Implanon NKTS - instructions for use, dose, side effects, contraindications

Active substanceEtonogestrelEtonogestrel

Similar drugsTo uncover

implant PC

Dosage form: & nbspImplants.

Composition:

Active substance: etonogestrel 68 mg.

Excipients: barium sulfate 15 mg, ethylene and vinyl acetate copolymer (28% vinyl acetate) 43 mg, magnesium stearate 0.1 mg, ethylene and vinyl acetate copolymer (15% vinyl acetate) 15 mg.

Description:

A single-core implant, from white to white with a yellowish or brownish hue of color, is placed in the needle of a sterile disposable applicator.

The implant should be easily removed from the applicator.

Dimensions of the implant:

Length - from 3.8 to 4.2 cm

Diameter - from 1.95 to 2.05 mm

The thickness of the shell is from 54 to 66 μm

Pharmacotherapeutic group:contraceptive

ATX: & nbsp

G.03.A..08 Etonogestrel

Pharmacodynamics:

The drug Implanon NKST® is placed in a sterile disposable applicator, radiopaque, containing etonogestrel implant for subcutaneous application, which does not undergo biological decay.

Etonogestrel is a biologically active metabolite of desogestrel, a progestogen widely used as an oral contraceptive hormone (OK). Structurally, it is a derivative of 19-nortestosterone and binds to the receptors of progesterone in the target organs with high affinity.

The contraceptive effect of etonogestrel is mainly achieved by suppressing ovulation. Ovulation was not observed during the first two years of use, and only rarely did they occur during the third year. In addition to suppressing ovulation etonogestrel also causes an increase in the viscosity of the secretion of the cervix, which prevents the passage of spermatozoa. Clinical studies were conducted in women aged 18-40 years.

Despite the absence of direct comparison, the contraceptive effect of the implant is at least comparable to the contraceptive effect of combined OC (more than 99%). A high degree of protection against pregnancy is achieved, among other reasons, by the fact that the contraceptive effect of Implanon NCST® does not depend on a woman's strict adherence to a daily, weekly or monthly regimen.

The contraceptive effect of etonogestrel is reversible, which is reflected in the rapid recovery of the normal ovulatory menstrual cycle after removal of the implant. Although etonogestrel suppresses ovulation, ovarian activity is not completely suppressed. The average concentrations of estradiol in the blood plasma remain above the value observed in the early phase of follicle formation.

Etonogestrel does not affect the change in bone mineral density and lipid metabolism.

The use of contraceptive hormonal agents containing progestogens may have an effect on insulin resistance and glucose tolerance.

It has been shown that dysmenorrhoea is less common in patients using Implanon NKST®.

Pharmacokinetics:

Suction

After insertion of the implant etonogestrel quickly absorbed into the circulating blood. Concentrations that suppress ovulation are achieved after 1 day. Maximum plasma concentrations (from 472 to 1270 pg / ml) are achieved after 1-13 days. The release rate of etonogestrel from the implant decreases over time, resulting in a rapid decrease in plasma concentration in the first few months after administration. By the end of the first year of use, the average concentration is approximately 200 pg / ml (150-261 pg / ml) and slowly decreases to 156 pg / ml (111-202 ng / ml) by the end of the third year. The observed variations in plasma concentrations may in part be due to differences in body weight.

Distribution

Etonogestrel is 95.5-99% bound to plasma proteins, mostly with albumin and to a lesser degree with globulin binding sex hormones.The volume of distribution in the central chamber and the total volume of distribution are 27 liters and 220 liters, respectively, and it is unlikely that these values change during the time of Implanon NCST®^® in the body of a woman.

Metabolism

Ethonogestrel undergoes hydroxylation and reduction. Metabolites are sulfates and glucuronides.

Excretion

With intravenous administration of etonogestrel, the average half-life is approximately 25 hours, and the clearance from the plasma is approximately 7.5 liters / hour. The clearance and half-life remain constant during the application of the drug.

Etonogestrel and its metabolites both in the form of free steroids and in the form of conjugates are excreted by the kidneys and through the intestine (ratio 1.5: 1).

After administration to women during breastfeeding etonogestrel is excreted in breast milk in a milk / plasma ratio of 0.44-0.50 during the first four months. The average dose of etonogestrel entering the body of a baby with breast milk is approximately 0.2% of the maternal daily dose of etonogestrel (about 2.2% when recalculated per kg of body weight of the baby).It is shown that concentrations gradually and statistically significantly decrease with time.

