Фемоден®

General characteristics. Structure:

Active agents: 0,075 mg of a gestoden and 0,03 mg of ethinylestradiol.
Excipients: lactoses monohydrate, corn starch, povidone 25000, calcium sodium эдетат, magnesium stearate, sucrose, povidone 700000, polyethyleneglycol (macrogoal) 6000, calcium carbonate, talc, wax montan гликолиевый.

Description. Dragee of white color, round form.

Pharmacological properties:

Pharmacodynamics. Femoden - the combined estrogen-gestagenny low-dosed monophase peroral contraceptive drug.
The contraceptive effect of Femoden is carried out by means of complementary mechanisms suppression of an ovulation and change of properties of a cervical secret therefore it becomes impenetrable for spermatozoa concern to the most important of which.
At the women accepting the combined oral contraceptives, the menstrual cycle becomes more regular, painful periods are less often observed, intensity of bleeding therefore the risk of an iron deficiency anemia decreases decreases. Besides, there are data that the risk of development of endometrial cancer and ovarian cancer decreases.

Pharmacokinetics. Gestoden
Absorption. After intake гестоден it is quickly and completely absorbed, its maximum concentration in blood serum, equal 3,5 ng/ml, is reached approximately in 1 hour. Bioavailability makes about 99%.
Distribution. Gestoden contacts albumine of blood serum and the globulin, connecting sexual steroids (G,CSS). In a free look there are only about 1,3% of the general concentration in blood serum; about 69% - are specifically connected with GSPS. Induction by ethinylestradiol of synthesis of GSPS influences linkng of a gestoden with a serumal protein.
Metabolism. Gestoden is almost completely metabolized. The clearance makes about 0,8 ml/min. of serum.
Removal. The maintenance of a gestoden in serum is exposed to two-phase decrease. The elimination half-life in a terminal phase makes about 12 h. In not changed form гестоден it is not removed but only in the form of metabolites which are removed with urine and bile in the ratio about 6:4 with an elimination half-life about 24 h.
Equilibrium concentration. The pharmacokinetics of a gestoden is influenced by the GSPG level in blood serum. As a result of daily administration of drug substance level in serum increases approximately by 4 times during the second half of a medical cycle.
•  Ethinylestradiol
Absorption. After intake ethinylestradiol is quickly and completely absorbed. The maximum concentration in blood serum, equal about 65 pg/ml, is reached for 1 - 2 h. During absorption and the first passing through a liver ethinylestradiol is metabolized therefore its bioavailability at intake averages about 45%. Distribution. Ethinylestradiol almost completely (about 98%), though it is not specific, communicates albumine. Ethinylestradiol induces synthesis of GSPG. The seeming volume of distribution of ethinylestradiol is equal to 2,8 - 8,6 l/kg. Metabolism. Ethinylestradiol is exposed to presistemny conjugation, both in mucous a small bowel, and in a liver. The main way of metabolism - an aromatic hydroxylation. Clearance speed makes 2,3 - 7 ml/min. of a blood plasma.
Removal. Reduction of concentration of ethinylestradiol in blood serum has two-phase character; the first phase is characterized by an elimination half-life about 1 hour, the second — 10 — 20 hours. In not changed view from an organism it is not removed. Metabolites of ethinylestradiol are removed with urine and bile in the ratio 4: 6 with an elimination half-life about 24 h.
Equilibrium concentration. Equilibrium concentration is reached approximately in one week.

Indications to use:

Contraception.

Route of administration and doses:

