Mersilon®

Pharmacological properties of the drug Mercilon

Pharmacodynamics. The contraceptive effect of combined oral contraceptives (COCs) is based on the interaction of various factors, the most important of which is suppression of ovulation and changes in cervical secretion. In addition to preventing pregnancy, PDA promotes the regularity of the menstrual cycle, reduces its pain and intensity of bleeding (which reduces the risk of developing iron deficiency anemia). There is evidence of a reduced risk of developing endometrial and ovarian cancer, ovarian cysts, pelvic inflammatory diseases, benign breast tumors and ectopic pregnancy. Pharmacokinetics of Desogestrel After oral administration, desogestrel is rapidly and completely absorbed and converted to etonogestrel. The maximum concentration of etonogestrel in blood plasma (on average 2 ng/ml) is achieved 1.5 hours after taking a single dose. Bioavailability is 62–81%. Etonogestrel binds to serum albumin and sex hormone binding globulin (SHBG). Only 2–4% of the total serum concentration is present as free steroid, and 40–70% is specifically associated with SHBG. The increase in SHBG content caused by ethinyl estradiol affects its distribution between serum proteins, contributes to an increase in the SHBG-bound fraction and a decrease in the albumin-bound fraction. The expected volume of distribution of desogestrel is 1.5 l/kg. Etonogestrel is completely metabolized similarly to other steroids. The rate of elimination of metabolites from blood plasma is about 2 ml/min/kg. No interactions with concomitantly taken ethinyl estradiol have been identified. The concentration of etonogestrel in the blood plasma decreases in 2 stages. The half-life at the last stage is 30 hours. Desogestrel and its metabolites are excreted in urine and bile in a ratio of 6:4. The pharmacokinetics of etonogestrel is affected by the level of SHBG, which increases 3 times under the influence of ethinyl estradiol. After daily administration, the level of the drug in the blood serum increases approximately 2-3 times, reaching a stable concentration in the second half of the period of drug administration. Ethinyl estradiol After oral administration, ethinyl estradiol is rapidly and completely absorbed. The maximum level of concentration in blood plasma is reached within 1–2 hours and is 80 pg/ml. Absolute bioavailability as a result of first-pass metabolism is 60%. Ethinyl estradiol has a strong but nonspecific binding to serum albumin (approximately 98.5%) and increases serum SHBG concentrations. The expected volume of distribution is 5 l/kg. Presystemic conjugation of ethinyl estradiol occurs both in the mucous membrane of the small intestine and in the liver. Ethinyl estradiol is first metabolized by aromatic hydroxylation to form a large number of hydroxylated and methylated metabolites, present both in free form and in combination with glucuronides and sulfates. The rate of metabolic clearance is 5 ml/min/kg. The level of ethinyl estradiol in the blood plasma decreases in 2 stages. The half-life at the last stage is about 24 hours. Ethinyl estradiol is not excreted unchanged; excretion of ethinyl estradiol metabolites occurs in urine and bile in a ratio of 4:6. The half-life of metabolites is 24 hours. Equilibrium concentrations are reached after 3-4 days, when the serum level is 30-40% higher than the concentration compared to a single dose.

Use of the drug Mercilon

1. General rules for taking Mercilon: Take 1 tablet per day at the same time every day for 21 days in the sequence indicated on the package. The tablets are swallowed without chewing, washed down with water if necessary. This is followed by a 7-day pill-free period (pill-free period). During this period, a menstrual-like reaction (withdrawal bleeding) occurs, which may be longer and less intense than normal menstruation. As a rule, it begins on the 2-3rd day after taking the last tablet and can continue until the start of taking tablets from the next pack. After 7 days without pills, start taking pills from the next package.

2. Start taking Mercilon If hormonal contraceptives were not used in the previous month , take the pills starting on the 1st day of menstrual bleeding. You can start taking it from days 2–5, but in this case, during the first 7 days of the first cycle of taking pills, it is recommended to additionally use a barrier method of contraception. When switching from another combined oral contraceptive, taking Mercilon should be started the day after taking the last active tablet of the previous COC or the day after a break in taking tablets. Switching from progestogen-only medications (mini-pill, implant, or injection) or from a progestogen-releasing intrauterine device can begin any day after stopping their use (in the case of an implant, on the day of its removal, in the case of an injection - instead of the next injection). In all of these cases, you should additionally use a barrier method of contraception during the first 7 days of taking the pills. You can start taking Mercilon immediately after an abortion in the first trimester. In this case, there is no need to use additional contraception. After childbirth or abortion in the second trimester, it is recommended to start taking Mercilon from the 21st or 28th day (during the 4th week). If you start taking the pills later, it is recommended to additionally use a barrier method of contraception during the first 7 days of taking the pills. If there were sexual contacts during this period, then before starting to use the PDA, you should exclude pregnancy or wait until your next menstruation.

