Tri-Mercy tablets No. 21

pharmachologic effect

The contraceptive effect of Tri-Mercy®, like all combined oral contraceptives (COCs), is based on various factors, the most important of which are inhibition of ovulation and changes in mucus secretion by the cervical epithelium. Along with contraceptive properties, COCs have a number of additional positive effects, which, after assessing possible negative effects (see Warnings, side effects), can be useful when choosing a method of contraception. Thus, the menstrual cycle becomes more orderly, menstruation is less painful, with less bleeding. The latter circumstance leads to a decrease in the incidence of iron deficiency anemia. When using COCs with a high content of hormones (50 mcg ethinyl estradiol), a reduction in the risk of developing fibrocystic mastopathy, ovarian cysts, pelvic inflammatory diseases, ectopic pregnancy, ovarian and endometrial cancer was shown. The applicability of these data to low-hormone COCs requires further confirmation.

Pharmacokinetics

Desogestrel

Absorption

Desogestrel taken orally is rapidly and completely absorbed and then converted to etonogestrel. Cmax in blood plasma (from approximately 1.5 ng in the first week to 5 ng in the third week) is achieved after approximately 1.5 hours. Bioavailability is 62-81%.

Distribution

Etonogestrel binds to plasma albumin and sex hormone binding globulin (SHBG). Only 2-4% of the total drug concentration in blood plasma is present as a free steroid, 40-70% is specifically bound to SHBG. The increase in SHBG levels caused by ethinyl estradiol affects the distribution between blood proteins, leading to an increase in the SHBG-bound fraction and a decrease in the albumin-bound fraction. The apparent volume of distribution of desogestrel is 1.5 l/kg.

Metabolism

Etongestrel is completely metabolized along the known pathways of steroid hormone metabolism; the rate of metabolic elimination from blood plasma is 2 ml/min/kg. There was no interaction between etonogestrel and concomitantly taken ethinyl estradiol.

Removal

The concentration of etonogestrel in the blood plasma decreases in two stages. The final stage is characterized by a T1/2 of the drug of about 30 hours. Desogestrel and its metabolites are excreted in urine and bile in a ratio of approximately 6:4.

Constant level

The pharmacokinetics of etonogestrel is influenced by SHBG, the level of which increases under the influence of ethinyl estradiol. When taken daily, the level of the drug in the blood plasma increases two to three times, reaching a steady-state concentration in the second half of the dosing cycle.

Ethinyl estradiol

Absorption

Orally administered ethinyl estradiol is rapidly and completely absorbed. Cmax in blood plasma (about 80 pg/ml) is achieved within 1-2 hours after oral administration. Absolute bioavailability, as a result of presystemic conjugation and first-pass metabolism through the liver, is about 60%.

Distribution

Ethinyl estradiol binds to blood albumin almost completely (98.5%) but nonspecifically; at the same time, it affects the increase in the concentration of SHBG. The apparent Vd of ethinyl estradiol is 5 l/kg.

Metabolism

Ethinyl estradiol undergoes presystemic conjugation both in the mucosa of the small intestine and in the liver. Ethinyl estradiol is initially metabolized by aromatic hydroxylation, producing a variety of hydroxylated and methylated metabolites, which are present both in the free state and as conjugates with glucoronides and sulfates. The rate of metabolic elimination of ethinyl estradiol from blood plasma is about 5 ml/min/kg.

Removal

The concentration of ethinyl estradiol in the blood plasma decreases in two stages. The final stage is characterized by T1/2 of the drug about 24 hours. In its original form, the drug is not excreted; ethinyl estradiol metabolites are excreted in urine and bile in a ratio of 4:6. T1/2 of metabolites is about a day.

Constant level

A constant level of ethinyl estradiol concentration is achieved after 3-4 days, when it increases by 30-40% compared to a single dose.

Dosage regimen

The tablets should be taken in the order indicated on the package, every day, at the same time, if necessary with a small amount of liquid. Take 1 tablet per day for 21 days. Taking the tablet from the next package begins 7 days after the end of the previous one, during these 7 days menstrual-like bleeding occurs. It usually starts 2-3 days after taking the last tablet and may not stop until you start taking the next pack.

How to start taking Tri-Mercy®

In the absence of previous use of hormonal contraceptives (in the last month)

Taking pills should start on day 1 of the menstrual cycle. It is possible to start on the 2-5th day, but then during the first cycle, during the first 7 days of taking the drug, it is recommended to use an additional (non-hormonal) method of contraception.

Switching from another combined oral contraceptive (COC).

It is advisable to start taking Tri-Mercy® the day after taking the last COC tablet containing hormones, or, as a last resort, immediately after a break in taking the tablet or tablet not containing hormones.

Switching from drugs containing only progestogen (mini-pills, injections, implants).

A woman taking the minipill can switch to Tri-Mercy® any day; using an implant, can switch to taking Tri-Mercy® on the day of drug removal; using the drug in the form of injections - on the day when the next injection should be given; in all cases, during the first seven days of taking Tri-Mercy®, it is recommended to use additional barrier contraception.

After an abortion performed in the first trimester.

A woman can start taking the drug immediately. In this case, there is no need to use any additional methods of contraception.

After childbirth or abortion in the second trimester.

