Regulon (Ethinyl Estradiol/Desogestrel) 21 film-coated tablets

The instruction for medical use


of REGULON® medicine

the Trade name
of Regulon®

the International unlicensed name
Is not present

the Dosage form
of the Tablet, film coated, 0.03 mg / 0.15 mg

Structure
One tablet contains
active agents: ethinylestradiol 0, 03 mg, dezogestret 0.150 mg,
excipients: α-tocopherol, magnesium stearate, silicon dioxide colloidal anhydrous, stearic acid, K-30 povidone, potato starch, lactoses monohydrate,
structure of a film cover: propylene glycol, macrogoal 6000, gipromelloza.

The description
of the Tablet, film coated white or almost white color, round, biconvex, with an engraving of P8 on one party and RG – on other party

Pharmacotherapeutic group
Sex hormones and modulators of a reproductive system. Hormonal contraceptives for system use. Progestogens and estrogen (the fixed combinations). Dezogestrel and estrogen
the ATX G03AA09 Code

the Pharmacological



Dezogestrel Vsasyvaniye Dezogestrel Pharmacokinetics properties is quickly and almost completely soaked up then it is metabolized up to 3-keto-dezogestrela (etonogestret) which is biologically active metabolite of a dezogestrel. Average maximum concentration in blood plasma (Cmax) of 2 ng/ml, is reached in 1.5 h after reception of a tablet. The bioavailability of a dezogestrel is 62-81%.
Distribution
3-keto-dezogestrel has the significant affinity to proteins of blood plasma, especially to albumine and the globulin, connecting sex hormones (G,CSH). In blood plasma only 2-4% of a free dezogestrel are defined. The increase in maintenance of GSPG induced by ethinylestradiol influences distribution of proteins of blood plasma that leads to increase GSPG-svyazannoy in fraction and reduces the number of the albuminrelated fraction. The volume of distribution is 1.5 l/kg.
Metabolism
Etonogestrel is completely metabolized by means of the known ways of metabolism of steroid hormones. Speed of metabolic clearance is 2 ml/min. of body weight of blood plasma, interaction with at the same time entered ethinylestradiol is not revealed.
Besides 3-keto-dezogestrela which is formed in a liver and a wall of intestines other metabolites of a dezogestrel are 3a-OH-dezogestrel, 3b-OH-dezogestrel and 3a-OH-5a-H-dezogestrel (so-called metabolites of the I phase). These metabolites have no pharmacological activity and subsequently are metabolized to polar metabolites, first of all, of sulfates and glucuronides, partially by conjugation (metabolism of the II phase).
Removal
3-keto-dezogestrela averages Elimination half-life 30 hours. Its metabolites are removed with urine and a stake, in the ratio 6:4.
Equilibrium concentration
influences the GSPG level in blood serum which increases three times under the influence of ethinylestradiol pharmacokinetics of an etonogestrel. At daily reception, stable concentration is established in the second half of a cycle. At this time the level of an etonogestrel in blood serum increases by 2-3 times.
Ethinylestradiol
Absorption
Ethinylestradiol is soaked up quickly and completely. Average maximum concentration in blood serum (Cmax) makes 80 pg/ml and is reached in 1-2 h (tmax). As ethinylestradiol is exposed to presistemny conjugation and presistemny metabolism, its absolute bioavailability is about 60%.

