Gestoden, Ethinylestradiol | Lindinet 20 tablets, 63 pcs.

Release form

coated tablets

Packing

63 pcs.

Pharmacological action

Lindinet is a combined drug whose action is due to the effects of the components that make up its composition. It inhibits the pituitary secretion of gonadotropic hormones. The contraceptive effect of the drug is associated with several mechanisms. The estrogenic component of the drug is a highly effective oral drug - ethinyl estradiol (a synthetic analogue of estradiol, which, together with the corpus luteum hormone, is involved in the regulation of the menstrual cycle).

The progestational component is a 19-nortestosterone derivative - gestodene, superior in strength and selectivity to not only the natural corpus luteum hormone progesterone, but also modern synthetic progestogens (levonorgestrel). Due to its high activity, gestodene is used in very low dosages, in which it does not exhibit androgenic properties and practically does not affect lipid and carbohydrate metabolism.

Along with the indicated central and peripheral mechanisms that prevent the fertilization of an egg capable of fertilization, the contraceptive effect is due to a decrease in the sensitivity of the endometrium to the blastocyst, as well as an increase in the viscosity of the mucus located in the cervix, which makes it relatively impassable for spermatozoa. In addition to the contraceptive effect, the drug, when taken regularly, also has a therapeutic effect, normalizing the menstrual cycle and helping to prevent the development of a number of gynecological diseases, including tumor nature.

Pharmacokinetics

Gestoden

Absorption. When taken orally, it is rapidly and completely absorbed. After taking a single dose, plasma Cmax is measured after an hour and is 2–4 ng / ml. Bioavailability is about 99%.

distribution. It is associated with albumin and sex hormone binding globulin (SHBG). 1–2% are in a free state, 50–75% are specifically associated with SHBG. An increase in SHBG levels due to ethinyl estradiol affects the level of gestodene, leading to an increase in the SHBG-related fraction and a decrease in the albumin-bound fraction. Vd of gestodene - 0.7–1.4 l / kg.

Metabolism. Corresponds to the metabolism of steroids. The average plasma clearance is 0.8–1 ml / min / kg.

Withdrawal. Blood levels are reduced in two stages. Time by sex hormone binding (SHBG). 1–2% are in a free state, 50–75% are specifically associated with SHBG. An increase in SHBG levels due to ethinyl estradiol affects the level of gestodene, leading to an increase in the SHBG-related fraction and a decrease in the albumin-bound fraction. Vd of gestodene - 0.7–1.4 l / kg.

Metabolism. Corresponds to the metabolism of steroids. The average plasma clearance is 0.8–1 ml / min / kg.

Withdrawal. Blood levels are reduced in two stages. Time by sex hormone binding (SHBG). 1–2% are in a free state, 50–75% are specifically associated with SHBG. An increase in SHBG levels due to ethinyl estradiol affects the level of gestodene, leading to an increase in the SHBG-related fraction and a decrease in the albumin-bound fraction. Vd of gestodene - 0.7–1.4 l / kg.

Metabolism. Corresponds to the metabolism of steroids. The average plasma clearance is 0.8–1 ml / min / kg.

Withdrawal. Blood levels are reduced in two stages. Time by 8–1 ml / min / kg.

Withdrawal. Blood levels are reduced in two stages. Time by 8–1 ml / min / kg.

Withdrawal. Blood levels are reduced in two stages. Time byluraspada in the final phase of 12–20 hours. It is excreted exclusively in the form of metabolites - 60% with urine, 40% with feces. T1 / 2 metabolites - approximately 1 day.

Stable concentration. The pharmacokinetics of gestodene is largely dependent on the level of SHBG. Under the influence of ethinyl estradiol, the concentration of SHBG in the blood increases 3 times with daily use of the drug, the level of gestoden in the plasma increases 3-4 times and reaches a saturation state in the second half of the cycle.

Ethinyl estradiol

Suction. When taken orally, it is absorbed quickly and almost completely. Cmax in the blood is measured after 1–2 hours and is 30–80 pg / ml. Absolute bioavailability ”60% (due to presystemic conjugation and primary metabolism in the liver).

distribution. It easily enters into a non-specific relationship with blood albumin (about 98, 5%) and causes an increase in the level of SHBG. The average Vd is 5–18 l / kg.

Metabolism. It is carried out mainly due to aromatic hydroxylation with the formation of large quantities of hydroxylated and methylated metabolites, which are partly in free, partly in conjugated form (glucuronides and sulfates). Plasma clearance »5–13 ml / min / kg.

