Lindinet 20.63 pcs.

Lindinet is a combined medicine, the action of which is caused by the effects of its constituent components. It inhibits pituitary secretion of gonadotropic hormones.

The contraceptive effect of the drug is associated with several mechanisms. The estrogenic component of the drug is highly effective oral drug – ethinyl estradiol (synthetic analog of estradiol which participates together with the corpus luteum hormone in the regulation of menstrual cycle). Gestagenic component is a derivative of 19-nortestosterone – gestoden, surpassing in power and selectivity of action not only natural corpus luteum hormone progesterone, but also modern synthetic gestagens (levonorgestrel). Due to high activity, gestoden is used in very low dosages in which it does not exhibit androgenic properties and practically has no effect on lipid and carbohydrate metabolism.

In addition to these central and peripheral mechanisms that prevent the maturation of a fertile egg, the contraceptive effect is due to a reduction in the endometrium’s receptivity to the blastocyst and an increase in the viscosity of the cervical mucus, which makes it relatively impassable to sperm. In addition to its contraceptive effect, when taken regularly, the drug also has a therapeutic effect, normalizing the menstrual cycle and contributing to the prevention of a number of gynecological diseases, including those of tumor nature.

Pharmacokinetics

Gestoden

Intake. When taken orally, it is quickly and completely absorbed. After a single dose, Cmax in plasma is measured after one hour and is 2-4 ng/ml. The bioavailability is about 99%.

Distribution. Binds to albumin and sex hormone binding globulin (hSPH). 1-2% are in the free state, 50-75% specifically bound to HSPH. The increase in HSPH levels due to ethinylestradiol affects gestoden levels, leading to an increase in the HSPH-bound fraction, and a decrease in the albumin-bound fraction. The Vd of gestoden is 0.7-1.4 L/kg.

Metabolism. Consistent with the metabolism of steroids. Average plasma clearance is 0.8-1 ml/min/kg.

Evacuation. Blood levels decrease in two steps. The half-life in the terminal phase is 12-20 h. It is excreted exclusively in the form of metabolites – 60% in the urine, 40% in the faeces. T1/2 of metabolites is about 1 day.

Stable concentration. The pharmacokinetics of gestodenes is largely dependent on the level of hGH. Under the influence of ethinylestradiol, the concentration of hGH in blood increases by a factor of 3; with daily administration of the drug, the plasma level of gestoden increases by a factor of 3-4 and reaches a saturation state in the second half of the cycle.

Ethinylestradiol

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

Distribution. Easily enters nonspecific binding with blood albumin (about 98.5%) and causes increase in HSPH levels. Average Vd is 5-18 l/kg.

Metabolism. Is carried out mainly by aromatic hydroxylation with the formation of large amounts of hydroxylated and methylated metabolites, which are partly in free and partly in conjugated form (glucuronides and sulfates). Plasma clearance “5-13 ml/min/kg.

Evacuation. Serum concentrations decrease in 2 phases. T1/2 in the second phase “16-24 hrs. It is excreted exclusively in the form of metabolites in the ratio of 2:3 with urine and bile. T1/2 of metabolites “1 day.

Stable concentration. Established by day 3-4, with ethinylestradiol levels 20% higher than after a single dose.

Indications

Contraception

Composition

1 tablet contains:

active ingredients:

Ethinylestradiol 20 mcg;

Hestoden 75 mcg;

auxiliary substances:

sodium calcium edetate,

magnesium stearate,

colloidal anhydrous silicon,

povidone,

corn starch,

lactose monohydrate;

The composition of the shell:

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

E104,

povidone,

titanium oxide C.I. 7791,

E171, macrogol 6000;

talc,

calcium carbonate,

sucrose.

How to take, the dosage

Overly, without chewing, with plenty of water, regardless of meals.

Take 1 tablet a day (at the same time of day, if possible) for 21 days. Then, taking a 7-day break from 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 withdrawal of the hormone.

The first use of the drug: Lindinet 20 should be started from the 1st to the 5th day of the menstrual cycle.

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

Transition from progestagen-containing medications (mini-pills, injectables, implant) to taking Lindinet 20. The transition from mini-pills can start any day of the menstrual cycle; for the implant, the day after its removal; for injectables, the day before the last injection.

In this case, an additional method of contraception must be used in the first 7 days of taking Lindinet 20.

The use of Lindinet 20 after an abortion in the first trimester of pregnancy. The contraceptive can be started immediately after the abortion and no additional contraceptive method is needed.

The use of Lindinet 20 after childbirth or after an abortion in the second trimester of pregnancy. The contraceptive can be started on the 21st to 28th days after childbirth or a second trimester abortion. If you start taking contraception later, in the first 7 days, it is necessary to use an additional, barrier method of contraception. If sexual intercourse took place before the start of contraception, you should rule out a new pregnancy or wait for the next menstruation before starting to take the drug.

