If any of the conditions, diseases and risk factors identified below are present, careful consideration should be given to the potential risk and the expected use of the drug Yarina® Plus in each individual case and discuss it with a woman before she decides to start taking this drug.
With violations of the cardiovascular system
There are epidemiological data on the increase in the incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) with COCs. 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 COC or the resumption of the use of the same or different COCs (after a break between doses of 4 weeks or more). Data from a large 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 patients taking low-dose COCs (<50 mcg ethinyl estradiol) is two to three times higher than in non-pregnant patients who do not take COC, however, this risk remains lower compared with the risk of VTE during pregnancy and childbirth .
VTE can lead to death (in 1-2% of cases).
VTE, manifested as deep vein thrombosis or pulmonary embolism may occur when using 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. A common opinion regarding the relationship between the occurrence of these events and the use of COC is absent.
Symptoms of deep vein thrombosis (DVT) include the following: unilateral edema of the lower limb or along the vein of the lower extremity, pain or discomfort in the lower extremity only in the vertical position or walking, local fever in the affected lower limb, reddening or discoloration of the lower extremity skin .
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; rapid or irregular heartbeat. Some of these symptoms (eg, dyspnea, cough) are nonspecific and can be misinterpreted as signs of other more or less severe events (eg, respiratory tract infection).
Arterial thromboembolism can lead to stroke, vascular occlusion or myocardial infarction. Symptoms of stroke are as follows: sudden weakness or loss of sensitivity of the face, upper or lower extremities, 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 include: pain, discomfort, pressure, heaviness, a feeling of constriction or raspiraniya in the chest, in the hand or behind the breastbone; discomfort with irradiation in the back, cheekbone, larynx, hand, stomach; cold sweats, nausea, vomiting or dizziness, severe weakness, anxiety, or shortness of breath; rapid or irregular heartbeat. Arterial thromboembolism can be fatal.
In women with a combination of several risk factors or high severity of one of them (for example, complicated heart valve disease, uncontrolled arterial hypertension, extensive surgical interventions with prolonged immobilization, etc.), the possibility of their mutual amplification should be considered. In such cases, the total value of the available risk factors increases. In this case, taking the drug Yarina® Plus is contraindicated (see the section "Contraindications"),
The risk of developing thrombosis (venous and / or arterial) and thromboembolism increases:
- with age;
- smokers (with the increase in the number of cigarettes or an increase in the age of the risk increases, especially in women older than 35 years);
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 a hereditary or acquired predisposition, a woman should be examined by the appropriate specialist to decide on the possibility of taking the drug Yarina® Plus;
- prolonged immobilization, serious surgical intervention, any operation on the lower extremities or extensive trauma. In these situations, it is desirable to stop using the drug Yarina® Plus (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;
- 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 venous thromboembolism 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 diseases (Crohn's disease or ulcerative colitis) and sickle cell anemia.
Increased frequency and severity of migraine during drug administration Yarina® Plus (which may precede cerebrovascular disorders) may be grounds for the immediate discontinuation of this drug.
Biochemical indicators indicating hereditary or acquired predisposition to venous or arterial thrombosis include the following: resistance to activated protein C, hyperhomocysteinemia, deficiency of antithrombin III, deficiency of protein C, protein deficiency S, antibodies to phospholipids (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 and with peculiarities of sexual behavior is discussed (more rare application of barrier methods of contraception).
Mega-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of developing breast cancer diagnosed in women taking COC at the current time (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 rarely seen in women under 40 years of age, an 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 be the result of careful monitoring 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, against the background of the use of COC, there was a development of benign, and in very rare cases, malignant liver tumors, which in some patients led to life-threatening intraabdominal hemorrhage.When severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding occur, this should be taken into account when making a differential diagnosis.
Other states
Clinical studies have shown no effect of drospirenone on the potassium concentration in the plasma of patients with mild and moderate renal insufficiency. Nevertheless, in patients with impaired renal function and initial potassium concentration at the upper limit of the norm, the risk of developing hyperkalemia can not be ruled out when taking medications leading to a delay in potassium in the body.
