Universal reference book for medicines
Name of the preparation: IMPLANON NKST® (IMPLANON NKST)

Active substance: etonogestrel

Type: Hormonal contraceptive for transdermal use

Manufacturer: NV ORGANON (The Netherlands)
Composition, form of production and packaging
A
single-stem, white to white implant with a yellowish or brownish hue of color is placed in the needle of a sterile disposable applicator;
Implant should be easily removed from the applicator; implant dimensions: length from 3.8 to 4.2 cm, diameter from 1.95 to 2.05 mm; shell thickness from 54 to 66 microns.
1 implant

etonogestrel 68 mg

Auxiliary substances: barium sulfate - 15 mg, ethylene and vinyl acetate copolymer (28% vinyl acetate) - 43 mg, magnesium stearate - 0.1 mg, ethylene and vinyl acetate copolymer (14% vinyl acetate) - 15 mg.

1 PC.
- the needle of the sterile disposable applicator (1) - the packaging of the contour of the cell (1) complete with the patient's card and 2 stickers for the outpatient card - a cardboard pack.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2015.

PHARMACHOLOGIC EFFECT

The drug Implanon NKST® is placed in a sterile single-use applicator radiopaque, containing an etonogestrel implant for use, which does not undergo biological decay.

Ethonogestrel is a biologically active metabolite of desogestrel, a progestogen widely used as an oral contraceptive hormone (PC).
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 2 years of use, and only rarely did they occur during the 3rd 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 PCs (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 the implantation, the etonogestrel is rapidly absorbed into the circulating blood.
Concentrations that suppress ovulation are achieved after 1 day. C max in plasma (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 pg / 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

The binding of etonogestrel to plasma proteins is 95.5-99%, mainly with 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 it is unlikely that these values ​​change during the finding of Implanon NKST ® in the woman's body.
After administration to women during breastfeeding, etonogestrel is excreted in breast milk at a milk / plasma ratio of 0.44-0.50 during the first 4 months.
The average dose of etonogestrel delivered to the body of a baby with breast milk is approximately 0.2% of the maternal daily dose of etonogestrel (about 2.2% in terms of body weight per child). It is shown that concentrations gradually and statistically significantly decrease with time.
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 the plasma is approximately 7.5 l / h.
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).
INDICATIONS

- Contraception.

DOSING MODE

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

The 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 procedures.

Before insertion of the implant, you should carefully read the instructions for use and follow the instructions for insertion and removal of the implant.

Rules for implant implantation Implanon NKST®

The drug Implanon NKTS ® is a long-acting contraceptive hormone.
A single implant is injected into the implant, which can stay at the injection site for 3 years.Remove the implant no later than 3 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 SC im injection in accordance with this instruction.
Impaired time and technique of implant administration can lead to pregnancy.
Implanon Implant NKST ® should be injected 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. Until the implant is confirmed, a woman should recommend the use of non-hormonal (barrier) method of contraception.
Packing Implanon NKST ® contains a user 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 user'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®

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 the 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 hormonal method of contraception to Implanon NKST®

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

The implant should preferably be administered on the day following the day of the last active tablet (the last tablet containing the active substances) of the PDA, but not later than the day following the usual interval in taking the tablets or the period during which the placebo tablets of the PDA 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, tablets containing only progestogen, injection, implant or hormone intrauterine system (IUD))

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

- injectable contraceptive hormonal agents: inject the implant daily, 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 must be inserted within 24 hours after the last tablet;
- Implant / Hormonal IUD: Implant is administered on the day of removal of the previous implant or IUD.

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 an abortion or miscarriage

- I trimester: the implant should be inserted within 5 days after the abortion or miscarriage in the I trimester;

- II trimester: the implant should be inserted between 21 and 28 days after abortion or miscarriage in the II 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

- with breastfeeding: the implant should be inserted at the end of the fourth week after childbirth.
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 inserted 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 enter Implanon NKST®

The basis for the successful application and subsequent removal of Implanon NKST® is the correct and accurately executed w / o 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.
Administration of Implanone NKST® should be performed 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.

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

2. Determine the place of injection, which is on the inside of the shoulder of the non-dominant hand approximately 8-10 cm above the medial epicondyle of the humerus.
Implant should be administered directly under the skin in order 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.
3. 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.The second mark will subsequently serve as a guide during the introduction.

