Rigevidon (Ethinyl Estradiol/Levonorgestrel) 63 tablets
- $32.10
Sku:
d4e44103fbb1
Brand:
Gedeon Richter (Hungary)
The instruction for medical use
of Rigevidon® medicine
the Trade name
of Rigevidon®
the International unlicensed name
Is not present
the Dosage form
of the Tablet, coated, 0.03 mg / 0.15 mg
Structure
One tablet contains
active agents: ethinylestradiol of 0.03 mg,
levonorgestrel of 0.15 mg,
excipients:
silicon dioxide colloidal anhydrous, magnesium stearate, talc, starch corn, lactoses monohydrate,
structure of a cover: sodium of a karmelloz, povidone, silicon dioxide colloidal anhydrous, a macrogoal 6000, kopovidon, the titan dioxide (E 171),
calcium a carbonate, talc, sucrose
the Description
of the Tablet, round shape, with a biconvex surface, coated white color
Pharmacotherapeutic group
Sex hormones and modulators of a reproductive system. Hormonal contraceptives for system use. Progestogens and estrogen (the fixed combinations). Levonorgestrel and estrogen
the ATX G03A A07 Code
the Pharmacological
Pharmacokinetics Ethinylestradiol Absorption Ethinylestradiol properties is quickly and completely soaked up in digestive tract, the maximum concentration of drug in blood plasma is reached in 1.5 hours. The absolute bioavailability after presistemny conjugation and the first passing through a liver is 60%. The area under a curve concentration time and Cmax can slightly increase eventually.
Distribution
makes Extent of linking of ethinylestradiol with proteins of blood plasma to 98.8%. Almost completely binding happens to albumine.
Metabolism
Ethinylestradiol is exposed to presistemny conjugation, both in a mucous membrane of a small intestine, and in a liver. As a result of hydrolysis of direct conjugates of ethinylestradiol, indestinal flora forms ethinylestradiol which can be repeatedly reabsorbirovan (enteropechenochny recirculation). The main way of metabolism of ethinylestradiol is hydroxylation in the system of R-450 cytochrome with formation of the main metabolites of 2-IT-ethinylestradiol and 2-metoksi-ethinylestradiol. 2-IT-ethinylestradiol is metabolized further to chemically active metabolites.
Removal
Ethinylestradiol is brought out of blood plasma with elimination half-life (Т½) about 29 hours (26-33 hours), the plasma clearance varies within 10-30 l/hour. Removal of conjugates of ethinylestradiol and its metabolites happens to urine and a stake (1:1).
Levonorgestrel
Absorption
After intake levonorgestrel is quickly and completely soaked up from digestive tract. The bioavailability is about 100%. Levonorgestrel is not exposed to metabolism at the first passing through a liver.
Distribution
In blood plasma levonorgestrel substantially contacts albumine and GSPG (the globulin connecting sex hormones). Metabolism
Metabolism, generally consists in eliminating of 4-3-oxo-group and hydroxylation in provisions 2α, 1β and 16β then there is a conjugation. The majority of the metabolites circulating in blood are sulfates 3α, 5β-тетрагидро-левоноргестрела. Excretion of drug happens generally in the form of glucuronides. A number of primary levonorgestrel also circulates in form 17β - sulfate. The metabolic clearance is subject to considerable individual variability which can partially explain the significant differences in concentration of levonorgestrel observed at patients.
Removal
Levonorgestrel is removed with average T½ about 36 hours in the conditions of equilibrium concentration of drug in plasma. Levonorgestrel and its metabolites are generally removed with urine (40-68%) and about 16-48% of drug are removed with excrements.
A pharmacodynamics
the Contraceptive effect of the drug Rigevidon® is based on interaction of various mechanisms, the most important of which are suppression of an ovulation and also change in endometrium and cervical slime.
Indications
- oral contraception
the Route of administration and doses
of the Tablet should be accepted in the order specified on blister strip packaging, every day approximately at the same time.
It is necessary to accept on one tablet daily within 21 days in a row. Tablets from each subsequent packing should begin to be accepted after the 7th day break during which usually there comes cancellation bleeding. Cancellation bleeding, as a rule, begins for the 2nd or 3rd day after reception of the last tablet and it can proceed prior to reception of tablets from the following packing of drug.
If the drug is taken the first time
of the Tablet it is necessary to begin to accept in the first day of periods. It is allowed to begin reception of the tablets Rigevidon® from 2-5 in the afternoon of periods, but in this case during the first 7 days, during the first cycle of use of drug, simultaneous use of additional non-hormonal (barrier) methods of contraception is recommended.
If earlier other combined hormonal contraceptive means (the combined oral contraceptive, a vaginal ring or a transdermalny plaster)
Administration of drug of Rigevidon® was used it is necessary to begin next day after reception of the last active tablet from the previous packing of contraceptive tablets (or removals of a vaginal ring or a transdermalny plaster), but no later than next day after a usual break in reception of tablets of a former contraceptive (either placebo, or removal of a vaginal ring or a transdermalny plaster).
If progestinovy contraceptive means (mini-saw, injections, implants or intrauterine spirals) were applied before
drank Transition to Rigevidon® from mini-it is possible to carry out in any day, when using an implant or intrauterine spiral – in day of their removal and at use of injections – in day when the following injection has to be made. In all these cases the simultaneous use of barrier methods of contraception for the first 7 days of administration of drug is recommended to the woman.
After abortion in 1 trimester of pregnancy
the Reception of the tablets Rigevidon® can be begun immediately. In this case use of additional contraceptive resources is not required.
After the delivery or abortion in the 2nd trimester of pregnancy
Are recommended to begin reception of the tablets Rigevidon® for 21-28 day after the delivery the women who are not nursing and after abortion in the 2nd trimester of pregnancy (in connection with the increased risk of tromboembolic episodes in a puerperal period). If reception of the tablets Rigevidon® begins after this term, during the first 7 days of use of drug it is in addition recommended to use barrier methods of contraception. At the same time, if sexual intercourse already took place, prior to reception of tablets it is necessary to exclude pregnancy or to postpone the beginning of reception of tablets before the first periods.
If reception of tablets is missed
If since then when the next pill had to be taken there passed less than 12 hours, contraceptive protection does not decrease. The woman has to take the passed pill at once as soon as she remembers it, the following pill should be taken in usual time.
