 pcs. n / a is implanted into the inner region of the shoulder according to the original technique, surgically for a period of 5 years. The intrauterine device is recommended to be inserted on the 46th day of the menstrual cycle. After an induced abortion, immediately or, more preferably, after the next menstruation. After uncomplicated spontaneous childbirth - no earlier than 6 weeks later. 3 months after capsule implantation and then 1 time per year, medical supervision is required. In overweight patients, the contraceptive effect of levonorgestrel is less effective.

Indications for immediate removal of capsules are: acute visual impairment; planned surgery followed by immobilization for 6 months (in this case, the capsules are removed 6 weeks before the operation); the first symptoms of thrombophlebitis or thromboembolism; symptoms of acute liver disease; migraine-like pains.

In acute and severe forms of chronic liver disease, it is necessary to monitor liver function tests with an interval of 8-12 weeks. If, against the background of the action of the drug, the expected menstruation did not occur within 6 weeks from the beginning of the previous menstruation or menstrual reaction, it is necessary to exclude the presence of pregnancy.

The IUD is designed to release levonorgestrel at a constant rate of 20 mcg / day. A high concentration of levonorgestrel is created in the endometrium, morphological changes in the endometrium are observed. Thickening of the mucous membrane of the cervical canal prevents the penetration of sperm into the uterus. In addition, there is an inhibition of sperm motility in the uterus and fallopian tubes. In some women, ovulation is suppressed. The IUD is valid for 5 years. After removal of the IUD, reproductive function is restored quickly.

The drug is not recommended for use during lactation, because levonorgestrel passes into breast milk. With prolonged and persistent intermenstrual spotting, an additional examination is necessary to clarify the diagnosis.

Side effect

Intermenstrual spotting, menstrual irregularities, sometimes mastalgia, nausea, headache, acne, fluid retention in the body. When using capsules, hirsutism, depression, dermatitis, hair loss, and rarely thromboembolism are also possible.

Contraindications

Pregnancy, acute and subacute inflammatory processes of internal and external genital organs, malignant tumors of the body and cervix, metrorrhagias of unknown origin, congenital anomalies of the body and cervix, endometriosis, uterine myoma, chronic salpingoopharitis and endometritis, cervical erosion in ectopic pregnancy nulliparous women.

In addition, the use of capsules is contraindicated in case of a history of hepatosis of pregnant women, acute liver diseases, Dubin-Johnson syndrome, Rotor syndrome, breast cancer, herpes, thrombosis of arteries and veins, a history of thromboembolism, bleeding of unclear etiology in history, disorders of fat metabolism.

The effectiveness of the drug can be reduced by inducers of enzymes of microsomal oxidation (barbiturates, phenytoin, rifabutin, ampicillin, tetracycline, ritonavir, griseofulvin, St. John's wort preparations). It is probably insignificant when using the intrauterine system, because in these cases, the drug has mainly a local effect.

Postcoital contraceptives

Synonyms

Microlut, Postinor. Escapelle.

Composition and form of release

Levonorgestrel. Tablets with "inor" sign on one side (750 mcg). Escapel. Tablets (1.5 mg). Microlute. Dragee (1.5 mg).

Pharmachologic effect.

At recommended doses, levonorgestrel induces inhibition of ovulation if intercourse occurs in the preovular phase of the menstrual cycle, i.e. during the period of the highest probability of fertilization. The drug-induced regression of endometrial proliferation prevents the implantation of a fertilized egg. With the implantation took place, the drug is ineffective. The effectiveness of contraception decreases as the time elapsed between intercourse and taking the drug increases.

Pharmacokinetics

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. Cmax in plasma is reached after 2 hours and is 18.5 ng / ml. Diseases of the gastrointestinal tract, proceeding with malabsorption, reduce the absorption of the drug. Bioavailability is 90%. Binds to blood plasma proteins - 97% (with SHBG and albumin) and only 2.5% is in free form. Vd - 137 liters. T1 / 2 - 14-20 hours. Metabolized with the formation of glucuronide conjugates. It is excreted in the urine 60% and in the feces 40% in the form of metabolites.

Indications

Emergency postcoital hormonal contraception.

Application

1 tablet of levonorgestrel is taken orally without chewing, with a small amount of water, regardless of food intake, after intercourse within 48 hours, but no later than 72 hours. With multiple intercourse, 8 hours after the first, an additional 1 tab is taken. It is not recommended to use levonorgestrel in such doses more often than once every 4-6 months. Levonorgestrel tablets can be used on any day of the menstrual cycle.

If vomiting occurs within 3 hours after taking the pill, the effectiveness of the drug decreases. To reduce bleeding, which may occur 2-3 days after discontinuation of the drug, ascorbic acid is prescribed and. In the case of more extensive bleeding, a gynecological examination is required before reapplying postinor.

Side effect

Nausea, vomiting, fatigue, lower abdominal pain, headache, dizziness; breast tension, menstrual bleeding, menstrual irregularities.

Contraindications

Diseases of the liver and biliary tract; jaundice during pregnancy, including history, pregnancy, puberty.

Interaction with other medications

The effectiveness of the drug is reduced by inducers of microsomal oxidation enzymes (barbiturates, phenytoin, carbamazepine, rifampicin, rifabutin, ampicillin, tetracycline, ritonavir, griseofulvin, St. John's wort preparations). Levonorgestrel may increase the toxicity of cyclosporine by inhibiting its metabolism.

Levonorgestrel belongs to the group of hormonal agents, gestagens, estrogens. Its main purpose of use is post-coital contraception and prevention of unwanted pregnancies.

Mechanism of action

Once in a woman's body, the drug with this substance slows down ovulation and changes the inner lining of the uterus, thereby blocking the possibility of an already fertilized egg to attach in the uterine cavity. In addition, levonorgestrel increases the density and viscosity of mucus in the cervix, which in turn slows down and disrupts the movement of sperm to the egg and prevents fertilization.

If levonorgestrel is used as part of intrauterine devices, then it has a direct effect on the endometrium, changing its structure, on the viscosity of mucus and on the patency of the fallopian tubes. After discontinuation of the drug, all reproductive functions are restored.

Indications for use

Indications for the use of the drug in tablet form are:

• Emergency contraception (postcoital) after unprotected intercourse
• Emergency contraception after unreliable or previously ineffective protection of sexual intercourse

The use of an intrauterine system containing this substance is indicated in the following situations:

• Long-term contraception (up to 5 years)
• Combined use in estrogen treatment (with replacement therapy) as a prophylaxis for endometrial hyperplasia (proliferation of cells in the inner lining of the uterus)
• Heavy and prolonged bleeding (menorrhagia) of unknown origin

Contraindications for use

Levonorgestrel is contraindicated in the following situations:

• Allergy to this substance or to other components of the drug
• During pregnancy
• During lactation
• Liver failure and acute inflammation in the liver
• Jaundice (both present and past)
• Period up to 17-18 years
• Inflammatory diseases of the genitourinary system (for intrauterine devices)
• Complicated abortion in the last 3-4 months (for intrauterine devices)
• Dysplasia on the cervix (for intrauterine devices)
• Malignant formations of the genital tract and breast (for intrauterine devices)

Side effects

The development of side effects when taking drugs with levonorgestrel reaches 5-15% of cases. However, they are poorly expressed and do not bring any particular inconvenience to a woman. The main ones include:

• Nausea
• Aching pain in the abdomen
• Violation of menstruation (sooner or later, scanty or profuse discharge)
• Headache, including migraine
• General weakness
• Diarrhea
• Breast tension
• Increased irritability
• Spotting spotting in the middle of the cycle
• Skin rash
• Swelling in the legs

They go away on their own after discontinuation of the drug. In some cases, symptomatic treatment may be necessary.

Overdose

Comparative table of all Levonorgestrel substitutes

Drug name	Bioavailability,%	Bioavailability, mg / l	Time to reach maximum concentration, h	Half-life, h
			1-1.5 weeks

A synthetic progestogen that transforms the endometrium minimizes ovulation by preventing the prepared egg from fertilizing. In addition, with its help, the receptors of the mucous membranes receive reduced sensitivity. In this article, we will consider a drug containing the named hormone.

Pharmacology

The drug "Levonorgestrel" is an estrogen that prevents the activation of sperm due to an increase in the viscous properties of mucus. The drug inside the uterus locally affects the fallopian tubes, endometrium, mucus consistency, as a result of which it reduces its activity.

When taken orally, the named drug is actively absorbed in the gastrointestinal tract, the bioindicators are up to 100%. In the blood, its components are maximally concentrated when 75 ml is taken once in 60 - 130 minutes. The hormone in question interacts with plasma and binding globulin components by about 50%.

Metabolism is focused on the liver, with the formation of pharmacologically passive metabolism. The main isoenzyme of this hormone is CYP3A4. The half-life can last up to 30 hours.

Properties

In response to the question "Levonorgestrel - what is this hormone?" you should be guided by the instructions for the drug of the same name and the recommendations of the attending doctor. The total difference is of the order of 1.0 ml / min / kg (from plasma). The hormone is eliminated mainly through the ureter, a small part is removed with feces.

With systemic therapy, the rate of entry into the uterus is no more than 20 μg daily, and after five years they drop to 11. On average, the rate of hormone release varies around 14 μg / 24 hours for 50-60 months.

Intrauterine therapy is allowed for women with hormone replacement therapy in conjunction with estrogens that do not include a progestogenic composition. Levonorgestrel is a hormone that is released into the plasma 60 minutes after ingestion. The maximum concentration in it is fixed after 14 days of use.

Indications

The use of this drug is possible with intrauterine therapy, as well as in the following cases:

• Menorrhagia of idiopathic orientation.
• Long-term contraceptive protection.
• Preventive measures for estrogen replacement recovery.
• Emergency postcoital contraception.

The hormone levonorgestrel, which has a wide range of effects, should be used only after a doctor's recommendation.

Application and dosage

The drug in question is activated by intrauterine injection - injected into the uterine cavity. It is used within 4 days after intercourse in a volume of 0.75 to 1.5 mg. Experts strongly advise against practicing emergency contraception more than once every six months.