3. What to do if you miss taking pills If the delay in taking the pill does not exceed 12 hours, the contraceptive effect of Mercilon will continue throughout the entire period of taking the drug. If for some reason a woman forgets to take a Mercilon tablet, it must be taken as soon as she finds out. In the future, taking tablets from this pack should continue as usual. If the delay in taking the pill exceeds 12 hours, the contraceptive effect may decrease. If you miss taking pills, you can follow 2 basic rules:

• never stop taking pills for more than 7 days;
• To achieve an adequate inhibitory effect of the drug on the hypothalamus-pituitary-ovarian axis, continuous use of the drug is required for 7 days.

In accordance with this, it is recommended to follow these tips. First week A woman should take the last missed pill as soon as she remembers the omission, even if she has to take 2 pills at the same time. She then continues to take the pills at the usual time. In addition, you must use a barrier method of contraception for the next 7 days. If you have had sexual intercourse within the previous 7 days, you should consider the possibility of pregnancy. The more pills you miss and the closer the missed pills are to the usual “pill-free” period, the higher the risk of pregnancy. Second week A woman should take the last missed pill as soon as she remembers, even if she has to take 2 pills at the same time. She then continues to take the pills at the usual time. If a woman has taken the pills correctly for 7 days before the missed pill, there is no need to use additional contraceptive measures. Otherwise, or if you miss more than 1 tablet, you should additionally use a barrier method of contraception for 7 days. Third week The risk of decreased contraceptive reliability increases as the break in taking pills approaches. However, if you follow the pill regimen, you can avoid a decrease in the level of contraception. If you adhere to one of the rules below, there will be no need to use additional contraceptives, provided that the woman took the pills correctly for 7 days before the missed pill. If not, then the woman should adhere to the first of the rules below and use additional methods of protection over the next 7 days. A woman should take the last missed pill as soon as she remembers, even if she has to take 2 pills at the same time. She then continues to take the pills at the usual time. Tablets from the next package should be started immediately after the previous one has ended, that is, there should be no break between taking tablets from different packages. It is unlikely that a woman will experience menstrual bleeding before finishing the second pack of tablets, although spotting or sudden bleeding may occur while taking the tablets. The woman may also be advised to stop taking the tablets in the current pack. In this case, the break should be 7 days, including days of missing pills; You should start taking the pills with the next pack. If a woman misses taking pills and does not have menstrual bleeding during the first regular break in taking the drug, pregnancy should be assumed.

4. Recommendations in case of vomiting If vomiting occurs within 3-4 hours after taking the tablet, then incomplete absorption of the drug may occur, which requires additional contraceptive measures. In this case, it is advisable to follow the recommendations regarding skipping pills. If a woman does not want to change her usual regimen of taking the drug, she needs to take an additional tablet from a different package.

5. How to change or delay the onset of menstruation To delay the onset of menstruation, a woman should continue taking Mercilon from a new package and not take a break. If desired, the period of administration can be extended until the completion of taking the tablets from the second package. In this case, sudden short-term bleeding or spotting may occur. Regular use of Mercilon is resumed after the usual 7-day break from taking pills. In order to change the timing of menstruation - move its onset to another day of the week, a woman can be advised to shorten the period without taking pills by the required number of days. The shorter this period, the greater the likelihood of no withdrawal bleeding and the occurrence of spotting or short-term bleeding while taking the next package (as with a delay in menstruation).

Contraindications to the use of the drug Mercilon

The use of combined contraceptives is contraindicated in any of the following conditions . If any of these conditions occur when using combined contraceptives for the first time, the drug should be stopped immediately: venous or arterial thrombosis/thromboembolism (current or in history); precursors of thrombosis (present or in history); cerebrovascular accident; angina pectoris; migraine with focal neurological symptoms; diabetes mellitus with vascular complications; risk factors for thrombosis (current presence or history); pancreatitis or previous pancreatitis with high hypertriglyceridemia; liver disease (until normalization of functional parameters); liver tumor (benign or malignant; present or in history); hormone-dependent malignant tumors (diagnosed and suspected); vaginal bleeding of unknown etiology; diagnosed or suspected pregnancy; hypersensitivity to any component of the drug. Use with caution in case of obesity (body mass index 30 kg/m2); AH (arterial hypertension); atrial fibrillation; heart valve diseases; dyslipoproteinemia; diseases of the liver and gall bladder; Crohn's disease and ulcerative colitis; sickle cell anemia; systemic lupus erythematosus; hemolytic uremic syndrome; epilepsy; smoking over the age of 35; prolonged immobilization; significant surgical interventions; fibrocystic mastopathy; uterine fibroids; diabetes mellitus; congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndrome); chloasmus (women prone to pigmentation should avoid exposure to the sun or ultraviolet radiation when taking COCs).