If since then when the next pill had to be taken there passed more than 12 hours, contraceptive protection can be reduced. In the situations connected with admissions in reception of tablets it is necessary to be guided by two basic rules:
1. having rummaged in reception of tablets never has to exceed 7 days,
2. continuous reception of tablets within 7 days is necessary for achievement of adequate suppression gipotalamo - a hypophysial and ovarian system.
Thus, in the conditions of daily practice can be the following recommendations are made
1 week
the Last passed pill has to be taken immediately after the patient remembered it even if she has to take 2 pill of drug at the same time. Further reception of tablets continues in the usual mode. During the next 7 days at the same time it is necessary to use barrier methods of contraception (for example, condom). If during the previous 7 days the sexual intercourse took place, it is necessary to consider pregnancy approach probability. What the bigger quantity of tablets was passed by, and the closer to the break period in administration of drug, the risk of approach of pregnancy is higher.
The 2nd week
the Last passed pill has to be taken immediately after the patient remembered it even if she has to take 2 pill of drug at the same time. Further reception of tablets continues in the usual mode. Under a condition if the pill Rigevidon® was taken correctly during the previous 7 days, use of additional contraceptive resources is not required. However, if it not so or reception more than 1 tablet was missed, during the next 7 days of administration of drug it is recommended to use barrier methods of contraception in addition.
The 3rd week
Risk of critical decrease in contraceptive protection is inevitable because of the subsequent break in administration of drug. However decrease in contraceptive effect can be prevented by change of the mode of reception of tablets. In this regard, following one of two offered modes of administration of drug, there is no need to apply additional resources of contraception provided that within 7 days preceding the first passed tablet, all doses of drug were accepted correctly. If it not so, the patient is recommended to follow the first of the offered alternatives.
Besides, during the next 7 days other method of contraception at the same time has to be used.
1. The last passed pill has to be taken at once as the patient remembered it even if 2 pill of drug at the same time have to be taken. Further reception of tablets continues in the usual mode. The patient has to begin to accept tablets from the following packing next day after reception of the last tablet from the current blister strip packaging, i.e. without interruption in administration of drug between them. Before the end of the second packing the probability of bleeding of cancellation is small, however against the background of reception of tablets the smearing bloody discharges can be observed or develop breakthrough bleeding.
2. Also it can be recommended to stop reception of tablets from the current packing. In this case the patient has to take a break in administration of drug lasting up to 7 days, including those days in which she forgot to take a pill, and then to begin to take a pill from the following packing of drug.
If the patient missed reception of tablets, and after that at her there did not come cancellation bleeding during the first break in administration of drug, it is necessary to assume pregnancy approach probability.
Recommendations in case of vomiting/diarrhea
If vomiting took place earlier, than in 3-4 hours after reception of a tablet, its absorption can be incomplete. In this case it is necessary to follow recommendations concerning the admission in reception of the tablets described above. Diarrhea can lead to decrease in efficiency of drug as a result of its incomplete absorption. If the woman does not want to change the usual mode of reception of tablets, she has to take an additional pill (i) from other blister strip packaging so many days how many it is necessary.
How to transfer or change time of approach of periods
to delay time of approach of periods, the patient has to begin reception of tablets from the following packing of the drug Rigevidon® next day after reception of the last tablet from its current packing, without taking a break in administration of drug between them. Thus, it is possible to delay time of approach of periods for any desirable time before the end of reception of tablets from the second packing. During this additional span the patient can have a breakthrough bleeding or be observed the smearing bloody discharges. After a usual 7-day break it is necessary to start regular administration of drug of Rigevidon® over again.
To transfer time of approach of periods the next day of week, concerning that day in which it came against the background of administration of drug it is recommended to reduce the forthcoming break in reception of tablets by so many days on how many it is necessary. The shorter having rummaged in administration of drug, the risk is higher that the patient will have no cancellation bleeding. Besides, the risk of breakthrough bleeding or emergence of the smearing bloody discharges increases during reception of tablets from the second packing (similar to when time of approach of periods is postponed). It is important to emphasize that having rummaged in administration of drug it is impossible to prolong.
Side effects
Often (≥1/100 to & lt, 1/10)
- increase in body weight
- a liquid delay
- a headache, migraine, nervousness, a depression, irritability, changes of a libido
- the irritation of eyes when carrying contact lenses, visual disturbances
- nausea
- acne rash
- irregular vaginal bleedings, an amenorrhea, a hypomenorrhea, morbidity of mammary glands
Infrequently (≥1/1000 to & lt, 1/100) and is rare (≥1/10000 to & lt, 1/1000)
- a breast cancer, liver adenoma, a hepatocellular carcinoma, cervical cancer
- a system lupus erythematosus
- a lipidemia
- a chorea
- an otosclerosis
- arterial hypertension, a venous thrombembolia, an arterial thrombembolia
- vomiting, a cholelithiasis, pancreatitis
- a knotty erythema, a multiformny erythema, a hloazma
- changes of a vaginal secret
At the women using the COOK were registered the following serious undesirable phenomena:
a venous thrombembolia, i.e. a deep vein thrombosis of the lower extremities and veins of a small pelvis and also an embolism of a pulmonary artery
an arterial thrombembolia
disturbance liver tumor cervical cancer from skin and hypodermic fabrics: the hloazma, a knotty erythema
among using the COOK is slightly raised the frequency of detection of a breast cancer. Because the breast cancer aged up to 40 years occurs in women seldom, the additional quantity of such cases are not enough in relation to the general risk of a disease of a breast cancer. The causal relationship with use the COOK is unknown.
Contraindications
- a venous thrombembolia or its existence in the anamnesis (for example, a deep vein thrombosis, a pulmonary embolism) in combination with risk factors or without them
an arterial thrombembolia or its existence in the anamnesis, in particular a myocardial infarction and disturbance of cerebral circulation
existence of serious or multiple factors of risk of venous or arterial thrombosis
existence in the anamnesis of harbingers of thrombosis (for example, passing disturbance of cerebral circulation or stenocardia)
cardiovascular diseases (for example, heart diseases, valves of heart and arrhythmia)
heavy arterial hypertension
diabetes with manifestations micro - or a macrovascular disease
of a disorder of vision of a vascular etiology
the diagnosed or suspected gormonzavisimy malignant tumors of a mammary gland and genitals
serious diseases of a liver or their existence in the anamnesis (before normalization of indicators of functional hepatic tests)
tumors of a liver or their existence in the anamnesis (benign or malignant), pancreatitis (or existence its anamnesis)
vaginal bleedings of an unknown etiology
migraine with focal neurologic symptomatology
hypersensitivity to active agent or to any of excipients
- pregnancy and the period of a lactation
- intolerance of a galactose, a lactose intolerance or a sprue of glucose and a galactose
Medicinal interactions
Medicines which can affect effects the COOK
for the purpose of identification of potential medicinal interactions it is always necessary to study information on use of any accompanying medicines!
