Universal reference book for medicines
Product name: IMPLANON (IMPLANON)

Active substance: etonogestrel

Type: Hormonal contraceptive for transdermal use

Manufacturer: NV ORGANON (The Netherlands)
Composition, form of production and packaging
A
single-stem contraceptive implant is placed in the needle of a sterile disposable applicator.

1 PC.

etonogestrel 68 mg

1 PC.
- needle applicator (1) sterile disposable - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2011.

PHARMACHOLOGIC EFFECT

The drug Implanon® is an implant for subcutaneous application that does not undergo biological decay, and which contains etonogestrel.
Ethonogestrel is a biologically active metabolite of desogestrel, a progestogen commonly used as an OC (oral contraceptive). 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 the drug Implanon® is mainly achieved due to oppression of ovulation. Ovulation was not observed during the first two years of use and only rarely occurred during the third year. In addition to suppressing ovulation, Implanon® also causes a change in the viscosity of cervical mucus, which prevents the passage of spermatozoa. Clinical studies were conducted among women aged 18-40 years.The contraceptive effect of Implanon® is reversible, which is reflected in the rapid recovery of the normal menstrual cycle after removal of the implant. Although the drug Implanon ® oppresses ovulation, the activity of the ovaries is not completely inhibited. The average concentrations of estradiol remain above the value observed in the early phase of follicle formation.
Implanon® does not affect the changes in bone mineral density and lipid metabolism.
The use of contraceptives containing progestogens may have an effect on insulin resistance and on glucose tolerance.
It has been shown that dysmenorrhoea is less common in patients who use Implanon®.

PHARMACOKINETICS

Suction.
After the introduction of Implanon®, etonogestrel is rapidly absorbed into the circulating blood. Concentrations that inhibit ovulation are achieved after 1 day.C max in the serum (between 472 and 1270 pg / ml) is achieved after 1-13 days. The release rate of etonogestrel from the implant decreases over time. As a result, serum concentrations decrease rapidly after the first few months. By the end of the first year, the mean concentration is approximately 200 pg / ml (range 150-261 pg / ml), which slowly decreases to 156 pg / ml (range 111-202 pg / ml) by the end of the third year. The observed variations in serum concentrations may partly be due to differences in body weight.
Distribution.
Etonogestrel is 95.5-99% bound to serum proteins, mainly albumin and to a lesser extent with globulin binding sex hormones. V d in the central chamber and the total V d are 27 L and 220 L, respectively, and these parameters are unlikely to change during the application of Implanon®.
Metabolism.
Ethonogestrel undergoes hydroxylation and reduction. Metabolites are sulfates and glucuronides.
Excretion.
With IV injection of etonogestrel, the average T 1/2 is approximately 25 hours, and the clearance from serum is approximately 7.5 liters / hour. Clearance and T 1/2 remain constant during application. 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 the administration of Implanon® to women breastfeeding, etonogestrel is excreted in breast milk at a milk / serum ratio of 0.44-0.50 during the first four months. In breast-feeding women who use Implanon®, the average dose of etonogestrel administered to the baby is approximately 0.2% of the maternal daily dose of etonogestrel (about 2.2% for the body weight of the child). It is shown that the concentrations gradually and statistically significantly decrease in time.
INDICATIONS

Contraception.

DOSING MODE

How to apply Implanon®

Before the introduction of the drug Implanon®, pregnancy should be excluded.

Before the introduction of Implanon®, you should carefully read the instructions for insertion and removal of the implant in the section "How to administer Implanon®" and in the section "How to Remove Implanon®".