To exclude a violation of the menstrual cycle, you must follow the recommended dosage without repeated use. You can not use the drug in question orally as a method of permanent contraception, as this provokes the appearance of side effects and reduces the effectiveness of the drug. In the case of uterine blood formation after emergency contraception, an examination by a gynecologist is strongly recommended, and if menopause is disturbed for more than one week, conception should be delayed.

Only after the consultation and informed decision of the gynecologist in extraordinary cases is it possible to use the drug for contraception in minors in case of emergency.

How is levonorgestrel hormone used?

How does the use of the described hormone affect the body, and what to do to avoid side effects? Many people ask this question. Strict adherence to the recommendations of a specialist, adherence to dosage and adherence to instructions are guarantees of the safe use of the drug.

Before using the IUD, it is necessary to undergo an examination by a gynecologist, including checking the mammary glands, pelvic organs, and making a smear of the cervix.

Re-examination is carried out after 30-40 days after the installation of the spiral, then annually, and if there are appropriate prerequisites, more often. This intrauterine therapy is effective for 4 to 5 years. Its installation should be carried out exclusively by a doctor specializing in this area or having experience with the drug sorting in question.

Risks

In women taking drugs with gestagen, an increase in venous thrombosis at a critical moment is possible. With such symptoms, it is necessary to urgently take urgent measures for diagnosis and treatment.

After the removal of the IUD, fertility is resuscitated in six months in half of the women who applied, after 12 months - in more than 96 percent. Contraceptive focus is less effective for obese patients.

Contraindications

Asking the question "Levonorgestrel - what is this hormone?" all contraindications should be studied. Among them:

• Over (hyper) sensitivity, thrombophlebitis formations.
• Thromboembolism, changes in arteries.
• focus, pregnancy.
• With regard to ingestion: jaundice (including a history), pathological complications of the withdrawal of bile or liver, lactation period.
• Sexual maturity.
• In addition, for the IUD - infections of the urogenital node, relapses or active inflammation in the small pelvis, excesses of postpartum liver disease.
• Septic abortive intervention in the last trimester, dysplasia transformation of the uterine cervix, pathology with similar bleeding of unexplained origin, malignant formations.
• Coming or congenital anomalies that deform fibroids.
• Progestogenosis (tumor, including breast cancer).

Restrictions

The limiting factor is often relevant for therapeutic intervention inside the uterus if the following symptoms or chronic diseases occur:

• severe headaches, common and local migraine with visual impairment, other symptoms focused on the possibility of ischemic disease;
• obvious hypertension of the arterial direction, jaundice, complex destructive processes in the circulatory system, including heart attacks and strokes;
• diabetes mellitus.

It is necessary to immediately consult about the elimination of the IUD during the formation or the presence of any of these conditions.

Pregnancy and lactation period

Although levonorgestrel is a female hormone, it should not be used during pregnancy. If it occurs, the elimination of the system is recommended due to the fact that any increases the risk of premature birth and miscarriage. Uterine intubation or elimination of the system sometimes results in a miscarriage that occurs spontaneously. You will need to consult a specialist on the advisability of artificial termination of pregnancy if it is impossible to correctly remove the contraceptive.

If it is impossible to remove the intrauterine system and a persistent desire to maintain pregnancy, the patient should be aware of the possible consequences and risks for the child due to premature birth. In such cases, careful monitoring of the course of pregnancy is imperative. The patient should be informed that she should immediately report all symptoms that will help suggest a complication of the process.

Lactation

When breastfeeding and using Levonorgestrel, approximately one tenth of the drug enters the baby's body. Oral breastfeeding for emergency contraception should be discontinued for 1.5 days.

For a therapeutic system installed intrauterinely, as for any purely gestagenic method of contraception, it is characteristic that the use one and a half months after childbirth does not have a detrimental effect on the development and growth of the child, therefore, the drug most likely does not pose a risk to the fetus at the recommended dosage ...

Side Symptoms

And returning to the question "Levonorgestrel" - what is it? ", Let's consider the possible side effects and contraindications of the drug. They can occur in different body systems and represent the following symptoms:

1. From the nervous system: fatigue, depression, headache, mood swings.
2. Gastrointestinal tract. Vomiting, upset, cramping, bloating.
3. Genitourinary organs. Bleeding, discharge, pain, candidiasis, the likelihood of the formation of malignant and benign tumors.
4. Skin rashes, manifestation of eczema, itching, urticaria, acne.
5. Others: edema, joint pain, pressure surges, sepsis.

In rare cases, epileptic seizures, seizures and fainting are possible.

Combination with other drugs

Studying "Levonorgestrel" (what kind of hormone), it is necessary to mention the possibility of its combination with other medicinal and organic preparations. In the case of using the substance under consideration with inducers of cytochrome P450 isoenzymes, a decrease in efficiency is possible due to an increase in its metabolic processes.

The following medicines can reduce the effect of Levonorgestrel:

• The group of barbiturates, "Tretinoin", "Carbamazepine", St. John's wort compounds and their composition.
• The effectiveness of anticoagulants, hypoglycemic, anticonvulsants decreases.
• "Levonorgestrel" increases the capacity of glucocorticosteroids in the blood, and is also capable of disorganizing metabolism.
• Due to the inhibition of the recirculation of sex steroids, which is due to the reorganization of the intestinal flora, an increase in menstrual bleeding may occur with the complex use of certain drugs.

One cannot but add, speaking about how "Levonorgestrel" is used, that this agent causes an increase in the side effects of other medications, there is no antidote to it. In case of overdose, it is required

Levonov; Levonorgestrel; Microlute; Mirena(intrauterine spiral); Norplant; Postinor; Escapel.

Levonorgestrel- a means for the prevention of pregnancy, contraception. It has a pronounced progestogenic and antiestrogenic activity, which helps to inhibit conception at an early stage and prevent pregnancy. Levonorgestrel is the most studied progestogen, which has long been successfully used in many contraceptives.

Active-active substance:
Levonorgestrel / Levonorgestrel.

Dosage forms:
Pills.
Dragee.
Capsules.
Intrauterine system (intrauterine device).

Levonorgestrel

Properties / Action:
Levonorgestrel has a pronounced progestogenic and antiestrogenic activity, which helps to inhibit conception at an early stage and prevent pregnancy. Levonorgestrel is an oral contraceptive (oral contraceptive). A distinctive feature of levonorgestrel drugs in comparison with combined progestogen-estrogenic oral contraceptives (microginon, tricvilar, femoden) is that they contain only progestogen (progestogen) as an active ingredient.
For emergency contraception, levonorgestrel is used at a dose of 0.75 mg. With prolonged daily intake at a dose of 0.03 mg, levonorgestrel has a contraceptive effect due to a number of mechanisms, among which the leading role is attributed to peripheral gestagenic effects.
Under the influence of the drug, the viscosity of the mucus in the neck (cervical or cervical mucus) increases, which makes it difficult for sperm to enter the uterine cavity. Levonorgestrel inhibits endometrial proliferation, which makes implantation of a fertilized egg impossible. Levonorgestrel is capable of inhibiting the release of releasing factors in the hypothalamus and reducing the production of luteinizing (LH) and follicle-stimulating (FSH) hormones by the pituitary gland, and lowering the function of the corpus luteum. The severity of these effects of levonorgestrel at a low dosage is insignificant, but sufficient to provide a contraceptive effect. In low doses, it does not completely suppress ovulation.
Intrauterine system:
An intrauterine contraceptive (Mirena) is a T-shaped polyethylene system (device), the vertical rod of which consists of a levonorgestrel-containing container covered with a special membrane, through which a controlled diffusion of levonorgestrel at 20 μg / day occurs continuously.
Levonorgestrel, entering directly into the uterine cavity, has a direct local effect on the endometrium, preventing proliferative changes in it and thereby reducing its implantation function, and also increases the viscosity of the mucus of the cervical canal, which prevents the penetration of spermatozoa into the uterine cavity. Levonorgestrel also has a slight systemic effect, manifested by the inhibition of ovulation in a certain number of cycles. Reduces the volume of menstrual bleeding, reduces pre- and menstrual pain.

Pharmacokinetics:
Tablets, dragees:
When taken orally, levonorgestrel is rapidly and completely absorbed in the gastrointestinal tract. The bioavailability of levonorgestrel is about 100%. Has a high (more than 90%) connection with plasma proteins. The maximum concentration in the blood is observed in 0.5-2 hours. In the future, the concentration of the drug is characterized by a two-phase decrease with a half-life of 2 or 24 hours. Metabolized in the liver. It is well distributed to organs and tissues. About 10% of the dose taken passes into breast milk. 60% of the drug is excreted in the urine, 40% through the intestines. Daily repeated intake is not accompanied by the accumulation of the active substance and its metabolites.
Intrauterine system:
Levonorgestrel goes directly into the uterine cavity. A small part of it is absorbed into the systemic circulation. The concentration of levonorgestrel in blood plasma is stable at 100-200 pg / ml (0.3-0.6 nmol / l).

Indications:
Pregnancy prevention.
Levonorgestrel tablets 0.75 mg are used for emergency contraception after intercourse, if the male condom breaks or in case of unprotected intercourse.
Dragee levonorgestrel 0.03 mg is used for long-term contraception, as well as an additional method of contraception in women using non-hormonal methods of preventing pregnancy and in cases of objective or subjective reasons that do not allow the use of gestagen-estrogenic contraceptives.
Idiopathic menorrhagia (for the intrauterine system).

Method of administration and dosage:
0.75 mg tablets:
0.75 mg (1 tablet) of levonorgestrel is taken within 72 hours (preferably immediately) after unprotected intercourse, another 1 tablet should be taken 12 hours after the first.
Dragee 0.03 mg:
0.03 mg (1 tablet) is taken orally, 1 tablet per day, for a long time, without interruption. Reception begins from the 1st day of menstruation, using pills of the corresponding day of the week from the calendar package. Dragee is taken without chewing, and washed down with a small amount of liquid. The time of admission does not matter, however, the subsequent administration of the drug should be carried out at the same selected hour, since the interval between taking the pills should be close to 24 hours.
Capsules:
S / c is implanted into the inner area of ​​the shoulder for a period of 5 years.