Side effects of the drug Mercilon

COC use is associated with an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism. These symptoms are rare. The use of any COC is associated with an increased risk of venous thromboembolism (VTE), which manifests itself in the form of deep venous thrombosis and/or pulmonary embolism, especially in the first year of use by a woman of a COC. Very rarely, thrombosis has been reported to occur in other blood vessels, such as the hepatic, mesenteric, renal, cerebral or retinal veins and arteries in women using COCs. Some epidemiological studies have shown that long-term use of COCs may further contribute to persistent human papillomavirus infection and an increased risk of cervical cancer. There is a negligible relative risk of developing breast cancer diagnosed in women who are currently taking COCs. Excessive risk gradually disappears over 10 years after discontinuation of COC use. Benign liver tumors and very rarely malignant liver tumors have been reported in rare cases in women who take COCs. In isolated cases, these tumors have led to life-threatening intra-abdominal bleeding. When using COCs in women with hypertriglyceridemia or a family history of it, there may be an increased risk of developing pancreatitis. The occurrence or worsening of conditions such as jaundice and/or itching associated with cholestasis has been reported; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes in pregnant women; hearing loss associated with otosclerosis, but there is no convincing evidence regarding an association with COC use. Crohn's disease and ulcerative colitis have been associated with COC use. Chloasma may occur periodically, especially in women with a history of chloasma during pregnancy. Other side effects have been reported in women taking COCs, but the relationship has not been confirmed or refuted (1)

1 The most appropriate MedDRA term (version 6.1) to describe the specific adverse reaction. Synonyms or similar conditions are not listed but should also be taken into account.

Mercilon tablets No. 21

Epidemiological studies have found that there may be an association between the use of COCs and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism. These diseases are extremely rare. The use of any COC is associated with an increased risk of venous thromboembolism (VTE), manifested as deep vein thrombosis and/or pulmonary embolism. The risk is higher in the first year of use than in women taking COCs for more than 1 year.

Some epidemiological studies show that women who took low-dose COCs containing third-generation progestins, including desogestrel, have an increased risk of VTE compared with those women who took low-dose COCs containing the progestin levonorgestrel.

Very rarely, thrombosis occurs in other blood vessels (for example, in the veins and arteries of the liver, mesentery, kidney, brain or retina). There is no consensus on whether this thrombosis is a consequence of the use of COCs.

An increase in the frequency and intensity of migraines while taking Mercilon® (which may be a sign of cerebrovascular disorders) may be grounds for immediate discontinuation of the drug. Tumors

The most important risk factor for developing cervical cancer is persistence of human papillomavirus (HPV infection). Epidemiological studies have shown an increased risk of cervical cancer in women who use COCs for a long time, however, there is still uncertainty about the extent to which this data is influenced by confounding factors, such as an increase in cervical screening examinations and differences in sexual behavior, including the use of barrier methods contraception, or their relationship.

There is evidence that there is a small increase in the relative risk (1.24) of developing breast cancer in women using COCs. The increased risk gradually decreases over 10 years after discontinuation of COCs. Because breast cancer is quite rare in women under 40 years of age, the increase in the likelihood of developing breast cancer in women who are currently using COCs or have recently stopped using them is small relative to the initial likelihood of developing breast cancer. These studies do not provide data on the etiology of cancer. The increased risk of breast cancer may be explained either by the earlier diagnosis of breast cancer in women taking COCs, by the biological effects of COCs, or by a combination of both. There is a trend that women who have ever taken COCs have less clinically advanced breast cancer than women who have never taken COCs.

Very rarely, when using the drug Mercilon®, cases of the development of benign, and even more rarely, malignant liver tumors were observed. In some cases, these tumors have led to life-threatening intra-abdominal bleeding. A physician should consider the possibility of a liver tumor in the differential diagnosis of diseases in a woman taking Mercilon® if symptoms include acute pain in the upper abdomen, liver enlargement, or signs of intra-abdominal bleeding. Other diseases

If a woman or her family members are diagnosed with hypertriglyceridemia, then the risk of pancreatitis may increase when taking Mercilon®.

If a woman using Mercilon® develops persistent clinically significant hypertension, the physician should discontinue Mercilon® and prescribe treatment for hypertension. In cases where antihypertensive therapy can achieve normal blood pressure values, the doctor may consider it possible for the patient to resume taking the drug.

There are reports that jaundice and/or itching caused by cholestasis; formation of gallstones, porphyria, systemic lupus erythematosus, hemolytic-uremic syndrome, Sydenham's chorea (minor chorea), herpes of pregnancy, hearing loss due to otosclerosis, (hereditary) angioedema develop or worsen both during pregnancy and when taking Mercilon ®, however, the evidence for this as it relates to taking Mercilon® is inconclusive.

Acute or chronic liver dysfunction may warrant discontinuation of Mercilon® until liver function tests return to normal. Recurrence of cholestatic jaundice, previously observed during pregnancy or when using sex steroids, requires discontinuation of the drug Mercilon®.

Although Mercilon® may affect peripheral tissue tolerance to insulin and glucose, there is no evidence that patients with diabetes mellitus need to change their therapeutic regimen for taking low-dose COCs (containing less than 0.05 mg ethinyl estradiol). In any case, women with diabetes should be carefully monitored by a doctor while taking Mercilon®.

There is evidence that there is a connection between taking COCs and Crohn's disease and ulcerative colitis.