Withdrawal. The concentration in serum is reduced in 2 stages. T1 / 2 in the second phase »16-24 hours. It is excreted exclusively in the form of metabolites in a ratio of 2: 3 with urine and bile. T1 / 2 metabolites »1 day.

Stable concentration. It is established by the 3-4th day, while the level of ethinyl estradiol is 20% higher than after taking a single dose.

Indications

Contraception.

Contraindications

individual hypersensitivity to the drug or its components

the presence of severe or multiple risk factors for venous or arterial thrombosis (including complicated valvular lesions of the heart, atrial fibrillation, cerebrovascular disease or coronary arteries) hypertension moderate or severe with blood pressure 160/100 mm RT. Art. and more)

precursors of thrombosis (including transient ischemic attack, angina pectoris), including a history of

migraine with focal neurological symptoms, including a history of

venous or arterial thrombosis / thromboembolism (including deep leg vein thrombosis, pulmonary embolism, myocardial infarction, stroke) or current

presence of venous thromboembolism in relatives of srdlkr (with the presence of angiopathy)

pancreatitis (including a history), accompanied by severe hypertriglyceridemia

dyslipidemia

severe liver disease, cholestatic jaundice (including during pregnancy), hep attit, including history (before normalization of functional and laboratory parameters and within 3 months after return of these parameters to normal)

jaundice due to taking drugs containing steroids

gallstone disease at present or history

syndrome Gilbert, Dubin-Johnson, Rotor

tumor liver (including a history of)

severe itching, otosclerosis, or the progression of otosclerosis during a previous pregnancy or while taking GCS

hormone-dependent malignant neoplasms of the genital organs and mammary glands (including suspected on them)

vaginal bleeding of unknown etiology

smoking over the age of 35 years (more than 15 cigarettes per day)

pregnancy or suspected

lactation.

Precautions: conditions, increasing the risk of developing venous or arterial thrombosis / thromboembolism (age over 35 years old, smoking, hereditary predisposition to thrombosis - thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the next of kin) hemolytic uremic syndrome hereditary angioedema of the disease first occurring or aggravated during pregnancy or against the background of previous use of sex hormones (including porphyria, herpes pregnant, small Orey - Sydenham's disease, Sydenham's chorea, chloasma) obesity (body mass index over 30) dyslipoproteinemia arterial hypertension migraine epilepsy valvular heart defects atrial fibrillation prolonged immobilization extensive surgery lower limb surgery severe trauma varicose veins and superficial thrombophlebitis postpartum 21 days after feeding (not food) women - after the lactation period) the presence of severe depression, including history of changes in biochemical parameters (resistance of activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C or S deficiency, antiphospholipid antibodies, including antibodies to cardiolipin, lupus anticoagulant) diabetes mellitus, not complicated by vascular disorders, systemic lupus erythematosus (SLE) Crohn's disease ulcerative colitis sickle cell anemia hypertriglyceridemia (including in the family history) acute and chronic liver diseases.

Special instructions

Before starting the use of the drug, it is recommended to collect a detailed family and personal history and then undergo a general medical and gynecological examination every 6 months (examination by a gynecologist, examination of a cytological smear, examination of the mammary glands and liver function, blood pressure monitoring, blood cholesterol concentration, Analysis of urine). These studies should be repeated periodically due to the need for timely identification of risk factors or contraindications that have arisen.

The drug is a reliable contraceptive - the Perl index (an indicator of the number of pregnancies that occurred during the use of the contraceptive method in 100 women within 1 year) when used correctly is about 0.05. Because, Since the contraceptive effect of the drug from the beginning of taking is fully manifested by the 14th day, then in the first 2 weeks of taking the drug it is recommended to additionally use non-hormonal methods of contraception.

In each case, before the appointment of hormonal contraceptives, the benefits or possible negative effects of their administration are individually evaluated. This issue must be discussed with the patient, who, after receiving the necessary information, will make the final decision on the preference for hormonal or any other method of contraception. The health status of a woman must be carefully monitored.

If any of the following conditions / diseases appears or worsens while taking the drug, you must stop taking the drug and switch 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 an estrogen-dependent tumor or estrogen-dependent gynecological diseases

- non-severe diabetes mellitus, if depression is associated with a violation of tryptophan metabolism, then vitamin B6)

, sickle cell anemia, can be used to correct in some cases (for example, infections, hypoxia), estrogen-containing drugs with this pathology can provoke

thromboembolism - the appearance of deviations in laboratory tests evaluating liver function.