It is recommended to start taking the drug on the 21st or 28th day after childbirth or abortion. When starting to take the drug at a later date, it is recommended to use barrier contraception methods during the first seven days of taking Tri-Mercy®. In any case, if a woman has already had sexual intercourse after childbirth or abortion before starting Tri-Mercy®, pregnancy should be excluded before starting to take COCs or wait until her first menstruation.

What to do if you miss the next dose of the drug.

If taking the next pill is delayed by less than 12 hours, the reliability of contraception does not decrease. A woman should take the pills as soon as she remembers and take subsequent pills at the usual time.

If taking the next pill is delayed by more than 12 hours, the reliability of contraception may be reduced. In this case, you should be guided by two basic rules: taking Tri-Mercy® should never be interrupted for more than 7 days; to achieve the necessary contraception and the degree of suppression of the hypothalamic-pituitary-ovarian axis, continuous use of Tri-Mercy® is required for 7 days;

Accordingly, the following advice can be given:

Week 1 (yellow tablets) A woman should take the missed tablet as soon as she remembers, even if this means taking two tablets at the same time. Then you should continue taking it as usual. Additionally, you should use a barrier contraceptive method (condom) for the next 7 days. If a woman has had sexual intercourse within the previous 7 days, the possibility of pregnancy should be considered. The more tablets are missed, and the closer the break in taking the drug is to the time of sexual intercourse, the higher the risk of pregnancy.

Week 2 (red pills) A woman should take the missed pill as soon as she remembers, even if this means taking two pills at the same time. Then you should continue taking it as usual. Provided that a woman has taken her pills on time during the 7 days preceding the first missed dose, there is no need to use additional (non-hormonal) methods of contraception. Otherwise, or if the woman has missed more than 1 tablet, it is recommended to use additional methods of contraception for the next 7 days.

Week 3 (white pills) The reliability of contraception may be reduced due to a subsequent interruption in taking the drug. This can be avoided by adapting the drug dosage regimen. If you use either of the following two regimens, there is no need to use additional contraceptive measures, provided that the woman has taken the pills on time for 7 days preceding the first missed dose.

Otherwise, it is recommended to use one of the two regimens below and use additional contraceptive measures for the next 7 days.

A woman should take the missed pill as soon as she remembers, even if this means taking two pills at the same time. Then you should continue taking it as usual. A new package should be started as soon as the current package is finished, i.e. there should be no break between packages. The likelihood of bleeding if you stop taking the drug before the end of the second package is small, but some may experience spotting or heavy bleeding while taking the drug.

It may be recommended to stop taking the drug from the current package. A woman should take a break from taking Tri-Mercy® for up to seven days, including days when she forgot to take the pills, and then start a new pack.

If you miss taking the drug and there is no subsequent bleeding during the next break in taking the drug, you should consider the possibility of pregnancy.

Recommendations in case of vomiting

If vomiting occurs within 3-4 hours after taking the drug, absorption may be incomplete. In this case, you should use the recommendations regarding skipping the next dose of the drug. If a woman does not want to change her usual dosing regimen, she needs to take additional tablet(s) from a different package.

How to change the date of menstruation.

In order to delay menstruation, you should continue taking the white tablets from another Tri-Mercy® package without the usual break. In this way, you can delay menstruation for up to 7 days, until the end of the white pills from the second package. During this period, a woman may experience spotting or heavy bleeding. Taking Tri-Mercy® according to the usual regimen should be resumed after a 7-day dosing interval.

In order to shift your menstruation to a different day of the week from the one expected when following your usual dosage regimen, you can shorten the usual break in dosage by as many days as necessary. The shorter the break, the higher the risk of absence of menstruation during the break and the occurrence of heavy or spotting bloody discharge while taking the drug from the second package.

Tri-mercy TB N21 28909

Latin name

Tri-Merci

Active substance

Desogestrel + Ethinylestradiol*(Desogoestrelum+ Aethinyloestradiolum)

ATX:

G03AA09 Desogestrel + ethinyl estradiol

Pharmacological group

Estrogens, gestagens; their homologs and antagonists in combinations

Storage conditions

In a dry place, protected from light, at a temperature of 2–30°C. Keep out of the reach of children.

Best before date

3 years. Do not use after the expiration date indicated on the package. 2000-2017. Register of Medicines of Russia

Indications

Contraception.

Contraindications

The combination of desogestrel + ethinyl estradiol is contraindicated in the presence of any of the diseases/conditions/risk factors listed below. If any of these occur while taking the combination, you should stop taking it immediately: hypersensitivity; the presence or history of venous thrombosis (including deep vein thrombosis, pulmonary embolism); the presence or history of arterial thrombosis (including myocardial infarction, stroke) or precursors of thrombosis (including transient ischemic attack, angina pectoris); identified predisposition to venous or arterial thrombosis, including resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant); migraine with a history of focal neurological symptoms; diabetes mellitus with diabetic angiopathy; the presence of multiple factors or a high degree of severity of one of the risk factors for the development of venous or arterial thrombosis, thromboembolism (see “Precautions”); uncontrolled arterial hypertension (BP 160/100 mm Hg and above); pancreatitis (including a history), accompanied by severe hypertriglyceridemia; severe dyslipoproteinemia; endometrial hyperplasia; liver failure, acute or severe liver diseases (until normalization of liver function indicators), incl. in the anamnesis; liver tumors (benign and malignant), incl. in the anamnesis; hormone-dependent malignant neoplasms of the genital organs or mammary glands (including suspected ones); bleeding from the vagina of unknown etiology; smoking over the age of 35 (more than 15 cigarettes per day); pregnancy (including suspected); breastfeeding period; adolescent girls under 18 years of age (data on the effectiveness and safety of use are lacking).

