Marvelon pills №21 * 3

Clinico-pharmacological group

Monophasic oral contraceptive

Mechanism of action

The contraceptive effect of Marvelon, like other combined oral contraceptives (CEC), is based primarily on the ability to suppress ovulation and increase the secretion of cervical mucus.

Progestin drug (desogestrel) inhibits the synthesis of luteinizing hormone (LH) and follicle stimulating hormone (FSH) by the pituitary gland and, thus, prevents the maturation of the follicle (blocks ovulation).

Ethinyl estradiol - a synthetic analogue of the follicular hormone estradiol, together with the hormone of the yellow body regulates the menstrual cycle.

Along with these central and peripheral mechanisms that prevent the maturation of an oocyte capable of fertilization, the contraceptive effect is due to an increase in the viscosity of the mucus in the cervix, which makes it relatively impassable for sperm.

Along with the contraceptive properties, COCs have a number of additional positive effects: the menstrual cycle becomes more regular, menstruation is less painful and is accompanied by less pronounced bleeding. The latter circumstance leads to a decrease in the frequency of concomitant iron deficiency anemia.When using HEC with a high content of hormones (50 mcg of ethinyl estradiol), a reduction in the risk of fibrocystic mastopathy, ovarian cysts, inflammatory diseases of the pelvic organs, ectopic pregnancy, ovarian cancer and endometrium has been shown. The applicability of these data to low-hormone COCs needs further study.

Marvelone has a beneficial effect on lipid metabolism, increases the content of high-density lipoprotein (HDL) in plasma, while not affecting the content of low-density lipoprotein (LDL). It has a beneficial effect on the skin, improves its condition in case of acne vulgaris.

Pharmacokinetics

Desogestrel, taken orally, is quickly and completely absorbed and then turns into etonogestrel. Its maximum plasma concentration (approximately 2 ng / ml) is reached after 1.5 hours. Bioavailability is 62-81%.

Etonogestrel binds to plasma albumin and the sex hormone-binding globulin (SHBG). Only 2-4% of the total concentration of etonogestrel in plasma are present as a free steroid, 40-70% are specifically associated with SHBG. An increase in the level of SHBG 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.

Etonogestrel is fully metabolized by the known metabolism of steroid hormones; the rate of metabolic elimination from plasma is 2 ml / min / kg. No etonogestrel interaction was detected with concurrent ethinyl estradiol.

The concentration of etonogestrel in plasma decreases in 2 stages. The final stage is characterized by a half-life (T_1/2), constituting about 30 hours. Desogesgrel and its metabolites are excreted in urine and bile in a ratio of about 6: 4.

The pharmacokinetics of etonogestrel are influenced by SHBG, the level of which arises under the influence of ethinyl estadiol 3 times. With daily intake, the concentration of etonogestrel in plasma increases by 2-3 times, reaching a constant level in the second half of the cycle.

Ethinyl estradiol after oral administration is rapidly and completely absorbed. Its maximum plasma concentration (about 80 pg / ml) is reached within 1-2 hours after administration. Absolute bioavailability (the result of presystemic metabolism) is about 60%.

Ethinyl estradiol non-specifically binds to plasma albumin almost completely (98.5%), increases the concentration of SHBG. The apparent volume of distribution of ethinyl estradiol is 5 L / kg.

Ethinyl estradiol is subjected to presystemic metabolism in both the mucous membrane of the small intestine and in the liver. Ethinyl estradiol is initially metabolized during aromatic hydroxylation to form various hydroxylated and methylated metabolites that are present both in the free state,so in the form of conjugates with glucuronides and sulfates. The rate of metabolic elimination of ethinyl estradiol from blood plasma is about 5 ml / min / kg.

The concentration of etonogestrel in plasma decreases in 2 stages. The final stage is characterized by T_1/2 about 24 hours. The drug is not excreted unchanged, metabolites of ethinyl estradiol are excreted in the urine and bile in the ratio 4: 6. T_1/2 metabolites is about one day.