Distribution
Ethinylestradiol completely contacts proteins of blood plasma, generally with albumine and causes increase in concentration in GSPG blood serum. The volume of distribution is 5 l/kg.
Metabolism
Ethinylestradiol is exposed to a presistemny konjyugirovaniye in a mucous membrane of a small intestine and in a liver. Ethinylestradiol at first is metabolized by aromatic hydroxylation, but at the same time a large number of hydroxylated and metilirovanny metabolites which are found in the form of free metabolites and in the form of glucuronides and sulfates is formed. Speed of metabolic clearance is about 5 ml/min.
Removal
Elimination half-life of ethinylestradiol makes about 30 hours. About 40% are removed with urine and 60% with a stake.
Equilibrium concentration
Equilibrium concentration is reached in 3-4 days of administration of drug, at the same time the level of ethinylestradiol is 30-40% higher, than after a single dose of drug.
The pharmacodynamics
of Regulon® is the combined contraceptive drug for oral administration which effect is shown in inhibition of synthesis of gonadotrophins and suppression of an ovulation and also slowing down of advance of spermatozoa through cervical slime and implantations of oospore.
Ethinylestradiol is synthetic estrogen.
Dezogestrel is the synthetic progestogen possessing the significant inhibiting effect on an ovulation, powerful progestagenny effect and anti-estrogenic activity, does not possess estrogenic action and has weak androgenic/anabolic effect.

Indications
- oral contraception

the Route of administration and doses
begin Reception of tablets from the first day of a menstrual cycle on 1 tablet a day within 21 days, whenever possible at the same time. After reception of the last tablet take a 7-day break during which there is menstrualnopodobny bleeding owing to drug withdrawal. For 8 day after a 7-day break (in 4 weeks after reception of the first tablet, on the same day weeks), resume reception of the following packing containing 21 tablets even if bleeding did not stop. This scheme of administration of drug has to remain until contraceptive protection is required. At observance of Regulations of Admission, contraceptive action remains also for the period of a 7-day break.
The first administration of drug
Reception of the first tablet should be begun from the first day of a menstrual cycle. In this case use of additional methods of contraception is not required.
Reception of tablets can also be begun and about 2 - 5 days of periods, but in this case in the first cycle it is necessary to use additional methods of contraception during the first 7 days of reception of tablets.
If there passed more than 5 days after the beginning of periods, it is necessary to postpone the beginning of reception until the following periods.
After termination of pregnancy in the first trimester
After an abortion or abortion, it is necessary to begin Regulon's reception ® from the first day, and in this case there is no need to use additional methods of contraception.
After the delivery or termination of pregnancy in the second trimester
not feeding women should begin reception of tablets in 21 days after the delivery or termination of pregnancy in the second trimester. In this case there is no need for use of other methods of contraception.
If administration of drug was begun later, it is necessary to use additional methods of contraception during the first 7 days.
If the sexual contact after the delivery took place, it is necessary to postpone the beginning of administration of drug until the first periods.
Transition to Regulon® from other oral contraceptive (21 or 28 day drugs)
it is recommended to take the First pill Regulona® next day after end of a rate of the previous drug. It is not required to maintain a break or began to wait for periods. There is no need for use of additional methods of contraception.
Transition from the oral contraceptive containing only progestogen
(mini-drank), on the drug Regulon®:
The first pill Regulona® should be taken in the first day of periods. There is no need for use of additional methods of contraception.
If at reception mini-drank there are no periods, then it is possible to begin reception of Regulona® in any day of a cycle, but in this case in the first 7 days it is necessary to apply additional methods of contraception.
In the above-stated cases as additional methods of contraception the use of non-hormonal methods is recommended: use of a cervical contraceptive cap with spermicidal gel, condom, or abstention from sexual contacts. Use of a calendar method in these cases is not recommended.
The delay of a menstrual cycle
If is available need for a periods delay, then reception of tablets should be continued from new packing, without 7-day break, according to the usual scheme. At a delay of periods there can be breakthrough or printing bleedings, but it does not reduce contraceptive effect of drug. Regular reception of Regulona® can be restored after a usual 7-day break.
The passed tablets
If the woman forgot to take a pill in due time, and after the admission there passed no more than 12 hours, it is necessary just to take the forgotten pill, and further to continue inclusion in usual time.
If between reception of tablets there passed more than 12 hours - it is considered the admission of a tablet, reliability of contraception in this cycle is not guaranteed and recommended use of additional methods of contraception.
At the admission of one tablet on the first or second week of a cycle, it is necessary to take 2 pill in the next day and then to continue regular reception, using additional methods of contraception until the end of a cycle.
At the admission of a tablet on the third week of a cycle it is necessary to take the forgotten pill, to continue regular reception and not to take a 7-day break. It is important to remember that in connection with the minimum dose of estrogen the risk of an ovulation and/or bloody discharges at the admission of reception of a tablet increases and therefore use of additional methods of contraception is recommended.
The measures recommended in case of vomiting or diarrhea
If after administration of drug there is vomiting or diarrhea, absorption of drug can decrease. If symptoms of disorder stopped within 12 hours, then it is necessary to take one more pill in addition. After that it is necessary to continue reception of other tablets usually. If symptoms proceed more than 12 hours, then it is necessary to use additional methods of contraception during vomiting or diarrhea and in the next 7 days.