Use during pregnancy and breastfeeding

FDA category of effect on the fetus is X. Use during pregnancy is contraindicated. If pregnancy occurs while using the combination of desogestrel + ethinyl estradiol, you should stop taking it. The combination may affect lactation, because COCs reduce the amount and change the composition of breast milk. Taking the combination is contraindicated until breastfeeding is stopped. Small amounts of sex hormones and/or their metabolites may be excreted into breast milk.

Precautionary measures

If you have any of the following diseases/conditions/risk factors, you should carefully weigh the benefits and possible risks of taking ethinyl estradiol + desogestrel combination. This issue should be discussed with the patient before starting the drug. In case of exacerbation of diseases, deterioration of the condition or the appearance of the first symptoms of the above-mentioned conditions or risk factors, the patient should immediately consult a doctor. The doctor decides whether to discontinue the drug individually. Heart and vascular diseases During epidemiological studies, it was found that there may be a connection between the use of COCs and an increased risk of arterial and venous thrombosis and thromboembolism, such as myocardial infarction, stroke, deep vein thrombosis and PE. 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 PE. The risk is higher in the first year of use than in women taking COCs for more than 1 year. When taking a combination of desogestrel and ethinyl estradiol, there is an increased (almost 2-fold) risk of developing VTE compared to drugs containing levonorgestrel, norgestimate or norethisterone as a progestin component. It is extremely rare that thrombosis occurs in other blood vessels (for example, in the veins and arteries of the liver, mesentery, kidneys, brain or retina). At the moment, there is no clear opinion about the possible role of varicose veins and superficial thrombophlebitis in the etiology of the development of VTE. If a hereditary predisposition to thromboembolic diseases is suspected, a woman should be referred for consultation with a specialist before deciding to prescribe any hormonal contraceptives. Risk factors for the development of venous and arterial thrombosis, thromboembolism High risk factors for the development of venous thrombosis are: - age over 35 years; - air travel lasting more than 4 hours (especially in the presence of other risk factors); - excess body weight (BMI >30 kg/m2). The risk of complications increases with increasing BMI, this is especially important to consider in the presence of other risk factors. - prolonged immobilization; - extended surgical interventions ;- neurosurgical operations; - surgical interventions in the pelvis or lower extremities; - severe trauma. With prolonged immobilization and the above surgical interventions, it is recommended to stop using the combination of desogestrel + ethinyl estradiol, for planned surgical interventions no later than 4 weeks before surgery, and not resume use within 2 weeks after complete rehabilitation. To prevent unwanted pregnancy, other methods of contraception should be used. If the combination has not been stopped in advance, then antithrombotic therapy is indicated in this case. - Presence of thromboembolic diseases in the family history (venous thrombosis/thromboembolism in siblings or parents at a young age); - other conditions/diseases associated with the development of venous thrombosis (oncological diseases, systemic lupus erythematosus, hemolytic-uremic syndrome, chronic inflammatory bowel diseases (Crohn's disease or ulcerative colitis), sickle cell anemia). The risk of developing VTE is increased both with the initial use of COCs and when resuming COC use after a break lasting 4 weeks or more. The development of VTE can be fatal in 1-2% of cases. Symptoms of VTE (deep vein thrombosis and PE) Symptoms of deep vein thrombosis may include: unilateral leg swelling, incl. feet, or along the affected vein; pain in the leg or tenderness when touching the leg, which can be felt, incl. only when standing or walking; a feeling of warmth in the affected limb, redness or discoloration of the skin of the leg. Symptoms of pulmonary embolism: a sudden attack of difficulty breathing or rapid breathing of unknown etiology; a sudden attack of coughing, which may be accompanied by hemoptysis; sharp chest pain; feeling very weak or dizzy; fast or irregular heart rhythm. Some of these symptoms (eg, difficulty breathing, cough) are nonspecific, which can make diagnosis difficult. It is possible to make a diagnosis of a more common or less dangerous disease (for example, a respiratory tract infection). Other signs of blockage of the vessel: sudden pain, swelling and blue discoloration of the limb. When a blocked blood vessel occurs in the eye, symptoms can range from painless blurred vision that can progress to complete loss of vision. Sometimes complete loss of vision can occur suddenly. Epidemiological studies have revealed an association between the use of COCs and an increased risk of arterial thrombosis (myocardial infarction) or cerebrovascular accidents (for example, transient ischemic attack, stroke). Arterial thromboembolism can be fatal. High risk factors for the development of arterial thrombosis are: - age over 35 years; - smoking. Women taking COCs are advised to refrain from smoking. Women over 35 years of age who smoke should not take COCs. - arterial hypertension; - overweight (BMI >30 kg/m2). The risk of complications increases with increasing BMI, this is especially important to consider if there are other risk factors. - the presence of thromboembolic diseases in family history (arterial thrombosis/thromboembolism in siblings or parents at a young age); - migraine. An increase in the frequency and intensity of migraine when taking COCs (which may be a sign of cerebrovascular disorders) is a reason to discontinue the combination of desogestrel + ethinyl estradiol. - Other conditions /diseases associated with the development of adverse vascular events (diabetes mellitus, hyperhomocysteinemia, heart valve disease and atrial fibrillation, dyslipoproteinemia and systemic lupus erythematosus). Symptoms of arterial thromboembolism Symptoms of cerebrovascular accidents: sudden numbness or weakness of the facial muscles, arms or legs, affecting one side or part of the body; sudden disturbance in gait, dizziness, loss of balance or coordination; sudden confusion, difficulty