It is recommended to inject it into the uterine cavity on the 4th-6th day of the menstrual cycle; after an induced abortion - immediately, or, preferably, after the next menstruation; after uncomplicated spontaneous childbirth - not earlier than after 6 weeks. The intrauterine system must be removed after 5 years. At the same time, it is possible to introduce a new intrauterine system at the same time.

Overdose:
In case of an overdose, the described side effects may increase.
There is no antidote, gastric lavage and symptomatic treatment are recommended.

With this method of application, an overdose is impossible.

Contraindications:
Pregnancy, breastfeeding (refusal of breastfeeding is mandatory);
Age of puberty;
Uterine bleeding of unknown etiology;
Infectious diseases of the genitourinary system, pelvic organs, the presence of herpes infection during a former pregnancy;
Malignant neoplasms of the genitals and mammary glands, hormone-dependent tumors;
Diseases of the liver and gallbladder, history of jaundice, liver tumors, Dubin-Johnson and Rotor syndromes (hereditary benign hyperbilirubinemia);
Tendency to thromboembolism, incl. with disorders of cerebral circulation and other cardiovascular diseases, thrombophlebitis;
Sickle cell anemia;
Otosclerosis;
Severe diabetes with vascular complications;
Hypersensitivity;
Intrauterine system (mirena):
Congenital and acquired uterine anomalies that prevent the introduction of intrauterine contraceptives.

Application during pregnancy and lactation:
Levonorgestrel is contraindicated during pregnancy and lactation.

Side effect:
After using levonorgestrel, nausea, vomiting, head and abdominal pain, intermenstrual bleeding, shortening or lengthening of the cycle, oligo- and amenorrhea, dysmenorrhea, breast engorgement, mastalgia, rarely acne, depressive conditions, changes in body weight and libido are possible.
Intrauterine system (mirena):
Side effects usually do not require additional therapy and disappear within a few months. It is possible to develop expulsion of the intrauterine system, perforation of the uterus, ectopic pregnancy, described with the use of other intrauterine contraceptives.

Special instructions and precautions:
0.75 mg tablets:
The drug in a dose of 0.75 mg is intended only for emergency postcoital contraception!
Recommended for women with regular menstrual cycles.
It is not allowed to use the drug at a dose of 0.75 mg as a means of permanent and continuous contraception. With regular sexual activity, it is recommended to use permanent methods of contraception (pills 0.03 mg).
In case of uterine bleeding, a gynecological examination is recommended.
Dragee 0.03 mg:
In most women, taking levonorgestrel tablets at a dose of 0.03 mg does not affect the menstrual cycle: menstruation occurs at regular intervals, bleeding has a normal duration and intensity. In some cases, there may be changes in the interval between menstruation and the intensity of menstrual bleeding, which is a consequence of the development of a new model of the menstrual cycle. If menstrual bleeding has not occurred 6 weeks after the last menstrual period, an examination should be made for the presence of pregnancy and only if it is absent, continue taking levonorgestrel. After stopping the administration of levonorgestrel, the functions of the gonads are quickly restored to their full extent, which ensures the normal ability to conceive.
To help your healthcare provider assess your menstrual cycle when taking levonorgestrel 0.03 mg, fill out the calendar and show it to your doctor.
During the period of taking the first 14 pills, it is recommended to use additional non-hormonal methods of contraception (with the exception of the temperature method).
The contraceptive effect of the drug can be influenced by: irregular intake of pills, vomiting and intestinal disorders accompanied by diarrhea, in rare cases - the individual characteristics of metabolism and the intake of certain groups of medications (see "Drug Interactions").
During the first months of admission, intermenstrual bleeding of varying intensity may occur, which does not prevent the continued use of the drug.
In cases of missed admission or when taking it more than 24 hours after the previous tablet, the contraceptive effect of the drug stops. In such cases, it is necessary to continue taking the pills. It should be borne in mind that the full contraceptive effect will occur only on the 14th day of daily intake of the drug. During this period, it is necessary to use non-hormonal methods of contraception (with the exception of the temperature method).
The use of levonorgestrel after childbirth, abortion, when using other hormonal contraceptives, as well as in nursing mothers, is carried out on the recommendation of a doctor.
Before starting and every 6 months of using levonorgestrel at a dose of 0.03 mg, it is recommended to undergo a general medical and gynecological examination (including examination of the mammary glands). In cases of the appearance of migraine-like headaches or unusually severe headaches, sudden visual and hearing impairments, signs of thrombophlebitis or thromboembolism, a significant increase in blood pressure, hepatitis, jaundice, generalized itching, increased frequency of epileptic seizures, severe pain in the epigastric region should be stopped immediately drug and consult a doctor.
Capsules:
Medical supervision is required 3 months after capsule implantation and once a year. Indications for immediate removal of capsules are acute visual disturbances, planned surgery followed by immobilization for 6 months, the appearance of symptoms of thrombophlebitis or thromboembolism, acute liver disease, migraine.
Intrauterine system (mirena):
Before the introduction of the intrauterine system (Mirena), a woman is recommended to undergo a thorough general medical and gynecological examination (including examination of the mammary glands), to exclude pregnancy. In addition, sexually transmitted diseases should be excluded. Preventive control examinations must be carried out at least once a year.
In some women, when using the intrauterine system (Mirena), oligomenorrhea or amenorrhea develops, which has a therapeutic effect with menorrhagia. After removal of the intrauterine system, menstrual function is restored.
The design of the intrauterine system provides the release of levonorgestrel at a rate of 20 mg / day. The intrauterine system is effective for 5 years. Fertility is restored in 50% of women 6 months after the removal of the contraceptive, in 96% - after 12 months.

Drug interactions:
It is possible to reduce the contraceptive effect of levonorgestrel when used together with rifampicin, ampicillin and tetracycline, some antiepileptic drugs (for example, carbamazepine, phenytion, etc.), barbiturates, benzodiazepines.
Due to the effect of steroid hormones on glucose tolerance, when taking gestagenic drugs, the dosage of antidiabetic drugs and insulin can be adjusted.

Gross formula

C 21 H 28 O 2

Pharmacological group of the substance Levonorgestrel

Nosological classification (ICD-10)

CAS code

797-63-7

Characteristics of the substance Levonorgestrel

A synthetic progestogen with a molecular weight of 315.45.

Pharmacology

pharmachologic effect- contraceptive, gestagenic.

Pharmacodynamics

Levonorgestrel is a synthetic progestogen with a contraceptive effect, pronounced progestogenic and antiestrogenic properties.

When taken orally in the recommended dosing regimen, levonorgestrel suppresses ovulation and fertilization if sexual intercourse occurs in the pre-ovulation phase, when the possibility of fertilization is greatest. It can also cause changes in the endometrium that prevent the implantation of a fertilized egg. Increases the viscosity of cervical secretions, which prevents the advancement of sperm. Levonorgestrel is ineffective if implantation has already occurred.

Efficiency: it is recommended to start taking levonorgestrel as soon as possible (but no later than 72 hours) after intercourse, if no protective contraceptive measures have been used. The more time elapsed between intercourse and taking the drug, the lower its effectiveness (95% during the first 24 hours, 85% - from 24 to 48 hours and 58% - from 48 to 72 hours). At the recommended dose, levonorgestrel does not significantly affect blood clotting factors, lipid and carbohydrate metabolism.

As part of the intrauterine therapeutic system (ITS), the released levonorgestrel exerts mainly a local progestogenic effect. Gestagen (levonorgestrel) is released directly into the uterine cavity, which allows it to be used in an extremely low daily dose. High concentrations of levonorgestrel in the endometrium contribute to a decrease in the sensitivity of its estrogen and progesterone receptors, making the endometrium immune to estradiol and having a strong antiproliferative effect. When using levonorgestrel as part of VTS, morphological changes in the endometrium and a weak local reaction to the presence of a foreign body in the uterus are observed. An increase in the viscosity of the cervical secretion prevents the penetration of sperm into the uterus. Levonorgestrel as part of VTS prevents fertilization due to inhibition of the mobility and function of sperm in the uterus and fallopian tubes. In some women, ovulation is suppressed. Previous use of levonorgestrel in VTS does not affect fertility. Approximately 80% of women who wish to have a child become pregnant within 12 months after the removal of the VTS.

In the first months of the use of levonorgestrel in the VTS, due to the process of inhibition of endometrial proliferation, an initial increase in spotting bleeding from the vagina may be observed. Following this, a pronounced suppression of endometrial proliferation leads to a decrease in the duration and volume of menstrual bleeding in women using levonorgestrel as part of the VTS. Lean bleeding often transforms into oligo- or amenorrhea. In this case, the function of the ovaries and the concentration of estradiol in the blood plasma remain normal.

Levonorgestrel in VTS can be used to treat idiopathic menorrhagia, i.e. menorrhagia in the absence of hyperplastic processes in the endometrium (endometrial cancer, metastatic lesions of the uterus, submucous or large interstitial myomatous node, leading to deformation of the uterine cavity, adenomyosis), endometritis, extragenital diseases and conditions accompanied by severe hypocoagulation (eg von Willebrand disease, severe) the symptoms of which are menorrhagia. After 3 months of using levonorgestrel as part of VTS, menstrual blood loss in women with menorrhagia decreases by 62-94% and by 71-95% after 6 months of use. When using levonorgestrel as part of VTS for two years, its effectiveness (reduction of menstrual blood loss) is comparable to surgical methods of treatment (ablation or resection of the endometrium). A less favorable response to treatment is possible with menorrhagias caused by submucous uterine myoma. Reducing menstrual blood loss reduces the risk of iron deficiency anemia. Levonorgestrel in VTS reduces the severity of dysmenorrhea symptoms.

The efficacy of levonorgestrel in VTS in the prevention of endometrial hyperplasia during continuous estrogen therapy was equally high with both oral and transdermal estrogen administration.