Indications:

Contraception.

The efficacy and safety of the drug are confirmed in women aged 18 to 40 years.

Contraindications:

Contraceptive hormones containing only progestagen should not be used in the presence of any of the conditions / diseases listed below. In the event of any of these conditions occurring during the period of use of the Implanon drug, NCST^® should immediately stop using the drug:

- pregnancy (including presumed);

- thromboses (arterial and venous) and thromboembolism now or in history (including thrombosis, deep vein thromboembolism, pulmonary embolism, myocardial infarction, ischemic or haemorrhagic cerebrovascular disorders);

- the presence of antibodies to phospholipids;

- migraine with focal neurological symptoms;

- breast cancer, including in history;

- established or suspected malignant hormone-dependent tumors;

- benign or malignant liver tumors at present or in the anamnesis;

- severe forms of liver disease (before the normalization of functional liver tests), including jaundice, congenital hyperbilirubinemia, including in history;

- uncontrolled arterial hypertension;

- children's age (under 18 years of age, due to the lack of clinical studies of the drug among adolescent girls under the age of 18);

- bleeding from the vagina of an unclear etiology;

- hypersensitivity to the active substance or to any auxiliary substance of Implanon NKST®.

Carefully:

In the presence of any of the conditions or risk factors indicated below, the use of the implant should be weighed against the possible risks for each individual woman and discuss them with her before. as she decides to start using Implanon NKST®. In case of worsening, strengthening, or the first appearance of any of these conditions, a woman should consult a doctor, after which the doctor should decide whether to continue or abolish Implanon NKST®:

- conditions preceding thrombosis (including transient ischemic attacks, angina pectoris, complicated heart valve apparatus lesions,atrial fibrillation, extensive trauma);

- Diabetes mellitus, including diabetes mellitus with diabetic angiopathy;

- hereditary or acquired predisposition to arterial thrombosis, including deficiency of protein C, protein deficiency S, insufficiency of antithrombin III;

- liver diseases of mild and moderate severity with normal indicators of functional liver samples;

- therapy with anticoagulants;

- severe depression;

- Chloasma, including in the anamnesis.

Pregnancy and lactation:

The use of Implanon NKST® is not indicated during pregnancy. In the case of pregnancy during the use of Implanon NKST®The implant should be removed. Pre-clinical studies have found that very high doses of progestogen compounds can cause masculinization of female fetuses. Information on the effect of the drug Implanon NKST® on the body of a pregnant woman and the fetus is insufficient.

The drug Implanon NKST® does not affect the formation or quality of breast milk (on protein, lactose or fat concentrations). However, it is known that a small amount of etonogestrel is excreted in milk.Based on the average daily milk intake of 150 ml / kg, the average daily dose of etonogestrel for a child, calculated after one month of etonogestrel release, is approximately 27 ng / kg / day. This corresponds to approximately 0.2% of the estimated absolute maternal daily dose (about 2.2% in terms of body weight per child). During the period of breastfeeding, the concentration of etonogestrel in milk gradually decreases.

Based on the available data, the use of Implanon NKST® during breastfeeding is possible, but only under the supervision of the doctor for the development and growth of the infant. The drug Implanone NKST® should be administered after the 4th week after childbirth.

Dosing and Administration:

Before the introduction of the drug Implanon NKST® it is necessary to exclude pregnancy.

The doctor-gynecologist is strongly encouraged to take part in the training session to become familiar with the use of the Implanon NKST® applicator and the Implanon NKST® implant insertion and removal techniques.

Before insertion of the implant, you must carefully read the instructions for use and follow the instructions for insertion and removal of the implant, as described in the sections on "How to administer Implanon NKST®" and "How to remove Implanon NKST®."

How to apply Implanon NKST®

The drug Implanon NKST® is a long-acting contraceptive hormone. A single implant is injected subcutaneously, which can remain at the injection site for three years. Remove the implant no later than three years from the date of administration. A woman should be informed about the possibility of removing the implant at any time at her request. A gynecologist may consider the possibility of an earlier removal of the implant in women with excessive body weight. After removal of the implant, the immediate introduction of another implant will lead to the continuation of contraceptive protection. If a woman does not want to continue using Implanon NKST®, but she needs contraception, another method of contraception should be recommended.

The basis for the successful application and subsequent removal of implant Implanon NKST® is the correct and accurately performed subcutaneous implant insertion in accordance with this instruction. Impaired time and technique (see the sections on "When to administer Implanon NKST®" and "How to administer Implanon NKST®") can lead to pregnancy.