speaking or understanding; sudden loss of vision in one or both eyes; sudden severe or prolonged headache of unknown etiology; loss of consciousness or severe weakness with or without convulsions. Temporary symptoms may indicate the development of a transit ischemic attack. Symptoms of myocardial infarction: pain, discomfort, a feeling of tightness, heaviness or fullness in the chest; pain in the arm or below the sternum; an unpleasant sensation (discomfort) radiating to the back, jaw, throat, arm, and stomach area; a feeling of fullness in the stomach, indigestion, or a feeling of suffocation; sweating, nausea, vomiting, or dizziness; extreme tiredness, anxiety, or difficulty breathing; rapid or irregular heart rhythm. The risk of developing thromboembolic complications increases when several risk factors for the development of these complications are combined. Biochemical indicators that may indicate hereditary or acquired predisposition to venous or arterial thrombosis are: resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency , protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant). Tumors The most important risk factor for the development of cervical cancer is the persistence of human papillomavirus (HPV infection). Some epidemiological studies indicate an increase in the risk of cervical cancer in women taking long-term COCs, but there is still controversy regarding the extent to which these data are influenced by a variety of factors, such as cervical screening examinations and sexual behavior, including less frequent use of barrier methods of contraception, or their relationships. 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 risk of developing breast cancer in women who are currently using COCs or who have recently stopped using them is small relative to the baseline risk of developing breast cancer. These studies do not provide data on the etiology of cancer. The increased risk of breast cancer may be a consequence of medical surveillance and earlier diagnosis of cancer in women taking COCs (they are diagnosed with earlier stages of cancer than women who have never taken COCs), the biological effects of COCs, or a combination of these two factors. Very rarely, when using the combination of desogestrel + ethinyl estradiol, 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 a woman taking desogestrel + ethinyl estradiol 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 has been diagnosed with hypertriglyceridemia, it is possible that the risk of pancreatitis may increase when taking the combination of desogestrel + ethinyl estradiol. If a woman receiving the combination develops persistent clinically significant hypertension, the physician should discontinue the drug and treat the hypertension. In cases where normal blood pressure values ​​are achieved during antihypertensive therapy, the doctor may consider it possible for the patient to resume taking it. 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 COCs, but evidence regarding the use of the combination of desogestrel + ethinyl estradiol are unconvincing. Acute or chronic liver dysfunction may warrant discontinuation of the drug until liver function tests return to normal. Recurrence of cholestatic jaundice, previously observed during pregnancy or when using sex hormones, requires discontinuation of the combination. Although taking the combination of ethinyl estradiol + desogestrel may affect peripheral insulin resistance and glucose tolerance, as a rule, adjustment of the dosage regimen of hypoglycemic agents in patients with diabetes mellitus is not required . However, careful monitoring of blood glucose concentrations is necessary, especially during the first months of taking COCs. There is evidence of an association between taking COCs and Crohn's disease and ulcerative colitis. Pigmentation of the facial skin (chloasma) may sometimes occur while taking the combination, especially if it was previously pregnant. Women predisposed to chloasma should avoid direct sunlight and UV exposure from other sources while taking the combination. Medical examinations/consultations Before starting or resuming the combination of ethinyl estradiol + desogestrel, the doctor should obtain a detailed medical history (including family history) from the patient. and conduct a thorough examination, taking into account contraindications and precautions. It is important to repeat periodic medical examinations because diseases that are contraindications to taking the combination (for example, transient ischemic attack) or risk factors (for example, a family history of venous or arterial thrombosis) may first appear while taking the drug. 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). In any case, special attention should be paid to measuring blood pressure, examining the mammary glands, abdominal and pelvic organs, including cytological examination of the cervix. The woman should be informed that COCs do not protect against HIV (AIDS) and other sexually transmitted infections. Reduced effectivenessEfficacy the combination of desogestrel + ethinyl estradiol may decrease in case of missed doses, gastrointestinal disorders, or when taking certain drugs concomitantly (see “Interactions”). Irregular bleeding When taking the combination of desogestrel + ethinyl estradiol, especially in the first months of use, irregular spotting or heavy discharge may occur. bloody issues. Therefore, assessment of irregular bleeding should be carried out only after the end of the adaptation period, lasting 3 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 a diagnostic curettage. Some women may not experience menstrual bleeding when not taking the combination. If the combination was taken according to the recommendations above, the likelihood of pregnancy is low. Otherwise, or if there is no bleeding 2 times in a row, you should exclude the possibility of pregnancy and consult a doctor. Laboratory tests COCs may affect the results of some laboratory tests, including biochemical indicators of liver, thyroid, adrenal and kidney function, and the content of transport proteins in the blood plasma , for example, SHBG and lipid/lipoprotein fractions, carbohydrate metabolism parameters, coagulation and fibrinolysis parameters. Usually these changes are within the normal values ​​of laboratory parameters. Impact on the ability to drive vehicles and machines. The effect of the drug on the ability to drive vehicles and operate machinery was not noted.