Medicinal interactions which lead to increase in clearance of sex hormones can be the cause of breakthrough bleeding and inefficiency of contraceptive protection. This effect is revealed at hydantoins (for example, Phenytoinum), barbiturates, Primidonum, carbamazepine and rifampicin. Other active agents which can reduce efficiency of COC are okskarbazepin, topiramat, griseofulvin and ritonavir.
The mechanism of their action is probably based on ability of these substances to increase activity of hepatic enzymes. The maximum induction of enzymes, as a rule, is observed not earlier, than in 2-3 weeks after the beginning of intake of these drugs, but can remain for not less than 4 weeks after their cancellation. Cases of inefficiency of contraceptive means also came to light at simultaneous use of antibiotics, such as, ampicillin and tetracycline, but the mechanism of action remains to unknown.
In case of short-term use of any of these drugs causing increase in activity of hepatic enzymes the use of additional barrier methods of contraception is recommended from the moment of the beginning of intake of these drugs, during the entire period of treatment and for 4 weeks after their cancellation. Women who receive the specified antibiotics a short course need to use temporarily barrier methods of contraception along with contraceptive tablets, that is during use of the accompanying medicine and within 7 days after its cancellation. If the next packing of tablets of the drug Rigevidon® ends earlier, than the span demanding use of additional contraceptive resources it is necessary to begin tablets from the following packing without interruption in administration of drug. In this case bleeding of cancellation should not be expected until, tablets from the second packing will not end yet. If at the patient there did not come cancellation bleeding after completion of reception of tablets from the second packing, she has to see a doctor for a pregnancy exception.
In case of prolonged use of these drugs, use of other contraceptive means is recommended to patients.
The St. John's wort
the Vegetable means containing the St. John's wort made a hole (Hypericum perforatum) which is made a hole (Hypericum perforatum) should not be accepted along with the drug Rigevidon® as it can potentially lead to loss of contraceptive effect. In this regard it was reported about cases of breakthrough bleedings and unwanted pregnancy. Induction of the enzymes participating in drug metabolism, the caused Hypericum perforatum was the cause. The inducing effect can remain for not less than 2 weeks after the termination of reception of the St. John's wort which is made a hole.
Impact of COC on other medicines
Sex steroid hormones can increase concentration in cyclosporine blood plasma that can lead to development of toxic effects. The concomitant use of a lamotrigin and COC can lead to decrease in concentration in plasma of a lamotrigin and to deterioration in control of convulsive attacks at the women who began to apply COC.
Special instructions
of the Patient have to be informed that oral contraceptives do not protect from infection with HIV infection (AIDS) and other infections, sexually transmitted (I,ST).
Smoking increases risk of development of serious side reactions from a cardiovascular system against the background of reception of the combined oral contraceptives (COC). This risk increases with age, depends on quantity of the smoked cigarettes and is especially high at women 35 years are more senior. All women accepting COC should not strongly recommend to smoke. Concerning the smoking women 35 years are more senior it is necessary to consider the possibility of purpose of other methods of contraception.
At identification of any state / risk factor from listed below, the ratio advantage/risk of use of the combined oral contraceptives has to be weighed in each case. Results of the carried-out analysis need to be discussed with the patient prior to reception of COC. In case of aggravation of a course or the first manifestation of any of these states or risk factors the woman is recommended to contact the attending physician. After that the attending physician has to make the decision on continuation of use or cancellation the COOK.
Blood circulation disturbances
Use of any the COOK is connected with the increased risk of developing a venous thrombembolia (VTE), in comparison with this indicator at women who do not use the COOK. On the available data, VTE frequency among the women who are not using the COOK is 5-10 people for 100000 patsiyento-years. Increase in risk of VTE is the most significant within the first year of use the COOK. This increase in risk is less, than the risk of VTE connected with pregnancy which is estimated as 60 cases on 100000 pregnancies. VTE leads to a lethal outcome in 1-2% of cases. In general, the absolute risk (incidence) of VTE against the background of use of the combined oral contraceptives containing levonorgestrel and less than 50 mkg of ethinylestradiol is about 20 cases for 100000 patsiyento-years of use of drug.
At the women using oral contraceptives the thrombosis of other blood vessels, i.e. veins and arteries of a liver, a mesentery of intestines, kidneys and a retina of an eye, meets very seldom. There is no consensus about whether these cases are connected with use the COOK.
Risk of developing a venous thrombembolia increases in the following cases:
with age
in case of the burdened family anamnesis (for example, a venous thrombembolia at brothers, sisters or parents at rather young age). At suspicion it is necessary to direct to genetic predisposition, the patient to the expert, to the solution of a question of a possibility of use of oral contraceptives
in obesity (body mass index is higher than 30 kg/m ²)
- in case of a long immobilization (after big operations, surgical interventions standing or an extensive injury). In such cases the reception of oral contraceptives is recommended to cancel (in case of planned operation not less than in 4 weeks prior to its carrying out). It is possible to resume their use not earlier than in 2 weeks after complete recovery of physical activity.
There is no consensus of rather possible role of a varicosity and thrombophlebitis of superficial veins in pathogenesis of a venous thrombembolia.
It is necessary to consider the increased risk of a thrombembolia in a puerperal period.
Use the COOK in general was connected with the increased risk of developing the acute myocardial infarction (AMI) and acute disorder of cerebral circulation which substantially depends on presence of other risk factors, for example, of smoking, increases in arterial blood pressure and age (see above). These complications develop seldom. Influence of administration of drug of Rigevidon® on risk of development of OIM was not studied.
Risk of developing an arterial thrombembolia increases in the following cases:
- with age
at smokers (with increase in quantity of the smoked cigarettes and age the further increase in risk is observed, especially at women 35 years)
in case of a dislipoproteinemiya are more senior
- in obesity (body mass index is higher than 30 kg/m ²)
- in case of arterial hypertension
- in a disease of valves of heart
- in an atrial fibrillation
- in the presence of the family anamnesis (for example, arterial thrombosis at brothers and sisters or parents at rather young age). If genetic predisposition is suspected, before making decision on purpose of any hormonal contraceptive means the patient should be directed to consultation to the expert.