Pharmacokinetics

Absorption

When taken orally, levonorgestrel is rapidly and almost completely absorbed. Absolute bioavailability is 100% of the dose taken.

After the introduction of VTS, levonorgestrel begins to be immediately released into the uterine cavity, as evidenced by measurements of its concentration in blood plasma. A high local exposure of levonorgestrel in the uterine cavity, which is necessary for its local effect on the endometrium, provides a high concentration gradient in the direction from the endometrium to the myometrium (the concentration of levonorgestrel in the endometrium exceeds its concentration in the myometrium by more than 100 times) and low concentrations of levonorgestrel in blood plasma ( the concentration of levonorgestrel in the endometrium exceeds its concentration in blood plasma by more than 1000 times). The rate of release of levonorgestrel into the uterine cavity in vivo initially it is approximately 20 μg / day, and after 5 years it decreases to 10 μg / day.

Distribution

After taking at a dose of 0.75 mg or 1.5 mg, C max of levonorgestrel in blood plasma is 14.1 or 18.5 ng / ml, respectively, and T max is 1.6 or 2 hours, respectively. After reaching C max, the concentration of levonorgestrel decreases.

Levonorgestrel binds nonspecifically to plasma albumin and specifically to SHBG. About 1-2% of circulating levonorgestrel is present as a free steroid, while 42-62% is specifically associated with SHBG.

During the use of levonorgestrel in the VTS, the concentration of SHBG decreases. Accordingly, the fraction associated with SHBG decreases during this period, while the free fraction increases. The average apparent Vd of levonorgestrel is about 106 liters.

After the start of the introduction in the composition of the VTS, levonorgestrel is found in the blood plasma after an hour, T max is 2 weeks. In accordance with the decreasing release rate, the median plasma concentration of levonorgestrel in women of reproductive age with a body weight above 55 kg decreases from 206 pg / ml (25-75th percentile: 151-264 pg / ml), determined after 6 months, to 194 pg / ml (146-266 pg / ml) after 12 months and up to 131 pg / ml (113-161 pg / ml) after 60 months.

It has been shown that body weight and concentration of SHBG in blood plasma affect the systemic concentration of levonorgestrel, i.e. with low body weight and / or high concentration of SHBG, the concentration of levonorgestrel is higher. In women of reproductive age with low body weight (37-55 kg), the median plasma concentration of levonorgestrel is approximately 1.5 times higher.

In postmenopausal women who use levonorgestrel as part of the VTS simultaneously with the use of estrogens intravaginally or transdermally, the median concentration of levonorgestrel in blood plasma decreases from 257 pg / ml (25-75th percentile: 186-326 pg / ml), determined after 12 months , up to 149 pg / ml (122-180 pg / ml) after 60 months. When using levonorgestrel as part of VTS simultaneously with oral administration of estrogens, the concentration of levonorgestrel in blood plasma, determined after 12 months, increases to about 478 pg / ml (25-75th percentile: 341-655 pg / ml), which is due to the induction of SHBG synthesis ...

Biotransformation

Levonorgestrel is extensively metabolized. The main metabolites in blood plasma are unconjugated and conjugated forms of 3α-, 5β-tetrahydrolevonorgestrel. Pharmacologically active metabolites of levonorgestrel are unknown. Based on research results in vitro and in vivo, the main isoenzyme involved in the metabolism of levonorgestrel is CYP3A4. The isoenzymes CYP2E1, CYP2C19 and CYP2C9 can also be involved in the metabolism of levonorgestrel, but to a lesser extent.

Elimination

The total clearance of levonorgestrel from blood plasma is approximately 1 ml / min / kg. In unchanged form, levonorgestrel is excreted only in trace amounts. Metabolites are excreted through the intestines and kidneys with an excretion coefficient equal to »1.77. T 1/2 after oral administration and when using levonogestrel as part of VTS (in the terminal phase, represented mainly by metabolites), is about a day.

Linearity / non-linearity

MTC. The pharmacokinetics of levonorgestrel depends on the concentration of SHBG, which, in turn, is influenced by estrogens and androgens. With the use of levonorgestrel in the VTS, a decrease in the average concentration of SHBG by approximately 30% was observed, which was accompanied by a decrease in the concentration of levonorgestrel in the blood plasma. This indicates the nonlinearity of the pharmacokinetics of levonorgestrel during the time of its use in the composition of the VTS. Given the predominantly local action of levonorgestrel in the VTS, the effect of changes in systemic concentrations of levonorgestrel on its effectiveness in this case is unlikely.

Application of the substance Levonorgestrel

Inside. Emergency postcoital contraception in women (after unprotected intercourse or unreliability of the contraceptive method used).

For military-technical cooperation. Contraception (long-term), idiopathic menorrhagia, prevention of endometrial hyperplasia during estrogen replacement therapy.

Contraindications

Inside. Hypersensitivity to levonorgestrel; severe liver failure; pregnancy (including presumed); breastfeeding period; age up to 16 years.

For military-technical cooperation. Pregnancy or suspicion of it; existing or recurrent inflammatory diseases of the pelvic organs; infections of the lower urinary tract and genital tract; postpartum endometritis; septic abortion within the last 3 months; cervicitis; diseases accompanied by increased susceptibility to infections; dysplasia of the cervix; malignant neoplasms of the uterus or cervix; progestogen-dependent tumors, incl. mammary cancer; pathological uterine bleeding of unknown etiology; congenital or acquired anomalies of the uterus, incl. fibroids leading to deformation of the uterine cavity; acute liver diseases or tumors; hypersensitivity to levonorgestrel.

The use of levonorgestrel as part of VTS has not been studied in women over 65 years of age, therefore it is not recommended for this category of patients.

Restrictions on use

Inside. Diseases of the liver or biliary tract, jaundice (including history), Crohn's disease; a history of pelvic inflammatory disease or ectopic pregnancy; the presence of a hereditary or acquired predisposition to thrombosis.

For military-technical cooperation. After consultation with a specialist: migraine, focal migraine with asymmetric loss of vision or other symptoms indicating transient cerebral ischemia; unusually severe headache; jaundice; severe arterial hypertension; severe circulatory disorders, incl. stroke and myocardial infarction; congenital heart defects or heart valve disease (due to the risk of developing septic endocarditis); diabetes.

Levonorgestrel should not be taken during pregnancy. If the pregnancy develops while taking it, then, based on the available data, an adverse effect of levonorgestrel on the fetus is not expected.

MTC... The use of levonorgestrel as part of VTS is contraindicated in pregnancy or suspected pregnancy. Pregnancy in women with established VTS containing levonorgestrel is extremely rare. But if there is a prolapse of VTS from the uterine cavity, the woman is no longer protected from pregnancy, and must use other methods of contraception before consulting a doctor.

During the use of levonorgestrel as part of VTS, some women do not have menstrual bleeding. Missing your period is not necessarily a sign of pregnancy. If a woman does not have menstruation and at the same time has other signs of pregnancy (nausea, fatigue, breast tenderness), then it is necessary to consult a doctor for examination and a pregnancy test.

If a woman becomes pregnant while using levonorgestrel as part of a VTS, it is recommended to remove the VTS, because any intrauterine contraceptive left behind in situ, increases the risk of miscarriage, infection, or premature birth. Removal of the PTS or probing of the uterus can lead to spontaneous abortion. If the intrauterine contraceptive cannot be removed carefully, the advisability of a medical abortion should be discussed. If a woman wants to preserve the pregnancy and it is impossible to remove VTS, the patient should be informed about the risks, in particular, about the possible risk of septic abortion in the second trimester of pregnancy, postpartum purulent-septic diseases that can be complicated by sepsis, septic shock and death, as well as possible consequences premature birth for the baby.

In such cases, the course of pregnancy should be closely monitored. Ectopic pregnancy must be ruled out. The woman should be explained that she should inform the doctor about all the symptoms that suggest complications of pregnancy, in particular about the appearance of spastic pain in the lower abdomen, bleeding or spotting from the vagina, and an increase in body temperature. Levonorgestrel as part of the VTS is released into the uterine cavity. This means that the fetus is exposed to a relatively high local concentration of the hormone, although the hormone enters it in small quantities through the blood and placenta. Due to the intrauterine use and the local action of the hormone, it is necessary to take into account the possibility of a virilizing effect on the fetus. Due to the high contraceptive efficacy of levonorgestrel in VTS, clinical experience regarding pregnancy outcomes with its use is limited. However, the woman should be advised that at this point in time there is no evidence of congenital defects caused by the use of levonorgestrel as part of the VTS in cases of continued pregnancy before delivery without removing the VTS.

Levonorgestrel passes into breast milk. After taking it, breastfeeding should be stopped for 24 hours.

MTC. Breastfeeding of a child when using levonorgestrel as part of a VTS is not contraindicated. About 0.1% of a dose of levonorgestrel can be absorbed by a baby during breastfeeding. However, it is unlikely to pose a risk to the baby at doses released into the uterine cavity after ITS insertion.

It is believed that the use of levonorgestrel as part of VTS 6 weeks after delivery does not have a harmful effect on the growth and development of the child. Monotherapy with gestagens does not affect the quantity and quality of breast milk. Rare cases of uterine bleeding have been reported in women using levonorgestrel as part of VTS during lactation.

Fertility After removal of VTS in women, fertility is restored.

Side effects of the substance Levonorgestrel

The incidence of side effects (AD) after taking levonorgestrel: very often (≥1 / 10); often (≥1 / 100,

Often- nausea, feeling tired, abdominal pain, acyclic spotting (bleeding).

Often- vomiting, diarrhea, dizziness, headache, breast tenderness, breast tension, dysmenorrhea, heavy menstrual bleeding, delayed menstruation (no more than 5-7 days; if menstruation does not occur for a longer period, pregnancy must be excluded). Allergic reactions are possible: urticaria, rash, itching, swelling of the face.

