Desogestrel, Ethinyl Estradiol

Pharmacological properties

the effect of combined oral contraceptives (PDA) is based on the interaction of various factors, the most important of which are inhibition of ovulation and changes in cervical secretion. In addition to preventing pregnancy, PDAs have a number of positive properties that can be useful when choosing a method of contraception. the menstrual cycle becomes more regular, menstruation less painful, and blood loss decreases. the latter can help reduce the incidence of iron deficiency anemia. There is evidence that the use of high-dose combined contraceptives (50 μg ethinyl estradiol) reduces the risk of developing benign diseases of the mammary glands, ovarian cysts, pelvic inflammatory diseases, ectopic pregnancy, endometrial and ovarian cancer.

Pharmacokinetics

Desogestrel

Suction. Orally administered desogestrel is rapidly and completely absorbed and converted to etonogestrel. WITH_max in blood plasma (about 2 ng / ml) is achieved approximately 1.5 hours after a single dose. Bioavailability is 62–81%.

Distribution. Etonogestrel binds to serum albumin and sex hormone binding globulin (SHBG). Only 2–4% of the total plasma concentration is present as a free steroid, and 40–70% are specifically associated with SHBG; the increase in SHBG induced by ethinyl estradiol affects the distribution between blood plasma proteins, which leads to an increase in SHBG-related fraction and a decrease in albumin-bound fraction; the expected volume of distribution of desogestrel is 1.5 l / kg.

Metabolism. Etonogestrel is completely metabolized along known pathways of steroid metabolism; the metabolic clearance rate from the blood is about 2 ml / min / kg body weight; no interaction with ethinyl estradiol administered at the same time.

The level of etonogestrel in the blood decreases two-phase; distribution in the final phase is characterized by T_½ about 30 hours; desogestrel and its metabolites are excreted in urine and bile in a ratio of 6: 4.

The pharmacokinetics of etonogestrel are affected by the level of SHBG, which increases three times under the influence of ethinyl estradiol; with daily intake, its serum level rises by about 2-3 times, reaching an equilibrium state in the second half of the course use of the drug.

Ethinyl estradiol

Suction. After oral administration, ethinyl estradiol is rapidly and completely absorbed; C_max in blood serum (about 80 pg / ml) is achieved within 1-2 hours; absolute bioavailability as a result of presystemic conjugation and the first stage of metabolism is about 60%.

Distribution. Ethinyl estradiol firmly, but non-specifically binds to serum albumin (about 98.5%) and causes an increase in serum concentration of SHBG; the volume of distribution is about 5 l / kg.

Metabolism. Ethinyl estradiol is susceptible to presystemic conjugation both in the mucous membrane of the small intestine and in the liver; ethinyl estradiol is first metabolized by aromatic hydroxylation, but a large number of hydroxylated and methylated metabolites are formed, which are subsequently present not only as free metabolites, but also as conjugates with glucuronides and sulfates; metabolic clearance rate is about 5 ml / min / kg.

The level of ethinyl estradiol in the blood decreases two-phase, the distribution in the final phase is characterized by T_½ about 24 hours. Unchanged active substance is not excreted, ethinyl estradiol metabolites are excreted in the urine and bile in a ratio of 4: 6; T_½ metabolites is about 1 day.

State of equilibrium.Equilibrium concentrations are reached after 3-4 days of taking the drug, when its level in the blood is 30-40% higher compared to taking a single dose.

Indications

Prevention of pregnancy (contraception).

Application

General rules for taking marvelon.

Tablets should be taken daily for 21 days in accordance with the specified order on the package without interruptions, approximately at the same time, one tablet per day, washed down with a small amount of liquid if necessary. After a 21-day course, take a break for 7 days. During this period, a menstrual-like reaction occurs, the duration of which can be shorter and the intensity is lower than normal menstruation. As a rule, it begins on the 2nd – 3rd day after taking the last pill and can continue until the next course of the drug (next pack) is taken. Reception of tablets from the following package begins after 7 days of the “without tablets” period.

Start taking Marvelon

Hormonal contraceptives in the previous period (last month) were not used

Pills are taken on the 1st day of the natural cycle (that is, on the first day of menstrual bleeding). You can start taking it from day 2-5, however, in this case, during the first cycle, it is recommended to additionally use the barrier method of contraception during the first 7 days of taking the tablets.

Switching from another PDA

It is advisable that the woman start taking Marvelon the day after taking the last active pill of the previous combined contraceptive, but no later than the day after the break in taking the pills or placebo of the previous combined contraceptive.

The transition from a method that is based on the use of only progestogen (mini-drank, injections, implants)

A woman can start taking Marvelon on any day after stopping the use of mini-saws (in the case of an implant - on the day of its removal, in the case of injections - instead of the next injection). However, in all cases, it is advised to additionally use the barrier method of contraception during the first 7 days of taking the tablets.

After an abortion in the first trimester

A woman can start taking Marvelon immediately. In this case, she does not need to use additional methods of contraception.

