Composition, form of production and packaging
Tablets covered with a film coating of white or almost white color, round, biconcave, labeled "P8" on one side and "RG" on the other.
1 tab.
ethinylestradiol 30 Ојg
desogestrel 150 Ојg
[PRING]? -tocopherol, magnesium stearate, silicon dioxide colloid, stearic acid, povidone, potato starch, lactose monohydrate.
Composition of the film shell: propylene glycol, macrogol 6000, hypromellose.
21 pcs. - blisters (1) - packs of cardboard.
21 pcs. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Monophasic oral contraceptive. The main contraceptive effect is the inhibition of gonadotropin synthesis and suppression of ovulation. In addition, by increasing the viscosity of cervical mucus, the movement of spermatozoa through the cervical canal slows down, and a change in the state of the endometrium prevents the implantation of a fertilized egg.
Ethinyl estradiol is a synthetic analogue of endogenous estradiol.
Desogestrel has a pronounced gestagenic and antiestrogenic action, similar to endogenous progesterone, weak androgenic and anabolic activity.
Regulon has a beneficial effect on lipid metabolism: it increases the concentration of HDL in the blood plasma, without affecting the content of LDL.
When taking the drug, the loss of menstrual blood is significantly reduced (with the initial menorrhagia), the menstrual cycle is normalized, a favorable effect on the skin is noted, especially in the presence of vulgar acne.
PHARMACOKINETICS
Desogestrel
Suction
Desogestrel is rapidly and almost completely absorbed from the digestive tract and is immediately metabolized into 3-keto-desogestrel, which is a biologically active metabolite of desogestrel.
C max is achieved in 1.5 hours and is 2 ng / ml. Bioavailability is 62-81%.
Distribution
3-keto-desogestrel binds to blood plasma proteins, mainly with albumins and with globulin binding sex hormones (SHBG). V d is 1.5 l / kg. C ss is set to the second half of the menstrual cycle. The level of 3-keto-desogestrel increases 2-3 times.
Metabolism
In addition to 3-keto-desogestrel (which is formed in the liver and in the intestinal wall), other metabolites are formed: 3? -OH desogestrel, 3? -ON desogestrel, 3? -OH-5? -H-desogestrel (metabolites of the first phase) . These metabolites do not have pharmacological activity and in part, by conjugation (the second phase of metabolism), are converted into polar metabolites - sulfates and glucuronates. The clearance from the blood plasma is about 2 ml / min / kg of body weight.
Excretion
T 1/2 3-keto-desogestrel is 30 hours. Metabolites are excreted in the urine and with feces (in a ratio of 4: 6).
Ethinylestradiol
Suction
Ethinyl estradiol is rapidly and completely absorbed from the digestive tract. C max is achieved in 1-2 hours after taking the drug and is 80 pg / ml. Bioavailability of the drug due to presystemic conjugation and the effect of "first passage" through the liver is about 60%.
Distribution
Ethinyl estradiol completely binds to blood plasma proteins, mainly with albumins. V d is 5 l / kg. C ss is set to 3-4 days of administration, while the level of ethinyl estradiol in the serum is 30-40% higher than after a single dose.
Metabolism
Pre-systemic conjugation of ethinyl estradiol is significant. Passing the intestinal wall (the first phase of metabolism), it undergoes conjugation in the liver (the second phase of metabolism). Ethinylestradiol and its conjugates of the first phase of metabolism (sulfates and glucuronides) are secreted into bile and enter enterohepatic circulation. The clearance from the blood plasma is about 5 ml / min / kg of body weight.
Excretion
T 1/2 ethinyl estradiol averages about 24 hours. About 40% is excreted in the urine and about 60% - with feces.
INDICATIONS
- Contraception.
DOSING MODE
The drug is prescribed inside.
The intake of tablets starts from the 1st day of the menstrual cycle. Assign 1 tablet / day for 21 days, if possible at the same time of day. After taking the last pill from the package, a 7-day break occurs, during which menstrual bleeding occurs due to withdrawal of the drug. The next day after a 7-day break (4 weeks after the first pill, on the same day of the week), the drug is resumed from the next package, also containing 21 tablets, even if the bleeding has not stopped. Such a regimen of taking tablets is adhered to as long as there is a need for contraception. If the rules of admission are observed, the contraceptive effect is maintained even for a 7-day break.