Symptoms of venous or arterial thrombosis can include:
a unilateral scelalgia and/or its hypostasis
sudden severe pain in a breast with irradiation in the left hand or without irradiation
sudden emergence of an asthma
sudden appearance of cough
any unusual severe and long headache
sudden partial or total loss of sight
a diplopia
the muffled speech or aphasia
dizziness
falling with a partial convulsive attack or without it
the weakness or a considerable anesthesia which suddenly developed from one party or in one part of a body
motive disturbances
a syndrome of an acute abdomen.
It is necessary to consider the increased risk of developing a venous thrombembolia in a puerperal period.
Diabetes, a system lupus erythematosus, a gemolitiko-uraemic syndrome, chronic inflammatory bowel diseases (for example, Crohn's disease or ulcer colitis) and a sickemia belong to other diseases which are connected with blood circulation disturbance.
In case of increase in frequency and weight of attacks of migraine (that can be a harbinger of development of more severe forms of disturbance of cerebral circulation) during use of oral contraceptives it is necessary to consider the possibility of their immediate cancellation.
To the biochemical parameters demonstrating the hereditary or acquired predisposition to venous or arterial thrombosis resistance the gipergomotsisteinemiya, deficiency of antithrombin III, deficit of a protein With, deficit of a protein of S, existence of anti-phospholipidic antibodies (antibodies to cardiolipin, lupoid anticoagulant) and a dislipoproteinemiya belong to the activated protein With (AP), a mutation Leiden of a factor of V.
Tumors
Cervical cancer
In some epidemiological researches was revealed the increased risk of developing cervical cancer at women is long accepting the COOK. Besides, it is not established yet in what degree this indicator can depend on sexual behavior and other factors, such as human papillomavirus (HP).
The breast cancer
Meta-analysis 54 pharmako-epidemiological researches showed that the women accepting the combined oral contraceptives have a little increased relative risk (the SHOUTING = 1.24) development of a breast cancer. This increased risk gradually decreases within 10 years after the reception termination the COOK. As the breast cancer is a rare disease at women younger 40 years, growth of number of the diagnosed cases of a breast cancer at the women accepting the COOK now or in the past – low, in comparison with risk of developing a breast cancer during the entire period of life.
The evidence of relationship of cause and effect in these researches is not produced. The observed picture of increase in risk can be connected with early diagnosis of a breast cancer at using the COOK, biological effects the COOK or a combination of both specified factors.
At the women using oral contraceptives, the breast cancer is diagnosed in a little earlier stage in comparison with women who did not use the COOK.
Liver tumors
At the women using the COOK were registered benign and malignant tumors of a liver. In some cases these tumors led to life-threatening intraperitoneal bleedings. In cases of severe pain in upper abdomens in combination with a hepatomegalia or symptoms of intraperitoneal bleeding at the women using the COOK differential diagnostics with a liver tumor has to be carried out.
Use the COOK can lead other states At women with a gipertriglitseridemiya and the burdened family anamnesis to increase in risk of developing pancreatitis. Women with a lipidemia, in case of their decision to accept the COOK, have to be under careful medical observation.
In case of an acute or chronic liver failure the use of the drug Rigevidon® has to be stopped until indicators of hepatic tests return to limits of normal values. At patients from the liver broken by function the exchange of steroid hormones can slow down.
That at many women using the COOK the small increase in arterial blood pressure was registered clinically significant increase in the ABP is observed seldom. If during reception the COOK develops the persistent and profound arterial hypertension, it is necessary to stop reception of a contraceptive and to begin treatment of arterial hypertension. In case of need use the COOK can be resumed if as a result of hypotensive therapy the AD normal values are reached.
It was reported that the following states can arise or become aggravated both during pregnancy, and during reception the COOK: jaundice and/or an itching in connection with a cholestasia, formation of stones in a gall bladder, a porphyria, a system lupus erythematosus, a gemolitiko-uraemic syndrome, Sydenham's chorea, herpes of pregnant women, a hearing loss, owing to an otosclerosis. However, existence of relationship of cause and effect is not proved.
The COOK can affect peripheral insulin resistance and tolerance to glucose. In this regard the patients having diabetes have to be observed carefully during reception the COOK.
Ригевидон® monohydrate contains lactoses. Women with rare hereditary diseases of intolerance of a galactose, deficiency of Lappa lactase and glyukozo-galaktozny malabsorption should not take this medicine.
Ригевидон® contains sucrose. Women with rare hereditary diseases of intolerance of fructose, glyukozo-galaktozny malabsorption and sakharozo-izomaltazny insufficiency should not take this drug.
It was reported about communication between reception of the combined oral contraceptives and a disease Krone / ulcer colitis.
The hloazma, especially at women from hloazmy pregnant women in the anamnesis can develop. Women with tendency to development of a hloazma during reception the COOK should avoid stay to the sun and influences of ultraviolet rays.
Women at whom during reception the COOK the heavy depression developed should stop administration of drug. Before clarification of a question of existence of communication between administration of drug and development of these symptoms the alternative method of contraception has to be recommended to the patient. Women who suffered from episodes of a heavy depression earlier have to be under careful observation and stop use the COOK in case of resuming of symptoms of a depression.
Decrease in efficiency
Efficiency of oral contraceptives can be reduced in case of admissions of reception of tablets, vomiting/diarrhea and a concomitant use of other medicines.
Disturbances of a menstrual cycle
during reception of all combined oral contraceptives can be observed irregular bleedings (bloody discharges or breakthrough bleedings), especially within the first months of use of these means. Thus, the clinical assessment of any irregular bleedings has to be carried out after the period of adaptation to drug throughout about 3 menstrual cycles.
If irregular bleedings arise after the previous regular cycles, it is necessary to consider the non-hormonal reasons of this state and to perform the corresponding examination for the purpose of an exception of malignant process or pregnancy.
Sometimes cancellation bleeding during a break in administration of drug can not be observed in general. If a pill was taken precisely according to iinstruktion, approach of pregnancy is improbable. At the same time, if instructions for use to the first break in administration of drug were violated and if bleeding of cancellation did not come or two bleedings of cancellation did not come in a row, it is necessary to exclude pregnancy before use continuation the COOK.
The laboratory
researches Intake of Contraceptive Steroid Hormones can affect results of some laboratory tests, including biochemical indicators of function of a liver, thyroid gland, adrenal glands and kidneys, concentration of transport proteins of plasma (for example, a corticosteroid - the connecting globulin, lipidno / lipoprotein fractions), indicators of carbohydrate metabolism, coagulation and fibrinolysis. Observed changes usually remain within referensny values.