MTC. In most women, after the installation of a VTS containing levonorgestrel, there is a change in the nature of cyclic bleeding. During the first 90 days of use, an increase in the duration of bleeding is noted by 22% of women, and irregular bleeding is noted in 67% of women, the frequency of these phenomena decreases, respectively, to 3 and 19% by the end of the 1st year of the use of VTS. At the same time, amenorrhea develops in 0%, and rare bleeding - in 11% of patients during the first 90 days of use. By the end of the first year of use, the frequency of these phenomena increases to 16 and 57%, respectively.

When using levonorgestrel as part of VTS in combination with long-term estrogen replacement therapy in most women, within 1 year of use, cyclic bleeding gradually stops.

Below are data on the incidence of PD reported with the use of levonorgestrel in the PTS. The incidence of PD: very often (≥1 / 10); often (≥1 / 100, MedDRA. Frequency data reflect the approximate incidence of PD reported in clinical trials of levonorgestrel in VTS for contraception and idiopathic menorrhagia in 5091 women.

PD reported in clinical studies of levonorgestrel as part of VTS for the indication "prevention of endometrial hyperplasia during estrogen replacement therapy" (with the participation of 514 women) were observed with the same frequency, except for cases indicated by asterisks (*, **) ...

From the immune system: frequency unknown - hypersensitivity to levonorgestrel, including rash, urticaria, and angioedema.

From the side of the psyche: often - depressed mood, depression.

From the nervous system: very often - headache; often - migraine.

From the gastrointestinal tract: very often - abdominal pain, pain in the pelvic area; often nausea.

On the part of the skin and subcutaneous tissues: often - acne, hirsutism; infrequently - alopecia, pruritus, eczema.

On the part of the musculoskeletal system and connective tissue: often back pain **.

On the part of the reproductive system and mammary glands: very often - a change in the volume of blood loss, including an increase and decrease in the intensity of bleeding, spotting spotting, oligomenorrhea, vulvovaginitis *, discharge from the genital tract *; often - infections of the pelvic organs, ovarian cysts, dysmenorrhea, pain in the mammary glands **, engorgement of the mammary glands, expulsion of VTS (complete or partial); rarely - perforation of the uterus (including penetration).

Survey results: frequency unknown - increased blood pressure.

* Often according to the indication "prevention of endometrial hyperplasia during estrogen replacement therapy."

** Very often, according to the indication “prevention of endometrial hyperplasia during estrogen replacement therapy”.

To describe certain reactions, their synonyms and associated conditions, in most cases, the terminology used is appropriate MedDRA.

Interaction

With the simultaneous use of drugs - inducers of liver microsomal enzymes, the metabolism of levonorgestrel is accelerated.

The following drugs can reduce the effectiveness of levonorgestrel: amprenavir, lansoprazole, nevirapine, oxcarbazepine, tacrolimus, topiramate, tretinoin, barbiturates (including primidone), phenobarbital, phenytoin and carbamazepine, drugs containing St. John's wort (Hypericum perforatum) as well as rifampicin, ritonavir, ampicillin, tetracycline, rifabutin, griseofulvin, efavirenz. Reduces the effectiveness of hypoglycemic and anticoagulant (coumarin derivatives, phenindione) drugs. Increases plasma concentrations of GCS. Medicines containing levonorgestrel may increase the risk of cyclosporine toxicity by inhibiting its metabolism.

Levonorgestrel may decrease the effectiveness of ulipristal by competitively affecting the progesterone receptor. Therefore, the simultaneous use of drugs containing levonorgestrel with ulipristal preparations is not recommended.

For MTC(additionally). The effect of inducers of microsomal liver enzymes on the effectiveness of levonorgestrel in VTS is unknown, but it is believed that it is insignificant, since levonorgestrel in VTS has a mainly local effect.

Overdose

Symptoms: nausea, vomiting, spotting / bleeding.

Treatment: symptomatic, no specific antidote.

For military-technical cooperation. Not applicable.

Route of administration

Inside, intrauterine.

Precautions for Levonorgestrel Substance

Ingestion

Levonorgestrel should only be taken for emergency contraception. Repeated intake within one menstrual cycle is not recommended.

Levonorgestrel should be taken as soon as possible, but no later than 72 hours after unprotected intercourse. The effectiveness of emergency contraception with delayed use is significantly reduced.

Levonorgestrel is not a substitute for regular methods of contraception. In most cases, it does not affect the nature of the menstrual cycle. However, acyclic bleeding and a delay in menstruation for several days are possible. If menstruation is delayed by more than 5-7 days and its nature changes (scant or abundant discharge), pregnancy must be excluded. The appearance of pain in the lower abdomen, fainting may indicate an ectopic (ectopic) pregnancy.

In adolescents under 16 years of age, the use of levonorgestrel is possible only in exceptional cases (including rape) and only after consulting a gynecologist. After emergency contraception, a repeated consultation with a gynecologist is recommended.

In diseases of the gastrointestinal tract (for example, Crohn's disease), as well as in overweight women, the effectiveness of levonorgestrel may be reduced.

Levonorgestrel should be used with caution in women with liver or biliary tract diseases, with a history of pelvic inflammatory disease or ectopic pregnancy, with a hereditary or acquired predisposition to thrombosis.

When using MTC

Before installing PTS containing levonorgestrel, pathological processes in the endometrium should be excluded, since in the first months of its use, irregular bleeding / spotting spotting is often noted. You should also exclude pathological processes in the endometrium if bleeding occurs after the start of estrogen replacement therapy in a woman who continues to use levonorgestrel as part of the VTS previously established for contraception. Appropriate diagnostic measures must also be taken when irregular bleeding develops during long-term treatment.

Levonorgestrel as part of PTS is not used for postcoital contraception.

Levonorgestrel in VTS should be used with caution in women with congenital or acquired valvular heart disease, bearing in mind the risk of septic endocarditis. When installing or removing PTS, these patients should be prescribed antibiotics for prophylaxis.

Levonorgestrel in low doses can affect glucose tolerance, and therefore its concentration in blood plasma should be regularly monitored in women with diabetes mellitus using levonorgestrel as part of VTS. As a rule, dose adjustment of hypoglycemic drugs is not required.

Some manifestations of polyposis or endometrial cancer can be masked by irregular bleeding. In such cases, an additional examination is required to clarify the diagnosis.

Levonorgestrel as part of VTS is not a first choice drug either for young women who have not previously become pregnant, or for postmenopausal women with severe uterine atrophy.

The available data indicate that the use of levonorgestrel in VTS does not increase the risk of breast cancer in postmenopausal women under the age of 50. Due to the limited data obtained during the study of this drug for the indication "prevention of endometrial hyperplasia during estrogen replacement therapy", the risk of breast cancer when used for this indication cannot be confirmed or refuted.

Oligo- and amenorrhea. Oligo- and amenorrhea in women of fertile age develops gradually, in about 57 and 16% of cases by the end of the first year of using levonorgestrel in the VTS, respectively. If menstruation is absent within 6 weeks after the start of the last menstrual period, pregnancy should be excluded. Repeated pregnancy tests for amenorrhea are not necessary if there are no other signs of pregnancy.

When levonorgestrel in VTS is used in combination with continuous estrogen replacement therapy, most women gradually develop amenorrhea during the first year.

Pelvic inflammatory disease (PID). The guide tube helps protect the levonorgestrel-containing PTS from infection during insertion, and the PTS delivery device is specially designed to minimize the risk of infection. PID in patients using VTS is often referred to as sexually transmitted diseases. It has been established that having multiple sexual partners is a risk factor for PID. PID can have serious consequences: it can interfere with fertility and increase the risk of ectopic pregnancy.

As with other gynecological or surgical procedures, severe infection or sepsis (including group A streptococcal sepsis) can develop after placement of VTS, although this is extremely rare.

For recurrent endometritis or PID, as well as for severe or acute infections that are resistant to treatment for several days, the PTS containing levonorgestrel should be removed. If a woman has persistent pain in the lower abdomen, chills, fever, pain associated with intercourse (dyspareunia), prolonged or profuse spotting / bleeding from the vagina, the nature of vaginal discharge should be consulted immediately. Severe pain or fever that appears shortly after the installation of PTS may indicate the presence of a severe infection that must be treated immediately. Even in cases where only a few symptoms indicate the possibility of infection, bacteriological examination and monitoring is indicated.

Expulsion. Possible signs of partial or complete expulsion of any VTS are bleeding and pain. Contractions of the muscles of the uterus during menstruation sometimes lead to displacement of the VTS or even to pushing it out of the uterus, which leads to the termination of contraceptive action. Partial expulsion may decrease the effectiveness of VTS containing levonorgestrel. Since levonorgestrel in VTS reduces menstrual blood loss, an increase may indicate expulsion of VTS. The woman is advised to check the threads with her fingers, for example while taking a shower. If a woman has found signs of displacement or loss of the VTS or has not felt the threads, intercourse or other methods of contraception should be avoided, as well as consult a doctor as soon as possible.

If the position in the uterine cavity is incorrect, the VTS should be removed. At the same time, a new system can be installed.

Perforation and penetration. Perforation or penetration of the body or cervix of VTS is rare, mostly during insertion, and may reduce the effectiveness of levonorgestrel in VTS. In these cases, the system should be removed. With a delay in the diagnosis of perforation and migration of VTS, complications such as adhesions, peritonitis, intestinal obstruction, intestinal perforation, abscesses or erosion of adjacent internal organs may occur. The risk of uterine perforation is increased in women who are breastfeeding. There may be an increased risk of perforation with VTS placement after childbirth and in women with a fixed bend of the uterus.

Ectopic pregnancy. Women with a history of ectopic (ectopic) pregnancies who have had tubal surgery or a pelvic infection are at a higher risk of ectopic pregnancy. The possibility of ectopic pregnancy should be considered in the case of lower abdominal pain, especially if it is combined with the cessation of menstruation or when a woman with amenorrhea begins to bleed. The incidence of ectopic pregnancy with VTS containing levonorgestrel is approximately 0.1% per year. The absolute risk of ectopic pregnancy in women using this drug is low. However, if a woman with an established PTS containing levonorgestrel becomes pregnant, the relative likelihood of ectopic pregnancy is higher.

