If any of the conditions / risk factors listed below are currently available, the potential risk and expected benefits of using COCs in each individual case should be carefully weighed and discussed with the woman before she decides to start taking the drug. In case of weighting, strengthening or the first manifestation of any of these conditions or risk factors, a woman should consult her doctor to decide whether to stop or continue taking the drug.
Diseases of the cardiovascular system
The results of epidemiological studies indicate the existence of a relationship between the use of combined oral contraceptives and an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis,thromboembolism of the pulmonary artery, myocardial infarction, cerebrovascular disorders). These diseases are rare.
The risk of developing venous thromboembolism (VTE) is maximal in the first year of taking such drugs.
The increased risk is present after the initial use of COCs (which include the drug Trikwilar®) or the resumption of the use of the same or different COCs after a break between doses of 4 weeks or more. The findings suggest that this increased risk is present primarily during the first 3 months.
The overall risk of VTE in patients taking low-dose COCs (<0.05 mg of ethinylestradiol) is two to three times higher than in non-pregnant patients who do not take COC, however, this risk remains lower compared to the risk of VTE in pregnancy and childbirth. VTE can be life threatening or lead to death (in 1-2% of cases).
VTE, manifested as deep vein thrombosis or pulmonary embolism, may occur with any COCs.
Very rarely, when using COC, thrombosis occurs in other blood vessels, for example, liver, mesenteric, renal, cerebral veins and arteries or retinal vessels.
Symptoms of deep vein thrombosis (DVT) include lower extremity edema unilateral or along the vein, pain or discomfort in a vertical position or during walking, the local increase in temperature, redness or discoloration of the skin in the affected lower limb.
Symptoms of thromboembolism of the pulmonary artery (PE) are as follows: shortness of breath or rapid breathing; sudden cough, including hemoptysis; acute pain in the chest, which can increase with a deep breath; sense of anxiety; severe dizziness; tachycardia or arrhythmia. Some of these symptoms (eg, dyspnea, coughing) are nonspecific and may be incorrectly interpreted as signs of other more or less severe conditions / diseases (e.g., respiratory infection).
Arterial thromboembolism can lead to stroke, vascular occlusion or myocardial infarction. Symptoms of stroke are as follows: sudden weakness or loss of sensitivity in the face, limbs, especially on one side of the body, sudden confusion,disorientation and dysarthria; sudden one- or two-sided loss of vision; sudden gait disturbance, dizziness, loss of balance or coordination of movements; sudden severe or prolonged headache for no apparent reason; loss of consciousness or fainting with or without an epileptic seizure. Other signs of vascular occlusion: sudden pain, puffiness and weak blueing of the extremities, "sharp" abdomen.
Symptoms of myocardial infarction include: pain, discomfort, pressure, heaviness, a feeling of squeezing or raspiraniya in the chest or behind the breastbone, with irradiation in the back, jaw, upper limb, epigastric region; cold sweats, nausea, vomiting or dizziness, severe weakness, anxiety, or shortness of breath; tachycardia or arrhythmia. Arterial thromboembolism can be life threatening or fatal.
Women with a combination of several risk factors or high severity of one of them should consider the possibility of their mutual reinforcement. In such cases, the degree of risk increase may be higher than with a simple summation of factors. In this case, the administration of Triclvar® is contraindicated.section "Contraindications").
The risk of developing thrombosis (venous and / or arterial) and thromboembolism or cerebrovascular disorders increases with multiple or significant risk factors for venous or arterial thrombosis:
- a burdened family history (for example, venous or arterial thromboembolism ever at close relatives or parents at a relatively young age). Some blood counts may indicate a predisposition to the development of venous or arterial thrombosis, namely, resistance to activated protein C, hyperhomocysteinemia, anthrombin III deficiency, protein C deficiency, protein deficiency S, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant). In case of a hereditary or acquired predisposition, a woman should be examined by the appropriate specialist to decide on the possibility of taking COC;
- obesity (body mass index more than 30 kg / m2);
- increased concentrations of fat metabolism products - cholesterol and triglycerides in the blood (dyslipoproteinemia);
- subacute bacterial endocarditis;
- arterial hypertension;
- migraine without concomitant neurologic symptoms;
- heart valve diseases;
- Atrial fibrillation;
- prolonged immobilization, serious surgical intervention, any operation on the lower extremities or extensive trauma. In these situations, it is necessary to stop taking Trikvilar® (in the case of a planned operation, at least four weeks before) and to resume taking it within two weeks after the end of immobilization. Temporary immobilization (for example, air travel lasting more than 4 hours) may also be a risk factor for the development of VTE, especially if there are other risk factors;
- with age;
- for smokers (with an increase in the number of cigarettes or an increase in age, the risk further increases, especially in women over 35 years of age).
The question of the possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial.
You should consider the increased risk of thromboembolism in the postpartum period.
Violations of the peripheral circulation can also occur in diabetes mellitus, systemic lupus erythematosus,hemolytic-uremic syndrome, chronic inflammatory bowel diseases (Crohn's disease or ulcerative colitis) and sickle cell anemia. An increase in the frequency and severity of migraine during the use of COCs (which may precede cerebrovascular disorders) may be the basis for the immediate discontinuation of Triclawar®.
When assessing the relationship between risk and benefit, it should be borne in mind that adequate treatment of the relevant diseases can reduce the risk associated with it. It should also be taken into account that the risk of thrombosis and thromboembolism in pregnancy is higher than when taking low-dose oral contraceptives (<0.05 mg of ethinyl estradiol).