The implant Implanon NKST® should be injected subcutaneously, directly under the skin on the inside of the shoulder to avoid injury to large blood vessels and nerves that are located deeper in the connective tissue between the biceps and triceps muscles.

Immediately after the introduction of the implant, palpation should be checked for its presence under the skin. If the implant can not be groped or its presence is in doubt, it is necessary to apply other diagnostic methods to confirm its presence (see section "How to administer Implanon NKST®"). Until the implant is confirmed, a woman should recommend the use of non-hormonal (barrier) method of contraception.

Packing Implanon NKST® contains the PATIENT CARD, designed to record the number of the implant series. The doctor-gynecologist should write down the date of administration, indicate the hand in which the implant was inserted, and the planned day of its removal in the patient's CARD. Packaging of the product contains stickers for records of a gynecologist, in which the number of the implant series is indicated.

When to introduce Implanon NKST®

IMPORTANT: before the introduction of the implant, pregnancy must be excluded.

The timing of administration depends on the woman's recent use of contraceptive hormones as follows.

In the absence of contraceptive hormonal use in the previous month

The implant should be administered between the 1st day (the first day of menstrual bleeding) and the 5th day of the menstrual cycle, even if menstrual bleeding is still ongoing.

With the correct introduction of the implant, an additional method of contraception is not required. In the event of a deviation from the recommended implantation period, a woman should be warned about the need for a barrier method of contraception within the next 7 days. If there were sexual intercourse during this period, pregnancy should be excluded.

Transition from the hormonal contraceptive method to Implanon NKST®

When switching from a combined hormonal method of contraception (combined oral contraceptive (COC), vaginal ring or transdermal patch)

Implant should be administered preferably per day,following the day of administration of the last active tablet (the last tablet containing the active substances) of the COC, but no later than the day following the usual interval in taking the tablets, or the period during which the placebo COC tablets were taken. In the event that a vaginal ring or transdermal patch has previously been used, the implant should be administered preferably on the day of removal, but not later than the day of the next application of the previous preparation.

With the correct introduction of the implant, an additional method of contraception is not required. In case of deviation from the recommended period of implant administration, a woman should be warned about the need to use the barrier method of contraception within 7 days. If there were sexual intercourse during this period, pregnancy should be excluded.

When switching from a progestogenic method of contraception (for example,, pills, containing only progestogen, injections, implant or hormonal intrauterine system (IUD))

Since there are several types of progestagenic methods, the implant should be administered as follows:

- Injectable contraceptive hormonal means: Implant is administered per day, when the next injection should be done;

- tablets containing only progestogen: a woman can switch from tablets containing only progestogen to Implanon NCST® any day. The implant should be inserted within 24 hours after the last pill;

- Implant / IUD: Implant is administered on the day of removal of the previous implant or IUD.

After an abortion or miscarriage

- First trimester: The implant should be inserted within 5 days after the abortion or miscarriage in the first trimester.

- Second trimester: The implant should be inserted between 21 and 28 days after an abortion or miscarriage in the second trimester.

With the correct introduction of the implant, an additional method of contraception is not required.In case of deviation from the recommended period of implant administration, a woman should be warned about the need to use the barrier method of contraception within 7 days. If there were sexual intercourse during this period, pregnancy should be excluded.

After childbirth

- When breastfeeding: the implant should be inserted at the end of the fourth week after childbirth (see section "Application during pregnancy and during breastfeeding"). A woman should use the barrier method of contraception within 7 days after the implantation. If there were sexual intercourse during this period, pregnancy should be excluded.

- In the absence of breastfeeding: the implant should be administered between 21 and 28 days after delivery. With the correct introduction of the implant, an additional method of contraception is not required. In case of deviation from the recommended period of implant administration, a woman should be warned about the need to use the barrier method of contraception within 7 days. If there were sexual intercourse during this period, pregnancy should be excluded.

How to administer Implanon NKST®

The basis for successful application and subsequent removal of the drugImplanone NKST® is the correct and neatly performed subcutaneous implant insertion into the non-dominant hand in accordance with the instructions. A gynecologist and a woman should palpatorically determine the presence of an implant after its introduction.

Implant should be administered directly under the skin. Too deep or incorrect insertion of the implant may be complicated by paresthesia (due to nerve damage), implant migration (due to intramuscular or fascial administration) and, in rare cases, intravascular injection. In addition, when the implant is inserted too deeply, it may not be palpable, and its localization and / or removal can be difficult.