Loss of threads. If, during a gynecological examination, the thread for the removal of VTS cannot be detected in the cervical region, pregnancy must be excluded. The threads can be pulled into the uterine cavity or cervical canal and become visible again after the next menstruation. If pregnancy is ruled out, the location of the threads can usually be determined by careful probing with an appropriate instrument. If the filaments cannot be found, it is possible that there was an expulsion of VTS from the uterine cavity. An ultrasound scan can be used to determine if the system is correctly positioned. If it is unavailable or unsuccessful, X-ray examination is used to determine the localization of PTS.

Ovarian cysts. Since the contraceptive effect of levonorgestrel in VTS is mainly due to its local action, ovulatory cycles with rupture of follicles are usually observed in women of fertile age. Sometimes follicular atresia is delayed, and their development can continue. Such enlarged follicles are clinically indistinguishable from ovarian cysts. Ovarian cysts have been reported as an adverse reaction in approximately 7% of women using levonorgestrel-containing VTS. In most cases, these follicles do not cause any symptoms, although sometimes they are accompanied by pain in the lower abdomen or pain during intercourse.

As a rule, ovarian cysts disappear on their own within two to three months of observation. If this does not happen, it is recommended to continue monitoring with ultrasound, as well as conducting therapeutic and diagnostic measures. In rare cases, it is necessary to resort to surgical intervention.

The use of levonorgestrel as part of VTS in combination with estrogen replacement therapy. When using levonorgestrel as part of VTS in combination with estrogens, it is necessary to additionally take into account the information specified in the instructions for use of the corresponding estrogen.

Influence on the ability to drive vehicles and working mechanisms. The effect of levonorgestrel on the ability to drive vehicles and operate machinery has not been studied. If dizziness develops, one should refrain from driving and working with mechanisms, mechanisms that require increased concentration of attention and speed of psychomotor reactions.

Formula: C21H28O2, chemical name: (17alpha) -13-ethyl-17-hydroxy-18,19-dinopregn-4-en-20-yn-3-one.
Pharmacological group: hormones and their antagonists / estrogens, gestagens; their homologues and antagonists.
Pharmachologic effect: gestagenic, contraceptive.

Pharmacological properties

Levonorgestrel is the pharmacologically active isomer of norgestrel. Levonorgestrel is 2 times stronger than norgestrel. Levonorgestrel alters the endometrium and slows down ovulation, prevents the implantation of a fertilized egg, reduces the sensitivity of progesterone and estrogen receptors in the endometrium, making it immune to estradiol and having a strong antiproliferative effect. Levonorgestrel interferes with the movement of sperm by increasing the viscosity of cervical mucus. Levonorgestrel as part of an intrauterine therapeutic system has a local direct effect on the fallopian tubes, endometrium, viscosity of mucus of the cervical canal. Levonorgestrel acts on the gonadotropic function of the pituitary gland, resulting in a slight decrease in the peak of luteinizing and follicle-stimulating hormones.
When taken orally, it is completely and rapidly absorbed in the gastrointestinal tract, bioavailability is approximately 100%. The maximum concentration in serum when taking 0.75 mg once is achieved after 0.9 - 2.3 hours and is 6.4 - 21.8 ng / ml. Levonorgestrel binds to plasma albumin by about 50% and to sex hormone binding globulin by 47.5%. The mean apparent volume of distribution of levonorgestrel is about 106 liters. Levonorgestrel is metabolized in the liver to form pharmacologically inactive metabolites (conjugated and unconjugated forms of 3alpha-, 5beta-tetrahydrolevonorgestrel). The main isoenzyme involved in the metabolism of levonorgestrel is CYP3A4. Isoenzymes CYP2E1, CYP2C19 and CYP2C9 can also participate, but to a lesser extent. The half-life is 19.1 - 29.7 hours. The total clearance of levonorgestrel from blood plasma is about 1.0 ml / min / kg. Levonorgestrel is excreted mainly in the urine, a small amount is excreted in the feces.
When using an intrauterine therapeutic system, the release rate of levonorgestrel into the uterus at the beginning is about 20 μg per day, and after five years it decreases to about 11 μg per day. The average release rate of levonorgestrel is about 14 mcg per day for up to 5 years. Intrauterine therapy systems can be used in women who are receiving hormone replacement therapy, together with transdermal or oral estrogen preparations that do not contain progestogen. After administration, levonorgestrel is found in plasma in an hour, the maximum concentration is reached 2 weeks after administration of the drug.

Indications

Intrauterine therapeutic system: idiopathic menorrhagia, contraception (long-term), prevention of endometrial hyperplasia with estrogen replacement therapy.
By mouth: emergency postcoital contraception in women (including after unprotected intercourse, and if the contraceptive method used is not reliable).

Levonorgestrel dosage and route

Levonorgestrel is taken orally, injected intrauterinely. Inside, used in the first 96 hours after intercourse at a dose of 0.75 - 1.5 mg. It is not recommended to use the emergency contraception method more often than 1 time in 4 - 6 months. Intrauterine, an intrauterine therapeutic system is inserted into the uterine cavity.
Due to the possibility of menstrual dysfunction, reuse of levonorgestrel by mouth during the same menstrual cycle should be avoided. Oral forms of levonorgestrel should not be used as a means of continuous and regular contraception, as this leads to an increase in side effects and a decrease in the effectiveness of the drug.
If uterine bleeding occurs after emergency postcoital contraception, a gynecological examination is recommended, and if menstruation is delayed by more than 5 to 7 days, pregnancy should be excluded.
Only after consulting a gynecologist and only in exceptional cases (including rape) is it possible to use levonorgestrel for emergency postcoital contraception in adolescents under 16 years of age.
Before installing an intrauterine therapeutic system, it is necessary to conduct a gynecological and general medical examination, including an examination of the mammary glands, pelvic organs, examination of a smear from the cervix.
Re-examination is necessary 4 - 12 weeks after the installation of the intrauterine therapeutic system, then once a year or more often, if indicated. The intrauterine therapy system remains effective for five years. An intrauterine therapeutic system should only be installed by a doctor who is well trained in this procedure or has experience with this form of the drug.
In women who take contraceptives containing progestogen, the risk of venous thrombosis may be increased. If symptoms of venous thrombosis appear, appropriate diagnostic and therapeutic measures should be taken immediately.
After removal of the intrauterine therapeutic system, fertility is restored in half a year in 50% of women, in a year - in 96.4%.
The contraceptive effect of levonorgestrel is less effective in overweight patients.

Contraindications for use

Hypersensitivity, thrombophlebitis, thromboembolic disorders, coronary artery disease, cerebrovascular disease, pregnancy (or suspicion of it); additionally for oral administration - jaundice (including a history), severe pathology of the biliary tract or liver, breastfeeding, puberty; additionally for the intrauterine therapeutic system - infections of the lower parts of the genitourinary tract, recurrent or existing inflammatory diseases of the pelvic organs, postpartum endometritis, cervicitis, acute diseases or liver tumors, septic abortion within the last 3 months, cervical dysplasia, pathological uterine bleeding of unknown origin, malignant neoplasms of the cervix or uterus, acquired or congenital malformations of the uterus, including fibroids that deform the uterine cavity; progestogen-dependent tumors, including breast cancer; pathology, which is accompanied by increased susceptibility to infections, age over 65 years (no safety data).

Restrictions on use

For intrauterine therapy system. After consulting a doctor: unusually severe headache, migraine, focal migraine with asymmetric loss of vision, or other symptoms that indicate transient cerebral ischemia; severe arterial hypertension, jaundice, severe circulatory disorders, including myocardial infarction and stroke; diabetes.
The advisability of removing the intrauterine therapeutic system should be discussed at the first occurrence or presence of any of the conditions listed above.

Application during pregnancy and lactation

The use of levonorgestrel is contraindicated in pregnancy.
If pregnancy occurs while using an intrauterine therapeutic system, it is recommended to remove the system, because any intrauterine contraceptive that is left in situ increases the risk of premature birth and miscarriage. Probing of the uterus or removal of the intrauterine therapeutic system may result in spontaneous miscarriage. It is necessary to discuss the advisability of artificial termination of pregnancy if it is impossible to carefully remove the intrauterine contraceptive. If the intrauterine therapeutic system cannot be removed and the woman wants to maintain the pregnancy, then the patient must be informed about the possible consequences and risks of preterm birth for the baby. In these cases, careful monitoring of the course of pregnancy is necessary. A woman with an intrauterine therapeutic system installed increases the risk of ectopic pregnancy, therefore it is necessary to exclude an ectopic pregnancy. The woman needs to be explained that she should immediately report all symptoms that suggest a complication of pregnancy (for example, colicky abdominal pain accompanied by fever, and others).
Levonorgestrel is excreted in breast milk: when breastfeeding, approximately 0.1% of the drug enters the child's body along with breast milk. Breastfeeding while taking oral levonorgestrel for emergency postcoital contraception should be discontinued for 36 hours.
For the intrauterine therapeutic system, it is considered that the use of any purely gestagenic method of contraception 6 weeks after delivery does not have a negative effect on the development and growth of the child, therefore it is unlikely that the drug poses a risk to the child at doses that are released by the intrauterine therapeutic system located in the uterine cavity. ...

Side effects of levonorgestrel

Nervous system and senses: nervousness, low mood, headache, depression, migraine, mood lability, fatigue, dizziness, change in the curvature of the cornea, intolerance to contact lenses.
Digestive system: abdominal pain, nausea, bloating, vomiting, diarrhea, flatulence, abdominal cramps.
Genitourinary system: spotting spotting, uterine / vaginal bleeding, benign ovarian cysts, oligo- and amenorrhea, heavy menstrual bleeding, pain in the pelvic organs, scanty menstrual bleeding, dysmenorrhea, vulvovaginitis, vaginal discharge, breast tension, decreased libido, breast tenderness , endometritis, pelvic inflammatory disease, cervicitis, uterine perforation, chloasma, vaginal candidiasis, changes in cervical secretion, ectopic pregnancy, sensation of threads by a partner during intercourse, breast cancer,
Skin integuments: acne, rash, alopecia, hirsutism, eczema, pruritus, rash, urticaria.
Others: back pain, weight gain, edema, weight loss, high blood pressure, hypersensitivity to the drug or drug component, including urticaria, rash, angioedema, sepsis.
During the procedure for inserting / removing an intrauterine therapeutic system: pain, bleeding, vasovagal reaction, accompanied by dizziness or fainting, epileptic seizure in patients with epilepsy.