Side effects
Very often ((& gt, 1/10)
- the breakthrough bleedings smearing discharges
- increase in body weight
Is frequent (& gt, 1/100 to & lt, 1/10)
- a headache, dizziness, migraine,
- nervousness, a depression, change of mood
- nausea, vomiting
- a cholelithiasis, cholestatic jaundice
- disturbances of a menstrual cycle (intermenstrual bleedings, a dysmenorrhea, an amenorrhea after administration of drug), a premenstrual syndrome, change of nature of vaginal discharge, growth of a fibromyoma of a uterus, deterioration in a course of endometriosis, appearance of vaginal infections (for example, candidiasis)
- decrease in a libido
- a nagrubaniye of mammary glands, sensitivity, increase and mammary gland pains, discharge from mammary glands
- an acne, skin rash, a nodal erythema, hloazma
- discomfort of a cornea when carrying contact lenses
- a liquid delay in an organism, change of body weight, decrease in tolerance to carbohydrates
Infrequently (& gt, 1/1,000 to & lt, 1/100)
- arterial hypertension
Seldom (& gt, 1/10,000 to & lt, 1/1,000)
- an otosclerosis
- a thrombembolia, venous thromboses / a thrombembolia, arterial thromboses, a deep vein thrombosis of the lower extremities, a pulmonary embolism
- a myocardial infarction, a stroke
Very seldom (& lt, 1/1 0000)
- arterial or venous thrombosis of vessels of a liver, a mesentery, kidneys or a retina
Serious by-effects at which emergence it is necessary to cancel administration of drug:
In case of development of a hypertension against the background of administration of drug it is necessary to cancel drug urgently.
Use of oral contraceptives can lead to development of cholestatic jaundice or a cholelithiasis.
At women with a giperglitseridemiya or the available disease in the family anamnesis the risk of developing pancreatitis when using oral contraceptives can be increased.
In case of an acute or chronic abnormal liver function use of drug should be stopped until results of functional trials of a liver are not normalized.
If in the early stages of pregnancy or at the previous use of drugs on the basis of sex hormones at the patient the cholestatic jaundice took place, oral contraceptive drug should be cancelled.
Though oral contraceptives can influence peripheral insulin resistance and tolerance of glucose, indications to obligatory change of the scheme of treatment at the women having diabetes when using there is no oral contraception. However, patients with the diabetes accepting oral contraceptives need careful observation of the doctor.
In certain cases against the background of reception of oral contraceptives the hloazma, especially at women with hloazmy pregnant women in the anamnesis develops. The women who are in risk group should abstain from influence of ultraviolet rays and the sun during reception of oral contraceptives.
Seldom or never use of oral contraceptives can provoke a reactive system lupus erythematosus.
One more rare complication when using oral contraceptives is Saint Vitus's dancing (a chorea, disturbance from nervous system), reversible after cancellation of tablets.