Implanone NKST® should be administered under aseptic conditions and only by a qualified gynecologist who is familiar with the administration technique. The implant should be implanted only with a special applicator.

It is recommended that the gynecologist be in the sitting position throughout the entire procedure of injection so that he can clearly see the place of injection and the movement of the needle under the skin.

- The woman needs to lie on the diagnostic table on her back, bending the non-dominant arm at the elbow and turning it outward so that the wrist is parallel to the ear, or that the hand was located next to the head (Figure 1).

- Determine the place of injection, which is on the inside of the shoulder of the non-dominant hand about 8-10 cm above the medial epicondyle of the humerus. Implant should be administered directly under the skin to avoid damage to large vessels and nerves that are located deeper in the subcutaneous tissues in the intermuscular groove between the biceps and triceps muscles.

- Make two marks with a sterile marker: first, mark the point at which the implant will be inserted; second, mark a point a few centimeters proximal to the first mark (Figure 2). The second mark will subsequently serve as a guide during the introduction.

- Treat the injection site with an antiseptic solution.

- Anesthetize the injection site (eg, using an anesthetic spray or injecting 2 ml of 1% lidocaine directly under the skin along the planned delivery channel).

- A sterile disposable Implanon NKST® applicator is removed from the blister in which the implant is located. The applicator is not used if there is any doubt about the sterility.

- The applicator is taken directly above the needle in the area of the textured surface and the transparent protective cap is removed from the needle containing the implant (Figure 3). If the cap is not easily removed, this applicator should not be used. You can see the white-colored implant by looking at the tip of the needle. Do not touch the purple slider until the needle is fully inserted subcutaneously, as this will lead to retraction of the needle and premature release of the implant from the applicator.

- Using a free hand, the thumb and forefinger stretch the skin around the injection site (Figure 4).

- The tip of the needle, located at an angle of approximately 30 °, is pierced by the skin (Figure 5).

- The applicator is lowered to the horizontal position. Raising the skin with the tip of the needle, the needle is continuously inserted over its entire length (Figure 6). You can feel a little resistance, but do not exert pressure with excessive force. If the needle is not inserted over its entire length, the implant will not be inserted properly. The movement of the needle is more convenient when the doctor sits and looks from the side, not from above. In this position, the place of introduction and movement of the needle is clearly visible.

- The applicator is held in the same position after insertion of the needle to its full length. If necessary, you can hold the applicator in the same position with your free hand during the next steps. Unlock the purple slider by gently pressing down on it. Slide the slider all the way back until it stops (Figure 7). Now the implant is under the skin, and the needle is blocked in the applicator. Then the applicator can be removed. If the applicator is not held in the same position during the procedure, or if the magenta slider is not completely moved back, the implant will not be inserted.

- After the introduction, it is necessary to check the presence of the implant under the skin of the shoulder with the help of palpation. If palpation of both ends of the implant is necessary, make sure the rod is 4 cm long (Figure 8).

If you can not feel the implant or doubt its availability

- Check the applicator.The needle should be drawn completely, and only the purple tip of the obturator should be visible.

- To confirm the presence of the implant, two-dimensional radiography, X-ray computed tomography (CT scan), ultrasound scanning with a high-frequency ultrasonic sensor for linear scanning (10 MHz or more) or magnetic resonance imaging (MRI) can be used. If these imaging methods can not confirm the presence of an implant, it is recommended to determine the concentration of etonogestrel in a woman's blood plasma. Until an implant is confirmed, a non-hormonal (barrier) contraceptive method should be used.

- Attach a small sticker from the adhesive plaster to the injection site. Ask a woman to palp an implant.

- Apply a sterile gauze bandage to reduce bruising. A woman can remove a pressure bandage after 24 hours, and a small sticker from the injection site in 3-5 days.

- Fill the Patient's CARD and transfer it to the woman for safekeeping. In addition, fill the stickers and attach them to the woman's medical record.

- The applicator is intended for single use only and must be properly disposed of in accordance with the existing requirements for the management of biohazardous wastes.

How to remove Implanon NKST®

Before starting the removal procedure, the gynecologist must locate the implant location indicated in the PATIENT CARD and check it palpably. If the implant is not palpable, additional testing methods should be used to confirm its presence (see "If you can not feel the implant or doubt its availability").

After localization of the non-palpable implant, the possibility of surgical removal of the implant under the control of the USS is considered.