Interaction of levonorgestrel with other substances

When levonorgestrel is used together with inducers of cytochrome P450 isoenzymes, the effect of levonorgestrel may decrease by increasing its metabolism. The following drugs may decrease the effectiveness of levonorgestrel: lansoprazole, amprenavir, nevirapine, tacrolimus, oxcarbazepine, topiramate, barbiturates (including primidone), tretinoin, carbamazepine, phenytoin, St. rifabutin, tetracycline, griseofulvin. Levonorgestrel reduces the effectiveness of anticoagulants (coumarin derivatives, phenindione), hypoglycemic, antihypertensive, anticonvulsants. Levonorgestrel increases serum glucocorticosteroids. Levonorgestrel may increase the toxicity of cyclosporine by inhibiting its metabolism. Levonorgestrel can disrupt the metabolic processes of chlordiazepoxide and diazepam, which leads to accumulation in the blood plasma of the latter. Due to the inhibition of enterohepatic recirculation of sex steroids, which is associated with a change in the intestinal flora, an increase in intermenstrual bleeding may occur when levonorgestrel is used together with sulfamethoxypyridazine, ampicillin, chloramphenicol, phenoxymethypenicillin, nitrofurantoin, neomycin.

Overdose

Overdose with levonorgestrel increases side effects. Symptomatic treatment is necessary, there is no specific antidote.

Trade names of drugs with active ingredient levonorgestrel

Combined drugs:
Levonorgestrel + Ethinyl estradiol: Anteovin, Mikroginon®, Minisiston, Minisiston® 20 fem, Ovidon, Oralcon, Trigestrel, Tricvilar®;
Levonorgestrel + Estradiol: Klimonorm®;
Ethinylestradiol + Levonorgestrel: Rigevidon®, Rigevidon® 21 + 7, Tri-regol®, Tri-regol® 21 + 7, Tricvilar®.

Levonorgestrel is a contraceptive drug.

Composition and form of release

The pharmaceutical industry produces a contraceptive in capsules and in the form of an intrauterine therapeutic system, where the active ingredient is levonorgestrel.

Pharmacological properties

Levonorgestrel is an isomer of norgestrel. The drug changes the endometrium, slows down ovulation, in addition, prevents the introduction of a fertilized egg into the tissue of the uterus, lowers the sensitivity of endometrial receptors, and has an antiproliferative effect.

The contraceptive drug increases the viscosity of the so-called cervical mucus, which prevents sperm from entering the uterus. Levonorgestrel, present in the intrauterine therapeutic system, affects the endometrium, fallopian tubes, and the viscosity of mucus.

When taking Levonorgestrel, its bioavailability is 100%. The maximum concentration in the blood occurs within two hours. In plasma, it binds to albumin by 50%. Metabolized in the liver. The half-life is from 19 to 29 hours. It is excreted in the urine, a small part in the stool.

When using an intrauterine therapeutic system, the active compound levonorgestrel is released into the uterus at 20 μg per day, after a five-year period - up to 11 μg per day.

Indications for use

The drug Levonorgestrel is indicated for use in the form of an intrauterine therapeutic system for idiopathic menorrhagia, in addition, as a long-term contraception, as well as for the prevention of endometrial hyperplasia.

Inside, the drug Levonorgestrel is prescribed for emergency so-called postcoital contraception for women.

Contraindications for use

I will list in what situations Levonorgestrel is contraindicated:

Hypersensitivity to the components of the drug;
With thrombophlebitis;
Pregnancy;
Thromboembolic disorders;
Coronary artery disease;
Lactation;
Jaundice;
Cerebrovascular diseases;
Pathology of the biliary tract;
Do not use the drug during puberty;
Urinary tract infections;
Cervicitis;
Inflammatory pathology of the pelvic organs;
Dysplasia of the cervix;
Postpartum endometritis;
Liver tumors;
Pathological uterine bleeding;
Anomalies of the uterus;
Tumors of the uterus;
Progestogen-dependent tumors;
Mammary cancer;
Over 65 years of age.

With caution, the contraceptive is used when a woman develops such symptoms, when installing an intrauterine therapeutic system, migraine, arterial hypertension, stroke, circulatory disorders, diabetes, myocardial infarction. When these symptoms appear, it is necessary to discuss with the doctor the advisability of removing the intrauterine system.

Application and dosage

The contraceptive Levonorgestrel is taken orally, in addition, it is administered intrauterinely. Inside, the capsule is used in the first four days after unprotected intercourse, usually the agent is used in a dose of 0.75 - 1.5 milligrams. Emergency contraception is not recommended more than once every 4 or 6 months.

Oral forms of the pharmaceutical Levonorgestrel should not be used as regular contraception, as this will lead to an increase in side effects, as well as reduce the effectiveness of the drug.

Before installing an intrauterine therapeutic system to a woman, a gynecological examination should be performed on the patient. It is necessary to re-examine one month or 12 weeks after the installation of this system, which remains effective over a five-year period.

Side effects

The use of the contraceptive Levonorgestrel can cause the following side effects: a woman becomes more nervous, her mood decreases, headache is possible, fatigue, depression, migraine headaches, in addition, mood lability, dizziness, and intolerance to contact lenses are noted.

The use of a contraceptive can cause negative manifestations on the part of digestion, which will manifest itself with abdominal pain, nausea, bloating, vomiting, diarrhea, flatulence, and the patient may also complain of abdominal cramps.

Other negative reactions to the drug will be as follows: spotting bleeding, uterine bleeding, ovarian cysts, vulvovaginitis joins, breast tension, endometritis, decreased libido, pain on palpation of the mammary glands, cervicitis, uterine perforation, vaginal candidiasis, on the skin there is a rash, acne, in addition, alopecia, hirsutism, urticaria.

Other side effects include: back pain, increased body weight, edema, increased blood pressure, in addition, hypersensitivity to contraceptives, angioedema, sepsis.

Overdose of the drug

In case of an overdose of the contraceptive pharmaceutical Levonorgestrel, symptomatic treatment is performed.

Special conditions

The contraceptive action of the pharmaceutical agent Levonorgestrel is less effective in overweight women.

Analogs

Pharmaceutical product Mikrolut, Postinor, in addition, Mirena, Eskinor-F, Norplant, and also Escapel.

Conclusion

Before using the contraceptive Levonorgestrel, a woman should consult with an experienced gynecologist.

Levonorgestrel is an active ingredient in a whole group of emergency and permanent contraception. Its effect on the female body is significant, has contraindications and frequent side effects. In order not to harm health, it is important to study these issues in advance - before using the substance.

What is levonorgestrel for?

The main field of application of drugs with the indicated active substance is to avoid unwanted pregnancy and emergency contraception.

Funds are issued in three forms- each has its own purpose of application:

• Pills... Most often, medications are intended for emergency contraception after unprotected or poorly protected intercourse;
• Intrauterine devices (IUDs)... Long-term contraceptive, valid for 5 years. In addition, the IUD can be used as a preventive measure of hyperplasia of the inner uterine membrane in estrogen treatment, as well as in heavy and painful menstruation;
• Capsules for subcutaneous implantation... Just like the IUD, it is a contraceptive with a duration of 5 years.

How levonorgestrel works

When taking a drug containing levonorgestrel, effect on a woman's body occurs according to the following mechanism:

1. Ovulation slows down, the intrauterine membrane lends itself to changes, as a result of which the fertilized egg cannot catch on and remain in the uterine cavity;
2. Under the influence of the active substance, the mucus contained in the cervix becomes denser, which prevents the sperm from approaching the egg.

Levonorgestrel as part of intrauterine devices acts on a similar principle:

1. The structure of the endometrium changes;
2. The mucus becomes more viscous, thick;
3. The patency of the fallopian tubes decreases.

After the drug is no longer used, the ability to become pregnant is restored.

To whom is levonorgestrel contraindicated?

Due to its significant effect, the substance has many contraindications.

Refuse to take drugs with levonorgestrel should be in such cases:

• when a woman is allergic to a substance;
• these contraceptives are prohibited during pregnancy and breastfeeding;
• contraindications are liver disease;
• can not be taken by girls under 18 years old;
• The IUD is not used for cervical dysplasia, malignant tumors in the genitals or mammary glands, and also if a woman has had a complicated abortion in the last 4 months.

Side effects from use

Based on which form of contraception is levonorgestrel, the likelihood of side effects can vary from 5 to 15%.

Most often, they are poorly perceptible, do not cause complications and special inconveniences.

The most common side effects:

• nausea, disruption of the intestinal tract;
• aching pain in the abdomen;
• loss of strength, irritation;
• disruptions in the menstrual cycle, changes in blood intensity, smearing discharge at 2-3 weeks of the cycle;
• frequent headaches;
• tension and enlargement of the mammary glands;
• rashes on the skin;
• edema of the lower extremities.

Medicines containing levonorgestrel

There is a large selection of contraceptives with the indicated active ingredient. The following funds are available in different forms and differ in the nature of the effect on the female body.

When choosing a contraceptive, be sure to pay attention to its bioavailability, or the ability to be absorbed.