Side effects

Possibly drug-related side effects that were observed when taking the combination of ethinyl estradiol + desogestrel or other COCs are listed below. The frequency of occurrence of adverse reactions is determined as follows: often - ≥1/100; uncommon—≥1/1000 and

Possible product names

• Tri-Mercy TB N21
• TRI-MERSI TAB. No. 21
• (Tri-Merci) Tri-Merci TB N21

Side effect

The following unwanted effects may sometimes occur in women using COCs. The relationship between them and taking the drug has not been proven or disproved, breast tenderness and the appearance of secretion, chest pain, migraine, changes in libido, depression, intolerance to contact lenses, nausea, vomiting, changes in vaginal.

Other diseases.

If a woman or her family members are diagnosed with hypertriglyceridemia, there may be an increased risk of pancreatitis when taking COCs.

Although many people taking COCs experience a slight increase in blood pressure, clinically significant increases are rare. No relationship has been established between taking COCs and the development of arterial hypertension. In any case, if an increase in blood pressure is observed when taking COCs for a long time, the doctor should discontinue the COC and prescribe treatment for arterial hypertension.

In cases where normal blood pressure levels are achieved with antihypertensive therapy, the doctor may consider it possible for the patient to resume taking COCs.

There are reports that jaundice and/or pruritus 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 develop or worsen as in pregnancy and when taking COCs, but the evidence for this in relation to taking COCs is inconclusive.

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

Although COCs may affect peripheral tissue insulin and glucose tolerance, there is no evidence that diabetic patients need to change their therapeutic regimen. In any case, women with diabetes should use COCs with caution.

There is evidence that COCs can cause Crohn's disease and ulcerative colitis.

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

Medical examinations/consultations

Before prescribing a COC, the doctor must carefully review the woman’s medical history, as well as conduct a medical examination, guided by contraindications and warnings; This procedure should be repeated when taking COCs at least once a year. Periodic medical examinations are important because diseases that are contraindications to taking COCs (for example, transient cerebrovascular accident) or risk factors (for example, a family history of venous or arterial thrombosis) may first appear while taking COCs. The frequency and list of studies should be selected individually for each woman, but in any case, special attention should be paid to measuring blood pressure, examining the mammary glands, abdominal and pelvic organs, including cytological examination of the cervix and relevant laboratory tests.

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

Reduced efficiency

The effectiveness of COCs may be reduced if you miss a dose, vomit, or take certain medications.

Irregular bleeding

When taking COCs, especially in the first months. use, irregular (not coinciding with menstruation) spotting or heavy bleeding may occur. Any secretions, various skin diseases, fluid retention, changes in body weight, hypersensitivity reaction.

Oral contraceptives may affect the results of some laboratory tests, including biochemical parameters of the liver, thyroid gland, adrenal and renal function, plasma levels of transport proteins, for example, corticosteroid binding globulin and lipid/lipoprotein fractions, parameters of carbohydrate metabolism, and parameters of blood coagulation and fibrinolysis . Typically, these changes are within the laboratory norm.

Tri-Merci®

If you have the conditions/diseases or risk factors listed below, you should discuss the benefit-risk ratio of using Tri-Mercy® with the woman. If any of these conditions or risk factors worsen or manifest for the first time, a woman should contact her doctor. The decision on the need to stop using Tri-Mercy® is made by the doctor.

Vascular diseases

Risk of venous thromboembolism (VTE)

-The use of any COC increases the risk of developing VTE. Drugs containing levonorgestrel, norgestimate, or norethisterone are associated with the lowest risk of VTE. When taking Tri-Mercy® and similar drugs, the risk of VTE almost doubles. The decision to use any drug, with the exception of drugs that have the lowest risk of developing VTE, should be made only after discussing with the woman the benefits and possible negative effects of the contraceptive. A woman should understand the risk of developing VTE. associated with taking the drug, the influence of her existing factors on this risk, and that the risk of developing VTE will be highest in the first year of use. There is also some evidence to show that the risk increases when taking COCs again after a break of more than 4 weeks.

-Among women who are not pregnant or do not use COCs, about 2 in 10,000 will experience VTE within 1 year. However, each woman may have a higher risk depending on her risk factors (see below).

-It is estimated that 1 in 10,000 women using desogestrel-containing COCs, 9-12 women will experience VTE within 1 year, compared with approximately 62 women using levonorgestrel-containing COCs.

-In both cases, the number of VTEs per year is the same as the expected number of VTEs during pregnancy or the postpartum period.

-VTE can be fatal in 1-2% of cases.

1 This incidence rate is based on all available epidemiological studies of the relative risks for various drugs compared with levonorgestrel-containing COCs.

2 The midpoint of the range of 5 to 7 per 10,000 woman-years demonstrates a relative risk for levonorgestrel-containing COC users compared with nonusers of hormonal contraception, for whom the risk is approximately 2.3 to 3.6.