The drug Implanon® is a long-acting hormonal contraceptive.
One implant is injected subcutaneously. A woman should be informed about the possibility of removing it at any time at her request, but the implant can not be left at the injection site for more than three years. Only a physician familiar with the removal technique should carry out the removal of Implanon® at the request of a woman or at the end of a 3-year period of use. After removal of the implant, the immediate introduction of another implant will lead to the continuation of contraceptive protection.
To remove the implant without complications, it is necessary that the Implanon® preparation is correctly inserted directly under the skin.
Subject to the instructions provided, the risk of complications is small.
Several cases have been reported, when the implant was inserted with a violation of the time of administration, or was incorrectly introduced or not at all.
This led to an unplanned pregnancy. The occurrence of such cases can be minimized with strict adherence to the instructions for insertion of the implant (the section "How to enter Implanon® and" When should Implanon® be administered "). After the introduction, the implant should be checked by palpation. If the implant fails to implant or the presence of an implant is in doubt, other methods should be used to confirm its presence (see "How to Introduce Implanon®). Until the presence of Implanon® is confirmed at the site of injection, a barrier method of contraception should be used.
Packaging with Implanon® contains the USER CARD intended for the user and an adhesive label intended for registration by the doctor who administered the drug.Among other things, the number of the implant series is registered in the USER CARD, and it allows to note the date of implant insertion, the arm in which the implant was inserted, the name of the doctor and / or the medical institution and the estimated date of implant removal.
In the adhesive label, the serial number and the date of implantation are recorded.
How to Introduce Implanon®

- Implanon® should be administered under aseptic conditions, and only by a doctor who owns this technique.

- Implanon is administered by a special applicator.
The use of this applicator differs significantly from the use of a classical syringe. The drawing of the disassembled applicator and its individual parts (cannula, obturator and needle, sharpened at a double angle) are shown below for a clearer understanding of their purpose.
- The method of administering the drug Implanon® is the opposite of the method of injection.
When Implanon® is administered, the obturator should remain in a fixed position when the cannula (needle) is removed from the shoulder. When carrying out a conventional injection, the piston is pushed, and the syringe body remains in a fixed position.
- A woman is offered to lie on her back with her hand turned (turned off and bent at the elbow) (a hand that the woman does not use for writing).

- The drug Implanon® should be administered from the inner (medial) side of the shoulder (non-dominant arm) approximately 8-10 cm above the medial epicondyle of the humerus.

- Mark the place of introduction.

- Clean the place of administration with a disinfectant.

- Conduct anesthesia with a spray or subcutaneously along the "channel of administration" inject 2 ml of lidocaine (1%).

- A sterile single-use applicator with Implanon® is removed from the blister.

- Leaving the protective cap on the needle, visually check the presence of the implant, which is visible as a white object inside the needle.
If the implant is not visible, then the upper end of the protective cap of the needle should be knocked on the hard surface, so that the implant is in the tip of the needle. After visual confirmation, the implant should be returned back to the needle by tapping the tip of the protective cap. Then you can remove the protective cap from the needle.
- It should be remembered that the implant can fall out of the needle before it is inserted.
Before application, the applicator is always held in an upright position (ie, with a needle pointing upwards). This prevents the implant from falling out. The needle and implant should be kept sterile. In case of contamination, a new packaging with a new sterile applicator should be used.
- Using the thumb and index finger, tighten the skin around the injection site.

- First enter only the tip of the needle at a slight angle (~ 20 °).

- Release the skin.

- Lower the applicator to the horizontal position.

- The tip of the needle lifts the skin, but the needle must remain in the subcutaneous connective tissue.

- Carefully without effort, lifting the skin, insert the needle to its full length, providing a superficial introduction.

- The applicator is held parallel to the skin surface.

- If the implant is placed too deep, then paresthesia can occur later, caused by nerve damage, and implant migration, if the implant is placed on the fascia or into the muscle.
In rare cases, improper administration may result in the implant falling into the vascular bed. In this case, the implant may not be palpable, and subsequently it may be difficult to remove it.
- Break the jumper of the applicator.

- Rotate the obturator by 90 °.

- One hand fix the obturator parallel to the shoulder, and the other hand slowly withdraw the cannula (needle) from the hand.

- Never press on the obturator.

- Check the absence of the implant in the needle.
After removing the cannula, the grooved tip of the obturator should be visible.
- It is always necessary to check the presence of the implant by palpation and the woman should also palpate the implant.

- In the event that the implant fails to palpate or when there are doubts about the presence of the implant, other methods should be used to confirm its presence.Acceptable methods for locating the implant are, first of all, ultrasound (ultrasound) and, secondly, magnetic resonance imaging (MRI).
Before conducting an ultrasound or an MRI to locate the Implanon® preparation, it is recommended that you consult the manufacturer for instructions. If it is not possible to locate the implant using these imaging techniques, it is recommended to check the presence of the implant by measuring the concentration of etonogestrel in the woman's blood.In this case, the manufacturer will also provide an appropriate methodology.
- Until the presence of Implanon® is confirmed, a barrier method of contraception must be used.

