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Active ingredients
Levonorgestrel + Ethinyl Estradiol
Release form
Dragee
Pharmacological effect
Triquilar is a low-dose three-phase oral combined estrogen-progestin contraceptive drug. The contraceptive effect of triquilar is accomplished through three complementary mechanisms: - suppress ovulation at the level of the hypothalamic-pituitary regulation; which makes implantation of a fertilized egg impossible. in women taking combined oral contra the menstrual cycle becomes more regular, painful periods are less frequent, the intensity of bleeding decreases, resulting in a reduced risk of iron deficiency anemia.
Pharmacokinetics
Levonorgestrel Absorption After oral administration, levonorgestrel is rapidly and completely absorbed, its Cmax in serum of 2.3 ng / ml is reached after approximately 1 hour. After a single oral administration, 0.125 mg of levonorgestrel together with 0.33 mg of ethinyl estradiol (which corresponds to the highest content of levonorgestrel in the three-phase preparation) the highest serum concentration, 4.3 ng / ml, was determined after about an hour. When administered orally, levonorgestrel is almost completely bioavailable. DistributionLevonorgestrel is bound by serum albumin and sex hormone-binding globulin (SHBG). In free form is only 1.4% of the total serum concentration; while 55% are specifically associated with SHBG and about 44% are not specifically associated with albumin. As a result of the induction by ethinylestradiol of the synthesis of the binding protein, the fraction associated with SHBG increases, while the fraction bound to albumin decreases. The apparent Vd of levonorgestrel is approximately 128 liters after a single oral administration of Triquilar pills containing the highest dose of levonorgestrel. Equilibrium concentration. The pharmacokinetics of levonorgestrel is influenced by the level of SHBG in serum, which increases approximately 2-fold over the 21-day course of taking Triquilar. As a result of the daily intake of the drug, the content of substances in serum increases by about 2 times, and the equilibrium concentration is reached in the second half of the course.At an equilibrium concentration, the volume of distribution and the rate of clearance are reduced, respectively, to 52 l and 0.5 ml / min / kg. Metabolism Levonorgestrel is fully metabolized, passing through the metabolic pathways characteristic of steroids. After a single oral administration of the highest dose of levonorgestrel, the rate of serum clearance is about 1.0 ml / min / kg. ExcretionThe content of levonorgestrel in the blood serum undergoes a two-phase decrease. T1 / 2 in the terminal phase is about 22 hours. Levonorgestrel is not excreted in unchanged form, but only in the form of metabolites, which are excreted with T1 / 2 for about 24 hours with urine and bile in a ratio of about 1: 1. Ethinyl estradiol Absorption After ingestion, ethinylestradiol is rapidly absorbed and completely. Cmax in serum, equal to about 116 pg / ml, is reached in 1.3 hours. During absorption and the first passage through the liver, ethinyl estradiol is metabolized, with the result that its bioavailability upon ingestion is on average about 45%, with significant individual differences within 20-65%. Distribution Etinilestradiol is almost completely (98%), although not specific, bound by albumin. Ethinyl estradiol induces synthesis of SHBG. The apparent Vd of ethinyl estradiol is 2.8–8.6 l / kg. Equilibrium concentration is reached after one week. Metabolism Etienyl estradiol undergoes systemic conjugation, both in the mucous membrane of the small intestine and in the liver. The main metabolic pathway is aromatic hydroxylation. The rate of metabolic clearance from blood plasma is 2.3-7 ml / min / kg. Excretion The concentration of ethinyl estradiol in serum decreases, and the decrease is biphasic; The first phase is characterized by T1 / 2 about 1 hour, the second - 10-20 hours. Unchanged from the body is not excreted. Ethinyl estradiol metabolites are excreted by the kidneys and liver in a ratio of 4: 6; with a T1 / 2 of about 24 h.
Indications
Contraception (prevention of unwanted pregnancy).