Women with hypertriglyceridemia (or having this condition in a family history) may have an increased risk of developing pancreatitis while taking COC.
Despite the fact that a small increase in blood pressure has been described in many women taking COC, clinically significant increases were rare. Nevertheless, if during taking the drug Yarina® Plus a persistent, clinically significant increase in blood pressure develops, this drug should be discontinued and the treatment of arterial hypertension should begin. The drug can be continued if normal LD 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. 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 discontinuation drug administration Yarina® Plus until the liver function indicators return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous reception of sex hormones, requires discontinuation of the drug Yarina® Plus.
Although COCs may affect insulin resistance and tolerance to glucose, there is no need to change the therapeutic regimen in patients with sugar diabetes using the drug Yarina® Plus. Nevertheless, women with diabetes should be carefully observed during the administration of this drug.
Sometimes chloasma can develop, especially in women with a history of pregnancy chloasma. Women with a tendency to chloasma at the time of taking the drug Yarina® Plus should avoid prolonged exposure to sunlight and exposure to ultraviolet radiation.
Folate can mask the lack of vitamin B 12.
Preclinical data but safety
Preclinical data 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 certain hormone-dependent tissues and tumors.
Laboratory Tests
Reception of the drug Yarina® Plus can affect the results of some laboratory tests, including indicators of liver function, kidney function, thyroid gland, adrenal glands, plasma protein concentration in the plasma, carbohydrate metabolism,parameters of blood coagulation and fibrinolysis. 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. There is a theoretical possibility of increasing the concentration of potassium in blood plasma in women receiving the drug Yarina® Plus simultaneously with other drugs that can increase the potassium content in the blood plasma. These drugs include angiotensin II receptor antagonists, potassium-sparing diuretics and aldosterone antagonists. However, in studies evaluating the interaction of drospirenone with angiotensin-converting enzyme (AIP) inhibitors or indomethacin, a significant difference was observed between the potassium concentration in plasma versus placebo.
Decreased efficiency
Effectiveness of the drug Yarina® Plus can be reduced in the following cases: when skipping tablets, with gastrointestinal disorders or as a result of drug interactions.
Frequency and severity of menstrual bleeding
Against the background of taking the drug Yarina® Plus irregular (acyclic) bleeding from the vagina ("spotting" spotting or "breakthrough" uterine bleeding) may occur during the first few months. Use hygiene products and continue taking the pills as usual. Assessment of any irregular bleeding should be performed after an adaptation period of approximately 3 cycles.
If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be conducted to exclude malignant neoplasms or pregnancy.
The absence of another menstrual bleeding
Some women may not develop during a break in taking pills bleeding "cancellation." If the drug Yarina® Plus was taken according to the recommendations, then pregnancy is unlikely. Nevertheless, with irregular application of the drug Yarina® Plus and the absence of two consecutive bleeding "cancellations", the drug can not be continued until pregnancy is excluded.
Medical examinations
Before starting or resuming the use of the drug, you need to familiarize yourself with the history of life,family history of a woman, conduct a thorough physical examination (including measurement of blood pressure, heart rate, body mass index, breast examination), gynecological examination, cervical cytology (Papanicolaou test), exclude pregnancy. When you resume taking the drug Yarina® Plus the amount of additional studies and the frequency of follow-up visits are determined individually, but at least once every 6 months.
It must be borne in mind that the drug Yarina® Plus does not protect against HIV infection and other sexually transmitted diseases!
Conditions requiring medical advice
- Any changes in health, especially the emergence of conditions listed in the sections "Contraindications" and "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 limb), hospitalization or surgery is planned (at least 3-4 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 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; inarticulate speech; sudden changes in hearing, smell, or taste; dizziness or fainting; weakness or loss of sensitivity in any part of the body; severe pain in the abdomen; severe pain in the lower limb or a sudden onset of swelling in either of the lower extremities.