- To prevent the occurrence of bruising, a sterile napkin and a pressure bandage are applied.

- Fill in the user's card and hand it to the patient to facilitate the timely removal of the implant afterwards.

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

When should Implanon® be administered

Without prior application of hormonal contraceptives.
The drug Implanon® should be administered within the first 5 days, but at the latest on the 5th day of the natural cycle of a woman (1st day is the first day of menstrual bleeding).
When switching from combined hormonal contraceptives (combined oral contraceptives (COCs), vaginal rings or transdermal patches).
The drug Implanon® is preferably administered the day after the last active tablet (the last tablet containing the active substances) of the COC, but no later than the next day after the usual period without taking the tablets or placebo of the previous COC tablet. If a vaginal ring or transdermal patch is used, Implanon® should be administered on the day of removal, but at the latest at the day the next application of the vaginal ring or transdermal patch is planned.
When switching from a contraceptive method based only on progestogen (minipill, injection, other implant, or progestogen-releasing intrauterine system [IUD]).
The drug Implanon® can be administered on any day when a woman goes from taking a mini-saw (from another implant or IUD on the day of removal, from injections to the day the next injection is due).
After abortion in the I trimester.
The drug Implanon® should be administered immediately.
After childbirth or after abortion in the II trimester.
With regard to breastfeeding women.
The drug Implanon® should be administered on the 21-28th day after childbirth or abortion in the second trimester.
If the implant is inserted later, then the woman should be advised to use the barrier method of contraception in the first 7 days after the introduction. Nevertheless, if a woman already had sex, then in this case, you should exclude pregnancy or wait until the first menstruation before the implant.
How to Remove Implanon®

- Removal of the Implanon® preparation should only be performed by a doctor who knows how to remove it.

- The exact location of the implant is indicated in the USER CARD.

- Determine the location of the implant by palpation (shown by an arrow in the figure) and mark the distal end (the nearest end to the elbow).

- Do not palpable implant before trying to remove it should always be determined either by ultrasound or by MRI, and then carry out its removal under the supervision of ultrasound.
In case of doubt, the presence of Implanon® can be checked by the determination of etonogestrel in the blood. Please contact the manufacturer for additional recommendations. Surgery to find an implant without knowing its exact location is strictly contraindicated. Removal of deep implant should be done with extreme caution and only by specialists who are well versed in the anatomy of the shoulder in order to minimize the risk of damage to nerve fibers and vessels.
- Wash the area of ​​the implant location and treat with an antiseptic.

- Conduct local anesthesia in the area of ​​the implant location by injecting 0.5-1 ml of lidocaine (1%) at the excision site, which is just below the distal end of the implant.
Note: Anesthetic should be administered under the implant. The introduction of an anesthetic over the implant will cause swelling of the skin, which can cause difficulties in determining the location of the implant.
- Pressing on the proximal end of the implant, fix it.
In this case, the distal end of the implant can be seen as a convexity. Starting below the distal end of the implant, a longitudinal incision 2 mm long along the arm axis is made towards the distal end of the implant.
- Gently push the implant in the direction of dissection until its end appears.
Grasp the implant with forceps (preferably tongs like "mosquito") and remove.
- If the tip of the implant is invisible, it may be due to the formation of fibrous tissue around the implant.
Fibrous tissue can be moved apart, continuing to make a dissection in the direction of the distal end until the implant is clearly visible. Then remove the implant with forceps.
- If the end of the implant is not visible, then in this case gently force the forceps into the dissection and grasp the implant.
The second forceps gently separates the tissue around the implant. Then remove the implant.
- Close the dissection with a "butterfly" clip.

- To prevent the occurrence of bruising, a sterile napkin and a pressure bandage are applied.

- There are separate reports on the displacement of the implant;
usually in this case there is a slight displacement of the implant relative to the original location of the implant. Sometimes this can complicate the implant localization by palpation, ultrasound and / or MPT, and removal may require more dissection and more time.
- If a woman wishes to continue using Implanon®, a new implant can be inserted immediately after retrieval of the old implant.