- Tumors
The most significant risk factor for developing cervical cancer is persistent papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with prolonged use of COCs. The connection with the reception of the COC has not been proved. There are contradictions as to the extent to which these findings are associated with screening for cervical pathology or with peculiarities of sexual behavior (more rare use of barrier methods of contraception).
A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking COC (relative risk 1.24). The increased risk gradually disappears within 10 years after discontinuation of these medications. Due to the fact that breast cancer is rare in women under 40 years of age, the increase in the incidence of breast cancer in women who are currently taking COCs or who have recently taken COC is insignificant in relation to the overall risk of this disease. His connection with the use of COC ns has been proved. The observed increase in risk may also be the result of an earlier diagnosis of breast cancer in women using COCs (they have earlier clinical forms of breast cancer diagnosed than women who did not take COCs), the biological effects of COCs, or a combination of both.
In rare cases, the development of benign, and extremely rare, malignant liver tumors, which in some cases led to life-threatening intraabdominal hemorrhage, was observed with the use of COCs.In the event of severe pain in the abdomen, liver enlargement, or signs of intra-abdominal bleeding, this should be taken into account when making a differential diagnosis.
- Other states
In women with hypertriglyceridemia (or the presence of this condition in a family history) during the administration of COCs, an increased risk of developing pancreatitis may occur. Although a small increase in blood pressure was described in many women taking COC, a clinically significant increase was rarely noted. However, if a persistent clinically significant increase in blood pressure develops during the administration of COCs, these drugs should be discontinued and treatment of hypertension should begin. Reception of COCs can be continued if normal blood pressure values are achieved with the help of antihypertensive therapy.
The following conditions have been reported to develop or worsen, both during pregnancy and when taking COC, but their association with COC use has not been proven: cholestatic jaundice and / or itching; formation of stones in the gallbladder; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes during pregnancy; losshearing, associated with otosclerosis. Cases of Crohn's disease and ulcerative colitis are also described against the background of COC use.
In women with hereditary forms of angioedema, exogenous estrogens can cause or worsen symptoms of angioedema. Acute or chronic liver dysfunction may require cancellation of the COC until the liver function returns to normal. Recurrence of cholestatic jaundice, which developed for the first time during previous pregnancy or previous reception of sex hormones, requires discontinuation of COCs.
Although COCs may have an effect on insulin resistance and glucose tolerance, there is usually no need to correct the dose of hypoglycemic drugs in diabetic patients using low-dose combined oral contraceptives (<0.05 mg ethinyl estradiol). Nevertheless, women with diabetes should be carefully monitored while taking COC.
Sometimes chloasma can develop, especially in women with a history of pregnancy chloasma. Women with a tendency to chloasma while taking COC should avoid prolonged exposure to the sun and exposure to ultraviolet radiation.
Laboratory Tests
The use of drugs such as Trikwilar® may affect the results of some laboratory tests, including biochemical parameters of the liver, thyroid, kidney and adrenal function. the concentration of transport proteins in the plasma (for example, globulin, corticosteroids, lipid / lipoprotein fractions, parameters of carbohydrate metabolism, coagulation and fibrinolysis). These changes, as a rule, remain within the limits of normal physiological values.
Decreased efficiency
The efficacy of COCs can be reduced in the following cases: when missing tablets, with vomiting and diarrhea, or as a result of drug interactions.
Effect on the character of menstrual bleeding
On the background of taking COC, irregular bleeding ("spotting" spotting or "breakthrough" bleeding) can occur, especially during the first months of use. Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately three cycles.
If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be conducted to exclude malignant neoplasms or pregnancy.
Some women during the break in taking pills may not develop a bleeding "cancellation". If the drug Trikwilar® was taken as directed, it is unlikely that a woman is pregnant. However, if the Trikwilar® medication was not taken regularly, or if there are no consecutive "bleeding" bleeds in a row, pregnancy should be excluded before continuing with the drug.
Medical examinations
Before starting or resuming the use of the drug Trikvilar®, you need to familiarize yourself with the history of life, the family history of the woman, and carry out a thorough medical examination (including measurement of blood pressure, heart rate, body mass index) and gynecological examination (including pelvic ultrasound and cervical epithelial cytology ), examination of the mammary glands, to exclude pregnancy. The volume of additional studies and the frequency of follow-up visits are determined individually. Usually, follow-up examinations should be conducted at least once every 6 months.
A woman should be warned that the drug Trikvilar® does not protect against HIV infection (AIDS) and other sexually transmitted diseases!
Conditions requiring medical advice
- Any changes in the state of health, especially the appearance of conditions listed in the sections "Contraindications" and "Use with caution";
- Local compaction in the mammary gland;
- Simultaneous reception of other medications (see also "Interaction with other drugs");
- If prolonged immobility is expected (for example, gypsum is applied to the lower extremity), hospitalization or surgery is planned (at least 4-6 weeks before the proposed operation);
- Unusually violent bleeding from the vagina;
- A tablet was missed in the first week of taking the package and there was sexual contact seven or less days before;
- The absence of another menstrual bleeding twice or in a row suspicion of pregnancy (do not start taking pills from the next package before consulting your doctor). The woman should stop taking the pills and immediately consult a doctor if there are possible signs of thrombosis, myocardial infarction or stroke (see section "Special instructions").