Thromboembolic disease

Epidemiological studies have proven that there is a relationship between taking 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). An increased risk of venous thromboembolic diseases has been proven, but it is significantly less than during pregnancy (60 cases per 100 thousand pregnancies). When using oral contraceptives, arterial or venous thromboembolism of the liver, mesenteric, renal vessels or retinal vessels is very rarely observed.

The risk of arterial or venous thromboembolic disease is increased:

- with age

- when smoking (heavy smoking and over 35 years old are considered risk factors)

- if there is a family history of thromboembolic diseases (for example, parents, brother or sister). If a genetic predisposition is suspected, it is necessary to consult a

specialist before using the drug - for obesity (body mass index above 30)

- for

dyslipoproteinemia - for sardlkp arterial hypertension - for heart valve diseases complicated by hemodynamic disturbances srdlkrp - for diabetes complicated by vascular lesions of

- with prolonged immobilization, after a large surgical intervention, surgical intervention on the lower end ostyah, severe injury.

In these cases, a temporary discontinuation of the drug is expected. It is advisable to stop no later than 4 weeks before surgery, and resume no earlier than 2 weeks after remobilization.

Increased risk of venous thromboembolic disease in women after childbirth.

Diseases such as diabetes mellitus, SLE, hemolytic uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, increase the risk of venous thromboembolic diseases.

Biochemical abnormalities such as resistance to activated protein C, hyperhomocysteinemia, protein C, S deficiency, antithrombin III deficiency, the presence of antiphospholipid antibodies, increase the risk of arterial or venous thromboembolic diseases.

When assessing the benefit / risk ratio of taking the drug, it should be borne in mind that targeted treatment of this condition reduces the risk of thromboembolism.

Signs of thromboembolism are:

- sudden chest pain that radiates to the left arm

- sudden shortness of breath

- any unusually severe headache that lasts a long time or appears 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 of half the body, motor disorders, severe unilateral pain in the calf muscle, acute abdomen.

Tumor diseases

Some studies have reported an increase in cervical cancer in those women who have been taking hormonal contraceptives for a long time, but the research results are contradictory. In the development of cervical cancer, sexual behavior, infection with the human papillomavirus and other factors play a significant role.

A meta-analysis of 54 epidemiological studies showed that there is a relative increase in the risk of breast cancer among women taking oral hormonal contraceptives, but a higher detection of breast cancer could be associated with a more regular medical examination. Breast cancer is rare among women under the age of 40, regardless of whether they take hormonal contraceptives or not, and increases with age. Taking pills can be regarded as one of many risk factors. Nonetheless, a woman should be made aware of the possible risk of developing breast cancer based on an assessment of the ratio of benefit and risk (protection against cancer of the ovary, endometrium and large intestine).

There are few reports of the development of a benign or malignant tumor of the liver in women who have been taking hormonal contraceptives for a long time. This should be borne in mind in the differential diagnostic assessment of abdominal pain, which may be associated with an increase in liver size or intra-abdominal bleeding.

A woman should be warned that the drug does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

The effectiveness of the drug may decrease in the following cases: missed tablets, vomiting and diarrhea, the simultaneous use of other drugs, reducing the effectiveness of birth control pills.

If the patient is simultaneously taking another drug that may reduce the effectiveness of birth control pills, additional methods of contraception should be used.

The effectiveness of the drug may decrease if, after several months of their use, irregular, spotting or breakthrough bleeding appears, in such cases it is advisable to continue taking the tablets until they are finished in the next package. If at the end of the 2nd cycle menstrual-like bleeding does not start or acyclic spotting does not stop, you should stop taking the tablets and resume it only after exclusion of pregnancy.

Chloasma

Chloasma can sometimes occur in women who have had a history of pregnancy. To those women who are at risk of chloasma, avoid contact with sunlight or UV while taking the pill.

Changes in laboratory parameters

Under the influence of oral contraceptive pills - due to the estrogen component - the level of some laboratory parameters may change (functional indicators of the liver, kidneys, adrenal glands, thyroid gland, hemostasis, lipoprotein and transport protein levels).

After acute viral hepatitis should be taken after normalization of liver function (not earlier than 6 months). With diarrhea or intestinal disorders, vomiting, the contraceptive effect may decrease (without stopping the drug, additional non-hormonal methods of contraception must be used). Smoking women have an increased risk of developing vascular diseases with serious consequences (myocardial infarction, stroke). The risk depends on age (especially women over 35 years old) and the number of cigarettes smoked. During lactation, milk excretion may decrease, in insignificant amounts, the components of the drug are excreted in breast milk.