- In women taking COCs, thrombosis extremely rarely occurs in other blood vessels, for example, the liver, mesentery, veins and arteries of the kidneys or retina.

Risk factors for VTE

The risk of venous thromboembolism for COC users may be significantly increased by the presence of additional risk factors, especially if there are several of them (see table). Tri-Mercy® is contraindicated if a woman has several risk factors that increase her risk of developing venous thromboembolism (see section “Contraindications”). If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors - in which case her resulting risk of VTE should be considered. If the risk outweighs the benefits of using the drug, COCs should not be used (see section “Contraindications”).

Table: Risk factors for VTE

There is no consensus on the possible role of varicose veins and superficial thrombophlebitis in the occurrence or progression of venous thromboembolism. The increased risk of thromboembolism during pregnancy and especially in the first 6 weeks of the postpartum period must be taken into account (for information on pregnancy and breastfeeding, see the section “Use during pregnancy and breastfeeding”).

Symptoms of VTE (deep vein thrombosis or pulmonary embolism).

If symptoms occur, a woman is advised to seek immediate medical attention and inform her doctor that she is using COCs.

The following symptoms may indicate deep vein thrombosis:

- unilateral swelling of the lower limb and/or foot or along a vein in the lower limb;

- pain or tenderness in the lower limb, which can only be felt when standing or walking;

- increased temperature of the affected lower limb, redness or paleness of the lower limb.

The following symptoms may indicate pulmonary embolism:

-sudden unexplained shortness of breath or rapid breathing;

-sudden cough, possibly with hemoptysis;

-acute pain in the chest;

- severe dizziness or feeling of lightheadedness;

-fast or irregular heartbeat.

Some of these symptoms (such as shortness of breath, cough) are nonspecific and may be misinterpreted as characteristic of less severe illnesses (eg, respiratory tract infections).

Other signs that may indicate vascular occlusion:

sudden pain, swelling and slightly bluish discoloration of the limb.

If the occlusion occurs in the vessels of the eyeball, symptoms can range from painless blurred vision to loss of vision. Sometimes vision loss can occur almost suddenly.

Risk of arterial thromboembolism (ATE)

Epidemiological studies have associated the use of COCs with an increased risk of arterial thromboembolism (myocardial infarction) or cerebrovascular accident (eg, stroke, transient ischemic attack). Cases of arterial thromboembolism can be fatal.

Risk factors for ATE

The risk of arterial thromboembolic complications or acute cerebrovascular accident (ACVA) is increased in women taking COCs and having risk factors (see table). Tri-Mercy® is contraindicated if a woman has several risk factors that increase the risk of developing arterial thromboembolism (see section “Contraindications”). If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors - in this case the resulting risk of ATE should be calculated. If the risk outweighs the benefit, COCs should not be used (see section "Contraindications").

Table: Risk factors for ATE

Symptoms of ATE

If symptoms occur, a woman is advised to seek immediate medical attention and inform her doctor that she is using COCs.

The following symptoms may indicate acute cerebrovascular accident:

sudden numbness or decreased strength of the muscles of the face, upper or lower limb, especially pronounced on one side;

-sudden difficulty walking, dizziness, loss of balance or coordination;

-sudden confusion, difficulty speaking or understanding;

-sudden unilateral or bilateral visual impairment;

- sudden severe or prolonged headache without a specific cause;

-loss of consciousness or fainting with or without convulsions.

Temporary symptoms indicate a transient ischemic attack.

The following symptoms may indicate myocardial infarction:

- pain, discomfort, pressure or a feeling of heaviness, squeezing or bursting pain in the chest, arm or below the sternum;

-discomfort radiating to the back, jaw, neck, arm, stomach;

- feeling of fullness in the stomach, indigestion or choking;

- sweating, nausea, vomiting or dizziness;

-severe weakness, restlessness or shortness of breath;

-fast or irregular heartbeat.

Tumors

— Epidemiological studies indicate that long-term use of COCs is a risk factor for the development of cervical carcinoma in women infected with human papillomavirus. An increased risk of developing cervical cancer may be due to the characteristics of a woman’s sexual behavior (more sexual intercourse and less frequent use of barrier methods of contraception).

-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 fact that women taking COCs are diagnosed with breast cancer at an earlier stage, by the biological effects of COCs, or by a combination of both. Breast cancer in women who had ever taken COCs was usually detected at an earlier stage than in women who had never taken COCs.

- Cases of benign liver tumors have been extremely rarely reported, and even more rarely, cases of malignant tumors have been reported in women using COCs. In isolated cases, such tumors led to life-threatening intra-abdominal bleeding. If severe upper abdominal pain, hepatomegaly or signs of intra-abdominal bleeding occur in a woman taking COCs, the possibility of a liver tumor should be considered in the differential diagnosis.

Other states

-If a woman or her family members are diagnosed with hypertriglyceridemia, there may be an increased risk of pancreatitis when taking COCs.

-If a woman using a COC develops persistent clinically significant hypertension, the physician should discontinue the COC and treat the hypertension. In some cases, after normalization of blood pressure against the background of antihypertensive therapy, you can resume taking COCs.

- Jaundice and/or pruritus caused by cholestasis have been reported: gallstones, porphyria, systemic lupus erythematosus, hemolytic uremic syndrome, Sydenham's chorea (chorea minor), herpes of pregnancy, hearing loss due to otosclerosis, (hereditary) angioedema edema develops or worsens both during pregnancy and when taking COCs, but the evidence for this in relation to COC use is inconclusive.