To develop
of Rigevidon® medicine
the Trade name
of Rigevidon®
the International unlicensed name
Is not present
the Dosage form
of the Tablet, coated, 0.03 mg / 0.15 mg
Structure
One tablet contains
active agents: ethinylestradiol of 0.03 mg,
levonorgestrel of 0.15 mg,
excipients:
silicon dioxide colloidal anhydrous, magnesium stearate, talc, starch corn, lactoses monohydrate,
structure of a cover: sodium of a karmelloz, povidone, silicon dioxide colloidal anhydrous, a macrogoal 6000, kopovidon, the titan dioxide (E 171),
calcium a carbonate, talc, sucrose
the Description
of the Tablet, round shape, with a biconvex surface, coated white color
Pharmacotherapeutic group
Sex hormones and modulators of a reproductive system. Hormonal contraceptives for system use. Progestogens and estrogen (the fixed combinations). Levonorgestrel and estrogen
the ATX G03A A07 Code
the Pharmacological
Pharmacokinetics Ethinylestradiol Absorption Ethinylestradiol properties is quickly and completely soaked up in digestive tract, the maximum concentration of drug in blood plasma is reached in 1.5 hours. The absolute bioavailability after presistemny conjugation and the first passing through a liver is 60%. The area under a curve concentration time and Cmax can slightly increase eventually.
Distribution
makes Extent of linking of ethinylestradiol with proteins of blood plasma to 98.8%. Almost completely binding happens to albumine.
Metabolism
Ethinylestradiol is exposed to presistemny conjugation, both in a mucous membrane of a small intestine, and in a liver. As a result of hydrolysis of direct conjugates of ethinylestradiol, indestinal flora forms ethinylestradiol which can be repeatedly reabsorbirovan (enteropechenochny recirculation). The main way of metabolism of ethinylestradiol is hydroxylation in the system of R-450 cytochrome with formation of the main metabolites of 2-IT-ethinylestradiol and 2-metoksi-ethinylestradiol. 2-IT-ethinylestradiol is metabolized further to chemically active metabolites.
Removal
Ethinylestradiol is brought out of blood plasma with elimination half-life (Т½) about 29 hours (26-33 hours), the plasma clearance varies within 10-30 l/hour. Removal of conjugates of ethinylestradiol and its metabolites happens to urine and a stake (1:1).
Levonorgestrel
Absorption
After intake levonorgestrel is quickly and completely soaked up from digestive tract. The bioavailability is about 100%. Levonorgestrel is not exposed to metabolism at the first passing through a liver.
Distribution
In blood plasma levonorgestrel substantially contacts albumine and GSPG (the globulin connecting sex hormones). Metabolism
Metabolism, generally consists in eliminating of 4-3-oxo-group and hydroxylation in provisions 2α, 1β and 16β then there is a conjugation. The majority of the metabolites circulating in blood are sulfates 3α, 5β-тетрагидро-левоноргестрела. Excretion of drug happens generally in the form of glucuronides. A number of primary levonorgestrel also circulates in form 17β - sulfate. The metabolic clearance is subject to considerable individual variability which can partially explain the significant differences in concentration of levonorgestrel observed at patients.
Removal
Levonorgestrel is removed with average T½ about 36 hours in the conditions of equilibrium concentration of drug in plasma. Levonorgestrel and its metabolites are generally removed with urine (40-68%) and about 16-48% of drug are removed with excrements.
A pharmacodynamics
the Contraceptive effect of the drug Rigevidon® is based on interaction of various mechanisms, the most important of which are suppression of an ovulation and also change in endometrium and cervical slime.
Indications
- oral contraception
the Route of administration and doses
of the Tablet should be accepted in the order specified on blister strip packaging, every day approximately at the same time.
It is necessary to accept on one tablet daily within 21 days in a row. Tablets from each subsequent packing should begin to be accepted after the 7th day break during which usually there comes cancellation bleeding. Cancellation bleeding, as a rule, begins for the 2nd or 3rd day after reception of the last tablet and it can proceed prior to reception of tablets from the following packing of drug.
If the drug is taken the first time
of the Tablet it is necessary to begin to accept in the first day of periods. It is allowed to begin reception of the tablets Rigevidon® from 2-5 in the afternoon of periods, but in this case during the first 7 days, during the first cycle of use of drug, simultaneous use of additional non-hormonal (barrier) methods of contraception is recommended.
If earlier other combined hormonal contraceptive means (the combined oral contraceptive, a vaginal ring or a transdermalny plaster)
Administration of drug of Rigevidon® was used it is necessary to begin next day after reception of the last active tablet from the previous packing of contraceptive tablets (or removals of a vaginal ring or a transdermalny plaster), but no later than next day after a usual break in reception of tablets of a former contraceptive (either placebo, or removal of a vaginal ring or a transdermalny plaster).
If progestinovy contraceptive means (mini-saw, injections, implants or intrauterine spirals) were applied before
drank Transition to Rigevidon® from mini-it is possible to carry out in any day, when using an implant or intrauterine spiral – in day of their removal and at use of injections – in day when the following injection has to be made. In all these cases the simultaneous use of barrier methods of contraception for the first 7 days of administration of drug is recommended to the woman.
After abortion in 1 trimester of pregnancy
the Reception of the tablets Rigevidon® can be begun immediately. In this case use of additional contraceptive resources is not required.
After the delivery or abortion in the 2nd trimester of pregnancy
Are recommended to begin reception of the tablets Rigevidon® for 21-28 day after the delivery the women who are not nursing and after abortion in the 2nd trimester of pregnancy (in connection with the increased risk of tromboembolic episodes in a puerperal period). If reception of the tablets Rigevidon® begins after this term, during the first 7 days of use of drug it is in addition recommended to use barrier methods of contraception. At the same time, if sexual intercourse already took place, prior to reception of tablets it is necessary to exclude pregnancy or to postpone the beginning of reception of tablets before the first periods.
If reception of tablets is missed
If since then when the next pill had to be taken there passed less than 12 hours, contraceptive protection does not decrease. The woman has to take the passed pill at once as soon as she remembers it, the following pill should be taken in usual time.
If since then when the next pill had to be taken there passed more than 12 hours, contraceptive protection can be reduced. In the situations connected with admissions in reception of tablets it is necessary to be guided by two basic rules:
1. having rummaged in reception of tablets never has to exceed 7 days,
2. continuous reception of tablets within 7 days is necessary for achievement of adequate suppression gipotalamo - a hypophysial and ovarian system.