Sometimes, when taking Mercilon®, pigmentation of the facial skin (chloasma) may occur, especially if it occurred earlier during pregnancy. Women with a predisposition to chloasma should avoid direct sunlight and ultraviolet radiation from other sources while taking Mercilon®. Medical examinations/consultations Before starting or resuming use of Mercilon®, a woman should obtain a detailed medical history (including family history) and conduct a thorough examination. Blood pressure should be measured and if clinically significant signs are detected, a physical examination should be performed, guided by contraindications and precautions. The woman should be instructed to carefully read these instructions for use and adhere to the recommendations. The frequency and list of examinations should be based on generally accepted practice and selected individually for each woman (but at least once every 6 months). The woman should be advised that oral contraceptives do not protect against HIV (AIDS) and other sexually transmitted infections. Reduced effectiveness The effectiveness of Mercilon® may be reduced if a dose is missed, gastrointestinal disorders, or when taking certain medications concomitantly (see section “Interactions with other drugs”). Irregular bleeding When taking Mercilon®, especially in the first months of use, irregular spotting or heavy bleeding may occur. Therefore, assessment of irregular bleeding should be carried out only after the end of the adaptation period, lasting three months. If irregular bleeding persists or appears after previous regular cycles, possible non-hormonal causes of cycle disruption should be taken into account and appropriate studies should be carried out to exclude malignant neoplasms or pregnancy. These measures may include diagnostic curettage. Some women may not experience menstrual bleeding during the interval between taking the drug. If Mercilon® is taken as recommended above, the likelihood that the woman is pregnant is low. Otherwise, or if there is no bleeding two times in a row, you should exclude the possibility of pregnancy and consult a doctor. Laboratory tests Oral contraceptives may affect the results of some laboratory tests, including biochemical indicators of liver, thyroid, adrenal and kidney function, plasma transport proteins, for example, corticosteroid binding globulin and lipid/lipoprotein fractions, parameters of carbohydrate metabolism, coagulation parameters and fibrinolysis. Usually these changes are within normal laboratory values. Lactose Each Mercilon® tablet contains less than 80 mg of lactose. Women with rare hereditary disorders, such as lactose intolerance, lactase deficiency, glucose-galactose malabsorption, who follow a lactose-free diet, should take into account the lactose content in Mercilon®.

Effect on the ability to drive a car and operate other mechanisms. The effect of the drug Mercilon® on the ability to drive a car and operate machinery has not been noted.

Special instructions for the use of Mercilon

The daily dose of lactose contained in the tablet is so low (≤80 mg) that even lactose-sensitive women will not experience any disturbances. Caution: If any of the conditions/risk factors listed in the CONTRAINDICATIONS section are present, the benefits and risks of using COCs should be considered by a physician individually for each woman and discussed with the patient before she decides to take this drug. In case of exacerbation, intensification or the first appearance of any of these conditions, a woman should consult a doctor. Your doctor must determine whether you should continue or stop taking the COC.

Circulatory disorders

• Epidemiological studies have suggested an association between COC use and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism. These symptoms are rare.
• The use of any COC is associated with an increased risk of venous thromboembolism (VTE), which manifests itself in the form of deep venous thrombosis and/or pulmonary embolism. In the first year of a woman's use of PDAs, the risk is highest.
• Some epidemiological studies suggest that women who take low-dose COCs with third-generation progestogens, including desogestrel, have an increased risk of developing VTE compared with women who take low-dose COCs with the progestogen levonorgestrel. These studies indicate an approximately two-fold increase in risk, which corresponds to an additional 1-2 cases of VTE per 10,000 women/years of use. However, data from other studies did not show this two-fold increase in risk.
• In general, the incidence of VTE in individuals using OCs with low doses of estrogen (≤0.05 mg ethinyl estradiol) is thought to be up to 4 per 10,000 women/years, compared with 0.5–3 per 10,000 women/years in non-PC users. The incidence of VTE that occurs during COC use is less than that associated with pregnancy (ie, 6 per 10,000 pregnant women/years).
• Very rarely, thrombosis has been reported to occur in other blood vessels, such as the hepatic, mesenteric, renal, cerebral or retinal veins and arteries in women using COCs. There is no general agreement as to whether these cases are related to the use of COCs.
• Symptoms of venous or arterial thrombotic/thromboembolic events or cerebrovascular disorders may include: unilateral leg pain and/or swelling; sudden severe pain in the chest, regardless of whether it radiates to the left arm; sudden dyspnea; sudden attack of coughing; any unusual, severe or prolonged headache; sudden partial or complete loss of vision; diplopia; slurred speech or aphasia; vertigo; collapse with/without focal epileptic seizure; weakness or severe numbness on one side or part of the body; movement disorder; "acute" stomach.
• The risk of venous or arterial thrombotic/thromboembolic events or cerebrovascular events increases due to: age; smoking (with more intense smoking and with age, the risk increases, especially in women over 35 years of age); relevant family history (i.e., the presence of venous or arterial thromboembolism in siblings or parents at a relatively early age). If there is a suspicion of a hereditary predisposition, the woman should be referred to a specialist for consultation before making a decision regarding taking COCs; obesity (body mass index over 30 kg/m2); dyslipoproteinemia; high blood pressure; migraine; heart valve disease; atrial fibrillation; prolonged immobilization, major surgery, any surgery on the lower extremities or severe trauma. In such situations, it is recommended to stop taking the COC (in the case of elective surgery, at least four weeks in advance) and not reintroduce it for two weeks after complete remobilization.
• There is no agreement regarding the possible role of venous varicose veins and superficial thrombophlebitis in venous thromboembolism.
• The increased risk of thromboembolism in the postpartum period should be considered (see section "Use during pregnancy or lactation").
• Other medical conditions that have been associated with adverse circulatory effects include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease and ulcerative colitis), and sickle cell anemia.
• An increase in the frequency or intensity of migraine while taking COCs (which may precede cerebrovascular accident) may be a reason to immediately stop taking COCs.
• Biochemical factors that may indicate an inherited or acquired predisposition to venous or arterial thrombosis include activated protein C (APC) resistance, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
• When considering the risks and benefits, the physician should consider that adequate treatment of the condition may reduce the risk of thrombosis and that the risk associated with pregnancy is greater than the risk associated with low doses of COCs (≤ 0.05 mg ethinyl estradiol).