Indications for use of the drug

- contraception.

Dosage and administration

Tablets should be taken orally in the order indicated on the packaging, every day at about the same time, with a little water, if necessary.

Take 1 tab. per day for 21 days. Acceptance of pills from the next package should be started 7 days after the end of the previous one. During these 7 days, menstrual bleeding occurs. It usually starts 2-3 days after taking the last pill and may not stop before the next pack is started.

How to start taking the drug Marvelon

If hormonal contraceptives have not been used during the last month, the intake should begin on the first day of the menstrual cycle. You can start taking the drug at 2-5 days after the start of the menstrual cycle, but in this case it is recommended to use an additional (non-hormonal) method of contraception during the first 7 days of taking the pills in the first cycle.

Transition from other combined oral contraceptives: It is desirable to start taking the drug Marvelon the next day after taking the last pill of a previously used drug containing hormones, in extreme cases, immediately after a break in taking the pills or after taking a pill that does not contain hormones.

Transition from progestogen-only drugs ("mini-pili", implant injection). A woman taking “mini-drank” can switch to taking Marvelon on any given day; using the implant - on the day of its removal; using the drug in the form of injections - on the day when there should be the next injection, in all cases during the first seven days of taking Marvelon, it is recommended to use additional methods of contraception.

After an abortion made in the first trimester: a woman can start taking the drug immediately. No need to use any additional methods of contraception.

After childbirth or an abortion made in the second trimester, it is recommended to start taking the drug on day 21 or 28 after the childbirth or abortion made in the second trimester of pregnancy. When starting the drug at a later date, it is recommended to use barrier methods of contraception during the first seven days of taking Marvelon. In any case, if a woman after childbirth or an abortion has already had sexual contact before starting to take Marvelon, you should exclude pregnancy before taking the drug or wait until the first menstruation.

What to do if you miss the next drug intake

If the reception of the next pill is delayed for less than 12 hours, the reliability of contraception is not reduced. A woman should take a pill as soon as she remembered it, and take the next pill at the usual time.

If the reception of a regular pill is delayed by more than 12 hours, the reliability of contraception can be reduced. In this case, the following rules should be followed:

Week 1. A woman should take a missed pill as soon as she remembered, even if it means taking two pills at the same time. Then you should continue to receive the usual pattern. Additionally, use the barrier contraceptive method for the next 7 days. If a woman has had sexual intercourse within the previous 7 days, consider the possibility of pregnancy. The more tab. missed, and the closer the break in taking the drug to the time of sexual intercourse, the higher the risk of pregnancy.

Week 2. A woman should take the missed pill as soon as she remembered it, even if it means taking two tabs. at the same time. Then you should continue to receive the usual pattern. Provided that the woman took the tab. on time within 7 days preceding the first missed dose, there is no need to use additional (non-hormonal) methods of contraception. Otherwise, or if the woman missed more than 1 tablet, it is recommended to use additional methods of contraception for the next 7 days.

Week 3The reliability of contraception can be reduced, due to the subsequent interruption in the intake of the drug. This can be avoided by adapting the regimen. If you use either of the following two schemes, there is no need to use additional contraceptive measures, provided that the woman took the tab. On time within 7 days preceding the first missed dose.

Otherwise, it is recommended to use one of the two following schemes and also to use additional contraceptive measures over the next 7 days.

A woman should take the missed pill as soon as she remembered it, even if it means taking two tabs. at the same time. Then you should continue to receive the usual pattern. New packaging should start as soon as the current packaging ends, i.e. do not break between packs. The likelihood of withdrawal bleeding before the end of the second package is small, but some may experience a spotting or heavy bleeding even while taking the drug.

It may be recommended to stop taking the drug from the current package. A woman should take a break in taking Marvelon for up to seven days, including the days when she forgot to take a tab., And then start a new package.

When you skip the drug intake and the subsequent absence of bleeding in the near interruption in the reception, 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 the admission of the next drug intake. If a woman does not want to change her usual regimen, she needs to take an additional pill from another package.