Contraindications
Do not use Triquilar if you have any of the conditions or diseases listed below. If you have any of them, tell your doctor. - Thrombosis (venous and arterial) and thromboembolism at present or in history, including: deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders. - The states preceding thrombosis (including transient ischemic attacks, angina pectoris) now or in history.- Migraine with focal neurological symptoms in history. - Diabetes with vascular complications. - Multiple or severe risk factors for venous or arterial thrombosis, including: cardiac valve system, cardiac arrhythmias, vascular diseases of the brain or coronary arteries, uncontrolled arterial hypertension. - Pancreatitis with severe hypertriglyceridemia now or in history. - Liver failure and severe liver disease (until liver tests return to normal). - Liver tumors (benign or malignant) currently or in history. - Identified hormone-dependent malignant diseases (including genitals or mammary glands) or suspicion of them. - Vaginal bleeding of unknown origin. - Pregnancy or suspicion of her. - The period of breastfeeding. - Hypersensitivity to any of the components of Triquilar. - Prolonged immobilization (for example, when a plaster bandage is applied to the leg), serious surgical intervention, surgery on the legs, extensive injuries. If any of these conditions appear for the first time while you receive Triquilar, immediately stop taking this drug and consult your doctor. In the meantime, use non-hormonal contraceptives. Use with caution. If Triquilar is used in the presence of any of the conditions listed below, you may need to be carefully monitored - why, the doctor will explain. Before you start taking Triquilar, tell your doctor if you have any of the following conditions and diseases: - Smoking. - Diabetes. - Overweight. - High blood pressure. - Inflammation of the veins (phlebitis of the superficial veins). - Thrombosis, myocardial infarction or cerebrovascular accident in any of your closest relatives. - Migraine. - Acceptance of antiepileptic drugs. - High cholesterol or triglycerides (fatty acids) in you or any of your close relatives, now or in the past. - Breast cancer in any of your closest relatives. - Diseases of the liver or gallbladder.- Crohn's disease or ulcerative colitis. - Systemic lupus erythematosus (SLE). - Hemolytic uremic syndrome. - Sickle cell anemia. - Diseases that first arose or aggravated during pregnancy or against the background of a previous intake of sex hormones (for example, hearing loss, porphyria, herpes of pregnant women, Sydengham's chorea). Chloasma (yellowish - brown foci of pigmentation on the skin, especially on the face) now or in the past. If they are, avoid prolonged exposure to the sun or ultraviolet radiation.
Precautionary measures
Store at a temperature not higher than 25 ° С, out of reach of children.
Use during pregnancy and lactation
Triquilar is not prescribed during pregnancy and during breastfeeding. If pregnancy is detected while taking Triquilar, the drug should be immediately canceled. However, extensive epidemiological studies have not revealed any increased risk of developmental defects in children born to women who received sex hormones before pregnancy or teratogenic effects, when sex hormones were taken by negligence in the early stages of pregnancy. therefore, their use is contraindicated during lactation. A small amount of sex steroids and / or their metabolites may be excreted in milk, but there is no evidence of their negative impact on the health of the newborn.
Side effects
Soreness and tension of the mammary glands, an increase in the mammary glands, discharge from the mammary glands; spotting and breakthrough uterine bleeding; headache; migraine; libido change; decrease / change of mood; poor tolerance to contact lenses; visual impairment; nausea; vomiting; stomach ache; changes in vaginal secretion; skin rash; erythema nodosum; erythema multiforme; generalized itching; cholestatic jaundice; fluid retention; change in body weight; allergic reactions. Rarely - fatigue, diarrhea. Sometimes chloasma can develop, especially in women with a history of pregnant chloasma. As with other combined oral contraceptives, thrombosis and thromboembolism may occur in rare cases.
Overdose
Symptoms that may occur with an overdose: nausea, vomiting, spotting or metrorrhagia. There is no specific antidote, symptomatic treatment should be carried out.
Interaction with other drugs
Sulfonamides, derivatives of pyrazolone are able to increase the metabolism of steroid hormones that make up the drug. Long-term treatment with drugs that induce liver enzymes, which increase the clearance of sex hormones, can lead to breakthrough bleeding and / or reduce the contraceptive effectiveness of the drug Triquilar. phenytoin, barbiturates, primidone, carbamazepine and rifampicin; There is also a suggestion for oxcarbazepine, topiramate, felbamate, ritonavir, and griseofulvin, and preparations containing St. John's wort. most, lowering the concentration of ethinyl estradiol. Oral combined contraceptives can affect the metabolism of other drugs (including cyclosporine), which leads to a change in their concentration concentrations in plasma and tissues.