The dragee should be accepted inside on the order specified on packaging, every day approximately at the same time with a small amount of water. Accept on one dragee a day continuously within 21 days. Reception of the following packaging begins after a 7-day break in reception of a dragee during which cancellation bleeding usually develops. Bleeding, as a rule, begins for 2-3 day after reception of the last dragee and can not end prior to reception of new packaging.
How to begin Femoden's reception
• In the absence of reception of any hormonal contraceptives last month.
Femoden's reception begins in the first day of a menstrual cycle (i.e. in the first day of menstrual bleeding). The beginning of reception on 2-5 menstrual cycles is allowed, but in this case it is recommended to use in addition a barrier method of contraception during the first 7 days of reception of a dragee from the first packaging.
• Upon transition from other combined oral contraceptives.
It is preferable to begin Femoden's reception next day after reception of the last active dragee from the previous packaging, but by no means no later than the next day after a usual 7-day break (for the drugs containing 21 dragees) or after reception of the last inactive dragee (for the drugs containing 28 dragees in packaging).
• Upon transition from the contraceptives containing only gestagena ("mini-drank", injection forms, an implant), or from the intrauterine contraceptive (Mirren) releasing гестаген.
The woman can pass with mini-saw on Femoden in any day (without interruption), from an implant or an intrauterine contraceptive with gestageny - in day of its removal, from an injection form - from the date of when the following injection has to be made. In all cases it is necessary to use in addition barrier method of contraception during the first 7 days of reception of a dragee.
• After abortion in the first trimester of pregnancy.
The woman can begin administration of drug immediately. At observance of this condition the woman does not need additional contraceptive protection.
• After the delivery or abortion in the second trimester of pregnancy.
It is recommended to begin administration of drug for 21-28 day after the delivery or abortion in the second trimester of pregnancy. If reception is begun later, it is necessary to use in addition barrier method of contraception during the first 7 days of reception of a dragee. However if the woman already led sex life, prior to reception Femodena has to be excluded pregnancy or it is necessary to wait for the first periods.
Reception of the passed dragees
If delay in administration of drug made less than 12 hours, contraceptive protection does not decrease. The woman has to accept a dragee as soon as possible, the following is accepted in usual time.
If delay in reception of a dragee made more than 12 hours, contraceptive protection can be reduced. At the same time it is possible to be guided by the following two basic rules:
• Administration of drug never has to be interrupted, more than for 7 days.
• 7  days  of continuous  reception  of a dragee  are required  for  achievement of adequate suppression гипоталамо - pituitary and ovarian regulation.
The following advice if delay in reception of a dragee made more than 12 hours (an interval can be respectively given from the moment of reception of the last dragee more than 36 hours):
• First week of administration of drug
The woman has to accept the last passed dragee as soon as possible as soon as remembers (even if it means reception of two dragees at the same time). The following dragee is accepted in usual time. The barrier method of contraception (for example, condom) during the next 7 days has to be in addition used. If the sexual intercourse took place within a week before the admission of a dragee, it is necessary to consider probability of approach of pregnancy.
Than more dragee is passed, and the closer they to a break in reception of active agents, the are higher probability of pregnancy.
• Second week of administration of drug
The woman has to accept the last passed dragee as soon as possible as soon as remembers (even if it means reception of two dragees at the same time). The following dragee is accepted in usual time.
Provided that the woman accepted a dragee correctly within 7 days preceding the first passed dragee there is no need for use of additional contraceptive measures. Otherwise, and also at the admission of two and more dragees it is necessary to use in addition barrier methods of contraception (for example, condom) within 7 days.
•  The third week of administration of drug the Risk  of decrease  in reliability  of contraception  is inevitable  because of  the forthcoming break in reception of a dragee.
The woman has to adhere strictly to one of two following options.
At the same time if in 7 days preceding the first passed dragee, all
dragees   were accepted   correctly,    there is no need    to use
additional contraceptive methods.
1. The woman has to accept the last passed dragee as soon as possible as soon as remembers (even if it means, reception of two dragees at the same time). The following dragees accept in usual time, dragees from the current packaging will not end yet. The following packaging should be begun at once. Bleeding of cancellation is improbable, the second packaging will not end yet, but the smearing allocations and breakthrough bleedings can be noted during reception of a dragee.
2. The woman can also interrupt reception of a dragee from the current packaging. Then it has to take a break for 7 days, including day of the admission of a dragee and then begin reception of new packaging.
If the woman missed reception of a dragee, and then during a break in reception of a dragee she has no cancellation bleeding, it is necessary to exclude pregnancy.
Recommendations in case of vomiting and diarrhea
If the woman had a vomiting or diarrhea in limits till 4 o'clock after reception of active dragees, absorption can be not full and additional contraceptive measures have to be taken. In these cases it is necessary to be guided by recommendations at the admission of a dragee.
Change of day of the beginning of a menstrual cycle
To delay the beginning of periods, the woman has to continue reception of a dragee from new packaging of Femoden right after all dragees from previous, without interruption in reception are accepted. Dragees from this new packaging can be accepted as long as the woman wishes (until packaging does not end). Against the background of administration of drug from the second packaging at the woman the smearing allocations or breakthrough uterine bleedings can be noted. It is necessary to resume Femoden's reception from a new pack after a usual 7-day break.
To transfer day began periods the next day of week, the woman needs to recommend to truncate the next break in reception of a dragee for so many days, on how many it wants. The interval is shorter, the risk is higher that it will have no cancellation bleeding, and further there will be smearing allocations and breakthrough bleedings during reception of the second packaging (just as in case she like to delay the beginning of periods).