Thus, in the conditions of daily practice can be the following recommendations are made
1 week
the Last passed pill has to be taken immediately after the patient remembered it even if she has to take 2 pill of drug at the same time. Further reception of tablets continues in the usual mode. During the next 7 days at the same time it is necessary to use barrier methods of contraception (for example, condom). If during the previous 7 days the sexual intercourse took place, it is necessary to consider pregnancy approach probability. What the bigger quantity of tablets was passed by, and the closer to the break period in administration of drug, the risk of approach of pregnancy is higher.
The 2nd week
the Last passed pill has to be taken immediately after the patient remembered it even if she has to take 2 pill of drug at the same time. Further reception of tablets continues in the usual mode. Under a condition if the pill Rigevidon® was taken correctly during the previous 7 days, use of additional contraceptive resources is not required. However, if it not so or reception more than 1 tablet was missed, during the next 7 days of administration of drug it is recommended to use barrier methods of contraception in addition.
The 3rd week
Risk of critical decrease in contraceptive protection is inevitable because of the subsequent break in administration of drug. However decrease in contraceptive effect can be prevented by change of the mode of reception of tablets. In this regard, following one of two offered modes of administration of drug, there is no need to apply additional resources of contraception provided that within 7 days preceding the first passed tablet, all doses of drug were accepted correctly. If it not so, the patient is recommended to follow the first of the offered alternatives.
Besides, during the next 7 days other method of contraception at the same time has to be used.
1. The last passed pill has to be taken at once as the patient remembered it even if 2 pill of drug at the same time have to be taken. Further reception of tablets continues in the usual mode. The patient has to begin to accept tablets from the following packing next day after reception of the last tablet from the current blister strip packaging, i.e. without interruption in administration of drug between them. Before the end of the second packing the probability of bleeding of cancellation is small, however against the background of reception of tablets the smearing bloody discharges can be observed or develop breakthrough bleeding.
2. Also it can be recommended to stop reception of tablets from the current packing. In this case the patient has to take a break in administration of drug lasting up to 7 days, including those days in which she forgot to take a pill, and then to begin to take a pill from the following packing of drug.
If the patient missed reception of tablets, and after that at her there did not come cancellation bleeding during the first break in administration of drug, it is necessary to assume pregnancy approach probability.
Recommendations in case of vomiting/diarrhea
If vomiting took place earlier, than in 3-4 hours after reception of a tablet, its absorption can be incomplete. In this case it is necessary to follow recommendations concerning the admission in reception of the tablets described above. Diarrhea can lead to decrease in efficiency of drug as a result of its incomplete absorption. If the woman does not want to change the usual mode of reception of tablets, she has to take an additional pill (i) from other blister strip packaging so many days how many it is necessary.
How to transfer or change time of approach of periods
to delay time of approach of periods, the patient has to begin reception of tablets from the following packing of the drug Rigevidon® next day after reception of the last tablet from its current packing, without taking a break in administration of drug between them. Thus, it is possible to delay time of approach of periods for any desirable time before the end of reception of tablets from the second packing. During this additional span the patient can have a breakthrough bleeding or be observed the smearing bloody discharges. After a usual 7-day break it is necessary to start regular administration of drug of Rigevidon® over again.
To transfer time of approach of periods the next day of week, concerning that day in which it came against the background of administration of drug it is recommended to reduce the forthcoming break in reception of tablets by so many days on how many it is necessary. The shorter having rummaged in administration of drug, the risk is higher that the patient will have no cancellation bleeding. Besides, the risk of breakthrough bleeding or emergence of the smearing bloody discharges increases during reception of tablets from the second packing (similar to when time of approach of periods is postponed). It is important to emphasize that having rummaged in administration of drug it is impossible to prolong.
Side effects
Often (≥1/100 to & lt, 1/10)
- increase in body weight
- a liquid delay
- a headache, migraine, nervousness, a depression, irritability, changes of a libido
- the irritation of eyes when carrying contact lenses, visual disturbances
- nausea
- acne rash
- irregular vaginal bleedings, an amenorrhea, a hypomenorrhea, morbidity of mammary glands
Infrequently (≥1/1000 to & lt, 1/100) and is rare (≥1/10000 to & lt, 1/1000)
- a breast cancer, liver adenoma, a hepatocellular carcinoma, cervical cancer
- a system lupus erythematosus
- a lipidemia
- a chorea
- an otosclerosis
- arterial hypertension, a venous thrombembolia, an arterial thrombembolia
- vomiting, a cholelithiasis, pancreatitis
- a knotty erythema, a multiformny erythema, a hloazma
- changes of a vaginal secret
At the women using the COOK were registered the following serious undesirable phenomena:
a venous thrombembolia, i.e. a deep vein thrombosis of the lower extremities and veins of a small pelvis and also an embolism of a pulmonary artery
an arterial thrombembolia
disturbance liver tumor cervical cancer from skin and hypodermic fabrics: the hloazma, a knotty erythema
among using the COOK is slightly raised the frequency of detection of a breast cancer. Because the breast cancer aged up to 40 years occurs in women seldom, the additional quantity of such cases are not enough in relation to the general risk of a disease of a breast cancer. The causal relationship with use the COOK is unknown.
Contraindications
- a venous thrombembolia or its existence in the anamnesis (for example, a deep vein thrombosis, a pulmonary embolism) in combination with risk factors or without them
an arterial thrombembolia or its existence in the anamnesis, in particular a myocardial infarction and disturbance of cerebral circulation
existence of serious or multiple factors of risk of venous or arterial thrombosis
existence in the anamnesis of harbingers of thrombosis (for example, passing disturbance of cerebral circulation or stenocardia)
cardiovascular diseases (for example, heart diseases, valves of heart and arrhythmia)
heavy arterial hypertension
diabetes with manifestations micro - or a macrovascular disease
of a disorder of vision of a vascular etiology
the diagnosed or suspected gormonzavisimy malignant tumors of a mammary gland and genitals
serious diseases of a liver or their existence in the anamnesis (before normalization of indicators of functional hepatic tests)
tumors of a liver or their existence in the anamnesis (benign or malignant), pancreatitis (or existence its anamnesis)
vaginal bleedings of an unknown etiology
migraine with focal neurologic symptomatology
hypersensitivity to active agent or to any of excipients
- pregnancy and the period of a lactation
- intolerance of a galactose, a lactose intolerance or a sprue of glucose and a galactose
Medicinal interactions
Medicines which can affect effects the COOK
for the purpose of identification of potential medicinal interactions it is always necessary to study information on use of any accompanying medicines!