-Acute or chronic liver dysfunction may necessitate a break in COC use until liver function tests return to normal. Recurrence of cholestatic jaundice and/or pruritus that occurred during pregnancy or previous use of sex hormones requires discontinuation of COCs.

-Despite the fact that COCs can affect peripheral insulin resistance and glucose tolerance, dose adjustment and dosage regimen of hypoglycemic drugs in patients with diabetes mellitus using low-dose COCs is usually not required. However, such women should be carefully monitored by a doctor 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.

Medical examinations/consultations

Before starting or resuming the use of Tri-Mercy® in a woman, it is necessary to obtain a detailed medical history (including family history) and exclude pregnancy. Blood pressure should be measured and a physical examination should be performed, guided by contraindications and precautions.

The woman should be provided with information regarding venous and arterial thromboembolism, including data indicating an increased risk when taking Tri-Mercy® compared to other COCs. The woman should be familiar with the symptoms of VTE and ATE, informed about known risk factors and what to do if thrombosis is suspected. The woman should be instructed to carefully read these instructions for use and adhere to the recommendations contained therein. The frequency and list of further periodic 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 hormonal contraceptives do not protect against HIV (AIDS) and other sexually transmitted infections.

Reduced efficiency

The effectiveness of COCs may be reduced if pills are missed (see section “What to do if a woman forgets to take a pill”) or if gastrointestinal disorders occur (see section “Recommendations in case of gastrointestinal disorders (vomiting, diarrhea)” ) or when used together with other drugs (see section “Interaction with other drugs”). Herbal medicines containing St. John's wort ( Hypericum perforatum

), should not be used in conjunction with Tri-Mercy®. as this may lead to a decrease in plasma concentrations and a decrease in the effectiveness of the Tri-Mercy® drug (see section “Interaction with other drugs”). Acyclic bleeding during use of the drug Tri-Mercy® Irregular bleeding (spotting or heavy) can occur when using any COC, more often in the first 3 months of adaptation.

If irregular bleeding occurs after previous regular cycles, non-hormonal causes should be considered and adequate diagnostic measures should be taken to exclude neoplasms or pregnancy. These examinations may include, but are not limited to, diagnostic curettage.

Some women may not have menstrual-like bleeding between pills. If COCs are taken as recommended above, there is little chance of pregnancy. If the dosage regimen was violated, then in the absence of the first “withdrawal” bleeding in a row, it is necessary to exclude pregnancy before resuming the use of COCs.

Laboratory indicators

The use of COCs may affect the results of a number of laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, plasma concentrations of carrier proteins, for example, corticosteroid binding globulin and lipid/lipoprotein fractions, some parameters of carbohydrate metabolism, as well as parameters of coagulation and fibrinolysis. Typically, these changes remain within normal laboratory values.

Lactose

Each Tri-Mercy® tablet contains less than 65 mg of lactose. Women with rare hereditary disorders such as lactose intolerance, lactase deficiency or glucose-galactose malabsorption who are on a lactose-free diet should not take Tri-Mercy®.

Contraindications to the use of the drug TRI-MERSY®

You should not take combined oral contraceptives if you have any of the diseases (conditions) listed below. If any of these occur while taking combined oral contraceptives, you should immediately stop taking the drug.

- thrombosis (venous or arterial) currently or in history (for example, deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke);

- the presence or history of possible clinical manifestations of vascular thrombosis (for example, coronary artery disease or angina pectoris);

— diabetes mellitus with vascular complications;

- the presence of severe or multiple risk factors for venous or arterial thrombosis;

- current or history of severe liver disease with a constant decrease in liver function (until normalization of liver function);

- presence or history of liver tumors (benign or malignant);

- established or suspected hormone-dependent malignant tumor of the genital organs or mammary glands;

- vaginal bleeding of unknown etiology;

- diagnosed or suspected pregnancy;

- hypersensitivity to any of the components of Tri-Mercy®.

Tri-mercy

Use during pregnancy and breastfeeding

Tri-Mercy® is contraindicated during pregnancy.
If pregnancy occurs while using Tri-Mercy®, further use should be discontinued. However, most epidemiological studies have not proven an increase in birth defects in children whose mothers used COCs before pregnancy, as well as the teratogenic effect of COCs when used in early pregnancy. Tri-Mercy® is contraindicated during breastfeeding. COCs can affect lactation, and there is evidence that they reduce the quantity and change the composition of breast milk. Small amounts of contraceptive steroids and/or their metabolites may be excreted in breast milk.

Use for liver dysfunction

Contraindications: current or history of severe liver disease with a constant decrease in liver function (until normalization of liver function).

Use in elderly patients

Use with caution in people over 35 years of age.

special instructions

Vascular diseases

Epidemiological studies have found an association between the use of COCs and an increased risk of venous or arterial thrombotic or thromboembolic complications such as myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism. These complications are 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, sometimes with fatal consequences. The risk is higher in the first year of use than in women taking COCs for more than 1 year.