There are rare reports on the movement of the implant; This usually refers to a slight displacement relative to the starting position, except for too deep introduction (see also the section "Special instructions"). This can complicate implant localization with the help of palpation, USS and / or MRI, and removal may require a larger incision and more time.

Removal of the implant should only be performed under aseptic conditions by a physician-gynecologist who is familiar with the removal technique.

Surgery to find an implant without knowing its exact location is not recommended.

Removal of deeply implanted implants should be carried out with care to avoid damage to the deep nerve or vascular structures of the shoulder and should be performed by a specialist well versed in the anatomy of the shoulder.

- The site of the future section is treated with an antiseptic. Determine the location of the implant by palpation and mark its distal end (the end closest to the elbow), for example, with a sterile marker (Figure 9).

- Anesthetize the place where a cut will be made, for example, 0.5-1 ml of 1% lidocaine (Figure 10). Make sure that the local anesthetic is inserted under the implant, so that it remains close to the surface of the skin.

- Press down on the proximal end of the implant (Figure 11) to fix it; On the skin, a bulge may appear, which will indicate the distal end of the implant. Starting from the distal end of the implant, a longitudinal incision of 2 mm is made towards the elbow.

- Carefully push the implant toward the incision until its tip appears.Capture the implant with a surgical clamp (preferably a "mosquito" type clamp) and remove the implant (Figure 12).

- If the implant is enclosed in a connective tissue sheath, a tissue incision is made and then the implant is removed with a surgical clamp (Figures 13 and 14).

- If the tip of the implant is not visible after the incision, carefully insert the surgical clamp into the incision (Figure 15). Grab the implant. The clamp is turned over and taken into the other arm (Figure 16). The second clamp should carefully cut off the tissue around the implant and grab the implant (Figure 17). After this, the implant can be removed.

- Be sure to remove the entire implant 4 cm long by measuring its length. There are reports of a violation of the integrity of the implant, located in the tissues of the patient's shoulder. In some cases, the extraction of such an implant was difficult. If part of the implant is less than 4 cm in length, the remaining part should be removed in accordance with the instructions (see "How to remove the Implanon NCST^®").

- If a woman wants to continue using Implanon NKST®, a new implant can be inserted immediately after removing the old implant in the same incision (see "How to replace Implanon NKST®").

- After the removal of the implant, the incision is closed with sterile strips of tissue (sterile strip) and a sticker of adhesive plaster is applied.

- To reduce bruising impose a sterile pressure bandage. A woman can remove a pressure bandage after 24 hours, and a sticker after 3-5 days.

How to replace Implanon NKST®

Immediate replacement can be done after removal of the previous implant, and it is similar to the introduction procedure described in the section on "How to administer Implanone NKST®%." A new implant can be inserted at the same location and through the same section from which the previous implant was removed. for the introduction of a new implant, use the same incision, anesthetize the injection site (for example, 2 ml of 1% lidocaine directly under the skin, starting with the incision for removal, along the injection channel) and follow the subsequent steps of the introduction instructions.

Data on the efficacy and safety of the Implanon NKST® preparation in adolescent girls under the age of 18 are not available.

Additional information and more detailed instructions for insertion and removal of the implant can be obtained from the manufacturer.

Side effects:

During the application of the drug Implanon NKST® in women, changes in the nature of menstrual bleeding are likely. They can include changes in the frequency of bleeding (absence, less or more frequent), intensity (decrease or increase), or duration of bleeding. The absence of menstrual bloody discharge was observed in 20% of women, the same number of women experienced more frequent and / or prolonged bleeding. Sometimes heavy bleeding was reported.

In clinical studies, a change in the character of bloody vaginal discharge was the most common reason for discontinuing the implant (approximately 11%).

During the application of Implanon NKST®the soreness of menstrual-like bloody discharge is reduced. The nature of bleeding that occurs during the first three months, allows you to predict the future nature of bleeding in most women.

Possible adverse effects associated with the use of the drug, reported in clinical trials, are listed in the table. Their relationship with the use of the drug has not been confirmed, nor has it been refuted.

