If any of the conditions, diseases and risk factors outlined below are present, careful consideration should be given to the potential risk and expected benefit of using Yarin® in each individual case and to discuss it with the woman before she decides to start taking preparation. In case of weighting, strengthening or the first manifestation of any of these conditions, diseases or risk factors, a woman should consult with her doctor who can decide whether to cancel the drug.
Diseases of the cardiovascular system
The results of epidemiological studies indicate the existence of a relationship between the use of COCs and an increase in the incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders) with COCs. These diseases are rare.
The risk of developing VTE is maximal in the first year of taking COC. An increased risk is present after the initial use of COC or the resumption of the use of the same or another COC (after a break between doses of 4 weeks or more). Data from a large-scale prospective study with 3 groups of patients show that this increased risk is present mainly during the first 3 months.
The overall risk of VTE in women taking low-dose COCs (<0.05 mg of ethinyl estradiol) 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 during 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, can 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: unilateral swelling of the lower extremity or edema along the veins on the lower extremity, pain or discomfort in the lower extremity only in the vertical position or walking, local temperature increase in the affected lower limb, reddening or discoloration of the skin on the lower extremity.
Symptoms of thromboembolism of the pulmonary artery: difficulty or rapid breathing; sudden cough, including hemoptysis; acute pain in the chest, which can increase with a deep breath; sense of anxiety; severe dizziness; rapid or irregular heartbeat. Some of these symptoms (eg, dyspnea, cough) are non-specific and may be misinterpreted as signs of other more or less severe conditions / diseases (eg, respiratory tract infections).
Arterial thromboembolism can lead to stroke, vascular occlusion or myocardial infarction.
Symptoms of a stroke: sudden weakness or loss of sensitivity of the face, limbs, especially on one side of the body, sudden confusion, problems with speech and understanding; 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: pain, discomfort, pressure, heaviness, a feeling of contraction or raspiraniya in the chest or behind the breastbone, with irradiation in the back, jaw, left upper extremity, epigastric region; cold sweats, nausea, vomiting or dizziness, severe weakness, anxiety, or shortness of breath; rapid or irregular heartbeat. 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 total value of the available risk factors is increased. In this case, taking Yarin® is contraindicated (see section "Contraindications").
The risk of developing thrombosis (venous and / or arterial) and thromboembolism or cerebrovascular disorders is increased:
- with age;
- for smokers (with an increase in the number of cigarettes smoked or an increase in the age, the risk increases, especially in women over 35);
in the presence of:
- obesity (body mass index more than 30 kg / m2);
- family history (for example, venous or arterial thromboembolism ever at close relatives or parents at a relatively young age). In the case of hereditary or acquired predisposition, a woman should be examined by an appropriate specialist to decide whether to take Yarin®;
- prolonged immobilization, extensive surgical intervention, any operation on the lower extremities or extensive trauma.In these cases, the drug Yarin® should be discontinued (in the case of a planned operation at least four weeks before it) and do not resume admission 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 venous thromboembolism, especially if there are other risk factors;
- dyslipoproteinemia;
- arterial hypertension;
- migraine;
- heart valve diseases;
- atrial fibrillation.
The question of the possible role of varicose veins and superficial thrombophlebitis in the development of VTE remains controversial.
You should consider the increased risk of thromboembolism in the postpartum period. Violations of peripheral circulation can also occur 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 COCs (which may precede cerebrovascular disorders) is the basis for the immediate withdrawal of these drugs.
Biochemical indicators indicating a hereditary or acquired predisposition to venous or arterial thrombosis include the following: resistance to activated protein C, hyperhomocysteinemia, antithrombin deficiency III, Protein C Deficiency, Protein Deficiency S, antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant).
When assessing the relationship between risk and benefit, it should be borne in mind that adequate treatment of the relevant condition can reduce the risk of thrombosis 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. However, the connection with the reception of the COC has not been proven. The possibility of interrelation of these data with screening of cervical diseases or with peculiarities of sexual behavior (a more rare application of barrier methods of contraception) is discussed.
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. AT the association with the fact that breast cancer is rarely seen in women under 40 years of age, the increase in the number of diagnoses 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 has not been proven. The observed increase in risk may also be due to careful follow-up and earlier diagnosis of breast cancer in women using COCs. Women who have ever used COC have earlier stages of breast cancer than women who have never used them.
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. Malignant tumors can be life threatening or lethal.
Other states
The progestin component in the Yarin® preparation is an aldosterone antagonist with potassium-sparing properties. In most cases there should be no increase in the concentration of potassium in the blood plasma. In clinical studies in some patients with mild or moderate renal failure and concomitant intake of potassium-sparing drugs, the potassium concentration in the blood plasma increased slightly during the administration of drospirenone. Therefore, the concentration of potassium in the blood plasma should be monitored during the first cycle of the drug in patients with renal insufficiency and at the initial concentration of potassium at the upper limit of the norm, especially with the concomitant intake of potassium-sparing drugs (see section "Interaction with other drugs").