Tumors

• The highest risk factor for cervical cancer is persistent infection with human papillomavirus (HPV). Some epidemiological studies have suggested that long-term COC use may further contribute to this increased risk, but the extent to which this finding relates to confounding effects such as cervical screening and sexual behavior, including barrier contraceptive use, is unknown.
• A meta-analysis of 54 epidemiological studies found that there was a slightly increased relative risk (RR = 1.24) of developing breast cancer diagnosed in women who were currently taking COCs. Excessive risk gradually disappears over 10 years after discontinuation of COC use. Because breast cancer rarely occurs in women under 40 years of age, the number of breast cancer diagnoses in women who are former or current users of COCs is small compared to the overall risk of breast cancer. These studies do not provide evidence of causation. An increased risk may occur as a result of early breast cancer diagnosis in women who take COCs, the biological effects of COCs, or a combination of both. Breast cancer diagnosed in women who have ever used COCs usually progresses less clinically than cancer diagnosed in women who have never used COCs.
• Benign liver tumors and very rarely malignant liver tumors have been reported in rare cases in women who take COCs. In isolated cases, these tumors have led to life-threatening intra-abdominal bleeding. If women who take COCs experience severe pain in the upper abdomen, liver enlargement, or signs of intra-abdominal bleeding, it is necessary to differentiate a liver tumor.

Other states

• When using COCs in women with hypertriglyceridemia or a family history of it, there may be an increased risk of developing pancreatitis.
• Although slight increases in blood pressure have been reported in many women who take COCs, clinically significant increases are rare. However, if prolonged clinically significant hypertension develops while taking a COC, the physician should prohibit the use of the COC and treat the hypertension. The use of COCs can be resumed if blood pressure is normalized with antihypertensive therapy.
• The occurrence or worsening of conditions such as jaundice and/or pruritus associated with cholestasis have been reported; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes in pregnant women; hearing loss associated with otosclerosis. These symptoms are associated with both pregnancy and COC use, but there is no convincing evidence regarding a connection with COC use.
• Acute or chronic liver dysfunction may require discontinuation of COCs until liver function tests return to normal. Recurrence of cholestatic jaundice, which first occurred during pregnancy or previous use of sex steroids, requires discontinuation of COC use.
• Although COCs may influence peripheral insulin resistance and impaired glucose tolerance, there is no need to alter treatment regimens in diabetic patients taking low doses of COCs (containing ≤ 0.05 mg ethinyl estradiol). However, women with diabetes must be carefully monitored while using COCs.
• Chloasma may occur periodically, especially in women with a history of chloasma during pregnancy. Women with a tendency to chloasma are advised to avoid exposure to the sun or ultraviolet radiation while taking COCs.

Medical examination/consultation Before starting or resuming oral use of combined contraceptives, a thorough medical examination of the woman should be performed, including obtaining a full medical history and performing instrumental studies, paying particular attention to possible contraindications. Such an examination must be repeated at least once a year during the entire period of taking combined contraceptives. Periodic medical evaluation is important regarding contraindications (for example, cerebrovascular accidents) or risk factors (for example, a family history of venous or arterial thrombosis) that may first appear while taking contraceptives. The frequency and nature of such examinations are determined for each woman individually, but in general they should include blood pressure measurement, examination of the mammary glands, abdominal and pelvic organs, cytological examination of the cervical epithelium and relevant laboratory tests. It is necessary to explain to women that oral contraceptives do not protect against HIV/AIDS and other sexually transmitted diseases. Decreased effectiveness The effectiveness of COCs may be reduced if tablets are missed (see APPLICATION), gastrointestinal disorders, or if certain medications are taken at the same time (see INTERACTIONS). Deterioration of control of the menstrual cycle While using COCs, irregular minor (spotting) or heavy bleeding may occur, especially during the first months of use. Therefore, assessment of any disturbances in menstrual cycle control can only be made after an adaptation period of approximately 3 cycles. If irregular bleeding persists or occurs after previous regular cycles, probable non-hormonal causes should be considered and the necessary diagnostic tests should be performed to exclude pregnancy or a tumor; curettage is possible. Some women may not experience withdrawal bleeding during the pill-free interval. If PDAs were used according to recommendations, then the possibility of pregnancy is low. However, if there has been a violation of these recommendations in the period before the first absence of bleeding during the period without taking pills, or if there is no bleeding twice in a row, the possibility of pregnancy should be excluded before continuing to take the COC. Use of the drug during pregnancy and/or breastfeeding. Pregnancy is a contraindication for the use of Mercilon. If a woman becomes pregnant while taking Mercilon, further use should be stopped immediately. Studies have shown neither an increased risk of pathology in children born to mothers who took COCs before pregnancy, nor a teratogenic effect from COCs that were unintentionally taken early in pregnancy. Lactation is influenced by estrogens because they can reduce the quantity and change the composition of breast milk, but there has been no evidence of a negative effect on the health of infants. However, it is not recommended to use COCs during breastfeeding; if necessary, the use of COCs should be completely stopped while breastfeeding. Impact on the ability to drive vehicles. Does not affect the ability to concentrate.