How to change the period of menstruation. In order to delay menstruation, you should continue taking tab. from another package of Marvelon without the usual interruption in the intake. You can postpone menstruation for any period until the end of the tab. from the second pack. During this period, women may experience a spotting or heavy bleeding. Reception of the drug in the usual way should be resumed after a 7-day interval in reception.

In order to shift menstruation on a day of the week that differs from that which is expected if the usual regimen is observed, it is possible to reduce the usual interruption in reception for as many days as necessary. The shorter the break, the higher the risk of the absence of menstruation during the break and the occurrence of heavy or spotting bleeding while taking the drug from the second package.

Side effect

If you have any of the following conditions or risk factors, you should carefully weigh the benefits and the possible harm of taking Marvelon. This question should be discussed with the patient before the start of the drug.In the 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 physician should decide whether to discontinue the drug.

Vascular diseases

In the course of mass studies, it was found that there may be a link between using COCs and increasing the 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.

Venous thromboembolism (VTE), manifested as deep venous thrombosis and / or pulmonary embolism, can occur when taking COCs. The approximate incidence of VTE in women taking low-estrogen COCK (less than 50 micrograms) is 4 cases per 10,000 patients, compared with 0.5–3 cases per 10,000 patients in women not taking COCs. In any case, the incidence of VTE in women taking COCs is significantly lower than in women during pregnancy (6 cases per 10,000 women).

Thrombosis occurs very rarely in other blood vessels (for example, in the hepatic, peritoneal, renal, and veins and arteries of the retina). There is no single point of view whether this thrombosis is a consequence of the use of combined oral contraceptives.

Symptoms of venous or arterial thrombosis may include:

Pain and / or swelling of the legs, unexpected acute chest pain that may radiate to the left arm, an unexpected feeling of lack of air, an unexpected attack of cough, any unusual, acute, prolonged headache, unexpected complete or partial loss of vision, diplopia, unintelligible speech or speech disorder, dizziness, collapse, accompanied or not accompanied by local convulsions, weakness or a pronounced feeling of numbness in one side or part of the body, impaired motor function, "acute" stomach.

The risk of thromboembolism (venous and / or arterial) increases: with age, in smoking patients (with age in hard-core smokers, the risk increases greatly, especially in women older than 35 years), in the presence of thromboembolic diseases in the family history (eg. Venous or arterial thrombosis in brothers, sisters or parents at a relatively early age). In the case of a suspected hereditary predisposition, a woman should consult a specialist before taking any COCs. Obesity (body mass index more than 30kg / m², dyslipoproteinemia, hypertension, valvular disease, atrial fibrillation, prolonged immobility, major surgery, any surgery on the legs or serious injuries. In these cases, it is recommended to stop taking COCs (in the case of elective surgical interventions at least four weeks before the operation) and not to begin reception until two weeks after the full functional recovery.

There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism.

It should be borne in mind that the risk of thromboembolism increases in the postpartum period, with other diseases that may cause disturbances in the circulatory system, including diabetes mellitus, systemic lupus erythematosus, hemolytic-uremic syndrome, inflammatory bowel disease (Crohn's disease or ulcerative colitis), and sickle cell anemia.

With an increase in the frequency and intensity of migraines when taking COCs (which may be a sign of cerebrovascular disorders), it can serve as a basis for the immediate abolition of COCs.

When changing biochemical parameters, which may be markers of congenital or acquired susceptibility to venous or arterial thrombosis, including with resistance of activated protein C (APC), hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant).

When evaluating the positive and negative effects of taking COC, the doctor should consider that with adequate treatment of these diseases, the risk of developing thrombosis can be significantly reduced, and that the risk of developing thrombosis during pregnancy against the background of these diseases is significantly higher than when taking COCs.

Tumors

According to some studies, in patients who use COC for a long time. the risk of cervical cancer increases, but the accuracy of these reports is questioned, since it is not known to what extent the specific sexual behavior of a woman and other factors, such as the human papillomavirus, influence this data.