Features of use:

If any of the states/risk factors provided below are available now, then it is necessary to weigh carefully potential risk and the expected advantage of use of the combined oral contraceptives in each individual case and to discuss it with the woman before she decides to begin administration of drug. In case of weighting, strengthening or the first manifestation of any of these states or risk factors, the woman has to consult with the doctor who can make the decision on need of drug withdrawal.
•  Diseases of cardiovascular system
There are frequencies of development of venous and arterial thromboses and thromboembolisms given about increase (such as deep vein thrombosis, thromboembolism of a pulmonary artery, myocardial infarction, stroke) at reception of the combined oral contraceptives.
The risk of development of a venous thromboembolism (VTE) is maximum in the first year of reception of such drugs. Approximate frequency of emergence of VTE among the women accepting the low-dosed oral contraceptives (<0,05 mg of ethinylestradiol), makes to 4 for 10 000 cheloveko-years in comparison with 0,5 - 3 for 10 000 cheloveko-years among the women who are not using Apprx. the Frequency of emergence of VTE against the background of pregnancy makes 6 for 10 000 cheloveko-years.
The risk of development of thrombosis (venous and/or arterial) and thromboembolisms increases:
- with age;
- at smokers (with increase in quantity of cigarettes or increase in age the risk increases further, especially at women 35 years are more senior);
in the presence:
- the family anamnesis (i.e. a venous or arterial thromboembolism ever at close relatives or parents at rather young age); in case of genetic predisposition, the woman has to be examined by the corresponding specialist for the solution of a question of a possibility of reception of the combined oral contraceptives;
- obesity (index of body weight of more than 30 kg/sq.m);
- dislipoproteinemiya;
- arterial hypertension;
- migraines;
- diseases of valves of heart;
- fibrillations of auricles;
- long immobilization, serious surgical intervention, any operation standing or extensive injury. In these situations it is desirable to stop use of the combined oral contraceptives (in case of the planned operation, at least, in four weeks prior to it) and not to resume reception within two weeks after the termination of an immobilization.
The question of a possible role of a varicosity and superficial thrombophlebitis in development of a venous thromboembolism remains disputable.
It is necessary to consider the increased risk of development of thromboembolisms in a puerperal period.
Disturbances of peripheric circulation can be also noted at a diabetes mellitus, a system lupus erythematosus, a hemolitic uraemic syndrome, chronic inflammatory diseases of intestines (a disease Krone or nonspecific ulcer colitis) and a sickemia.
Increase in frequency and weight of migraine during use of the combined oral contraceptives (that can precede cerebrovascular disturbances) can be the basis for the immediate termination of reception of these drugs.
•  Tumors
The most essential risk factor of development of cancer of neck of uterus, the persistent human papillomavirus infection is. There are messages on some increase in risk of development of cancer of neck of uterus at prolonged use of the combined oral contraceptives. Communication with reception of the combined oral contraceptives is not proved. Contradictions concerning in what degree these finds are connected with screening regarding pathology of a neck of uterus or with features of a sexual behavior (more rare use of barrier methods of contraception) remain.
Also it was revealed that there is a little increased relative risk of development of the breast cancer diagnosed for women who used the combined oral contraceptives (relative risk 1,24). The increased risk gradually disappears within 10 years after the termination of reception of these drugs. Its communication with reception of the combined oral contraceptives is not proved. Observed increase in risk can be also a consequence of earlier diagnosis of a breast cancer at the women applying the combined oral contraceptives. At the women ever using the combined oral contraceptives earlier stages of a breast cancer, than at women, never their applying come to light.
In rare instances against the background of use of the combined oral contraceptives development of tumors of a liver which in some cases led to life-threatening intra belly bleeding was observed. In case of severe pains in a stomach, increases in a liver or symptoms of intra belly bleeding it should be considered when carrying out the differential diagnosis.
•  Other states
At women with a gipertriglitseridemiya (or in the presence of this state in the family anamnesis) increase in risk of development of pancreatitis is possible during reception of the combined oral contraceptives.
Though small increase in arterial pressure was described at many women accepting the combined oral contraceptives, clinically significant increases were noted seldom. Nevertheless, if during reception of the combined oral contraceptives permanent, clinically significant increase in arterial pressure develops, it is necessary to cancel these drugs and to begin treatment of arterial hypertension. Reception of the combined oral contraceptives can be continued if by means of hypotensive therapy normal values of arterial pressure are reached.
The following states as it was reported, develop or worsen both during pregnancy, and at reception of the combined oral contraceptives, but their communication with reception of the combined oral contraceptives is not proved: jaundice and/or the itch connected with a cholestasia; formation of stones in a gall bladder; porphyria; system lupus erythematosus; hemolitic uraemic syndrome; Sydenham's chorea; herpes of pregnant women; the hearing loss connected with an otosclerosis. Disease cases Krone and nonspecific ulcer colitis against the background of use of the combined oral contraceptives are also described.
Acute or chronic abnormal liver functions can demand cancellation of the combined oral contraceptives until indicators of function of a liver do not return to norm. Recurrent cholestatic jaundice which develops for the first time in time of pregnancy or previous reception of sex hormones demands the termination of reception of the combined oral contraceptives.
Though the combined oral contraceptives can exert impact on resistance to insulin and tolerance to glucose, the patients with a diabetes mellitus using the low-dosed combined oral contraceptives have no need of change of the therapeutic mode (<0,05 mg of ethinylestradiol). Nevertheless, women with a diabetes mellitus have to be observed carefully during reception of the combined oral contraceptives.
The hloazma can sometimes develop, especially women with existence in the anamnesis have hloazma of pregnant women. Women with tendency to a hloazma during reception of the combined oral contraceptives have to avoid long stay to the sun and influences of ultraviolet radiation.
Laboratory tests
Reception of the combined oral contraceptives can influence results of some laboratory tests, including indicators of function of a liver, kidneys, a thyroid gland, adrenal glands, level of transport proteins in plasma, indicators of carbohydrate metabolism, parameters of coagulation and a fibrinolysis. Changes usually do not overstep the bounds of normal values.
Influence on a menstrual cycle
Against the background of reception of the combined oral contraceptives the irregular bleedings (smearing bloody allocations or breakthrough bleedings), especially within the first months of use can be noted. Therefore, assessment of any irregular bleedings has to be carried out only after the period of adaptation making about three cycles.
If irregular bleedings repeat or develop after the previous regular cycles, it is necessary to conduct careful examination for an exception of malignant new growths or pregnancy.
At some women during a break in reception of a dragee cancellation bleeding can not develop. If the combined oral contraceptives were accepted as directed, it is improbable that the woman is pregnant. Nevertheless, if before the combined oral contraceptives were accepted irregularly or if there are no in a row two bleedings of cancellation, before continuation of administration of drug pregnancy has to be excluded.
Medical examinations
Before the beginning or resuming of use of drug Femoden it is necessary to study the anamnesis of life, the family anamnesis of the woman, to carry out careful all-medical (including measurement of the ABP, heart rate, definition of an index of body weight) and gynecologic inspection (including a research of mammary glands and a cytologic research of cervical slime), to exclude pregnancy. The volume of additional researches and frequency of control surveys is defined individually. Usually control examinations should be conducted at least 1 time a year.
It is necessary to warn the woman that Femoden drugs do not protect from HIV infection (AIDS) and other diseases, sexually transmitted!