A number of epidemiological studies suggest that women using low-dose COCs containing third-generation progestogens, including desogestrel, have an increased risk of VTE compared with women using low-dose COCs containing second-generation progestogens. These studies suggest an approximately twofold increase in risk, which may correspond to 1-2 additional cases of VTE per 10,000 women per year. However, other studies have not observed a 2-fold increase in risk.

Overall, the estimated incidence of VTE in women taking low-dose estrogen COCs (<50 mcg ethinyl estradiol) is up to 4 cases per 10,000 woman-years, compared with 0.5 to 3 cases per 10,000 woman-years in women not using oral contraceptives. However, the incidence of VTE during COC use is significantly lower than the incidence of this complication during pregnancy (i.e., 6 cases per 10,000 woman-years).

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.

Symptoms of venous or arterial thrombosis/thromboembolism or stroke may include: unilateral leg pain and/or swelling; sudden severe chest pain with or without radiation to the left arm; sudden shortness of breath; sudden attacks of coughing; unusual, severe, long-lasting headache; sudden complete or partial loss of vision; diplopia; a veil before the eyes; aphasia; dizziness; collapse with or without focal convulsions; weakness or very severe numbness that suddenly affects one side or part of the body; movement disorders; symptom complex “acute abdomen”.

The increased risk of thromboembolism during the postpartum period must be considered.

Other diseases that increase the risk of cardiovascular disease include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis), and sickle cell disease.

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

Biochemical indicators that may indicate a hereditary or acquired predisposition to venous or arterial thrombosis are: activated protein C resistance (APC), hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant) .

When evaluating the positive and negative effects of COC use, the physician should remember that adequate treatment of the disease may reduce the associated risk of thrombosis, and that the risk of thrombosis associated with pregnancy may be greater than the risk associated with the use of low-dose COCs (<50 mcg ethinyl estradiol).

Tumors

The most important risk factor for developing cervical cancer is persistence of human papillomavirus (HPV infection). Some epidemiological studies have reported an increased risk of cervical cancer in women receiving Tri-Mercy® over a long period of time, but there is still controversy regarding the extent to which these findings are influenced by confounding factors such as cervical screening and 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 in women under 40 years of age is quite rare, and the increase in the likelihood of developing breast cancer in women who are currently receiving COCs or who have recently stopped using them is small relative to the initial likelihood of developing cancer. These studies do not provide data on the etiology of cancer. The increased risk of breast cancer may be explained by either the earlier diagnosis of breast cancer in women receiving COCs, the biological effects of COCs, or 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.

It is extremely rare that 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. If severe upper abdominal pain, hepatomegaly, or signs of intra-abdominal bleeding occur in a woman taking COCs, the possibility of a liver tumor should be considered in the differential diagnosis.

Other diseases

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

If a woman receiving a COC develops persistent clinically significant hypertension, the physician should discontinue the COC and prescribe treatment for hypertension. In cases where normal blood pressure levels are achieved with antihypertensive therapy, the doctor may consider it possible for the patient to resume taking COCs.

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

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 steroids, requires discontinuation of COCs.

Although COCs may influence peripheral tissue insulin and glucose tolerance, there is no evidence that the therapeutic regimen for low-dose COCs (containing less than 50 mcg ethinyl estradiol) should be altered in patients with diabetes mellitus. While taking COCs, patients with diabetes require careful medical supervision.

There is evidence of 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 was previously during pregnancy. Women with a predisposition to chloasma should avoid direct sunlight and UV exposure from other sources when taking COCs.

Medical examinations/consultations

Before starting or resuming taking COCs, your doctor should obtain a detailed medical history (including family history) and rule out pregnancy. 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 of the drug 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 efficiency

The effectiveness of COCs may be reduced if a dose is missed, gastrointestinal disorders or when taking certain medications concomitantly.

Irregular bleeding while taking Tri-Mercy®

Irregular bleeding (spotting or heavy) can occur when using any PDA, more often in the first 3 months of adaptation

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 neoplasms or pregnancy. These measures may include diagnostic curettage.

Some women may not experience menstrual bleeding during the interval between taking the drug. If you take COCs according to the above recommendations, the likelihood of pregnancy is low. If the dosage regimen is violated before the first failed withdrawal bleeding or in the absence of 2 bleedings in a row, the possibility of pregnancy should be excluded before using the COC.

Laboratory research

The use of COCs 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 and lipid/lipoprotein fractions, some parameters of carbohydrate metabolism, parameters of coagulation and fibrinolysis . Usually these changes are within normal laboratory values.

Lactose

Each Tri-Mercy® tablet contains less than 65 mg of lactose. When prescribing to women with rare hereditary disorders, such as lactose intolerance, lactase deficiency, glucose-galactose malabsorption, who follow a lactose-free diet, the lactose content in Tri-Mercy® should be taken into account.

Impact on the ability to drive vehicles and operate machinery

The effect of Tri-Mercy® on the ability to drive vehicles and operate machinery has not been noted.

Use of the drug TRI-MERSI® during pregnancy and breastfeeding

Extensive studies have not found an increased risk of defects in children whose mothers used COCs before pregnancy, nor a teratogenic effect in COCs when they were used incorrectly during pregnancy.

COCs can affect lactation, reducing the amount and changing the composition of milk. As a result, the use of COCs is not recommended until the baby is weaned. Small amounts of steroids and their metabolites may be excreted in milk, but there is no evidence that they have an adverse effect on the health of the child.