Missed pills. If the next scheduled pill has been missed, then you should make up the missed dose as soon as possible. If a delay does not exceed 12 hours, the contraceptive effect of the drug is not reduced, and there is no need to use an additional method of contraception. The remaining pills are taken as usual.

In a delay of more than 12 hours, the contraceptive effect may decrease. In these cases, the missed dose should not be made up, the drug should continue as usual, but an additional contraceptive method should be used for the next 7 days. If there are fewer than 7 pills left in the pack, the pills from the next pack can be taken without a break. In such cases, uterine bleeding of withdrawal occurs only at the end of the 2nd package; smeary or breakthrough bleeding may occur while taking pills from the 2nd package.

If you do not have withdrawal bleeding at the end of your 2nd package pills, then you should rule out pregnancy before continuing the contraceptive.

The measures taken in case of vomiting and diarrhea. If vomiting occurs within the first 3-4 hours of taking the next pill, the pill has not been fully absorbed. In these cases, follow the instructions described under Missed tablets.

If the patient does not want to deviate from her normal contraceptive regimen, the missed pills should be taken from another package.

Delayed menstruation and accelerated menstrual timing. In order to delay menstruation, the pills from the new pack are taken without observing a break. Menstruation may be delayed at will until all pills in the 2nd package have run out. Menstrual delays may result in breakthrough or oozing uterine bleeding. The pills can be returned to normal use after a 7-day break.

In order to have 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 it is that breakthrough or smeared bleeding will occur during the next pill pack (similar to cases of delayed menstruation).

Interaction

The contraceptive effect of oral contraceptives is reduced when rifampicin is used concomitantly, and breakthrough bleeding and menstrual disorders are more 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 drugs, it is recommended to use an additional method of contraception (condom, spermicidal gel) simultaneously with oral contraception. After the end of treatment, the use of a complementary method of contraception should be continued for 7 days, in the case of treatment with rifampicin – for 4 weeks.

Interactions related to drug absorption

In diarrhea the absorption of hormones is reduced (due to increased intestinal motility). Any drug that shortens the time the hormone stays in the large intestine leads to low concentrations of the hormone in the blood.

Interactions related to drug metabolism

The intestinal wall. Drugs that undergo sulfation in the intestinal wall like ethinylestradiol (e.g. ascorbic acid) inhibit metabolism and increase the bioavailability of ethinylestradiol.

Metabolism in the liver. Inducers of microsomal liver enzymes reduce plasma levels of ethinylestradiol (rifampicin, barbiturates, phenylbutazone, phenytoin, griseofulvin, topiramate, guidantoin, felbamate, rifabutin, oxcarbazepine). Liver enzyme blockers (itraconazole, fluconazole) increase plasma levels of ethinylestradiol.

The effect on intrahepatic circulation. Some antibiotics (e.g., ampicillin, tetracycline), by preventing intrahepatic circulation of estrogen, reduce plasma levels of ethinylestradiol.

Influence on metabolism of other drugs

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

The simultaneous use of the Hypericum perforatum with the Lindinet 20 pills is not recommended (because of possible decrease of contraceptive active substances contraceptive effect, which can be accompanied by breakthrough bleeding and unwanted pregnancy). Hypericum activates liver enzymes; after discontinuation of Hypericum preparations, the effect of enzyme induction may persist for the next 2 weeks.

The concomitant use of ritonavir and the combined contraceptive is accompanied by a 41% reduction in the average AUC of ethinylestradiol. During treatment with ritonavir, use of a higher ethinylestradiol product or a non-hormonal contraceptive method is recommended. Correction of the dosing regimen may be required when using hypoglycemic agents because oral contraceptives may decrease carbohydrate tolerance and increase the need for insulin or oral antidiabetic agents.

Special Instructions

Before starting to use the drug it is recommended to take a detailed family and personal anamnesis and every 6 months thereafter to undergo general medical and gynecological examination (gynecological examination, cytological smear examination, breast and liver function tests, BP control, blood cholesterol concentration, urine tests). These examinations should be repeated periodically due to the need for timely identification of risk factors or emerging contraindications.

The drug is a reliable contraceptive drug: the Perl index (the number of pregnancies which occurred while using a contraceptive method in 100 women within 1 year) is about 0.05 when used correctly. Due to the fact that the contraceptive effect of the drug from the beginning of use is fully manifested by the 14th day, it is recommended to use additional non-hormonal methods of contraception in the first 2 weeks of using the drug.

In each case, the benefits or possible adverse effects of hormonal contraceptives are evaluated individually before they are prescribed. This question must be discussed with the patient, who, after obtaining the necessary information, will make a final decision about her preference for hormonal or any other method of contraception. The woman’s health needs to be carefully monitored.