Contraindications
- pregnancy or suspicion on pregnancy
- a hypertension of average or heavy degree
- a giperlipoproteinemiya
- existence or the instruction in the anamnesis on arterial or venous thromboembolic diseases (for example, a deep vein thrombosis, a pulmonary embolism, a myocardial infarction, cerebrovascular disturbances)
- presence of risk of developing an arterial or venous thrombembolia
- a diabetic angiopatiya
- existence or the instruction in the anamnesis on a serious illness of a liver, cholestatic jaundice, hepatitis, jaundice during pregnancy, against the background of use of steroids, the syndrome the Cudgel Johnson or the Syndrome of the Rotor (chronic family not hemolytic jaundice), hepatocellular tumors and the Porphyria
- presence of hepatitis (before restoration of laboratory parameters and within 3 months after return of these indicators to norm)
- presence of cholelithiasis
- existence in the anamnesis of tumors of a liver (benign or malignant)
- existence is oestrogenic - dependent tumors or suspicion on them, the endometrium hyperplasia, genital bleedings of not clear etiology
- existence (or the instruction in the anamnesis) a system lupus erythematosus
- a severe itching, herpes of pregnant women, an otosclerosis, deterioration in an otosclerosis during the previous pregnancy or at intake of steroid drugs
- hypersensitivity to any of drug components
- intolerance of a galactose, a lactose intolerance or a sprue of glucose and a galactose

Medicinal interactions
Medicinal interactions which lead to increase in clearance of sex hormones, can provoke breakthrough bleedings and decrease in contraceptive effect of drug. Such interactions were shown concerning hydantoins, barbiturates, Primidonum, carbamazepine and rifampicin, okskarbatsepin, topiramat, felbamat and griseofulvin can also have similar effect. The mechanism of this interaction, is based on ability of these drugs to induce activity of enzymes of a liver. The maximum extent of induction of enzymes usually becomes noticeable only in 2-3 weeks after an initiation of treatment, however, can remain within at least 4 weeks after treatment cancellation.
Leads also concomitant use of antibiotics, such as ampicillin and tetracyclines to decrease in contraceptive efficiency of oral contraceptives though the mechanism of this action is not clear.
The women receiving treatment by drugs of the listed above groups within a short period of time have to use temporarily additional barrier methods of contraception, along with tablets, during the period of use of the accompanying drug and within 7 days after cancellation of this drug.
The women receiving rifampicin have to use additional barrier methods of contraception during the entire period of use of rifampicin and within 28 days after cancellation of this drug. In case the period of intake of the accompanying drug exceeds number of tablets in packing of an oral contraceptive, it is necessary to begin to take a pill of an oral contraceptive from the following packing at once, without taking a break.
Experts recommend to increase a dosage of contraceptive hormones to women who receive treatment by the drugs activating liver enzymes for a long time. If it is not recommended to appoint high doses of hormones or if the high dose of hormones is insufficient or unsafe, for example, in irregular bleedings of cancellation, it is necessary to recommend use of other method of contraception.
Medicine of plant origin the St. John's wort which is made a hole (Hypericum perforatum, a St. John's wort pronzennolistny) can reduce contraceptive efficiency of drug, and this effect can remain within at least 2 weeks after treatment cancellation by the St. John's wort which is made a hole.
Oral contraceptives can reduce tolerance of glucose therefore increase in a dose of insulin or antidiabetic drugs for oral administration can be required.