Mercilon®

If any of the following conditions/diseases/risk factors are present, a careful assessment of the benefit-risk ratio of the use of COCs should be carried out. This issue should be discussed with the woman before starting the drug. In case of exacerbation of diseases, deterioration of condition, or the appearance of the first symptoms of conditions/diseases or risk factors, a woman should immediately consult a doctor to decide whether to stop taking the drug. In this section, the term CHC is used when data are available for both oral and non-oral contraceptives; the term COC is used when data is available only for oral contraceptives.

Risk of developing VTE and ATE

- Epidemiological studies have established an association between the use of CHCs and an increased risk of arterial and venous thrombosis and thromboembolism, such as myocardial infarction, stroke, DVT and PE. These diseases are extremely rare.

- The use of any CHC is associated with an increased risk of developing VTE, manifested as DVT and/or PE. The greatest risk of developing VTE is observed in the first year of CHC use. An increased risk of developing this complication is also observed when the use of CHCs is resumed after a break of 4 weeks or more.

- The use of drugs containing levonorgestrel, norgestimate or norethisterone as a progestogen is associated with the lowest risk of developing VTE. The use of low-dose COCs containing third-generation progestogens, including desogestrel, may double the risk of developing VTE. The incidence of VTE within 1 year in women taking COCs containing desogestrel ranges from 9 to 12 cases; those containing levonorgestrel - 6-7 cases per 10,000 women. In women who do not use COCs, the incidence of VTE is 2 cases per 10,000 women. The incidence of VTE with the use of COCs is lower than the incidence of this complication during pregnancy and the postpartum period. VTE can be fatal in 1-2% of cases.

- It is extremely rare that when taking COCs, thrombosis occurs in other blood vessels (for example, in the veins and arteries of the liver, mesentery, kidneys, brain or retina).

— Symptoms of VTE, ATE or acute cerebrovascular accident may include: sudden pain and/or swelling of the lower extremity; sudden intense chest pain, with or without radiation to the left arm; sudden shortness of breath; sudden cough; unusually severe or prolonged headache; sudden partial or complete loss of vision; diplopia; speech impairment or aphasia; dizziness; collapse with or without convulsive attack; weakness or severe numbness that suddenly appears on one side of the body; movement disorders; "acute belly"

— The risk of developing VTE increases with the presence of the following risk factors:

• age;
• obesity (BMI >30 kg/m2);
• a family history of venous or arterial thrombosis, or thromboembolism in brothers, sisters or parents under the age of 50 years (if a hereditary predisposition is suspected, you should consult a specialist before starting to take CHC);
• prolonged immobilization, major surgery, any surgery on the lower extremities, pelvis or neurosurgery, or major trauma. In these cases, you should stop taking the COC (at least 4 weeks before planned surgery) and resume it only 2 weeks after the woman has fully recovered her mobility (see also section “Contraindications”);
• temporary immobilization, including air travel lasting more than 4 hours, is also a risk factor for the development of VTE, especially in women with other risk factors;
• the possible role of varicose veins and superficial thrombophlebitis in the development of VTE remains controversial.

— The risk of developing ATE increases in the presence of the following risk factors:

• age;
• smoking (the risk increases even more with heavy smoking, especially in women over 35 years of age);
• dyslipoproteinemia;
• obesity (BMI >30 kg/m2);
• arterial hypertension;
• migraine;
• heart valve disease;
• atrial fibrillation;
• a family history of venous or arterial thrombosis, or thromboembolism in brothers, sisters or parents under the age of 50 years (if a hereditary predisposition is suspected, a specialist should be consulted before starting CHC use).

— It is necessary to take into account the increased risk of thromboembolism in the postpartum period.

— Other conditions/diseases that cause poor circulation include: diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (eg, Crohn's disease or ulcerative colitis), and sickle cell anemia.

— An increase in the frequency or intensity of migraine (which may be a prodromal symptom of cerebrovascular accidents) while taking a COC is grounds for immediate discontinuation of its use.