If any of the following conditions/diseases occur or worsen while taking the medication, the medication should be discontinued and an alternative, non-hormonal contraceptive method should be used:

– diseases of the hemostatic system;

– conditions/diseases predisposing to the development of cardiovascular, renal failure;

– epilepsy;

– migraine;

– risk of estrogen-dependent tumor or estrogen-dependent gynecological disease;

– diabetes mellitus not complicated by vascular disorders;

– severe depression (if depression is related to a tryptophan metabolism disorder, vitamin B6 may be used to correct it);

– sickle cell anemia, becauseBecause in some cases (e.g., infections, hypoxia), estrogen-containing medications in this pathology can provoke thromboembolic events;

The appearance of abnormalities in laboratory tests to assess liver function.

Thromboembolic diseases

Epidemiologic studies have proven that there is an association between taking oral hormonal contraceptives and an increased risk of arterial and venous thromboembolic disease (including myocardial infarction, myocardial infarction, and thromboembolic disease).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 much lower than in pregnancy (60 cases per 100,000 pregnancies). Arterial or venous thromboembolism of hepatic, mesenteric, renal or retinal vessels is very rare with the use of oral contraceptives.

The risk of arterial or venous thromboembolic disease is increased:

– with age;

– with smoking (heavy smoking and age over 35 are among the risk factors);

– with a family history of thromboembolic disease (such as parents, brother or sister). If genetic predisposition is suspected, it is necessary to consult a specialist before using the drug;

– in obesity (body mass index over 30);

– in dyslipoproteinemia;

– in arterial hypertension;

– In heart valve disease complicated by hemodynamic disorders;

– In atrial fibrillation;

– In diabetes mellitus complicated by vascular lesions;

– in prolonged immobilization, after major surgical intervention, surgical intervention on the lower extremities, severe trauma.

In these cases, temporary discontinuation of the drug is expected. It is advisable to stop at least 4 weeks before surgical intervention, and resume at least 2 weeks after remobilization.

The risk of venous thromboembolic disease in women after childbirth is increased.

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

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

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

The signs of thromboembolism are:

– sudden chest pain that irradiates to the left arm;

– sudden shortness of breath;

– any unusually severe headache of long duration or occurring for the first time, especially when combined with sudden total or partial loss of vision or diplopia, aphasia, dizziness, collapse, focal epilepsy, weakness or marked numbness of half the body, motor disturbances, severe unilateral calf muscle pain, acute abdominal pain.

Tumor diseases

Some studies have reported an increased incidence of cervical cancer in women who have taken hormonal birth control for a long time, but the results are inconsistent. Sexual behavior, human papillomavirus infection and other factors play a significant role in the development of cervical cancer.

A meta-analysis of 54 epidemiological studies found that there was a relative increase in breast cancer risk among women taking oral hormonal contraceptives, but the higher detection of breast cancer could be related to more regular health screenings. Breast cancer is rare among women under age 40, whether or not they take hormonal contraceptives, and increases with age. Taking the pill can be considered one of many risk factors. Nevertheless, a woman should be made aware of the possibility of breast cancer risk based on a benefit-risk assessment (protection against ovarian, endometrial and colorectal cancer).

There are few reports of the development of benign or malignant liver tumors in women taking hormonal contraceptives for a long time. This should be kept in mind in the differential diagnostic assessment of abdominal pain, which may be associated with increased liver size or intra-abdominal bleeding.

The 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 be reduced in the following cases: missed pills, vomiting and diarrhea, concomitant use of other drugs that reduce the effectiveness of birth control pills.

If a patient is taking another medication at the same time that may decrease the effectiveness of the birth control pills, additional contraceptive methods should be used.

The pills may be less effective if irregular, heavy, or intermittent bleeding occurs after a few months of use, in which case it is helpful to continue taking the pills until they end in the next package. If menstrual bleeding does not begin at the end of the 2nd cycle, or if acyclic bleeding persists, you should stop taking the pills and resume only after ruling out pregnancy.

Chloasma

Chloasma may occasionally occur in women who have a history of it during pregnancy. Those women who are at risk for chloasma should avoid contact with sunlight or UV while taking the pill.

The effects of the oral contraceptive pill – due to the estrogenic component – may change the level of some laboratory parameters (functional parameters of the liver, kidneys, adrenal glands, thyroid, hemostasis parameters, lipoprotein and transport proteins levels).

After acute viral hepatitis should be taken after normalization of liver function (not earlier than 6 months). In diarrhea or intestinal disorders, vomiting the contraceptive effect may decrease (without stopping the drug, it is necessary to use additional non-hormonal methods of contraception). Women who smoke have an increased risk of vascular disease with serious consequences (myocardial infarction, stroke). The risk depends on age (especially in women over 35 years old) and on the number of cigarettes smoked. During lactation the production of milk may decrease, in small amounts the components of the drug are excreted with breast milk.