Medicinal interactions which lead to increase in clearance of sex hormones can be the cause of breakthrough bleeding and inefficiency of contraceptive protection. This effect is revealed at hydantoins (for example, Phenytoinum), barbiturates, Primidonum, carbamazepine and rifampicin. Other active agents which can reduce efficiency of COC are okskarbazepin, topiramat, griseofulvin and ritonavir.
The mechanism of their action is probably based on ability of these substances to increase activity of hepatic enzymes. The maximum induction of enzymes, as a rule, is observed not earlier, than in 2-3 weeks after the beginning of intake of these drugs, but can remain for not less than 4 weeks after their cancellation. Cases of inefficiency of contraceptive means also came to light at simultaneous use of antibiotics, such as, ampicillin and tetracycline, but the mechanism of action remains to unknown.
In case of short-term use of any of these drugs causing increase in activity of hepatic enzymes the use of additional barrier methods of contraception is recommended from the moment of the beginning of intake of these drugs, during the entire period of treatment and for 4 weeks after their cancellation. Women who receive the specified antibiotics a short course need to use temporarily barrier methods of contraception along with contraceptive tablets, that is during use of the accompanying medicine and within 7 days after its cancellation. If the next packing of tablets of the drug Rigevidon® ends earlier, than the span demanding use of additional contraceptive resources it is necessary to begin tablets from the following packing without interruption in administration of drug. In this case bleeding of cancellation should not be expected until, tablets from the second packing will not end yet. If at the patient there did not come cancellation bleeding after completion of reception of tablets from the second packing, she has to see a doctor for a pregnancy exception.
In case of prolonged use of these drugs, use of other contraceptive means is recommended to patients.
The St. John's wort
the Vegetable means containing the St. John's wort made a hole (Hypericum perforatum) which is made a hole (Hypericum perforatum) should not be accepted along with the drug Rigevidon® as it can potentially lead to loss of contraceptive effect. In this regard it was reported about cases of breakthrough bleedings and unwanted pregnancy. Induction of the enzymes participating in drug metabolism, the caused Hypericum perforatum was the cause. The inducing effect can remain for not less than 2 weeks after the termination of reception of the St. John's wort which is made a hole.
Impact of COC on other medicines
Sex steroid hormones can increase concentration in cyclosporine blood plasma that can lead to development of toxic effects. The concomitant use of a lamotrigin and COC can lead to decrease in concentration in plasma of a lamotrigin and to deterioration in control of convulsive attacks at the women who began to apply COC.
Special instructions
of the Patient have to be informed that oral contraceptives do not protect from infection with HIV infection (AIDS) and other infections, sexually transmitted (I,ST).
Smoking increases risk of development of serious side reactions from a cardiovascular system against the background of reception of the combined oral contraceptives (COC). This risk increases with age, depends on quantity of the smoked cigarettes and is especially high at women 35 years are more senior. All women accepting COC should not strongly recommend to smoke. Concerning the smoking women 35 years are more senior it is necessary to consider the possibility of purpose of other methods of contraception.
At identification of any state / risk factor from listed below, the ratio advantage/risk of use of the combined oral contraceptives has to be weighed in each case. Results of the carried-out analysis need to be discussed with the patient prior to reception of COC. In case of aggravation of a course or the first manifestation of any of these states or risk factors the woman is recommended to contact the attending physician. After that the attending physician has to make the decision on continuation of use or cancellation the COOK.
Blood circulation disturbances
Use of any the COOK is connected with the increased risk of developing a venous thrombembolia (VTE), in comparison with this indicator at women who do not use the COOK. On the available data, VTE frequency among the women who are not using the COOK is 5-10 people for 100000 patsiyento-years. Increase in risk of VTE is the most significant within the first year of use the COOK. This increase in risk is less, than the risk of VTE connected with pregnancy which is estimated as 60 cases on 100000 pregnancies. VTE leads to a lethal outcome in 1-2% of cases. In general, the absolute risk (incidence) of VTE against the background of use of the combined oral contraceptives containing levonorgestrel and less than 50 mkg of ethinylestradiol is about 20 cases for 100000 patsiyento-years of use of drug.
At the women using oral contraceptives the thrombosis of other blood vessels, i.e. veins and arteries of a liver, a mesentery of intestines, kidneys and a retina of an eye, meets very seldom. There is no consensus about whether these cases are connected with use the COOK.
Risk of developing a venous thrombembolia increases in the following cases:
with age
in case of the burdened family anamnesis (for example, a venous thrombembolia at brothers, sisters or parents at rather young age). At suspicion it is necessary to direct to genetic predisposition, the patient to the expert, to the solution of a question of a possibility of use of oral contraceptives
in obesity (body mass index is higher than 30 kg/m ²)
- in case of a long immobilization (after big operations, surgical interventions standing or an extensive injury). In such cases the reception of oral contraceptives is recommended to cancel (in case of planned operation not less than in 4 weeks prior to its carrying out). It is possible to resume their use not earlier than in 2 weeks after complete recovery of physical activity.
There is no consensus of rather possible role of a varicosity and thrombophlebitis of superficial veins in pathogenesis of a venous thrombembolia.
It is necessary to consider the increased risk of a thrombembolia in a puerperal period.
Use the COOK in general was connected with the increased risk of developing the acute myocardial infarction (AMI) and acute disorder of cerebral circulation which substantially depends on presence of other risk factors, for example, of smoking, increases in arterial blood pressure and age (see above). These complications develop seldom. Influence of administration of drug of Rigevidon® on risk of development of OIM was not studied.
Risk of developing an arterial thrombembolia increases in the following cases:
- with age
at smokers (with increase in quantity of the smoked cigarettes and age the further increase in risk is observed, especially at women 35 years)
in case of a dislipoproteinemiya are more senior
- in obesity (body mass index is higher than 30 kg/m ²)
- in case of arterial hypertension
- in a disease of valves of heart
- in an atrial fibrillation
- in the presence of the family anamnesis (for example, arterial thrombosis at brothers and sisters or parents at rather young age). If genetic predisposition is suspected, before making decision on purpose of any hormonal contraceptive means the patient should be directed to consultation to the expert.