System-Organic grade	Undesirable reactions
System-Organic grade	Very often> 1/10	Frequently <1/10, ≥1 / 100	Uncommon <1/100, ≥1 / 1000
Infectious and parasitic diseases	vaginal infection (vulvovaginitis)	-	pharyngitis, rhinitis; infection urinary tract (urethritis, cystitis)
Immune system disorders	-	-	hypersensitivity to any component of the drug
Disorders from the metabolism and nutrition	-	increased appetite	-
Disorders of the psyche	-	emotional lability, depression, nervousness, decreased libido	anxiety, insomnia
Disturbances from the nervous system	headache	dizziness	Migraine, drowsiness
Vascular disorders	-	"tides"	-
Disorders from the gastrointestinal tract	-	abdominal pain, nausea, bloating	Vomiting, constipation, diarrhea
Disturbances from the skin and subcutaneous tissues	acne	alopecia	hypertrichosis, rash, itching
Disturbances from musculoskeletal and connective tissue	-	-	back pain, arthralgia, myalgia, musculoskeletal pain
Disorders from the kidneys and urinary tract	-	-	dysuria
Violations of the genitals and mammary gland	soreness in the mammary glands, chest pain, irregular menstruation	dysmenorrhea, ovarian cyst	discharge from the vagina, discomfort in the vulva and vagina, galactorrhea, increased mammary glands, itching in the vulva and vagina
General disorders and disorders at the site of administration	-	pain in the location of the implant, reaction at the implant site, fatigue, influenza-like state, pain	hyperthermia, edema
Laboratory and instrumental data	weight gain	weight loss	'-

In the clinical study, violations at the site of administration were also studied, which were noted in 8.6% of women. The most common disorder observed during administration or for a short period after administration was erythema (3.3% of women). Also, hematomas (3.0%), bruising (2.0%), pain (1.0%) and local edema (0.7%) were observed.

During post-marketing surveillance, a clinically significant increase in blood pressure was observed in rare cases. There are also reports of seborrhea. Anaphylactic reactions, hives and angioedema (or its more severe course) and / or a more severe course of hereditary angioedema may develop. The introduction and removal of the implant can cause bruising, minor local irritation, pain or itching.At the site of dissection, fibrosis can develop, a scar may form or an abscess develop. Paresthesia or similar phenomena may occur, and implant loss or migration may occur. When removing the implant, surgical intervention may be required.

In rare cases, ectopic pregnancy has been reported (see section "Special instructions").

In women using contraceptive hormonal drugs, the following (serious) adverse reactions were noted:

- venous thromboembolism (VTE, deep vein thrombosis and pulmonary embolism);

- arterial thromboembolism;

- hormone-dependent tumors (liver tumors, breast cancer);

- Chloasma;

- jaundice and / or itching associated with cholestasis;

- cholelithiasis:

- porphyria;

- systemic lupus erythematosus;

- hemolytic-uremic syndrome;

- chorea;

- herpes during pregnancy;

- hearing loss associated with otosclerosis.

Overdose:

The implant should always be removed before the introduction of a new one. There are no data on an overdose of etonogestrel. There are no reports of serious side effects due to an overdose of contraceptive hormonal drugs in general.

Interaction:

Effect of other drugs on Implanon NKST®

The interaction between contraceptive hormonal drugs and other drugs can lead to "breakthrough" bleeding and / or a reduction in the contraceptive effect.

Special studies devoted to the study of interaction with the Implanon NCST® preparation have not been carried out. In the literature, the following interactions are reported (mainly with COCs, but sometimes also reported for contraceptive hormonal agents containing only progestogen).

Hepatic metabolism: interaction is possible with drugs - inducers of microsomal liver enzymes, especially cytochrome P450 enzymes (for example, with phenytoin, phenobarbital, primidon, bosentan, carbamazepine, rifampicin and possibly also with oxcarbazepine, topiramate, felbamate, griseofulvin and herbal preparations containing St. John's wort Perforated (Hypericum perforatum)), HIV protease inhibitors (eg, ritonavir, nelfinavir) and non-nucleoside reverse transcriptase inhibitors (eg, nevirapine, efavirenz) and combinations thereof, which may lead to an increase in sex hormone clearance.

Women receiving treatment with one of the above medicines should additionally use the barrier method of contraception during their use and within 28 days after stopping their intake.

Women who receive long-term treatment with drugs that induce microsomal enzymes of the liver, it is recommended to remove the implant and prescribe a non-hormonal (barrier) method of contraception.

Increase in the concentration of hormones in the plasma, associated with the joint use of medications: medicinal products (for example, ketoconazole), which inhibit microsomal liver enzymes, such as CYP3A4, can increase the concentration of hormones in the plasma.

Effect of Implanon NKST® on other medications

Contraceptive hormonal agents can affect the metabolism of other drugs. Accordingly, concentrations of drugs in plasma and in tissues may increase (eg, cyclosporine) or decrease (eg, lamotrigine).