- If a woman does not want to continue using Implanon® and does not want to become pregnant, then another method of contraception should be recommended.

How to replace Implanon®

- The replacement of Implanon ® should only be carried out under aseptic conditions and only by a doctor who is familiar with the methods of administration and disposal.

- Replacement can be performed immediately after removal of the previous implant, as described in the "How to Remove Implanon®" section.

- The procedure for replacing Implanon® is similar to the procedure for administration, which is described in the section "How to administer Implanon®".
The new implant can be inserted into the same arm, and through the same incision from which the previous implant was removed. If you are using the same incision, you should take into account the instructions below.
- a small incision, left after removal procedures can be used for insertion of the needle new applicator.
- Anesthesia dissection carried place 2 ml lidocaine (1%), are introduced directly into the skin, starting from the incision and along the "incision channel."
- When replacing the implant introduction needle applicator for the rest of its length it is crucial; partial introduction of the needle will result in the fact that the dissection of the skin to remove the implant to be partially visible.
- Close the clip cut "butterfly" type.
- To prevent the occurrence of bruising impose a sterile towel and a pressure bandage. Women are advised to keep the bandage for at least 48 hours to cut to remove healed.
SIDE EFFECT

In the application of OK note the following adverse events:
- a small increase in the risk of developing breast cancer. Expected number of diagnosed cases of breast cancer among 10,000 women using combined oral (including during the 10 years after cessation of use), with respect to women who had not used them, in the same period, calculated for the respective age groups, was 4.5 / 4 (16-19 years), 17.5 / 16 (20-24) 48.7 / 44 (25-29), 110/100 (30-34 years), 180/160 (35-39 ) and 260/230 (40-44 years). Risk in women using contraceptive methods that contain only progestin, perhaps similar to that in the application of combined OK. The risk increases with age, gradually declines for 10 years after discontinuation of OC and is not associated with the duration of reception OK;
- Venous thromboembolism (VTE, deep venous thrombosis and pulmonary embolism);
- chloasma;
- jaundice and / or pruritus related to cholestasis;
- the formation of gallstones; porphyria;
- systemic lupus erythematosus;

- hemolytic-uremic syndrome;
- Sydenham's chorea;
- herpes gestationis in the anamnesis;
- hearing loss associated with otosclerosis. Other side effects observed during treatment with Implanon® preparation are listed in the table. Communication side effects with taking the drug is not proven, but it is possible.
System-organ class Very often 1/10? Often, <1/10, 1/100? Uncommon <1/100, 1/1000?
Infections and infestations Vaginal infections (vulvovaginitis) - pharyngitis, rhinitis; Urinary tract infections (urethritis, cystitis)
Immune system disorders - - Hypersensitivity to any component of the drug
metabolic disorders and nutrition - decreased appetite -
Mental disorders - emotional lability, depression, anxiety, decreased libido, anxiety, insomnia
Nervous system headache, dizziness, headache, somnolence
Vascular disorders - "tides" -
the part of the gastrointestinal tract - abdominal pain, nausea, bloating, vomiting, constipation , diarrhea
part of the skin acne alopecia hypertrichosis, rash, itching,
the part of the musculoskeletal system - - back pain, arthralgia, myalgia, musculoskeletal pain
urinary system - - dysuria
On the part of the reproductive system and mammary glands tenderness in the breast, chest pain, irregular menstruation dysmenorrhea, ovarian cyst vaginal discharge, discomfort in the vulva and vagina, galactorrhea, increased mammary glands, itching of the vulva and vagina
Local reactions and general disorders - pain at the implant location, fatigue, influenza-like condition, pain, pyrexia, edema
Laboratory parameters weight gain weight loss -
On rare occasions, during the application of the drug Implanon® clinically significant increase in blood pressure. Use of the drug may cause development or exacerbation of urticaria and / or angioedema (including hereditary). Introduction and removal of Implanon® drug can cause bruising, slight local irritation, pain or itching. Sometimes in place of dissection can develop fibrosis, or scar formed to develop an abscess. In rare cases, there may be paresthesia or similar phenomena and possible loss or migration Implanon® drug. When removing Implanon® product may require a small surgical intervention.
CONTRAINDICATIONS