The first drug intake
The first pill should be taken from the first day of the menstrual cycle. In this case, no additional methods of contraception are needed. You can start taking pills from the 2nd-5th day of menstruation, but in this case, in the first cycle of using the drug, you need to apply additional methods of contraception in the first 7 days of taking the tablets.
If more than 5 days have passed since the onset of menstruation, it should be postponed the start of the drug until the next menstruation.
Taking the drug after giving birth
Non-breastfeeding women can start taking pills no earlier than 21 days after giving birth, after consulting with a doctor. In this case, there is no need to use other methods of contraception. If after the birth had already had sexual contact, then taking pills should be postponed until the first menstruation. If a decision is made to take the drug later than 21 days after the birth, then in the first 7 days it is necessary to use additional methods of contraception.
Admission after abortion
After abortion, in the absence of contraindications, the taking of tablets should begin from the first day after the operation, and in this case there is no need for additional methods of contraception.
Transition from another oral contraceptive
When switching from another oral preparation (21- or 28-day): the first Regulon tablet is recommended to be taken the day after the completion of the course of the 28-day package of the drug. After the completion of the 21-day course, it is necessary to make an ordinary 7-day break and then proceed to receive Regulon. There is no need for additional methods of contraception.
Transition to Regulon after the use of oral hormone preparations containing only progestogen ("mini-pili")
The first tablet of Regulon should be taken on the 1st day of the cycle. There is no need for additional methods of contraception.
If you do not experience menstruation when taking mini-pills, then after the exception of pregnancy, you can start taking Regulon on any day of the cycle, but in this case, additional methods of contraception (using a cervical cap with spermicidal gel, a condom, or abstinence from sexual contacts). The use of the calendar method in these cases is not recommended.
Delayed menstrual cycle
If there is a need to delay menstruation, you should continue taking the pills from the new package, without a 7-day break, according to the usual scheme. When delaying menstruation, breakthrough or spotting bleeding may occur, but this does not reduce the contraceptive effect of the drug. Regular reception of Regulon can be restored after an ordinary 7-day break.
Missed tablets
If the woman forgot to take the pill on time, and after the pass was no more than 12 hours, you need to take a forgotten pill, and then continue the reception at the usual time. If more than 12 hours have passed between taking the tablets - this is considered a missing tablet, the reliability of contraception in this cycle is not guaranteed and the use of additional methods of contraception is recommended.
If you miss one tablet on the first or second week of the cycle , you need to take 2 tab. the next day and then continue with regular admission, using additional contraceptive methods until the end of the cycle.
If you miss a pill in the third week of the cycle, you must take a forgotten pill, continue with regular reception and do not take a 7-day break. It is important to remember that in connection with the minimal dose of estrogen, the risk of ovulation and / or bleeding is increased when a pill is missed and therefore additional methods of contraception are recommended.
Vomiting / diarrhea
If vomiting or diarrhea occurs after taking the drug, then the absorption of the drug may be inadequate. If the symptoms stop within 12 hours, then you need to take another pill in addition. After this, you should continue taking the tablets in the usual way. If vomiting or diarrhea lasts more than 12 hours, then you need to use additional methods of contraception during vomiting or diarrhea and for the next 7 days.
SIDE EFFECT
Side effects that require drug withdrawal
From the side of the cardiovascular system: arterial hypertension; rarely - arterial and venous thromboembolism (including myocardial infarction, stroke, deep vein thrombosis of the lower limbs, thromboembolism of the pulmonary artery); very rarely - arterial or venous thromboembolism of the hepatic, mesenteric, renal, retinal arteries and veins.
From the sense organs: loss of hearing due to otosclerosis.
Other: hemolytic-uremic syndrome, porphyria; rarely - exacerbation of reactive systemic lupus erythematosus; very rarely - Sydenham's chorea (passing after withdrawal of the drug).