Note: To identify possible interactions, you should review the instructions for using concurrentlymedicines.

Special instructions:

- The risk of developing breast cancer increases with age. During the application of OK (including combined), the risk of diagnosing breast cancer increases slightly. This increased risk gradually decreases within 10 years after discontinuation of the use of OC, and it is not associated with the duration of the OC application, but is related to the age of the woman in whom it applies the OC. The expected number of diagnosed cases of breast cancer among 10,000 women who used combined OK (in t.10 years after the termination of their application), for women who never used them, for the same period, calculated for the corresponding age groups, was: 4.5 / 4 (16-19 years), 17.5 / 16 (20-24 years), 48.7 / 44 (25-29 years), 110/100 (30-34 years), 180/160 (35-39 years) and 260/230 (40-44 years).

The risk in women using contraceptive methods containing only gestagens may be similar to the risk of using combined OCs. Nevertheless, the data on these methods are not so specific. Compared to the risk of breast cancer throughout life, an increase in the risk associated with OC is small.Women who use OC are diagnosed with earlier clinical stages of breast cancer than women who have never used OC. The increased risk observed in women who use OC may be due to earlier diagnosis, biological effects of OC, or a combination of these two factors.

- In case of acute or exacerbation of chronic liver diseases, a woman should consult a specialist for examination and counseling.

- In the course of epidemiological studies, it was found that there is a correlation between the use of combined OC and an increase in the incidence of venous thromboembolism (deep vein thrombosis and pulmonary embolism). Although the clinical significance of these results for etonogestrel (a biologically active metabolite of desogestrel) used as a contraceptive hormone is unknown in the absence of an estrogen component, in the case of thrombosis, the implant should be removed.

It should also consider the possibility of removing the implant in the case of prolonged immobilization due to surgery or illness.Although Implanon NKST® is a contraceptive hormone containing only progestogen, it is recommended to evaluate risk factors that are known to increase the risk of venous or arterial thromboembolism. Women with thromboembolic disease in history should be warned about the possibility of their recurrence.

- In the post-marketing period of implant application, containing etonogestrel, reports were received of severe arterial and venous thromboembolic complications, including pulmonary embolism (including fatal), deep vein thrombosis, myocardial infarction, and stroke. Implanone NKST®should be removed in case of thrombosis.

- If during the period of application of Implanon NCST®, persistent arterial hypertension develops or if significantly high blood pressure does not decrease adequately in response to ongoing antihypertensive therapy, Implanon NKST® implant should be removed.

- Although progestogens can influence the resistance of peripheral tissues to insulin and to glucose tolerance,that there is a need to adjust the dose of hypoglycemic drugs in patients with diabetes using contraceptive hormones containing only progestogen. Nevertheless, patients with diabetes should be carefully monitored during the entire period of hormonal contraceptives containing only progestogen.

- It is necessary to conduct periodic examinations of women who are undergoing therapy for hyperlipidemia. Some progestogens can increase concentrations of low-density lipoproteins and worsen the control of hyperlipidemia.

- Sometimes, chloasma may occur, especially in women with a history of pregnant women with chloasma. Women with a predisposition to chloasma should avoid exposure to sunlight or ultraviolet radiation during the use of the drug Implanon NCST^®.

- The contraceptive effect of the drug Implanon NKST® is related to the concentration of etonogestrel in the blood plasma, which in inverse proportion is related to body weight and decreases with time after administration of the drug.Clinical experience in women with overweight in the third year of use of the drug is limited. It can not be ruled out that the contraceptive effect of such women during the third year of use of the drug may be lower than in women with normal body weight, so the doctor may need to provide for an earlier replacement of the implant in women with excessive body weight.

- As a result of local inflammation or if the implant is not administered in accordance with the instructions in the section on "How to administer Implanon NKTS®," implantation may occur.

- In rare cases, mainly as a result of too deep introduction (see also the section on "How to administer Implanon NKST®") and / or as a result of external forces (for example, implant manipulation or contact sports), the implant can migrate from the injection site. In such cases, the location of the implant can be difficult and extraction may require more incision and time (see also "How to remove Implanon NKST®"). If the implant is not removed then contraception and the risk of undesirable effects associated with progestogen may persist beyond the time desired by the woman.