Contraceptives which contain only progestogen should not be used under any of the conditions / diseases listed below. In case of any of these conditions during treatment Implanon® should immediately stop using the product.
- pregnancy (including putative);
- Venous thrombosis / embolism, including in history;
- breast cancer, including in history;
- severe liver disease (before normalization of liver function), including: in history;
- progestogenzavisimye tumor;
- vaginal bleeding of unknown etiology;
- increased sensitivity to the active substance or to any component Implanon® preparation.
Carefully.
In the presence of any of the conditions or risk factors mentioned below, should weigh the benefit of the application of the progestogen on the possible risks for each individual woman and discussed with her before she decides to start using the drug Implanon®. In case of deterioration, the gain or the first occurrence of any of these conditions, the woman should consult a physician. After that, the doctor must decide whether to continue or cancel the use of the drug Implanon®.
- liver cancer;
- long-term immobilization due to surgery or other causes;
- diabetes;

lactation period.

PREGNANCY AND LACTATION

Implanon® drug during pregnancy is contraindicated. In case of pregnancy during use Implanon® drug, the implant should be removed. When conducting preclinical studies have found that very high doses may cause progestogenic compounds masculinization female fetuses. For information on the effect of the drug on Implanon® body of a pregnant woman and the fetus are not sufficient.
Implanon® drug does not affect the formation or the quality of breast milk (protein concentration, lactose, or fat). However, it is known that a small amount of etonogestrel is excreted in the milk. Based on the mean daily milk intake 150 ml / kg, the average daily dose of etonogestrel for a child, calculated after one month release of etonogestrel is about 27 ng / kg / day. This corresponds to approximately 0.2% estimated absolute maternal daily dose (about 2.2% when calculated as kg body weight). During the lactation period of etonogestrel concentration in the milk decreases successively. Based on available data, the use of Implanon® drug during lactation is possible, but only under the supervision of a physician for the development and growth of the infant.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Is contraindicated in severe liver disease (before normalization of liver function), including: history. Precautions: liver cancer (because it is impossible to eliminate the negative effect of progestogens on liver cancer, should be an individual assessment of benefit-risk ratio in women with liver cancer). If, during the use of the drug Implanon® having acute or chronic disturbances of liver function, in this case a woman should go to a specialist for examination and advice for Implanon® discontinuation of the drug.
APPLICATION FOR CHILDREN

Clinical trials in women aged less than 18 years have not been conducted. The use of this drug is not shown before menarche