A meta-analysis of 54 large-scale studies has shown that there is a slight increase in the relative risk (1.24) of breast cancer in women using COCs. Excess risk gradually decreases over 10 years after the abolition of COC. Since breast cancer in women under 40 years of age is quite rare, the increase in the likelihood of developing breast cancer in women using COCs currently or recently abandoned their use is small relative to the initial probability of developing cancer. These studies do not provide data on the etiology of cancer. The increase in the risk of breast cancer can be explained both by the fact that women taking COCs, the diagnosis of breast cancer is established earlier, and the biological effects of COCs, or a combination of both of these factors. There is a tendency that women who have ever taken COCs have breast cancer that is less clinically advanced than women who have never taken COCs.

It is extremely rare, with the use of COCs, cases of benign, and even more rarely, malignant liver tumors have been observed.In some cases, these tumors led to life-threatening intraperitoneal bleeding. The physician should consider the possibility of having a liver tumor in the differential diagnosis of the disease in a woman taking COCs if the symptoms include severe pain in the upper abdomen, enlarged liver or signs of intraperitoneal bleeding.

Other diseases

If a woman or her family members are diagnosed with hypertriglyceridemia, an increase in the risk of pancreatitis is possible when taking COCs.

Although many people taking COCs show a slight increase in blood pressure, a clinically significant increase in this indicator is rarely observed. The relationship between taking COCs and clinically significant hypertension has not been established. In any case, if a clinically significant increase in pressure is observed during a long-term administration of COC, the physician should abolish the COC and prescribe the treatment of hypertension.

In cases where it is possible to achieve normal blood pressure with antihypertensive therapy, the doctor may find it possible for the patient to resume taking COCs.

There are reports that jaundice and / or pruritus caused by cholestasis, the formation of gallstones, porphyria, systemic lupus erythematosus, hemolytic-uremic syndrome, Sydengham's chorea (minor chorea), pregnant herpes, hearing loss due to otosclerosis develop or worsen during pregnancy, and at reception of KOK, however proofs of it regarding the reception of KOK, are inconclusive.

Acute or chronic abnormal liver function may serve as a basis for the abolition of COC until the liver function normalizes. Relapse of cholestatic jaundice, observed earlier during pregnancy or when using sex steroids, requires the abolition of COC.

Although COCs may affect peripheral tissue tolerance to insulin and glucose, there is no evidence that diabetics need to change the 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 can be pigmentation of the skin of the face, especially if it was previously during pregnancy. Women prone to pigmentation should avoid direct sunlight and ultraviolet radiation from other sources when taking COCs.

The following adverse events were also observed in women using COCs: breast tenderness and secretion, headache, changes in libido, depression, contact lens intolerance, nausea, vomiting, changes in vaginal secretion, various skin diseases, fluid retention, changes in body weight hypersensitivity reactions.

Oral contraceptives can affect the results of some laboratory tests, including biochemical indicators of the liver, thyroid gland, adrenal function and kidney function.plasma transport protein levels, for example, corticosteroid binding globulin and lipid / lipoprotein fractions, carbohydrate metabolism parameters, and coagulation and fibrinolysis parameters. Usually these changes are within the limits of laboratory norms.

Contraindications to the use of the drug

Combined oral contraceptives should not be taken if any of the diseases (conditions) listed below are present. If any of them occurs while taking the drug, you should immediately stop taking it:

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

the presence at present or in the history of possible clinical manifestations of thrombosis (for example, ischemic disease or angina);

- diabetes mellitus with vascular lesions;

- the presence of severe or multiple risk factors for venous or arterial thrombosis (see “Side Effects”);

- the presence at present or in the history of severe liver diseases (if the indicators of liver function have not returned to normal);

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

- an established or suspected hormone-dependent malignant tumor of the genitals or mammary glands;

- vaginal bleeding of unknown etiology;

- established or suspected pregnancy;

- lactation period;

- Hypersensitivity to any of the components of the drug;

- migraine with focal neurological symptoms;

- hypertriglyceridemia.