The effect of the drug on the ability to drive and operate machinery. No studies have been conducted to investigate the possible effect of Lindinet 20 on the ability to drive or operate machinery.

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Contraindications

• individual hypersensitivity to the drug or its components;
• the presence of severe or multiple risk factors for venous or arterial thrombosis (including Complicated cardiac valvular disease, atrial fibrillation, cerebrovascular disease, or coronary artery disease;
• Uncontrolled moderate to severe arterial hypertension with BP 160/100 mm Hg
• Uncontrolled arterial hypertension of moderate or severe degree (BP 160/100 mmHg or more);
• precedents of thrombosis (including transient ischemic attack, angina pectoris), including a history of thrombosis

.history;

• migraine with focal neurological symptoms, including history;
• venous or arterial thrombosis/thromboembolism (including
• current or history of deep vein thrombosis in shin, pulmonary embolism, myocardial infarction, stroke;
• presence of venous thromboembolism in relatives;
• serious surgical intervention with prolonged immobilization;
• diabetes mellitus (with angiopathy);
• pancreatitis (including history).
• pancreatitis (including history) accompanied by marked hypertriglyceridemia;
• dislipidemia;
• severe liver disease, cholestatic jaundice (including during pregnancy), hepatitis, including in anamnesis (before normalization of functional and laboratory parameters and within 3 months after returning to normal values);
• jaundice due to steroid-containing medication;Jaundice due to steroid medications;
• Jellitus due to current or past history
• Jilbert, Dubin-Johnson, Rothor syndrome
• Hepatic tumors (including past history.
• Hepatic tumors (including history);
• High pruritus, otosclerosis, or progression of otosclerosis during previous pregnancy or while taking GCS;
• hormone-dependent malignancies of the genitals and mammary glands (including suspicion of such
• Vaginal bleeding of unknown etiology;
• smoking >35 years (more than 15 cigarettes per day);
• pregnancy or suspected pregnancy;
• pregnancy.

With caution: Conditions that increase the risk of venous or arterial thrombosis/thromboembolism (age over 35 years, smoking, hereditary predisposition to thrombosis – thrombosis, myocardial infarction or cerebral circulation disorder at a young age in any immediate family member); Hemolytic uremic syndrome; hereditary angioedema; liver disease; diseases first developed or aggravated during pregnancy or from previous use of sex hormones (includingч. Porphyria, herpes of pregnancy, small chorea – Sidengam’s disease, Sidengam’s chorea, chloasma); obesity (body mass index over 30); dyslipoproteinemia; arterial hypertension; migraine; epilepsy; valve heart disease; atrial fibrillation; long-term immobilization; extensive surgical intervention; surgery on lower extremities; severe trauma; varicose veins and superficial thrombophlebitis; postpartum period (non-lactating women 21 days after delivery; lactating women after completion of lactation); presence of severe depression, includinghistory; changes in biochemical parameters (activated protein C resistance, 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 family history); acute and chronic liver disease.

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Side effects

Side effects in case of which immediate discontinuation of the drug is necessary:

– arterial hypertension;

– hemolytic-uremic syndrome;

– porphyria;

– hearing loss due to otosclerosis.

Rarely occurring – 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 hepatic, mesenteric, renal, retinal arteries and veins; Sydenham’s chorea (resolving after drug withdrawal).

Other side effects, less severe but more common, the appropriateness of continuing the drug is decided on an individual basis after consultation with a physician, based on the benefit/risk ratio.

Reproductive system disorders: acyclic bleeding/bloody vaginal discharge, amenorrhea after drug withdrawal, changes in vaginal mucus, development of vaginal inflammatory processes (e.g., candidiasis), changes in libido.

Mammary gland side: tension, pain, enlargement of the mammary glands, galactorrhea.

Gastrointestinal and hepatobiliary system: nausea, vomiting, diarrhea, epigastric pain, Crohn’s disease, ulcerative colitis, hepatitis, liver adenoma, occurrence or exacerbation of jaundice and/or itching associated with cholestasis, cholithiasis.

Skin disorders: erythema nodosum/exudative erythema, rash, chloasma, increased hair loss.

CNS disorders: headache, migraine, mood changes, depression.

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

Sensory organs: decreased hearing, increased sensitivity of the cornea while wearing contact lenses.

Others: allergic reactions.

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Overdose

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

Symptoms: nausea, vomiting, in young girls small vaginal bleeding.

Treatment: symptomatic, no specific antidote.

Pregnancy use

The drug is contraindicated for use during pregnancy.

If it is necessary to prescribe the drug during lactation, discontinuation of breastfeeding should be considered.

The active substances of the drug are excreted in small amounts with breast milk, affecting the quantity and quality of milk.