special instructions
During the reception of antibiotics (such as ampicillins and tetracyclines) and for 7 days after their cancellation, you should additionally use a barrier method of contraception. If the period of use of the barrier method of protection ends later than the pills in the package, you should proceed to the next package of Triquilar without the usual break in If any of the conditions / risk factors listed below are presently present, then the potential risk and the expected benefit of the Triquilar treatment in each and dividual case and discuss it with the woman before she decides to start taking the drug. In the case of weighting, amplification, or the first manifestation of any of these conditions or risk factors, the woman should consult with her physician, who may decide to discontinue the drug. Cardiovascular diseases A slight increase in the incidence of venous and arterial thrombosis and thromboembolism was detected combined oral contraceptives. The approximate frequency of venous thromboembolism (deep vein thrombosis or pulmonary embolism) in women taking x oral contraceptives,with a low dose of estrogen (less than 50 micrograms of ethinyl estradiol) is up to 4 per 10,000 women per year compared to 0.5–3 per 10,000 women per year for women who do not use OK. However, the incidence of venous thromboembolism (VTE) developing when taking combined oral contraceptives is less than the frequency associated with pregnancy (6 per 10,000 pregnant women per year). For women taking combined oral contraceptives, extremely rare cases of other thrombosis are described. blood vessels such as the hepatic, mesenteric, renal arteries and veins, the central vein of the retina and its branches. The relationship with taking oral oral contraceptives has not been proven. Women should stop taking the drug and consult a doctor if they develop symptoms of venous or arterial thrombosis or cerebrovascular disorders, which may include: unilateral pain in the leg and / or edema; sudden severe chest pain, with or without irradiation to the left hand; sudden shortness of breath; sudden coughing attack; any unusual, severe, prolonged headache; sudden partial or complete loss of vision; diplopia; inarticulate speech or aphasia; dizziness; loss of consciousness with / or without convulsive seizure; weakness or a very significant loss of sensitivity, suddenly appearing on one side or in one part of the body; movement disorders; symptoms of acute abdomen. The risk of thrombosis (venous and / or arterial) and thromboembolism increases: - with age; - in smokers (with an increase in the number of cigarettes or an increase in age, the risk further increases, especially in women over 35 years old); if available: - family history (t. e. venous or arterial thromboembolism ever in close relatives or parents at a relatively young age); if a hereditary predisposition is assumed, the woman should be examined by an appropriate specialist to decide on the possibility of taking COCs - obesity (body mass index more than 30 kg / m2); - dyslipoproteinemia; - hypertension; - migraine; - valvular heart disease; - atrial fibrillation; - prolonged immobilization, serious surgery, any surgery on the legs or an extensive injury. In the case of a planned operation, it is recommended to stop taking the drug, at least4-6 weeks before her and not to resume reception for 2 weeks after the end of immobilization. You should take into account the increased risk of thromboembolism in the postpartum period. Circulatory disorders can also be observed in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease ( Crohn's disease or ulcerative colitis) and sickle cell anemia. An increase in the frequency and severity of migraine during the use of combined oral contraceptives (Th may precede cerebrovascular disorders) may be grounds for immediate discontinuation of these drugs. Biochemical parameters that may be indicators of hereditary or acquired susceptibility to venous or arterial thrombosis include resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S, antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant). Tumors have an increased risk of developing Cervical aka long-term use of combined oral contraceptives has been reported in some epidemiological studies. His connection with the reception of combined oral contraceptives has not been proven. There are contradictions regarding the extent to which these findings relate to sexual behavior and other factors, such as the human papillomavirus (HPV). There is evidence of a slightly increased relative risk (RR = 1.24) of breast cancer diagnosed in women who are the time of the study used combined oral contraceptives. His connection with the reception of combined oral contraceptives has not been proven. The observed increase in risk may be due to an earlier diagnosis of breast cancer in women using combined oral contraceptives. Breast cancers in women who had ever taken combined oral contraceptives were less clinically pronounced than women who had never used them. In rare cases, the use of combined oral contraceptives was observed during the use of combined oral contraceptives.In case of severe abdominal pain, enlarged liver or signs of intra-abdominal bleeding, this should be taken into account when making a differential diagnosis. Other conditions increased blood pressure has been described in many women taking combined oral contraceptives, clinically significant increases in mark chalis rare. However, if a persistent, clinically significant increase in blood pressure develops while taking combined oral contraceptives, these drugs should be canceled and treatment of hypertension should begin. Reception of combined oral contraceptives can be continued if normal blood pressure values are achieved using antihypertensive therapy. The following conditions have been reported to develop or worsen both during pregnancy and when combined oral contraceptives are taken, but they are associated with combined oral contraceptives not proven: jaundice and / or itching associated with cholestasis; the formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes pregnant; hearing loss associated with otosclerosis. Also described are cases of Crohn's disease and ulcerative colitis associated with the use of combined oral contraceptives. Acute or chronic liver dysfunction may require discontinuation of the use of combined oral contraceptives until the liver function returns to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous sex hormones, requires the discontinuation of combined oral contraceptives. Although combined oral contraceptives may affect insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients who low-dose combined oral contraceptives (<0.05 mg ethinyl estradiol).However, women with diabetes should be carefully monitored while taking combined oral contraceptives. Women who have a tendency to chloasma while taking combined oral contraceptives should avoid prolonged exposure to the sun and exposure to ultraviolet radiation. laboratory tests, including indicators of liver, kidney, thyroid, adrenal glands, transport proteins in plasma, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond the normal range. Influence on the menstrual cycleIn a background of taking combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, any irregular bleeding should be evaluated only after an adaptation period of approximately three cycles. If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be carried out to exclude malignant neoplasms or pregnancy. Some women may have do not develop withdrawal bleeding. If combined oral contraceptives were taken as directed, it is unlikely that the woman is pregnant. However, if previously combined oral contraceptives were taken irregularly or, if there are no two withdrawal bleeding in a row, pregnancy should be ruled out before continuing to take the drug. Medical examinations examination of cervical mucus), exclude pregnancy. In addition, violations of the blood coagulation system should be excluded. In case of long-term use of the drug, it is necessary to conduct control tests every 6 months. A woman should be warned that drugs such as Triquilar do not protect against HIV infection (AIDS) and other sexually transmitted diseases! on the ability to drive vehicles and management mechanismsNo detected.