The effect of the drug on the ability to drive a car and working mechanisms. Studies on the possible effect of the drug Lindinet 20 on the ability to drive a car or other cars have not been conducted.

Composition

1 tablet contains:

active ingredients:

ethinyl estradiol 20 ?g

gestodene 75 ?g

excipients:

sodium calcium edetate, srdlklcdum shell:

D + C yellow N 10 C.I. 47005,

E104,

povidone,

titanium oxide CI 7791,

E171,

macrogol 6000

talc,

calcium carbonate,

sucrose.

Dosage and administration

Inside, without chewing, drinking plenty of water, regardless of food intake.

Take 1 tablet. per day (if possible at the same time of day) for 21 days. Then, after taking a 7-day break in taking the pills, resume oral contraception (i.e. 4 weeks after taking the 1st pill, on the same day of the week). During a 7-day break, uterine bleeding occurs as a result of hormone withdrawal.

First dose: Lindinet 20 should be taken from the 1st to the 5th day of the menstrual cycle.

Switching from combined oral contraceptive to taking Lindinet 20. 1st table Lindinet 20 is recommended to be taken after taking the last hormone-containing tablet of the previous drug, on the 1st day of withdrawal bleeding.

Switching from progestogen-containing drugs (mini-tablets, injections, implant) to taking Lindinet 20. Switching from mini-tablets can be started any day of the menstrual cycle in the case of an implant - the day after its removal in the case of injections - on the eve of the last injection.

Moreover, in the first 7 days of taking Lindinet 20, an additional method of contraception is necessary.

Taking Lindinet 20 after an abortion in the first trimester of pregnancy. Contraceptive administration can begin immediately after an abortion, and there is no need to use an additional method of contraception.

Taking Lindinet 20 after birth or after an abortion in the second trimester of pregnancy. Contraceptive administration can begin on the 21–28th day after childbirth or abortion in the second trimester of pregnancy. With a later start of contraception, in the first 7 days, it is necessary to apply an additional, barrier method of contraception. In the event that sexual contact took place before contraception, before starting to take the drug, you should exclude the presence of a new pregnancy or wait for the next menstruation.

Missed Pills. If the next scheduled pill was missed, then you should fill in the missed dose as soon as possible. With a delay not exceeding 12 hours, the contraceptive effect of the drug does not decrease, and there is no need for an additional method of contraception. The remaining tablets are taken as usual.

With a delay of more than 12 hours, the contraceptive effect may be reduced. In such cases, you should not make up for the missed dose, taking the drug is continued as usual, however, in the next 7 days, an additional method of contraception is necessary. If at the same time less than 7 tablets remained in the package, then the tablets are taken from the next package without a break. In such cases, uterine withdrawal bleeding occurs only at the end of the 2nd package while taking tablets from the 2nd package, smearing or breakthrough bleeding is possible.

If, upon completion of taking the tablets from the 2nd package, withdrawal bleeding does not occur, then pregnancy should be excluded before continuing with contraception.

Measures for vomiting and diarrhea. If vomiting occurs in the first 3-4 hours after taking the next pill, the tablet is not completely absorbed. In such cases, proceed in accordance with the instructions described in the item Missed tablets.

If the patient does not wish to deviate from the usual regimen of contraception, missed tablets should be taken from a different package.

Delayed menstruation and accelerate the onset of menstruation. In order to delay menstruation, taking tablets from a new package is started without observing a break. Menstruation can be delayed as desired until all tablets from the 2nd package have run out. With a delay in menstruation, breakthrough or spotting uterine bleeding is possible. You can return to your regular pill regimen after a 7-day break.

With the aim of an earlier onset of menstrual bleeding, you can shorten the 7-day break by the desired number of days. The shorter the break, the more likely the occurrence of breakthrough or spotting bleeding while taking the tablets from the next package (similar to cases with delayed menstruation).

Side effects

Side effects, the appearance of which requires immediate discontinuation of the drug:

- arterial hypertension

- hemolytic-uremic syndrome

- porphyria

- hearing loss due to otosclerosis.

Rarely encountered - arterial and venous thromboembolism (including myocardial infarction, stroke, deep vein thrombosis of the lower extremities, pulmonary embolism) exacerbation of reactive SLE.

Very rare - arterial or venous thromboembolism of the hepatic, mesenteric, renal, retinal arteries and veins of Sydenham chorea (passing after drug withdrawal).