- With the use of all low-dose contraceptive hormonal agents, follicles can grow, and sometimes the follicle can reach a size larger than in the normal cycle. Usually, these follicles disappear spontaneously and are often asymptomatic; in some cases, there is a slight pain in the abdomen. In rare cases, surgical intervention is necessary.

- Prevention of ectopic pregnancy with traditional progestogen-containing contraceptive hormonal agents is not as effective as when combined OC is used, which is associated with the frequent occurrence of ovulation during the application of these methods. This statement does not apply to the use of progestin-only oral contraceptives containing desogestrel, and an implant with desogestrel th. Although the Implanon NKST® drug suppresses ovulation, if a woman has amenorrhea or abdominal pain, differential diagnosis should take into account the risk of an ectopic pregnancy.

- There are reports of the following conditions that occurred both during pregnancy and when using sex steroid hormones,but the association with the use of progestogens has not been established: jaundice and / or pruritus associated with cholestasis; the formation of gallstones; porphyria; systemic lupus erythematosus: hemolytic-uremic syndrome; Sydengam's chorea: herpes during pregnancy; hearing loss associated with otosclerosis; (hereditary) angioedema.

- The safety and efficacy of Implanon NKST® was evaluated for women of reproductive age. The safety and efficacy of the Implanon NKST® drug in adolescent girls under the age of 18 years have not been studied.

Medical examinations / consultations

Before starting or before replacing the Implanon NKST® drug, you should carefully read the woman's history (including family history) and exclude pregnancy. It is necessary to measure blood pressure, conduct a physical examination and be guided by contraindications (see the section "Contraindications") and warnings (see "With caution").

It is recommended that a woman three months after the introduction of Implanon NKTT® visit a doctor for medical examination.During the medical examination, you should measure blood pressure and find out whether there are any questions, complaints or undesirable effects. The frequency and nature of further periodic medical examinations should be set individually for each woman (at least once every 6 months).

A woman should be informed that Implanon NCST® does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Decreased efficiency

The effectiveness of the drug Implanon NKST® can be reduced when the drug is used in combination with other medicines (see section "Interaction with other drugs").

Changes in the character of spotting

During the application of the drug Implanon NKST® in women, changes in the nature of menstrual bleeding are likely. They may include changes in frequency (absence, less or more frequent), intensity (decrease or increase), or bleeding time. Amenorrhea was observed in 20% of women, while the other 20% had more frequent and / or prolonged bleeding.Dysmenorrhea tends to improve during application of Implanon NCCT®. The nature of bleeding that occurs during the first three months, allows you to predict the future nature of bleeding in most women. Informing, additional explanations and keeping an individual diary will help a woman to adequately perceive bleeding. Evaluation of vaginal bleeding should be done individually. It may include examination to exclude gynecological pathology or pregnancy.

Laboratory indicators

Data on combined OCs showed that the use of contraceptive hormonal drugs may affect some laboratory indicators, including biochemical parameters of liver, thyroid, adrenal and kidney functions, and the concentration of (transport) proteins in plasma, for example. corticosteroid-binding globulin and lipid / lipoprotein fraction. parameters of carbohydrate metabolism, blood clotting and fibrinolysis. Usually these changes remain within the normal range.It is not known to what extent this applies to contraceptive hormonal agents containing only progestogen.

Imbalance of the integrity or shape of the implant, located in the tissues of the patient's shoulder

There are reports of a violation of the integrity or shape of the implant located in the tissues of the patient's shoulder. Research in vitro showed that in such cases, the release rate of etonogestrel may increase slightly, but this change is not of clinical significance. After the implant has been removed, it is necessary to make sure that the entire implant is removed (see "How to remove Implanon NKST®").

Effect on the ability to drive transp. cf. and fur:

Reactions in the management of vehicles and the use of complex equipment have not been studied. Implanone NKST® can cause dizziness. Patients should be warned that when dizziness occurs, do not drive or use complicated equipment.

Form release / dosage:Implant, 68 mg.

Packaging:

The implant is placed in a stainless steel needle ready for use with a sterile disposable applicator.The applicator is hermetically sealed in a contoured cellular package of transparent polyethylene-terephthalate-glycol. sealed with a film of HDPE and an ethylene-vinyl acetate copolymer.

The outline package with instructions for use, the patient's card and 2 stickers for the outpatient card are packed in a cardboard box.

Storage conditions:

At a temperature of 2 to 30 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:PL-000317

Date of registration:22.02.2011 / 23.03.2016

Expiration Date:Unlimited

The owner of the registration certificate:Organon, N.V.Organon, N.V. Netherlands