Name (release form)	Maximum concentration after application	Advantages	disadvantages
Levonorgestrel (tablets)	1 to 2 hours	1. The most inexpensive among analogs; 2. Long half-life; 3. The dosage is divided into 2 tablets. Due to this, the effective concentration of the active substance is maintained for a longer time.	1. An insignificant amount of assimilation; 2. Side effects often occur - in 15% of cases.
Postinor (pills)		1. Low price; 2. The package contains 2 tablets; 3. Side effects are observed in 8% of cases; 4. High bioavailability; 5. Maximum half-life.	1. The time required to reach maximum concentration is above average.
Escapel (tablets)		1. Maximum bioavailability; 2. The maximum half-life; 3. Side effects were seen in only 5% of cases.	1. An expensive drug; 2. Available in 1 tablet, because the high concentration in the body does not last long.
Eskinor-F (pills)		1. It is produced in 2 different dosages, which allows to maintain efficiency for a long time; 2. Inexpensive medication; 3. Maximum digestibility.	1. A fairly high probability of side effects - about 11%.
Microlut (tablets, IUD)	1 to 1.5 weeks	1. Can be used for permanent contraception; 2. Provides a therapeutic effect in some gynecological pathologies; 3. On average, only 6% of the use of the drug showed side effects.	1. Poorly absorbed; 2. Short half-life.
Norplant (capsules for implantation under the skin)		1. Convenient form of release allows you to use the drug for contraception for 5 years, without uterine intervention; 0

Levonorgestrel

Latin name

Levonorgestrel

Chemical name

(17alpha) -13-Ethyl-17-hydroxy-18,19-dinopregn-4-en-20-in-3-one

Gross formula

C 21 H 28 O 2

Pharmacological group

Estrogens, gestagens; their homologues and antagonists

Nosological classification (ICD-10)

N92 Heavy, frequent and irregular menses
N95.1 Menopause and climacteric state in women
Z30.0 General advice and advice on contraception
Z30.5 Supervision of contraceptive (intrauterine) use

CAS code

797-63-7

Characteristic

Contraceptive (gestagen).

Pharmacology

Pharmacological action - contraceptive, gestagenic.

It slows down ovulation and changes the endometrium, prevents the implantation of a fertilized egg. Increases the viscosity of cervical mucus, which interferes with the movement of sperm.

As part of the intrauterine therapeutic system (IUD), levonorgestrel has a direct local effect on the endometrium, fallopian tubes and the viscosity of the mucus of the cervical canal.

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract, bioavailability is about 100%. C max in plasma after taking a single dose of 0.75 mg is noted after (1.6 ± 0.7) hours and is (14.1 ± 7.7) ng / ml. Binds to serum albumin (approximately 50%) and sex hormone binding globulin (47.5%). It is metabolized in the liver, the metabolites are pharmacologically inactive. T 1/2 - (24.4 ± 5.3) hours. It is excreted mainly in the urine, a small amount in the feces.

When using the IUD, the release rate of levonorgestrel into the uterine cavity is initially approximately 20 μg / day and decreases after five years to approximately 11 μg / day. The average release rate of levonorgestrel is approximately 14 mcg / day for up to 5 years. The IUD can be used in women receiving hormone replacement therapy in combination with progestogen-free oral or transdermal estrogen preparations.

Application

Inside. Emergency postcoital contraception in women (including after unprotected intercourse and if the contraceptive method used cannot be considered reliable).

For intrauterine therapy system. Contraception (long-term), idiopathic menorrhagia, prevention of endometrial hyperplasia during estrogen replacement therapy.

Contraindications

Hypersensitivity, pregnancy (or suspicion of it); for oral administration (additionally) - severe liver or biliary tract diseases, jaundice (including history), puberty, breastfeeding; for the IUD (optional) - existing or recurrent inflammatory diseases of the pelvic organs, infections of the lower parts of the genitourinary tract, postpartum endometritis, septic abortion within the last 3 months, cervicitis, diseases accompanied by an increased susceptibility to infections; dysplasia of the cervix, malignant neoplasms of the uterus or cervix, progestogen-dependent tumors, incl. mammary cancer; pathological uterine bleeding of unknown etiology, congenital or acquired uterine anomalies, incl. fibroids leading to deformation of the uterine cavity; acute diseases or tumors of the liver.

Restrictions on use

For the Navy. After consultation with a specialist: migraine, focal migraine with asymmetric loss of vision or other symptoms indicating transient cerebral ischemia; unusually severe headache; jaundice, severe arterial hypertension; severe circulatory disorders, incl. stroke and myocardial infarction.

The advisability of removing the IUD should be discussed in the presence or first occurrence of any of the conditions listed below.

Application during pregnancy and lactation

Contraindicated in pregnancy.

If pregnancy occurs while using the IUD, it is recommended that the system be removed. any intrauterine device left in situ increases the risk of miscarriage and premature birth. Removing the IUD or probing the uterus can lead to miscarriage. If it is not possible to carefully remove the intrauterine contraceptive, the advisability of artificial termination of pregnancy should be discussed. If a woman wants to preserve the pregnancy and the IUD cannot be removed, the patient should be informed about the risks and possible consequences of preterm birth for the baby. In such cases, the course of pregnancy should be closely monitored. It is necessary to exclude ectopic pregnancy (if a woman with an installed IUD becomes pregnant, the relative risk of ectopic pregnancy increases). The woman should be told that she should report all symptoms suggestive of a pregnancy complication, in particular colicky abdominal pain with fever.

Penetrates into breast milk: during breastfeeding, about 0.1% of levonorgestrel enters the newborn's body along with breast milk. Breastfeeding after taking the drug inside for the purpose of emergency postcoital contraception should be discontinued for 36 hours.

For the Navy. It is believed that the use of any purely gestagenic method of contraception 6 weeks after birth does not adversely affect the growth and development of the child, it is unlikely that it poses a risk to the child at doses released by the IUD located in the uterine cavity.

Side effects

In clinical trials, the most common cases in women taking oral levonorgestrel (0.75 mg) were nausea (23.1%), abdominal pain (17.6%), fatigue (16.9%), headache (16, 8%), menstrual irregularities, incl. heavy menstrual bleeding (13.8%), scanty menstrual bleeding (12.5%), dizziness (11.2%), breast tension (10.7%), vomiting (5.6%), diarrhea (5, 0%).

When using the IUD

On the part of the nervous system and sensory organs: ≥1%,<10% — пониженное настроение, нервозность, головная боль; ≥0,1%, <1% — лабильность настроения, мигрень.

From the digestive tract: ≥1%,<10% — боль в животе, тошнота; ≥0,1%, <1% — вздутие живота.

From the genitourinary system: ≥1% - uterine / vaginal bleeding, spotting spotting, oligo- and amenorrhea, benign ovarian cysts; ≥1%,<10% — боль в области органов малого таза, дисменорея, вагинальные выделения, вульвовагинит, напряженность молочных желез, болезненность молочных желез, снижение либидо; ≥0,1%, <1% — воспалительные заболевания органов малого таза, эндометрит, цервицит; ≥0,01%, <0,1% — перфорация матки.

On the part of the skin: ≥1%,<10% — угри; ≥0,1%, <1% — алопеция, сыпь, гирсутизм, зуд, экзема; ≥0,01%, <0,1% — сыпь, крапивница.

Others: ≥1%,<10% — боль в спине, повышение массы тела; ≥0,1%, <1% — отеки.

Interaction

With the simultaneous administration of inducers of cytochrome P450 isoenzymes, the metabolism of levonorgestrel may increase and the effect may decrease. The following drugs may decrease the effectiveness of levonorgestrel: amprenavir, lansoprazole, nevirapine, oxcarbazepine, tacrolimus, topiramate, tretinoin, barbiturates (including primidone), phenytoin and carbamazepine, drugs containing St. , rifabutin, griseofulvin. Levonorgestrel reduces the effectiveness of hypoglycemic drugs and anticoagulants (coumarin derivatives, phenindione), increases plasma concentrations of HA. Medicines containing levonorgestrel may increase the risk of cyclosporine toxicity by inhibiting its metabolism.

Method of administration and dosage

Inside, intrauterine. Inside, it is used in the first 96 hours after intercourse at a dose of 0.75-1.5 mg. It is not recommended to use the emergency contraception method more often than once every 4-6 months.

Intrauterine, an IUD is inserted into the uterine cavity.

Precautionary measures

Repeated use of the drug inside during the same menstrual cycle should be avoided due to the possibility of menstrual dysfunction. It is not allowed to use the oral dosage form as a means of regular and continuous contraception, because this leads to a decrease in the effectiveness of the drug and an increase in adverse reactions. If menstruation is delayed by more than 5-7 days after emergency postcoital contraception, pregnancy must be excluded, and in case of uterine bleeding, a gynecological examination is recommended.

In adolescents under 16 years of age, the use of emergency postcoital contraception is possible only in exceptional cases (including rape) and only after consulting a gynecologist.

Before installing the IUD, it is necessary to conduct a general medical and gynecological examination, including examination of the pelvic organs and mammary glands, as well as examination of a smear from the cervix. The woman must be re-examined 4-12 weeks after the installation of the IUD, and then once a year or more often, if clinically indicated. The IUD remains effective for five years. This should only be installed by a physician who has experience with the IUD or is well trained in this procedure.

The results of some recent studies show that women taking contraceptives containing only progestogen may have an increased risk of venous thrombosis; however, these results are not well defined. However, if symptoms of venous thrombosis appear, appropriate diagnostic and treatment measures should be taken immediately.

After removal of the IUD, fertility is restored in 50% of women after 6 months, in 96.4% - after 12 months.

Year of last adjustment

2011

Interaction with other active ingredients

Acarbose *
Glipizid *	Against the background of levonorgestrel, the hypoglycemic effect is weakened; with a combined appointment, constant monitoring of the concentration of glucose in the blood is necessary.
Soluble insulin [porcine monocomponent] *	Against the background of levonorgestrel, the hypoglycemic effect is weakened (an increase in the dose may be required).
Carbamazepine *	Carbamazepine induces the activity of the CYP450 system in the liver, decreases plasma levels and reduces the reliability of the contraceptive effect of levonorgestrel.
Levothyroxine sodium *	Against the background of levonorgestrel, the plasma level of thyroxine-binding globulin increases (an increase in the dose may be required).
Retinol *	Against the background of levonorgestrel, a significant increase in plasma levels is possible.
Rifampicin *	Rifampicin, as an inducer of liver enzymes, accelerates biotransformation, can weaken the effect of levonorgestrel and reduce the reliability of contraception.
Phenytoin *	Phenytoin induces the activity of cytochrome P450, accelerates biotransformation, and can weaken the contraceptive effect of levonorgestrel.