Special instructions
in the presence of one of below the listed states, in each case are individually estimated advantages or possible negative effects of oral contraceptives. This issue needs to be discussed with the patient who after obtaining the necessary information will make the final decision on whether she wants to take a contraceptive pill or not.
The condition of the woman needs to be controlled carefully. In case of deterioration, aggravations or emergence of any of the listed states against the background of administration of drug, it is necessary to stop administration of drug and to pass to other, non-hormonal method of contraception:
- disturbance of blood clotting
- all diseases connected with the increased risk of development of disturbance of blood circulation: latent or obvious heart failure, a renal failure and also presence of these diseases in the anamnesis
- presence of epilepsy, including in the anamnesis
- presence of migraine, including in the anamnesis
- the cholelithiasis in the anamnesis
- existence of one of risk factors of development is oestrogenic - dependent tumors, is oestrogenic - sensitive gynecologic diseases, such as fibroma and endometriosis
- diabetes
- presence of a heavy depression, including in the anamnesis. If the depression is connected with tryptophane exchange disturbance, then for the purpose of correction it is possible to apply B6 vitamin
- drepanocytic anemia as in some cases (for example, infections, a hypoxia) it is oestrogenic - the containing drugs in this pathology can provoke the thrombembolia phenomena
- if deviations in functional laboratory parameters of a liver appear, then administration of drug needs to be stopped.
Thromboembolic diseases
Data of epidemiological researches proved that there is a communication between intake of oral hormonal contraceptives and increase in risk of arterial and venous trombotichesky and thromboembolic diseases, such as myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism. These states meet seldom.
The increased risk of venous thromboembolic diseases is proved, but it is much less, than at pregnancy (60 cases on 100,000 pregnancies). Frequency of spontaneous emergence of new cases of venous thromboembolic diseases in the healthy non-pregnant women who are not accepting oral contraceptives is about 5 cases on 100,000 women a year. At use of drugs of the second generation is a number of 15 cases on 100 thousand women a year, and at use of drugs of the third generation is a number of 25 cases on 100 thousand women a year. Probability of appearance of venous thromboembolic diseases increases with age and with other risk factors (for example, obesity).
Risk of developing an arterial and/or venous thrombembolia increases at the following states:
- with age
- when smoking (intensive smoking and age of women are more senior than 35 years is the increased risk)
- in the presence in the family anamnesis of thromboembolic diseases (for example, at parents, the brother or the sister). If there is a suspicion on genetic predisposition, then it is necessary to consult before use of drug with the expert
- in obesity (body mass index is higher than 30 kg/sq.m)
- at dislipoproteinemiya
- in a hypertension
- in diseases of valves of heart
- at fibrillation of auricles
- in diabetes
- at long an immobilization, extensive surgical intervention, the lower extremity surgery or an extensive injury. In these cases it is recommended to stop reception of oral contraceptives (at least in 4 weeks prior to planned operation) and not to resume it before the expiration of two weeks after complete recovery.
In a puerperal period it is necessary to consider possible increase in risk of developing a thrombembolia.
Diseases in which blood circulation disturbances can take place, such as, diabetes, a system lupus erythematosus, a gemolitiko-uraemic syndrome, Crohn's disease, nonspecific ulcer colitis, drepanocytic anemia, represent the increased risk of formation of venous thromboembolic diseases.
At migraine attacks the administration of drug should be stopped.
Inborn or the acquired biochemical defects which increase risk of formation of arterial or venous thromboembolic diseases: resistance to the activated protein With (AP), a giperkhromotsisteinemiya, deficiency of antithrombin-III, deficit of proteins of C and S, existence of anti-phospholipidic antibodies (antibodies to cardiolipin, lupoid anticoagulant).
At assessment of a ratio of advantage and risk of administration of drug it must be kept in mind that purposeful treatment of this state reduces risk of formation of a thrombembolia and also that the risk of forming of a thrombembolia is more at pregnancy, than at use of contraceptive tablets.
The symptoms demonstrating development of thrombosis include:
- sudden severe pain in a breast which irradiates in the left hand
- a sudden asthma
- any unusual, severe headache proceeding long time or developing for the first time, especially, if it is combined with the following signs: sudden partial or full loss of sight, a diplopia, aphasia, dizziness, collapse which can appear with focal epilepsy, weakness or the significant numbness of a half of a body, motive disturbances, severe unilateral pain in a gastrocnemius muscle, an acute abdomen.