- Biochemical factors that may indicate hereditary or acquired predisposition to VTE or ATE include activated protein C resistance, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

— When assessing the benefit/risk ratio, it should be taken into account that therapy for these conditions/diseases can reduce the associated risk of thrombosis.

Tumors

— The most important risk factor for the development of cervical cancer (CC) is persistent human papillomavirus infection (HPV). Epidemiological studies show an increased risk of developing cervical cancer in women infected with HPV and long-term users of COCs (>5 years), however, there is still controversy regarding the degree to which these data are influenced by various factors, in particular, cervical screening examinations or characteristics of a woman’s sexual behavior ( number of sexual partners and the use of barrier methods of contraception), as well as the cause-and-effect relationship of these factors.

— According to a meta-analysis of the results of 54 epidemiological studies, a slight increase (1.24) in the risk of developing breast cancer (BC) in women using COCs was identified. The increased risk gradually decreases over 10 years after discontinuation of COCs. Due to the fact that breast cancer is rare in women under 40 years of age, the increase in the incidence of breast cancer in women who are currently or recently taking COCs is small relative to the overall risk of developing this disease.

— The connection between breast cancer and COC use has not been proven. The observed increased risk may be a consequence of earlier diagnosis of breast cancer in women taking COCs (they are diagnosed with earlier clinical forms of breast cancer than women not taking COCs), the biological effects of COCs, or a combination of both.

- Very rarely, when using COCs, cases of the development of benign, and even more rarely, malignant liver tumors were observed. In some cases, these tumors have led to life-threatening intra-abdominal bleeding. In case of severe abdominal pain, liver enlargement or signs of intra-abdominal bleeding, this should be taken into account when making a differential diagnosis.

Hepatitis C

In clinical studies of patients receiving hepatitis C virus therapy with drugs containing ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin, increases in ALT levels greater than 5 times the upper limit of normal were observed significantly more often in women using ethinyl estradiol-containing drugs. drugs such as CHCs. Taking Mercilon® should be discontinued before starting antiviral therapy and can be resumed 2 weeks after completion of therapy with these antiviral drugs.

Other states

- Women with hypertriglyceridemia or a corresponding family history have an increased risk of developing pancreatitis when taking COCs.

- Many women taking COCs experienced a slight increase in blood pressure (BP), but clinically significant increases in BP were rare. The connection between taking COCs and arterial hypertension has not been established. However, if persistent arterial hypertension develops while taking COCs, then it is advisable to stop taking COCs and prescribe antihypertensive therapy. With adequate blood pressure control using antihypertensive drugs, it is possible to resume taking COCs.

— During pregnancy and during the use of COCs, the development or worsening of the following conditions was noted, although their relationship with the use of contraceptives has not been definitively established: jaundice and/or itching caused by cholestasis, formation of gallstones, porphyria, systemic lupus erythematosus, hemolytic uremic syndrome, Sydenham's chorea (minor chorea), gestational herpes, hearing loss due to otosclerosis, hereditary angioedema.

— Acute or chronic liver dysfunction may warrant discontinuation of COCs until liver function tests return to normal. Recurrence of cholestatic jaundice, previously observed during pregnancy or when using sex hormones, requires discontinuation of COCs.

— Despite the fact that COCs can have an effect on insulin resistance and glucose tolerance, there is usually no need to adjust the dose of hypoglycemic drugs in patients with diabetes mellitus taking COCs. However, patients with diabetes mellitus should be under close medical supervision while taking COCs.

— There is evidence that there is a connection between taking COCs and Crohn's disease and ulcerative colitis.

- Sometimes, when taking COCs, pigmentation of the facial skin (chloasma) may occur, especially if it occurred earlier during pregnancy. Women with a predisposition to chloasma should avoid direct sunlight and ultraviolet radiation from other sources when taking COCs.

— 1 tablet of Mercilon® contains less than 80 mg of lactose. The drug is contraindicated for women with rare hereditary diseases associated with lactase deficiency, lactose intolerance, glucose-galactose malabsorption, and those on a lactose-free diet.

All of the above information should be taken into account when choosing a contraceptive method. Medical examinations/consultations

Before prescribing or resuming the use of the drug Mercilon®, you should carefully familiarize yourself with the woman’s life history (including family history), conduct a thorough general medical examination (including measuring blood pressure and determining body mass index) and gynecological examination (with mandatory examination of the mammary glands and cytological examination of a vaginal smear). and cervix), exclude pregnancy. The volume of additional studies and the frequency of control examinations are determined individually; control examinations should be carried out at least once every 6 months. It is important to draw a woman's attention to the risk of developing venous and arterial thrombosis, including the risk of using Mercilon® in comparison with other CHCs, symptoms and known risk factors for the development of VTE and ATE, and what to do if thrombosis is suspected.

The woman should be advised that oral contraceptives do not protect against HIV (AIDS) and other sexually transmitted infections.