Other side effects, less severe, but more common - the appropriateness of continuing the use of the drug is decided individually after consulting a doctor, based on the benefit / risk ratio.

From the reproductive system: acyclic bleeding / spotting from the vagina, amenorrhea after discontinuation of the drug, a change in the condition of the vaginal mucus, the development of inflammatory processes of the vagina (e.g. candidiasis), a change in libido.

From the mammary glands: tension, pain, enlargement of the mammary glands, galactorrhea.

From the gastrointestinal tract and hepatobiliary system: nausea, vomiting, diarrhea, epigastric pain, Crohn's disease, ulcerative colitis, hepatitis, liver adenoma, the occurrence or exacerbation of jaundice and / or itching associated with cholestasis, cholelithiasis.

From the skin: nodular / exudative erythema, rash, chloasma, increased hair loss.

From the side of the central nervous system: headache, migraine, mood changes, depressive states.

Metabolic disorders: fluid retention in the body, change (increase) in body weight, increased amounts of triglycerides and sugar in the blood, decreased carbohydrate tolerance.

On the part of the sensory organs: hearing loss, increased sensitivity of the cornea when wearing contact lenses.

Other: allergic reactions.

Drug interaction

The contraceptive effect of oral contraceptives decreases with the use of rifampicin, breakthrough bleeding and irregular menstruation are frequent. A similar, but less studied, interaction exists between contraceptives and carbamazepine, primidone, barbiturates, phenylbutazone, phenytoin and, presumably, griseofulvin, ampicillin and tetracyclines. During treatment with the above listed drugs, along with oral contraception, it is recommended to use an additional method of contraception (condom, spermicidal gel). After completing the course of treatment, the use of an additional method of contraception should be continued for 7 days, in the case of rifampicin treatment - for 4 weeks.

Interactions associated with the absorption of the drug

During diarrhea, the absorption of hormones decreases (due to increased intestinal motility). Any drug that shortens the residence time of the hormone in the colon leads to low concentrations of the hormone in the blood.

Interactions associated with the metabolism of the drug

Intestinal wall. Drugs that undergo sulfation in the intestinal wall like ethinyl estradiol (e.g. ascorbic acid), inhibit metabolism and increase the bioavailability of ethinyl estradiol.

Metabolism in the liver. Inducers of microsomal liver enzymes reduce the level of ethinyl estradiol in blood plasma (rifampicin, barbiturates, phenylbutazone, phenytoin, griseofulvin, topiramate, hydantoin, felbamate, rifabutin, oxcarbazepine). Liver enzyme blockers (itraconazole, fluconazole) increase the level of ethinyl estradiol in blood plasma.

Effect on intrahepatic circulation. Some antibiotics (for example, ampicillin, tetracycline), interfering with the intrahepatic circulation of estrogens, reduce the level of ethinyl estradiol in plasma.

Effect on the metabolism of other drugs

By blocking liver enzymes or accelerating conjugation in the liver, mainly by increasing glucuronidation, ethinyl estradiol affects the metabolism of other drugs (e.g. cyclosporine, theophylline), leading to an increase or decrease in their plasma concentrations.

The simultaneous use of St. John's wort preparations (Hypericum perforatum) with Lindinet 20 tablets (due to a possible reduction in the contraceptive effect of the contraceptive active substances, which may be accompanied by breakthrough bleeding and unwanted pregnancy). St. John's wort activates liver enzymes after stopping the use of St. John's wort preparations, the effect of induction of enzymes can persist for the next 2 weeks.

The simultaneous use of ritonavir and a combined contraceptive is accompanied by a decrease in the average AUC of ethinyl estradiol by 41%. During treatment with ritonavir, it is recommended to use a drug with a higher content of ethinyl estradiol or a non-hormonal method of contraception. It may be necessary to adjust the dosage regimen when using hypoglycemic agents, because oral contraceptives can reduce carbohydrate tolerance, increase the need for insulin or oral antidiabetic agents.

Overdose

The use of large contraceptive doses was not accompanied by the development of severe symptoms.

Symptoms: nausea, vomiting, young girls have slight vaginal bleeding.

Treatment: symptomatic, no specific antidote.

Storage conditions

Do not store above 25 РC, out of the reach of children.

Shelf life

3 years.

Terms and conditions

prescription

dosage form

tablets

Prescribing

Prescribing

For women in postmenopausal women, for 10 postmenopause For women of childbearing age

Gedeon Richter Vengriya