APPLICATION IN ELDERLY PATIENTS

The drug is used only in women of reproductive age.
SPECIAL INSTRUCTIONS

- It is strongly recommended that physicians before beginning his medical practice associated with the administration of the drug Implanon®, passed training courses organized by the manufacturing company. Physicians who have little experience of subcutaneous administration is recommended to get the hang of the proper techniques under the supervision of a more experienced person.
- Additional information and more detailed instructions on adding and removing Implanon® drug available free on request representative of the manufacturer or can be found on the site www.implanonlocalization.
- The risk of developing breast cancer increases with age. There should be an individual assessment of risk-benefit ratio of hormonal contraceptives in the presence of breast cancer.
- Since it is impossible to eliminate the negative effect of progestogens on liver cancer, should be an individual assessment of benefit-risk ratio in women with liver cancer.
- Application Implanon® drug should be discontinued in case of thrombosis. It should also consider the possibility of eliminating the use of Implanon® drug in case of a possible surgery or require long-term immobilization of the disease. Women with a history of thromboembolic disorders should be warned about the possibility of their recurrence.
- Although progestogens may influence the resistance of peripheral tissues to insulin and glucose tolerance, there is no evidence that there is a need to change the hypoglycemic therapy in diabetic patients who use the drug Implanon®. However, women with diabetes should be monitored closely throughout the period of application of the drug Implanon®.
- Prevention of ectopic (tubal) pregnancy traditional progestogensoderzhaschimi OK is not as effective as when using COCs, since the application of the first, some women ovulate. Additional risk factors include the presence of an ectopic pregnancy, ectopic pregnancy, a history of the disease and the fallopian tubes as a result of infection or surgical procedure. Despite the fact that the drug Implanon® constantly inhibits ovulation, when it is used it is impossible to completely eliminate the development of ectopic pregnancy in the differential diagnosis in the case of amenorrhea or abdominal pain.
- If during treatment Implanon® developing stable hypertension or a significant increase in blood pressure is not adequately reduced in response to ongoing antihypertensive treatment, in such cases, you should consider discontinuing use of the drug Implanon®.
- If, during the use of the drug Implanon® having acute or chronic disturbances of liver function, in this case a woman should go to a specialist for examination and advice for Implanon® discontinuation of the drug.
- During the use of the drug may occur Implanon® chloasma, especially in women with a history of chloasma in. Women with a tendency to chloasma should avoid exposure to sunlight or UV radiation during use Implanon® drug.
- Implanon® contraceptive effect of the drug due to the concentration of etonogestrel in blood plasma, which is inversely proportional to the associated weighing and decreases over time after administration. The clinical experience with the drug Implanon® women with overweight in the third year of application of the drug is limited. Therefore, we can not exclude that the contraceptive effect in these women during the third year of the drug can be lower than that of women with normal body weight. Therefore, your doctor may need to provide for earlier replacement of the implant in women who are overweight.
- As a result of local inflammation or if the implant is introduced in accordance with the instructions set out in the section "How should I enter Implanon®", may occur out of the implant.
- In rare cases, mostly related to either too deep introduction (see also "How should I enter Implanon®."), And / or due to external forces (eg manipulation of the implant or contact sports) the implant may migrate from injection site. In such cases, the determination of the localization of the implant may be difficult and removal may require a larger incision (see. See also "How to be removed Implanon®" section). If Implanon® drug fails to find the contraception and the risk of adverse effects associated with the progestogen can be maintained over time, desirable woman.
- The safety and efficacy of the drug were evaluated Implanon® for women of reproductive age. It is expected that the efficacy and safety of adolescents in post-pubertal will be similar. However, clinical trials in women aged less than 18 years have not been conducted. The use of this drug is not shown before menarche.
Medical examination / consultation.should be carefully read before use or before replacing Implanon® drug with a history of women (including family history) and to exclude pregnancy. It should determine blood pressure and a physical examination, guided contraindication and warnings. It is recommended that a woman three months after administration of the drug Implanon® visited a doctor for a medical examination. During the medical examination, measure blood pressure, and to find out the existence of any questions, complaints or the occurrence of undesirable effects. The frequency and nature of further periodic medical examinations should be set individually for each woman (at least 1 time in 6 months). The woman should be informed that Implanon® drug does not protect against HIV infection (AIDS) and other diseases,sexually transmitted diseases.
Reduced effectiveness. Efficacy Implanon® drug can be reduced when using the drug in combination with other drugs.
Changes in bleeding patterns. During application of the drug Implanon® most women occur acyclic prolonged bleeding from the vagina, while the other women - spotting become more rare or terminated (approximately 1 out of 5 women).
Information, additional explanations and maintaining an individual's diary will help women to perceive emerging bleeding. Evaluation of vaginal bleeding should be performed on a regular basis, and can include examination to exclude pregnancy or gynecological pathology.
Follicular development. When receiving low-dose oral contraceptives of follicular development occurs and occasionally can reach the follicle size exceeding the normal size. Typically, the enlarged follicles disappear spontaneously and without symptoms; In some cases, there is slight pain in the lower abdomen, in rare cases, surgery.
Lab tests.The data obtained regarding COCs showed that the use of hormonal contraceptives may affect the results of some laboratory tests, including biochemical liver function tests, thyroid, adrenals and kidneys, the concentration of transport proteins in plasma, e.g., for binding globulin corticosteroids, fractionating lipids / lipoproteins, carbohydrate metabolism, blood coagulation and fibrinolysis. Usually, these changes are within the normal range. It is unknown to what extent this applies to contraceptives containing only progestogen.
Effects on ability to drive and use machines. Based on the pharmacodynamic profile, it is believed that Implanon® drug has no or a negligible effect on the ability
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