In women with hypertriglyceridemia (or the presence of this condition in a family history), an increased risk of developing pancreatitis during COC administration is possible. Despite the fact that a small increase in blood pressure was described in many women taking COC, clinically significant increases were rarely noted. Nevertheless, if a persistent, clinically significant increase in blood pressure develops during the administration of the drug, these drugs should be discontinued and the treatment of hypertension should begin. Reception of the drug 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 relationship with COCs has not been proven: jaundice and / or pruritus associated with cholestasis; formation of stones in the gallbladder; porphyria; systemic lupus erythematosus: hemolytic-uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis. Also, cases of worsening of the course of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis are described along with the use of COCs.
In women with hereditary forms of angioedema, exogenous estrogens can cause or worsen symptoms of angioedema.
Acute or chronic liver dysfunction may require discontinuation of the drug until the liver function test results return to normal. Recurrence of cholestatic jaundice, which developed for the first time during previous pregnancy or previous reception of sex hormones, requires discontinuation of the drug.
Although COCs may have an effect on insulin resistance and glucose tolerance, the need for dose adjustment for hypoglycemic drugs in patients with diabetes mellitus using low-dose COCs (<0.05 mg ethinylestradiol) generally does not occur. Nevertheless, women with diabetes should be carefully observed while taking COC.
Sometimes chloasma can develop, especially in women with a history of pregnancy chloasma. Women with a tendency to chloasma during taking Yarin® should avoid prolonged exposure to sunlight and exposure to ultraviolet radiation.
Preclinical safety data
Preclinical data obtained from routine studies to detect toxicity with multiple doses of the drug, as well as genotoxicity, carcinogenic potential, and toxicity to the reproductive system, do not indicate a particular risk to humans. Nevertheless, it should be remembered that sex hormones can promote the growth of some hormone-dependent tissues and tumors.
Laboratory Tests
The intake of Yarin® can affect the results of some laboratory tests, including liver, kidney, thyroid, adrenal, plasma protein, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond the limits of normal values. Drospirenone increases plasma renin activity and aldosterone concentration, which is associated with its antimineralocorticoid effect.
Decreased efficiency
The effectiveness of the drug Yarina® can be reduced in the following cases: when missing tablets, gastrointestinal disorders or as a result of drug interactions.
Frequency and severity of menstrual bleeding
Against the background of taking the drug Yarin®, irregular (acyclic) bleeding from the vagina ("spotting" bleeding and / or "breakthrough" uterine bleeding) can occur, especially during the first months of use. Therefore, any irregular menstrual bleeding should be evaluated after an adaptation period of approximately three cycles. If irregular menstrual bleeding repeats or develops after previous regular cycles, a thorough examination should be performed to exclude malignant neoplasms or pregnancy.
Some women during the break in taking pills may not develop bleeding "withdrawal". If the drug Jarina® was taken according to recommendations, it is unlikely that a woman is pregnant. However, with irregular use of the drug and the absence of two consecutive menstrual bleeding, the drug intake can not be continued until pregnancy is excluded.
Medical examinations
Before starting or resuming the use of the drug Yarin®, you need to familiarize yourself with the history of life, the family history of a woman, conduct a thorough general medical and gynecological examination, and exclude pregnancy.The scope of research and the frequency of follow-up examinations should be based on existing standards of medical practice, taking into account the individual characteristics of each patient. As a rule, blood pressure, heart rate, body mass index are measured, the condition of mammary glands, abdominal cavity and pelvic organs is checked, including cytological examination of the cervical epithelium (Pap test). Usually, follow-up examinations should be conducted at least once every 6 months.
It must be borne in mind that the drug Yarina® does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
States, requiring medical advice:
- any changes in health, especially the emergence 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 placed on the lower limb),planned hospitalization or operation (at least 4 weeks before the proposed operation);
- unusually heavy bleeding from the vagina;
- skipped the tablet in the first week of taking the package and had sex for seven or less days before;
- the absence of another menstrual bleeding twice or a suspicion of pregnancy (do not start taking the pills from the next package before consulting a doctor).
You should stop taking the pills and immediately consult a doctor if there are possible signs of thrombosis, myocardial infarction or stroke: an unusual cough; unusually severe pain behind the sternum, giving to the left arm; unexpected shortness of breath, unusual, severe and prolonged headache or migraine attack; partial or complete loss of vision or double vision in the eyes; inarticulate speech; sudden changes in hearing, smell, or taste; dizziness or fainting; weakness or loss of sensitivity and any part of the body; severe pain in the abdomen; severe pain in the lower extremity or sudden arisen edema of any from the lower extremities.