Influence on ability to drive the car and the equipment.
It is not revealed.

Side effects:

At reception of the combined oral contraceptives the irregular bleedings (smearing bloody allocations or breakthrough bleedings), especially within the first months of use can be noted.
Against the background of reception of the combined oral contraceptives at women also other undesirable effects were observed
System of bodies        Often (> 1/100)      Infrequently (> 1/1000 and <1/100)   it is rare (<1/1000)
Organ of sight                                                                                          intolerance 
                                                                                                              contact lenses 
                                                                                                               (unpleasant oshchu-
                                                                                                              shcheniya at them 
                                                                                                               carrying)
Gastro              nausea, pain in    vomiting, diarrhea
intestinal path       stomach
Immune system                                                                                  allergic reactions
General symptoms     increase in weight                                                    weight reduction
Metabolism                                               liquid delay
Nervous system      headache       migraine
Psychiatric      decrease              decrease in a libido                    increase in a libido
frustration            of mood, 
                                differences
                                    moods
Reproductive          pain in                   a hypertrophy                        vaginal
system and milk                                     allocations of mammary mammary glands,
glands                       glands,                                                                allocations from
                                    nagrubaniye                                                           of mammary glands
                                    mammary glands
Skin and                                                        rash, urticaria                knotty erythema,
hypodermic fabrics                                                                                      multiformny
                                                                                                                    erythema

As well as at reception of other combined oral contraceptives development of thromboses and thromboembolisms in rare instances is possible (see also "Special instructions").