4. Treat the injection site with an antiseptic solution.

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

6. Remove from the blister sterile disposable applicator Implanon NKST ® , in which the implant is located.
The applicator is not used if there is any doubt about the sterility.
7. 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.
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.
8. Using a free hand, the thumb and forefinger stretch the skin around the injection site.

9. The tip of the needle, located at an angle of approximately 30 °, is pierced by the skin.

10. Applicator is lowered to the horizontal position.
Raising the skin with the tip of the needle, smoothly insert the needle to its full length. 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 to observe when the doctor sits and watches from the side, and does not look from above. In this position, the place of introduction and movement of the needle is clearly visible.
11. The applicator is held in the same position after insertion of the needle over its entire 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. 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.
12. 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 to ensure the presence of a rod 4 cm in length.
If the doctor can not feel the implant or doubts its availability

1. Check the applicator.
The needle should be drawn completely, and only the purple tip of the obturator should be visible.
2. Two-dimensional X-ray, X-ray computed tomography (CT scan), ultrasound scanning (UZS) with high-frequency ultrasonic sensor for linear scanning (10 MHz or more) or MRI can be used to confirm the presence of the implant.
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. Not yet confirmed the presence of the implant, a non-hormonal (barrier) contraceptive method should be used.
3. Apply a small sticker of the plaster to the site of administration. Asking a woman palpate the implant.
4. Apply a sterile gauze pressure bandage to minimize bruising. The woman may delete pressure bandage after 24 hours and a small sticker from the site of administration - after 3-5 days.
5. Fill the user card and give it to the woman of the deposit. In addition, fill stickers and stick them to the woman's medical card.
6. The applicator is intended for single use and should be properly disposed of in accordance with the existing requirements for the handling of biohazardous waste.
How to remove Implanon NCTS®
Before starting the removal gynecologist procedures must establish the location of the implant, the user in the card and check it by palpation. If the implant is not palpable, additional methods of examination should be used to confirm its presence.
After localization of non-palpable implant considering the possibility of surgical removal of the implant under the control of the PSM.
There are rare reports of displacement of the implant; usually for slight movement relative to the reference position, except too deep insertion. This may complicate localization of the implant by means of palpation, USS and / or MRI, and removal may require a larger incision and more time.
Removal of the implant should only be carried out under aseptic conditions by a gynecologist who is familiar with the procedure of removal.
Surgery in order to find the implant without the knowledge of its exact location is not recommended.
Removing deep insertion of the implant must be conducted with caution in order to avoid damage to deeper neural or vascular structures, and shoulder should be performed by a specialist who is familiar with the anatomy of the shoulder.
1. Place a future cut processed antiseptic. Determine the location of the implant by palpation and mark the distal end (the end closest to the elbow), for example, with a sterile marker.
2. Carry anesthesia place where the incision will be made, for example, 0.5-1 mL of 1% lidocaine. Make sure that the local anesthetic is injected under the implant, in order to remain close to the surface of the skin.
3. Jam at the proximal end of the implant to fix it; the skin may appear a bulge, which will be denoted by the distal end of the implant. Since the distal end of the implant, a longitudinal incision of 2 mm in the direction towards the elbow.
4. Gently push the implant towards the incision until then, until its tip. Grab implant surgical clip (preferably clamp type "mosquito") and removing the implant.
5. If the implant is enclosed in a connective tissue sheath incision fabric shell is then removed and the implant surgical clip.
6. If the tip of the implant is not visible after the cut, gently injected surgical clip into the incision. Capture the implant. Clamp inverted and take in the other hand. The second clip must be carefully otseparovat tissue around the implant and take an implant. After that, the implant can be removed.
7. Be sure that the entire implant is removed (length 4 cm), measuring its length. If part of the implant (less than 4 cm in length) was removed, the remaining part has to be removed in accordance with the instruction.
8. If a woman wants to continue to use the drug Implanon NCTS ®, A new implant may be inserted immediately following the removal of the old implant, the same incision.
9. After removal of the implant incision closed with sterile strips of fabric (steristrip) and applying a label from the adhesive tape.
10. To reduce bruising impose a sterile pressure bandage. The woman may remove the pressure bandage in 24 hours and a sticker - 3-5 days.
How to replace Implanon NCTS ®
Immediate replacement can be done after removal of the previous implant, and it is similar to the introduction of the procedure described in "How to introduce Implanon NCTS ®. "The new implant can be introduced into the same place through the same incision from which the previous implant has been deleted. If the introduction of the new implant using the same incision, swipe anesthesia insertion location (e.g., 2 ml of 1% lidocaine), the introduction of directly under the skin, starting with the section to be deleted, along the "channel administration" and follow the subsequent steps for the introduction of instructions. for more information and more detailed instructions for insertion and removal of the implant can be obtained from the manufacturer of .
SIDE EFFECT