After childbirth or abortion in the II trimester

Women should be advised to start taking Marvelon on the 21st or 28th day after childbirth or abortion in the second trimester. At a later start, you should additionally use the barrier method of contraception during the first 7 days of taking the tablets. However, if sexual intercourse has already occurred, then before starting the use of CPC, it is necessary to establish the presence of pregnancy or wait for the next menstruation.

What to do if you miss a pill

If the delay in taking the pill did not exceed 12 hours, the contraceptive effect of Marvelon will continue throughout the entire period of taking the drug. If, for any reason, the woman forgot to take the Marvelon pill, she must be taken as soon as she finds out. In the future, taking tablets from this pack should be continued as usual.

If the time delay for taking the pill exceeds 12 hours, the contraceptive effect may decrease. In case of skipping pills, you can follow 2 basic rules:

taking tablets cannot be interrupted for more than 7 days;

to achieve an adequate inhibitory effect of the drug on the axis of the hypothalamus - pituitary - ovaries, continuous administration of the drug is necessary for 7 days.

Accordingly, they recommend that you follow these tips.

First week

A woman should take the last missed pill as soon as she remembers the pass, even if you have to take 2 tablets at the same time. Then she continues to take pills at the usual time.In addition, over the next 7 days it is necessary to use the barrier method of contraception. If during the previous 7 days, sexual intercourse took place, you should consider the possibility of pregnancy. The more tablets missed and the closer the pass to the normal period without tablets, the higher the risk of pregnancy.

Second week

A woman should take the last missed pill as soon as she remembers the pass, even if you have to take 2 tablets at the same time. Then she continues to take pills at the usual time. If a woman took the pill correctly for 7 days before skipping, then there is no need to use additional contraceptive measures. Otherwise, or if more than 1 tablet is missed, the barrier method of contraception should additionally be used for 7 days.

Third week

The risk of a decrease in the reliability of contraception increases as the break in pills is approaching. However, if you follow the pill regimen, you can avoid lowering the level of contraception. If you adhere to one of the following rules, then there will be no need to use additional contraceptives, provided that the woman took the pill correctly for 7 days before skipping. If not, the woman should adhere to the first of the following rules and use additional methods of protection for the next 7 days.

A woman should take the last missed pill as soon as she remembers the pass, even if you have to take 2 tablets at the same time. Then she continues to take pills at the usual time. Tablets from the next package should be taken 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 begin to have menstrual-like discharge before completing taking the tablets from the second package, although smearing or sudden bleeding may be noted during the administration of the tablets.

A woman can also be advised to stop taking pills from the packaging used. In this case, the break should be 7 days, including days of skipping pills; taking tablets should begin with the next package. If a woman missed taking the pills and she did not have menstrual discharge during the first usual break in taking the drug, pregnancy should be assumed.

Recommendations for vomiting

If vomiting occurs within 3-4 hours after taking the pill, then incomplete absorption of the drug is possible. In this case, it is advisable to adhere to the recommendations regarding skipping the pill. If a woman does not want to change her usual regimen, she needs to take an extra tablet from another package.

How to change or delay the onset of menstruation

To delay the onset of menstruation, a woman should continue taking Marvelon from a new package and not take a break. If desired, the period of administration can be extended until the completion of the administration of tablets from the second package. In this case, sudden short-term bleeding or smearing may occur. Marvelon’s regular intake resumes after the usual 7-day pill break.

In order to change the period of menstruation - to move its beginning to another day of the week, a woman can be recommended to shorten the period without taking pills by the required number of days. The shorter this period, the greater the likelihood of the absence of bleeding cancellation and the occurrence of smearing or short-term bleeding during the reception of the next package (as with a delay in menstruation).

Contraindications

Taking combined contraceptives is contraindicated in any of the following conditions.if any of these conditions occurs during the first use of combined contraceptives, the drug should be stopped immediately:

thrombosis (venous or arterial), including medical history (e.g. deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);

the presence, including a history, of the precursors of thrombosis (e.g. angina pectoris, cerebrovascular accident);

migraine with focal neurological symptoms;

diabetes mellitus with vascular complications;

the presence of thrombosis;

pancreatitis or transferred pancreatitis, accompanied by high hypertriglyceridemia;

severe liver diseases, including a history of indications (until normalization of liver function indicators);

liver tumors (benign or malignant), including a history of;

hormone-dependent malignant tumors (established or suspected, for example, genital or mammary gland tumors);

vaginal bleeding of unknown etiology;

established or suspected pregnancy;

hypersensitivity to any component of the drug.

PDA products should be taken with caution in any of the following conditions: obesity (body mass index 30 kg / m²); high blood pressure; atrial fibrillation; heart valve disease; dyslipoproteinemia; liver and gall bladder disease; Crohns 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; congenital hyperbilirubinemia (Gilbert syndrome, Dubin-Johnson and Rotor syndrome); chloasma (for women predisposed to pigmentation, it is recommended to avoid exposure to the sun or under the influence of ultraviolet radiation when taking CPC).