Use of the drug during pregnancy and lactation

The drug is contraindicated during lactation.

Application for violations of the liver

Contraindication: the presence or current history of severe liver disease (if the indicators of liver function have not returned to normal).

special instructions

Women who take any of the drugs listed above in the Interaction section for a short period of time should use a barrier contraceptive method in addition to COC throughout the course of treatment and for 7 days after discontinuation of the drug. When taking rifampcin, the method of barrier contraception should be used in addition to taking COCs during the entire course of treatment and within 28 days after discontinuation of the drug.

If the treatment with any of the above mentioned drugs ends later than the current package of the COC, you should start taking the drug from the next package without the usual interruption in reception.

Women, for a long period of time taking drugs that induce liver enzymes, it is recommended to increase the dosage of steroid contraceptives. If high dosages of contraceptives are undesirable, or if they cannot achieve satisfactory and reliable results, for example, in the case of irregular bleeding, other methods of contraception should be used.

Medical examinations / consultations

Before you assign a COC, the doctor should carefully read the medical history of the woman, as well as conduct a medical examination, guided by contraindications and warnings; This procedure should be repeated when taking COC at least once a year. Periodic medical examinations are important because diseases that are contraindications to taking COCs (for example, a transient cerebral circulation disorder) or risk factors (for example, the presence of family members of venous or arterial thrombosis) may appear for the first time 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 blood pressure measurement. examination of the mammary glands, abdominal organs and small pelvis, including cervical cytology and relevant laboratory tests.

You should inform the woman that oral contraceptives do not protect against HIV (AIDS) and other sexually transmitted diseases.

Reduced efficiency

The effectiveness of COCs may decrease if you miss a drug, vomit, or take certain drugs.

Irregular bleeding

When taking COCs, especially in the first months. use, there may be irregular (not coincident in time with menstruation) spotting or heavy bleeding.Any bleeding acquire clinical significance only after the adaptation period, lasting three menstrual cycles.

If a woman with a previously established menstrual cycle continues to be observed or irregular bleeding occurs, possible non-hormonal causes of a violation of the cycle should be taken into account and appropriate studies should be conducted to exclude malignant tumors or pregnancy. These measures may include diagnostic curettage.

Some women do not experience bleeding in the interval between taking the drug. If KOCs were taken as recommended above, the likelihood that a woman is pregnant is small. Otherwise, or if there is no bleeding twice in a row, the possibility of pregnancy should be excluded before resuming COCs.

Influence on ability to drive a car and other mechanisms

The effect of Marvelon on the ability to drive and operate machinery was not observed.

Overdose

No serious complications were observed in case of an overdose of Marvelon. Phenomena that may occur during overdose: nausea, vomiting, in young girls - bloody discharge from the vagina. There are no antidotes and further treatment should be symptomatic.

Drug interaction

Interaction with certain medicinal substances can lead to heavy bleeding and ineffectiveness of oral contraceptives.Such cases were observed when taking hydantoins, barbiturates, primidone, Carbamazepine, rifampicin, isoniazid; they are possible with the appointment of oxcarbazepine, topiramate, felbamate and Griseofulvin . The mechanism of interaction is based on the induction of these drugs of certain liver enzymes involved in the metabolism of COCs. The maximum level of induction is usually achieved not earlier than in 2-3 weeks, but then it can last up to 4 weeks after drug withdrawal. A decrease in the effectiveness of oral contraceptives has also been observed when taking certain antibiotics, such as ampicillin, Tetracycline, neomycin, penicillins, chloramphenicol, Activated carbon, and laxatives.

Reduces the effectiveness of oral anticoagulants, anxiolytics (diazepam), tricyclic antidepressants, theophylline, caffeine, hypoglycemic drugs, clofibrate and glucocorticosteroids.

Terms and conditions of storage

Store at a temperature of 2-30 ° C. Protect from light and moisture. Keep out of the reach of children.