During the drug Implanon NCTS ® in women likely changes in menstrual bleeding patterns. These may include changing the frequency of bleeding (no less or more frequent), the intensity (increase or decrease) or duration of bleeding. Menstrualnopodobnoe absence of bleeding was observed in 20% of women who have the same number of women seen more frequent and / or prolonged bleeding. Sometimes it reported heavy bleeding. In clinical studies, the changing nature of vaginal bleeding was the most frequent reason for discontinuation of the implant (approximately 11%). During application of the drug Implanon NCTS ®painful menstrualnopodobnye spotting tend to improve. Bleeding patterns, which takes place during the first three months, predicts a future bleeding pattern in most women. Possibly related to the use of the drug adverse effects reported in clinical studies are listed in the table below. Their connection with the use of the drug if not confirmed, has not been refuted.
Very common (1/10?) Often (1/100, <1/10?) Uncommon (1/1000, <1/100?)
Infections and infestations
Vaginal infections (vulvovaginitis) - pharyngitis, rhinitis, urinary tract infection (urethritis , cystitis)
From the immune system

- - Hypersensitivity to any component of the preparation
part of metabolism
- increased appetite -
Mental disorders
- emotional lability, depression, anxiety, decreased libido, anxiety, insomnia
From the nervous system

headache, dizziness, headache, somnolence
Vascular disorders
- the tides -
From the digestive system

- abdominal pain, nausea, bloating, vomiting, constipation, diarrhea,
part of the skin
acne alopecia hypertrichosis, rash, pruritus
From the musculoskeletal system

- - back pain, arthralgia, myalgia, musculoskeletal pain
From the urinary system

- - dysuria
part of the reproductive system and breast
tenderness in the breast, chest pain, irregular menstruation dysmenorrhea, ovarian cyst vaginal discharge, discomfort in the vulva and vagina, galactorrhoea, breast enlargement, itching of the vulva and vagina
Local reactions and general disorder
- pain at the implant location, fatigue, influenza-like condition, pain, pyrexia, edema
Laboratory values
increase in weight reduction in body weight body -
In a clinical study further investigated disorders at the injection site, which have been observed in 8.6% of women. The most common disorder that observed during administration, or for a short period after administration, was erythema (3.3% in women). Also observed hematoma (3%), bruising (2%), pain (1%) and local edema (0.7%).
During post-marketing surveillance in rare cases, clinically significant increase in blood pressure. There are also reports of seborrhea. May develop anaphylactic reactions, urticaria and angioedema (or more severe) and / or a more severe course of hereditary angioedema. Introduction and removal of the implant may cause bruising, slight local irritation, pain or itching. In place of dissection can develop fibrosis, formed scar or develop an abscess. You may experience paresthesia or similar phenomena, and possible loss or migration of the implant.
When removing the implant may require surgical intervention.
In rare cases reported of ectopic pregnancy.
Women who use birth control pills hormonal, note the following (serious) adverse reactions:
- venous thromboembolism (VTE, deep venous thrombosis and pulmonary embolism);
- arterial thromboembolism;
- hormone-dependent tumors (liver tumors, breast cancer);
- chloasma;
- jaundice and / or pruritus related to cholestasis;
- cholelithiasis;
- porphyria;

- systemic lupus erythematosus;

- hemolytic-uremic syndrome;
- Sydenham's chorea;
- herpes during pregnancy;
- hearing loss associated with otosclerosis.
CONTRAINDICATIONS