Other side effects that occur more often, but less severe. The expediency of continuing the use of the drug is decided individually after consultation with the doctor, based on the benefit / risk ratio.
On the part of the reproductive system: acyclic bleeding / spotting from the vagina, amenorrhea after drug withdrawal, changes in the state of vaginal mucus, development of inflammatory processes of the vagina, candidiasis, stress, pain, breast enlargement, galactorrhea.
On the part of the digestive system: nausea, vomiting, Crohn's disease, ulcerative colitis, the appearance or exacerbation of jaundice and / or itching associated with cholestasis, cholelithiasis.
Dermatological reactions: erythema nodosum, exudative erythema, rash, chloasma.
From the side of the central nervous system: headache, migraine, lability of mood, depression.
From the side of the organ of vision: increasing the sensitivity of the cornea (when wearing contact lenses).
From the side of metabolism: fluid retention in the body, change (increase) in body weight, reduced tolerance to carbohydrates.
Other: allergic reactions.
CONTRAINDICATIONS
- presence of severe and / or multiple risk factors for venous or arterial thrombosis (including severe or moderate arterial hypertension with BP ≥ 160/100 mm Hg);
- the presence or indication in the anamnesis of the precursors of thrombosis (including transient ischemic attack, angina pectoris);
- Migraine with focal neurologic symptoms, incl. in the anamnesis;
- Venous or arterial thrombosis / thromboembolism (including myocardial infarction, stroke, deep vein thrombosis of the lower leg, pulmonary embolism) at present or in the anamnesis;
- presence of a venous thromboembolism in the anamnesis;
- diabetes mellitus (with angiopathy);
- pancreatitis (including in the anamnesis), accompanied by severe hypertriglyceridemia;
- dyslipidemia;
- severe liver disease, cholestatic jaundice (including during pregnancy), hepatitis, incl. in the anamnesis (before normalization of functional and laboratory parameters and within 3 months after their normalization);
- jaundice when taking GCS;
- cholelithiasis at present or in anamnesis;
- Gilbert's syndrome, Dubin-Johnson syndrome, Rotor syndrome;
- Liver tumors (including in the anamnesis);
- severe itching, otosclerosis or its progression with a previous pregnancy or SCS;
- hormone-dependent malignant neoplasms of genital organs and mammary glands (including when suspected of them);
- vaginal bleeding of unclear etiology;
- smoking at the age of over 35 years (more than 15 cigarettes a day);
- Pregnancy or suspicion of it;
- lactation period;
- Hypersensitivity to the components of the drug.
Caution should be given to the drug at conditions that increase the risk of venous or arterial thrombosis / thromboembolism: age over 35 years, smoking, family history, obesity (body mass index more than 30 kg / m 2 ), dyslipoproteinemia, arterial hypertension, migraine, epilepsy, valvular heart disease, atrial fibrillation, prolonged immobilization, extensive surgical intervention, lower extremity surgery, severe trauma, varicose veins and superficial thrombophlebitis, postroids(including anamnesis), changes in biochemical parameters (resistance of activated protein C, hyperhomocysteinemia, deficiency of antithrombin III, deficiency of protein C or S, antiphospholipid antibodies, including antibodies to cardiolipin, in including lupus anticoagulant), diabetes mellitus not complicated by vascular disorders, SLE, Crohn's disease, ulcerative colitis, sickle cell anemia, hypertriglyceridemia (incl. in family history), acute and chronic liver disease.
PREGNANCY AND LACTATION
The use of the drug during pregnancy and during breast-feeding is contraindicated.
During the period of breastfeeding, it is necessary to decide whether to abolish the drug or stop breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution and only after a thorough evaluation of the benefits and risks of use should prescribe the drug in case of renal failure (including in the anamnesis).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in liver failure.
With caution should prescribe the drug for acute and chronic liver disease.
APPLICATION IN ELDERLY PATIENTS
Contraceptive drug, in the elderly is not applied.