Interaction with other medicines:

Interaction of oral contraceptives with other medicines can lead to breakthrough bleedings and/or decrease in contraceptive reliability. In literature it was reported about the following types of interaction.
Influence on hepatic metabolism: use of the drugs inducing microsomal enzymes of a liver can lead to increase of clearance of sex hormones. Treat such medicines: Phenytoinum, barbiturates, Primidonum, carbamazepine, rifampicin; also there are assumptions concerning an okskarbazepin, a topiramata, a felbamata, a ritonavir and the griseofulvin and drugs containing a St. John's Wort.
Influence on enterohepatic circulation: according to separate researches, some antibiotics (for example, penicillin and tetracycline) can reduce kishechnopechenochny circulation of estrogen, thereby, lowering concentration of ethinylestradiol.
During administration of drugs, influencing microsomal enzymes, and within 28 days after their cancellation it is necessary to use a barrier method of contraception in addition.
During reception of antibiotics (such as penicillin and tetracyclines) and within 7 days after their cancellation it is necessary to use a barrier method of contraception in addition. If the period of use of a barrier method of protection comes to an end later, than a dragee in packaging, it is necessary to pass to the following packaging of Femoden without usual break in reception of a dragee.
The oral combined contraceptives can influence metabolism of other drugs (including, cyclosporine) that leads to change of their concentration in plasma and fabrics.

Contraindications:

Drug Femoden should not be used in the presence of any of the states which are listed below. If any of these states develop for the first time against the background of reception, drug has to be immediately cancelled.
• Fibrinferments (venous and arterial) and thromboembolisms now or in the anamnesis (including, a deep vein thrombosis, a thromboembolism of a pulmonary artery, a myocardial infarction, cerebrovascular disturbances).
• The states preceding thrombosis (including, the tranzitorny ischemic attacks, stenocardia) now or in the anamnesis.
• Migraine with focal neurologic symptoms now or in the anamnesis
• A diabetes mellitus with vascular complications.
• The multiple or expressed risk factors of venous or arterial thrombosis, including defeat of the valve device of heart, disturbance of a cordial rhythm, a disease of vessels of a brain or coronary arteries of heart; uncontrollable arterial hypertension.
• Pancreatitis with the expressed gipertriglitseridemiya now or in the anamnesis.
• A liver failure and a serious illness of a liver (until hepatic tests do not return to normal).
• Liver tumors (high-quality or malignant) now or in the anamnesis.
• The revealed hormonedependent malignant diseases (including generative organs or mammary glands) or suspicion of them.
• Vaginal bleeding of not clear genesis.
• Pregnancy or suspicion on it.
• Feeding period breast.
• Hypersensitivity to any of drug components Femoden.

Use with care
If any of the states/risk factors provided below are available now, then it is necessary to weigh carefully potential risk and the expected advantage of use of the combined oral contraceptives in each individual case:
• Risk factors of development of thrombosis and thromboembolisms: smoking; thromboses, a myocardial infarction or disturbance of cerebral circulation at young age at any of the immediate family; obesity; dislipoproteinemiya   (for example,   arterial   hypertension;   migraine;
diseases of valves of heart; disturbances of a cordial rhythm, long immobilization, serious surgical interventions, extensive injury)
• Other diseases at which disturbances of peripheric circulation can be noted: diabetes mellitus; system lupus erythematosus; hemolitic uraemic syndrome; disease Krone and nonspecific ulcer colitis; sickemia; and also phlebitis of superficial veins
• Gipertriglitseridemiya
• Liver diseases
• The diseases which for the first time arose or aggravated during pregnancy or against the background of the previous reception of sex hormones (for example, jaundice, a cholestasia, diseases of a gall bladder, an otosclerosis with deterioration in hearing, a porphyria, herpes of pregnant women, Sydenham's trochee)

Pregnancy and lactation
Femoden is not appointed during pregnancy and during feeding by a breast.
If pregnancy comes to light during administration of drug Femoden, drug should be cancelled at once. However extensive epidemiological researches did not reveal any increased risk of defects of development in the children born by women, receiving sex hormones before pregnancy or teratogenic action when sex hormones were accepted on imprudence in early durations of gestation.
Reception of the combined oral contraceptives can reduce amount of breast milk and change its structure therefore, as a rule, their use is not recommended at a lactation. A small amount of sexual steroids and/or their metabolites can be removed with milk, however there is no confirmation of their negative impact on health of the newborn.

Overdose:

About serious violations at overdose it was not reported. Symptoms which can be noted at overdose: nausea, vomiting, the smearing bloody allocations or a metrorrhagia.
There is no specific antidote, it is necessary to carry out a symptomatic treatment.

Storage conditions:

At a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity of 5 years. Not to use after the period of validity specified on packaging!

Issue conditions:

According to the recipe

Packaging:

On 21 dragees in the blister from PVC and aluminum foil. The blister, an envelope for carrying the blister from the laminated cardboard together with the application instruction place in a cardboard pack.