Symptoms of venous or arterial thrombosis can include:
a unilateral scelalgia and/or its hypostasis
sudden severe pain in a breast with irradiation in the left hand or without irradiation
sudden emergence of an asthma
sudden appearance of cough
any unusual severe and long headache
sudden partial or total loss of sight
a diplopia
the muffled speech or aphasia
dizziness
falling with a partial convulsive attack or without it
the weakness or a considerable anesthesia which suddenly developed from one party or in one part of a body
motive disturbances
a syndrome of an acute abdomen.
It is necessary to consider the increased risk of developing a venous thrombembolia in a puerperal period.
Diabetes, a system lupus erythematosus, a gemolitiko-uraemic syndrome, chronic inflammatory bowel diseases (for example, Crohn's disease or ulcer colitis) and a sickemia belong to other diseases which are connected with blood circulation disturbance.
In case of increase in frequency and weight of attacks of migraine (that can be a harbinger of development of more severe forms of disturbance of cerebral circulation) during use of oral contraceptives it is necessary to consider the possibility of their immediate cancellation.
To the biochemical parameters demonstrating the hereditary or acquired predisposition to venous or arterial thrombosis resistance the gipergomotsisteinemiya, deficiency of antithrombin III, deficit of a protein With, deficit of a protein of S, existence of anti-phospholipidic antibodies (antibodies to cardiolipin, lupoid anticoagulant) and a dislipoproteinemiya belong to the activated protein With (AP), a mutation Leiden of a factor of V.
Tumors
Cervical cancer
In some epidemiological researches was revealed the increased risk of developing cervical cancer at women is long accepting the COOK. Besides, it is not established yet in what degree this indicator can depend on sexual behavior and other factors, such as human papillomavirus (HP).
The breast cancer
Meta-analysis 54 pharmako-epidemiological researches showed that the women accepting the combined oral contraceptives have a little increased relative risk (the SHOUTING = 1.24) development of a breast cancer. This increased risk gradually decreases within 10 years after the reception termination the COOK. As the breast cancer is a rare disease at women younger 40 years, growth of number of the diagnosed cases of a breast cancer at the women accepting the COOK now or in the past – low, in comparison with risk of developing a breast cancer during the entire period of life.
The evidence of relationship of cause and effect in these researches is not produced. The observed picture of increase in risk can be connected with early diagnosis of a breast cancer at using the COOK, biological effects the COOK or a combination of both specified factors.
At the women using oral contraceptives, the breast cancer is diagnosed in a little earlier stage in comparison with women who did not use the COOK.
Liver tumors
At the women using the COOK were registered benign and malignant tumors of a liver. In some cases these tumors led to life-threatening intraperitoneal bleedings. In cases of severe pain in upper abdomens in combination with a hepatomegalia or symptoms of intraperitoneal bleeding at the women using the COOK differential diagnostics with a liver tumor has to be carried out.
Use the COOK can lead other states At women with a gipertriglitseridemiya and the burdened family anamnesis to increase in risk of developing pancreatitis. Women with a lipidemia, in case of their decision to accept the COOK, have to be under careful medical observation.
In case of an acute or chronic liver failure the use of the drug Rigevidon® has to be stopped until indicators of hepatic tests return to limits of normal values. At patients from the liver broken by function the exchange of steroid hormones can slow down.
That at many women using the COOK the small increase in arterial blood pressure was registered clinically significant increase in the ABP is observed seldom. If during reception the COOK develops the persistent and profound arterial hypertension, it is necessary to stop reception of a contraceptive and to begin treatment of arterial hypertension. In case of need use the COOK can be resumed if as a result of hypotensive therapy the AD normal values are reached.
It was reported that the following states can arise or become aggravated both during pregnancy, and during reception the COOK: jaundice and/or an itching in connection with a cholestasia, formation of stones in a gall bladder, a porphyria, a system lupus erythematosus, a gemolitiko-uraemic syndrome, Sydenham's chorea, herpes of pregnant women, a hearing loss, owing to an otosclerosis. However, existence of relationship of cause and effect is not proved.
The COOK can affect peripheral insulin resistance and tolerance to glucose. In this regard the patients having diabetes have to be observed carefully during reception the COOK.
Ригевидон® monohydrate contains lactoses. Women with rare hereditary diseases of intolerance of a galactose, deficiency of Lappa lactase and glyukozo-galaktozny malabsorption should not take this medicine.
Ригевидон® contains sucrose. Women with rare hereditary diseases of intolerance of fructose, glyukozo-galaktozny malabsorption and sakharozo-izomaltazny insufficiency should not take this drug.
It was reported about communication between reception of the combined oral contraceptives and a disease Krone / ulcer colitis.
The hloazma, especially at women from hloazmy pregnant women in the anamnesis can develop. Women with tendency to development of a hloazma during reception the COOK should avoid stay to the sun and influences of ultraviolet rays.
Women at whom during reception the COOK the heavy depression developed should stop administration of drug. Before clarification of a question of existence of communication between administration of drug and development of these symptoms the alternative method of contraception has to be recommended to the patient. Women who suffered from episodes of a heavy depression earlier have to be under careful observation and stop use the COOK in case of resuming of symptoms of a depression.
Decrease in efficiency
Efficiency of oral contraceptives can be reduced in case of admissions of reception of tablets, vomiting/diarrhea and a concomitant use of other medicines.
Disturbances of a menstrual cycle
during reception of all combined oral contraceptives can be observed irregular bleedings (bloody discharges or breakthrough bleedings), especially within the first months of use of these means. Thus, the clinical assessment of any irregular bleedings has to be carried out after the period of adaptation to drug throughout about 3 menstrual cycles.
If irregular bleedings arise after the previous regular cycles, it is necessary to consider the non-hormonal reasons of this state and to perform the corresponding examination for the purpose of an exception of malignant process or pregnancy.
Sometimes cancellation bleeding during a break in administration of drug can not be observed in general. If a pill was taken precisely according to iinstruktion, approach of pregnancy is improbable. At the same time, if instructions for use to the first break in administration of drug were violated and if bleeding of cancellation did not come or two bleedings of cancellation did not come in a row, it is necessary to exclude pregnancy before use continuation the COOK.
The laboratory
researches Intake of Contraceptive Steroid Hormones can affect results of some laboratory tests, including biochemical indicators of function of a liver, thyroid gland, adrenal glands and kidneys, concentration of transport proteins of plasma (for example, a corticosteroid - the connecting globulin, lipidno / lipoprotein fractions), indicators of carbohydrate metabolism, coagulation and fibrinolysis. Observed changes usually remain within referensny values.
To develop
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