SPECIAL INSTRUCTIONS
Before starting the drug, it is necessary to conduct general medical (detailed family and personal history, measurement of blood pressure, laboratory tests) and gynecological examination (including examination of mammary glands, pelvic organs, cytological analysis of cervical smear). Such a survey during the period of taking the drug is carried out regularly, every 6 months.
The drug is a reliable contraceptive: Perl index (the indicator of the number of pregnancies that occurred during the application of the method of contraception in 100 women for 1 year), with proper application is about 0.05.
In each case, before the appointment of hormonal contraceptives individually evaluated the benefits or possible negative effects of their reception. This issue should be discussed with the patient, who after receiving the necessary information will make the final decision on the preferences of hormonal or some other method of contraception.
The state of women's health must be carefully monitored. If during the reception of the drug appears or worsens any of the below listed conditions / diseases, you must stop taking the drug and go to another, non-hormonal method of contraception:
- diseases of the hemostasis system;
- conditions / diseases predisposing to the development of cardiovascular, renal failure;
- epilepsy;
- Migraine;
- risk of developing estrogen-dependent tumors or estrogen-dependent gynecological diseases;
- diabetes mellitus, not complicated by vascular disorders;
- severe depression (if depression is associated with a violation of tryptophan metabolism, then vitamin B 6 can be used to correct it);
- sickle-cell anemia, tk. in some cases (for example, infections, hypoxia), estrogen-containing drugs can provoke thromboembolic events in this pathology;
- the appearance of abnormalities in laboratory tests assessing liver function.
Thromboembolic diseases
Epidemiological studies have shown that there is a link between the intake of oral hormonal contraceptives and an increased risk of arterial and venous thromboembolic diseases (including myocardial infarction, stroke, deep vein thrombosis of the lower extremities, pulmonary embolism). The increased risk of venous thromboembolic diseases has been proven, but it is significantly less than in pregnancy (60 cases per 100,000 pregnancies).
Some researchers suggest that the probability of venous thromboembolic disease is greater when using preparations containing desogestrel and gestodene (third-generation drugs) than with drugs containing levonorgestrel (second-generation drugs).
The incidence of spontaneous emergence of new cases of venous thromboembolic disease in healthy non-pregnant women who do not take oral contraceptives is about 5 cases per 100,000 women per year. When using second-generation drugs - 15 cases per 100 thousand women per year, and with the use of third-generation drugs - 25 cases per 100 thousand women per year.
When using oral contraceptives, arterial or venous thromboembolism of hepatic, mesenteric, renal vessels or retinal vessels is very rare.
The risk of arterial or venous thromboembolic disease increases:
- with age;
- when smoking (intensive smoking and age over 35 are among the risk factors);
- if there is a family history of thromboembolic diseases (for example, in parents, a brother or a sister). If you suspect a genetic predisposition, you must consult a specialist before using the drug;
- with obesity (body mass index more than 30 kg / m 2 );
- with dyslipoproteinemia;
- with arterial hypertension;
- with diseases of the heart valves complicated by hemodynamic disorders;
- with atrial fibrillation;
- with diabetes mellitus, complicated by vascular lesions;
- with prolonged immobilization, after a big surgery, after surgery on the lower extremities, after a serious injury.
In these cases, temporary suspension of the drug is supposed to (not later than 4 weeks prior to surgery, and renew - not earlier than 2 weeks after remobilization).
In women after giving birth increases the risk of venous thromboembolic disease.
Keep in mind that diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, increase the risk of venous thromboembolic disease.
Note that the resistance to activated protein C, hyperhomocysteinemia, deficiency of protein C and S, antithrombin III deficiency, the presence of antiphospholipid antibodies, increase the risk of arterial or venous thromboembolic disease.
In assessing the benefit / risk ratio of the drug should be considered that the targeted treatment of this condition reduces the risk of thromboembolism. Symptoms of thromboembolism include:
- sudden chest pain that radiates to the left arm;
- sudden shortness of breath;
- Any unusually severe headache, which lasts a long time or appearing for the first time, especially when combined with a sudden complete or partial loss of vision, or diplopia, aphasia, dizziness, collapse, focal epilepsy, weakness or severe numbness in half of the body, movement disorders, severe unilateral pain gastrocnemius muscle, acute abdomen.