Hormonal 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 NCTS ® should immediately stop using the product:
- pregnancy (including putative);
- thrombosis (arterial and venous) and thromboembolism currently or history (including thrombosis, deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic or hemorrhagic cerebrovascular disorders);
- the presence of antibodies to phospholipids;
- Migraine with focal neurological symptoms;
- breast cancer (including history);
- malignant or suspected hormone-dependent tumors;
- benign or malignant liver tumors currently or history;
- severe liver disease (before normalization of liver function tests), including: jaundice;
- congenital hyperbilirubinemia (including history);
uncontrolled arterial hypertension;

- childhood;

- vaginal bleeding of unknown etiology;
- increased sensitivity to the active substance or auxiliary substance any drug Implanon NCTS ® .
With caution

In the presence of any of the conditions or risk factors mentioned below, should weigh the benefits of the implants in relation to the possible risks for each individual woman and discussed with her before she decides to start using the drug Implanon NCTS ® . In case of deterioration, the gain or at the first appearance of any of these states a woman should see a doctor, then the doctor needs to decide whether to continue or cancel the use of the drug Implanon NCTS ® :
- long-term immobilization due to surgery or other causes;
- state prior thrombosis (including transient ischemic attack, angina, complicated lesions valvular atrial fibrillation, major trauma);
- resistant hypertension;
- diabetes, including diabetes with diabetic angiopathy;
- hereditary or acquired predisposition to arterial thrombosis, including protein C deficiency, protein deficiency S, deficiency of antithrombin III;
- liver disease of mild to moderate severity with normal values in liver function tests;
- anticoagulant therapy;
- severe depression.
PREGNANCY AND LACTATION

Use of the drug Implanon NCTS ® not shown in pregnancy. In case of pregnancy during use of the drug Implanon NCTS ® , the implant should be removed. When conducting preclinical studies have found that very high doses may cause progestagenic compounds masculinization female fetuses. For information on the effect of the drug Implanon NCTS ® on the body of the pregnant woman and the fetus are not sufficient.
Preparation Implanon NCTS ®It 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 the drug Implanon NCTS ®during breastfeeding is possible, but only under the supervision of a physician for the development and growth of the infant. NCTS drug Implanon ® should be administered after the 4th week after birth.
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

As a general rule, the risk of developing breast cancer increases with age. During the application of the PC (including combined) diagnosing the risk of breast cancer increases slightly. This increased risk gradually declines for 10 years after the cessation of the use of a PC, and it is not associated with the duration of use of the PC, and is associated with a woman's age, where it applies OK. Expected number of diagnosed cases of breast cancer among 10,000 women using PDAs (including over 10 years after the termination of their 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). The risk in womenapplying methods of contraception containing only progestogens may similar risk when using CPC. However, data on these methods are not so certain. Compared with the risk of breast cancer throughout the life of an increased risk of cancer associated with the PC it is small. The cases of breast cancer diagnosed in women who use PCs tend to be less symptomatic than cancer cases diagnosed in women who have never used a PC. The increased risk observed in women using a PC, it is possible due to earlier diagnosis, biological effects of the PC, or a combination of these two factors.Compared with the risk of breast cancer throughout the life of an increased risk of cancer associated with the PC it is small. The cases of breast cancer diagnosed in women who use PCs tend to be less symptomatic than cancer cases diagnosed in women who have never used a PC. The increased risk observed in women using a PC, it is possible due to earlier diagnosis, biological effects of the PC, or a combination of these two factors.Compared with the risk of breast cancer throughout the life of an increased risk of cancer associated with the PC it is small. The cases of breast cancer diagnosed in women who use PCs tend to be less symptomatic than cancer cases diagnosed in women who have never used a PC. The increased risk observed in women using a PC, it is possible due to earlier diagnosis, biological effects of the PC, or a combination of these two factors.applying a PC, it is possible due to earlier diagnosis, biological effects of the PC, or a combination of these two factors.applying a PC, it is possible due to earlier diagnosis, biological effects of the PC, or a combination of these two factors.
In the case of acute exacerbation or chronic liver disease woman should consult a specialist for examination and consultation.
Epidemiological studies have found that there is a relationship between the use of PDAs and increased incidence of venous thromboembolism (deep vein thrombosis and pulmonary embolism). Although the clinical significance of these findings with regard etonogestrel (the active metabolite of desogestrel) used as a hormonal contraceptive agents, in the absence of estrogen assembles
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