Side effects

There are reports of the following side effects (however, their relationship with the use of the drug is not confirmed or refuted): soreness and swelling of the mammary glands and the occurrence of secretion; headache, migraine; change in libido; depressive state; intolerance to contact lenses; nausea; vomiting changes in vaginal secretion; various skin manifestations; fluid retention in the body; change in body weight; hypersensitivity reactions.

special instructions

The daily dose of lactose contained in the tablet is so low (80 mg) that even women who are sensitive to lactose will not feel any disturbance.

Warning

In the presence of any of the indicated conditions / risk factors in the CONTRAINDICATIONS section, the benefits and risk of using CPC should be considered by a doctor individually for each woman and discussed with the patient before she decides to take this drug. In the event of an exacerbation, amplification, or first occurrence of any of these conditions, a woman should consult a doctor. The doctor must determine whether to continue or stop taking the PDA.

Medical examination / consultation

Before starting or before resuming ingestion of combined contraceptives, a thorough medical examination of the woman should be carried out, including a complete history and instrumental studies, paying particular attention to possible contraindications. Such an examination must be repeated at least 1 time per year during the entire intake of combined contraceptives. Periodic medical evaluations are important for contraindications (such as cerebrovascular accidents) or risk factors (such as the presence of venous or arterial thrombosis in relatives) that may occur during contraceptive use for the first time. The frequency and nature of such examinations is set individually for each woman, however, in general, they should include measurement of blood pressure, examination of the mammary glands, abdominal and pelvic organs, cytological examination of the cervical epithelium and appropriate laboratory tests.

Women should be made aware that oral contraceptives do not protect against HIV / AIDS and other sexually transmitted diseases.

Decreased efficiency

The effectiveness of the CPC may decrease if you miss the pill (see APPLICATION), gastrointestinal disturbances, or while taking certain drugs (see INTERACTIONS).

Menstrual cycle deterioration

During use, CCPs may indicate irregular minor (smearing) or heavy bleeding, especially during the first months of admission. Therefore, the assessment of any violations of the control of the menstrual cycle can be carried out only after an adaptation period of approximately 3 cycles.

If irregular bleeding persists or occurs after previous regular cycles, you should consider the possible non-hormonal causes and conduct the necessary diagnostic tests to rule out pregnancy or tumor; curettage is possible.

In some women, withdrawal bleeding may not occur during the tablet-free period. If PDAs were used according to the recommendations, then the probability of pregnancy is small. Nevertheless, if violations of these recommendations were noted in the period before the first absence of bleeding in the period without taking pills or if bleeding is absent twice in a row, pregnancy should be excluded before continuing with CPC.

The use of the drug during pregnancy and / or breastfeeding. Pregnancy is a contraindication for the use of Marvelon. If a woman becomes pregnant while taking Marvelon, further administration should be stopped immediately. The studies did not reveal an increase in the risk of pathology in children born to mothers who took CPC during pregnancy, nor the teratogenic effect of CPC, which were inadvertently taken at the beginning of pregnancy.

Estrogens have an effect on lactation, since they can reduce the amount and change the composition of breast milk, however, there were no signs of a negative effect on the health of infants. However, it is not recommended to use CPC during breastfeeding; if necessary, use of CPC should completely stop breastfeeding.

Impact on the ability to drive vehicles. The ability to concentrate is not affected.

Interactions

The interaction between oral contraceptives and other drugs can lead to sudden bleeding and / or weakening of the contraceptive effect of the drug. interactions can be noted with drugs that induce microsomal enzymes, which can lead to increased metabolism of sex hormones. such drugs include phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and St. Johns wort preparations. the effectiveness of the drug may also decrease with the concomitant use of certain antibiotics, such as penicillins and tetracyclines. these drugs reduce the enterohepatic circulation of estrogen, which leads to a decrease in the concentration of ethinyl estradiol.

Women taking any of these drugs should temporarily use a barrier method of contraception in addition to CPC or choose another method of protection against unwanted pregnancy. Women taking antibiotics (except rifampicin and griseofulvin) need to use the barrier method while taking the appropriate drug and for 7 days after its cancellation. When taking drugs that stimulate microsomal enzymes, it is necessary to use the barrier method in addition to CPC for the entire duration of treatment and for another 28 days after stopping the dose. If the administration of the drug should be continued, and the tablets in the CPC package have already ended, the next package should be started immediately, without the usual break.

PDAs can affect the metabolism of other drugs. Accordingly, the concentration of such drugs (for example, cyclosporine) in blood plasma and tissues may change.

Note.To determine the possible interaction, you should study the information on the purpose of the drug, which is used in parallel.

Laboratory tests. Contraceptive steroids can affect the results of certain laboratory tests, including biochemical indicators of liver, kidney, thyroid, adrenal gland function, serum protein (transporters), e.g. globulin, corticosteroid binding and / or lipid / lipoprotein fractions, carbohydrate metabolism, coagulation and fibrinolysis. Changes usually remain within the normal range.

Overdose

No significant adverse effects in overdose have been reported. The following symptoms may occur: nausea, vomiting, and in girls - minor spotting from the vagina. there is no antidote. if necessary, symptomatic therapy is indicated.

Storage conditions

In a place protected from light and moisture at a temperature of 2-30 ° c.