Oncological diseases
the Estrogen-containing hormonal contraceptives promote growth of sexual gormonalnozavisimy tumors therefore in the presence of such tumors, use of hormonal contraceptives is contraindicated.
A number of researches for identification of communication between use of oral contraceptives and frequency of developing of endometrial cancer, a neck of the uterus and mammary glands was conducted. By results of researches, intake of oral hormonal contraceptives provides significant protection against ovarian cancer and endometrium.
In some researches reported about increase in quantity of cases of cervical cancer at women who long time accepted oral contraceptives, but results of researches are rather contradictory.
Meta-analysis of 54 epidemiological researches showed that there is a relative increase in danger of cancer of mammary glands among the women accepting oral contraceptives, but in these cases cancer of mammary glands was revealed earlier, likely because of regular medical control.
The breast cancer occurs seldom among women more young than 40 years irrespective of, they accept the combined oral contraceptives or not. Risk of developing cancer of mammary glands increases with age. The quantity of cases of cancer of mammary glands is small among the women accepting hormonal contraceptives, and use of tablets can be only one of many risk factors. The woman needs to be informed on a possibility of risk of developing cancer of mammary glands and the decision on reception of tablets, it has to be accepted after assessment of a ratio of advantage and risk (protection against cancer of an ovary and endometrium).
In rare instances at long use of oral contraceptives benign and malignant tumors of a liver were found. It can be a differential and diagnostic question in the presence of an abdominal pain which can be sign of increase in the size of a liver or intra belly bleeding.
Medical examination
before use of contraceptive tablets should be collected the detailed family and personal anamnesis and to have the general and gynecologic examination (measurement of the ABP, laboratory researches, a research of mammary glands and bodies of a small pelvis, a cytologic research of a smear). These researches need to be repeated periodically. Periodic researches are important because risk factors or contraindications come to light at first reception of tablets.
It is necessary to inform the woman that oral contraceptives do not protect from HIV (AIDS) and other diseases, sexually transmitted (D,ST).
Changes of indicators of the laboratory
researches Use of Oral Contraceptives, because of existence in them of an estrogenic component, can affect results of a number of laboratory researches, including, functional tests of a liver, kidneys, adrenal glands and a thyroid gland, parameters of fibrillation and a fibrinolysis, the maintenance of lipoproteins and transport proteins in blood plasma.
Hloazma
In certain cases against the background of reception of oral contraceptives, hloazma, especially at women at whom hloazma met during pregnancy develop. The women who are in risk group should abstain from influence of ultraviolet rays and the sun during reception of tablets.
Pregnancy and a lactation
the Conducted epidemiological researches proved that the frequency of congenital malformations at newborns whose mothers took a hormonal contraceptive pill before pregnancy does not increase, teratogenic effect of drug is not revealed if the woman took a pill in early pregnancy.
Lactation: hormonal contraceptive tablets can lead to decrease in amount of breast milk, and change of its structure, in a small amount drug gets to maternal milk therefore use of these drugs during feeding by a breast is not shown.
Features of influence of medicine on ability to run the vehicle and potentially dangerous mechanisms
of the Researches studying influence of drug on ability of driving and work with mechanisms with the increased risk of traumatism it was not carried out.

Overdose
Symptoms: nausea, vomiting, bloody discharges from a vagina.
Treatment: symptomatic. If the overdose is found in the first 2-3 hours, it is possible to make gastric lavage. There is no specific antidote.

A form of release and packing
On 21 tablets in blister strip packaging from a polyvinylchloride film and aluminum foil.
On 1 or 3 blister strip packagings together with the instruction for medical use in the state and Russian languages and a paper envelope place in a cardboard pack.


To Store storage conditions at a temperature from 15 of 0C up to 30 0C.
To store out of children's reach!


3 years
not to use a period of storage after expiry date!

Prescription status
According to the prescription


the Name and the country

of JSC Gideon Richter manufacturing organization 1103 Budapest, st. Dyomryo, 19-21, Hungary

the Name and the country of the owner of the registration certificate
of JSC Gideon Richter, Budapest, Hungary

the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products:
Representative office of JSC Gideon Richter in RK
E-mail: info@richter.kz
Phone number: 8-(727)-258-26-22, 8-(727)-258-26-23

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