Reduced efficiency

The effectiveness of Mercilon® may be reduced if you miss pills, have gastrointestinal disorders, or take concomitant medications that reduce the concentration of the active metabolite of desogestrel (etonogestrel) in the blood plasma. Herbal preparations containing St. John's wort ( Hypericum perforatum

), should not be used simultaneously with Mercilon® due to the risk of reducing the concentration of etonogestrel and the contraceptive effectiveness of the drug (see sections “Method of administration and dosage” and “Interaction with other drugs”).

Insufficient cycle control

When taking COCs, especially in the first months of use, irregular spotting or heavy bleeding may occur, so assessment of irregular bleeding should be carried out only after the end of the adaptation period of three months.

If irregular bleeding persists or appears after previous regular cycles, possible non-hormonal causes of cycle disruption should be taken into account and appropriate studies should be carried out to exclude malignant neoplasms or pregnancy. Diagnostic curettage of the cavity and cervical canal of the uterus may be required.

Some women may not experience menstrual bleeding during the interval between taking the drug. If the COC was taken as recommended above, there is little chance that the woman is pregnant. Otherwise, or if there is no bleeding twice in a row, the possibility of pregnancy should be excluded before continuing to use the COC.

Laboratory research

Oral contraceptives may affect the results of some laboratory tests, including biochemical indicators of liver, thyroid, adrenal and kidney function, the content of transport proteins in plasma, for example, corticosteroid binding globulin (CBG) and lipid/lipoprotein fractions, parameters of carbohydrate metabolism, coagulation parameters and fibrinolysis. Usually these changes are within normal laboratory values.

Interactions of the drug Mercilon

Interactions between oral contraceptives and other drugs can lead to sudden bleeding and a decrease in the contraceptive effect of the drug. Interactions may occur with drugs that induce microsomal enzymes, which can lead to increased metabolism of sex hormones. These drugs include phenytoin, barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and preparations containing St. John's wort. The effectiveness of the drug may also be reduced if certain antibiotics are taken concomitantly, such as penicillins and tetracyclines. These drugs reduce the enterohepatic circulation of estrogens, which leads to a decrease in ethinyl estradiol concentrations. Women taking any of these drugs should temporarily use a barrier method of contraception in addition to POCs or choose another method to protect against unwanted pregnancy. Women taking antibiotics (except rifampicin and griseofulvin) need to use a barrier method while taking the corresponding drug and for 7 days after its discontinuation. When taking drugs that stimulate microsomal enzymes, it is necessary to use a barrier method in addition to COCs throughout the entire period of treatment and for another 28 days after stopping treatment. If the administration of the drug must be continued, and the tablets in the CCP pack have already run out, the next pack should be started immediately, without the usual break. COCs may affect the metabolism of other drugs. Accordingly, the concentration of such drugs (for example, cyclosporine) in the blood plasma and tissues may change. Note. To determine possible interactions, information regarding the prescription of the drug that is used in parallel should be reviewed. Laboratory tests. Contraceptive steroids may affect the results of certain laboratory tests, including biochemical indicators of liver, kidney, thyroid, adrenal function, serum levels of proteins (transporters), such as corticosteroid binding globulin and/or lipid/lipoprotein fractions, indicators of carbohydrate metabolism, coagulation and fibrinolysis. Changes usually remain within the normal range.

Mercilon

The first microdose combined oral contraceptive based on desogestrel and ethinyl estradiol. The contraceptive effect is achieved by suppressing ovulation, affecting cervical mucus and changing the endometrium.

Reception scheme

Taking Mercilon begins on the first day of menstruation. One tablet is taken every day, it is advisable to stick to the same time. The period of administration is 21 days, according to the number of tablets in the package. This is followed by a week-long break, during which menstrual-like bleeding occurs. A week later, you begin taking tablets from the next package of Mercilon.

After an abortion, taking the drug should be started immediately, that is, on the same day.

After childbirth, in the absence of breastfeeding, administration begins on the 21st day. If this particular day is missed, then you can start taking Marvelon on any subsequent day, but you must rule out pregnancy and use barrier methods of birth control for a week.

The manufacturer of Mercilon does not provide a clear list of side effects that may occur. You can get acquainted with the side effects of other low-dose oral contraceptives on our website.

Contraindications may include:

• Cardio- or cerebrovascular disorders or their consequences;
• severe hypertension;
• liver dysfunction;
• vaginal bleeding of unknown etiology;
• endometrial hyperplasia;
• porphyria;
• hyperlipoproteinemia

[[see_also_3]]

Mercilon should not be taken during pregnancy and breastfeeding. It is not recommended for smoking women over 35 years of age.

The effectiveness of Mercilon can be reduced when taking a number of medications, including: barbiturates, antibiotics (in particular, tetracycline, rifampicin), activated charcoal, laxatives.

In the case of planned surgery or severe injury that leads to temporary severe limitation in physical activity, the drug should be discontinued.

If a woman has chloasma, then while taking Mercilon she needs to limit her exposure to the sun.

If you are taking the drug for a long time, preventive examinations by a gynecologist should be carried out 2-3 times a year.

With extreme caution and close monitoring, Mercilon should be taken for the following diseases:

• heart failure,
• renal dysfunction,
• hypertension,
• epilepsy,
• migraine
• estrogen-dependent gynecological diseases.