Neoplastic diseases
Some studies have reported the quickening of cervical cancer in women who took a long time, hormonal contraceptives, but research results are contradictory. In the development of cervical cancer play a significant role sexual behavior, infection with the human papilloma virus and other factors.
A meta-analysis of 54 epidemiological studies showed that there is a relative increase in the danger of breast cancer among women taking oral hormonal contraceptives, however, a higher detection rate of breast cancer could be linked to a regular medical examination. Breast cancer is rare in women younger than 40, regardless of whether they are taking hormonal contraceptives or not, and increases with age. Receiving tablets can be regarded as one of the many risk factors. However, women should be advised of the risk of the possibility of breast cancer, based on the assessment of benefit-risk ratio (from ovarian cancer and endometrial protection).
There are a few reports on the development of benign or malignant liver tumors in women receiving long-term hormonal contraceptives. It should be borne in mind in the differential-diagnostic evaluation of abdominal pain, which may be associated with an increase in liver size or intraperitoneal bleeding.
Chloasma
chloasma may occur in women with the disease during pregnancy in history. Those women who have a risk of chloasma, it is necessary to avoid exposure to sunlight or ultraviolet radiation while taking regulon.
Efficiency
Efficacy may be reduced under the following conditions: missing tablets, vomiting and diarrhea, concurrent use of other drugs that reduce the effectiveness of the contraceptive pill.
If the patient simultaneously receives a different drug, which may reduce the effectiveness of the contraceptive pill should apply additional methods of contraception.
Efficacy can be reduced if, after several months of their applications appear irregular, spotting or breakthrough bleeding, in such cases it is advisable to continue taking the tablets before their next closure in the package. If at the end of the second cycle menstrualnopodobnoe bleeding begins or acyclic bleeding does not stop, stop taking the tablets and to resume it only after the exclusion of pregnancy.
Changes in laboratory parameters
under the action of oral contraceptive pills - in connection with the estrogenic component - may change the level of some laboratory parameters (liver function indicators, kidney, adrenals, thyroid, hemostasis, lipoprotein and transport proteins).
Additional Information
After acute viral hepatitis drug should be taken after the normalization of liver function (not earlier than 6 months).
Diarrhea or intestinal disorders, vomiting contraceptive effect may be reduced. Without stopping taking the drug, it is necessary to use additional non-hormonal methods of contraception.
Women who smoke have an increased risk of cardiovascular disease with serious consequences (myocardial infarction, stroke). The risk depends on the age (especially in women older than 35 years) and the number of cigarettes smoked.
Woman should notify that the drug does not protect against HIV infection (AIDS) and other diseases, sexually transmitted diseases.
Impact on the ability to drive vehicles and manage mechanisms
The drug does not affect the ability to drive a car and operate machinery.
OVERDOSE
Symptoms: nausea, vomiting, girls - bleeding from the vagina.
Treatment: the first 2-3 hours after drug administration in a high dose is recommended to conduct gastric lavage. No specific antidote, symptomatic treatment.
DRUG INTERACTION
Drugs that induce hepatic enzymes such as hydantoin, barbiturates, primidone, carbamazepine, rifampicin, oxcarbazepine, topiramate, felbamate, griseofulvin, Hypericum ordinary formulations, reduce the effectiveness of oral contraceptives and increase the risk of breakthrough bleeding. The maximum induction level is not typically achieved previously 2-3 weeks but may extend up to 4 weeks after drug withdrawal.
Ampicillin and tetracycline reduce efficiency regulon (interaction mechanism is not installed). If necessary, co-administration is recommended to use an additional barrier method of contraception throughout the course of treatment and 7 days (for rifampicin - 28 days) after drug withdrawal.
Oral contraceptives can reduce the tolerance to carbohydrates, increase the need for insulin or oral antidiabetic agents.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be kept out of reach of children at a temperature of from 15 В° to 30 В° C. Shelf life - 3 years.
