If any of the conditions, diseases or risk factors identified below are present, careful consideration should be given to the potential risk and expected benefit of the drug Dienogest + Ethinylestradiol in each individual case and discuss it with a woman before she decides to start taking the drug. 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
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. 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 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 ethinylestradiol) in 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 may occur when using any COCs.
It rarely occurs when using COCs thrombosis other blood vessels, for example, hepatic, mesenteric, renal, and cerebral arteries veins or the retinal vascular eye.
Symptoms of deep vein thrombosis: a unilateral edema or swelling of the lower limbs along the veins in the lower limbs, pain or discomfort in the lower limb in a vertical position or during walking, the local temperature rise in the affected lower limb, redness or discoloration of the skin of the lower limb.
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 common and less severe conditions / diseases (eg, respiratory tract infections). Arterial thromboembolism can lead to stroke, vascular occlusion or myocardial infarction. Symptoms of a stroke include: 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 epileptic a fit or without it.Other signs of 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 degree of risk increase may be higher than with a simple summation of factors. In this case, taking the drug Dienogest + Ethinylestradiol contraindicated (see section "Contraindications").
The risk of developing thrombosis (venous and / or arterial) and thromboembolism or cerebrovascular disorders is increased:
- 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 in close relatives or parents aged less than 50 years). 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 Dienogest + Ethinylestradiol;
- prolonged immobilization, extensive surgical intervention, any operation on the lower extremities or extensive trauma. In these cases, taking the drug Dienogest + Ethinylestradiol it is necessary to stop (in the case of the planned operation, at least four weeks before it) and not to resume reception within two weeks after the end of immobilization. Temporary immobilization (for example, air travel lasting more than 4 hours) may also be a factor risk of venous thromboembolism, especially in the presence of other factors risk;
- dyslipoproteinemia;
- arterial hypertension;
- migraine;
- heart valve diseases;
- atrial fibrillation.
The possible role of varicose veins and superficial thrombophlebitis in the development ofVTE 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.
Increased frequency and severity of migraine during drug administration Dienogest + Ethinylestradiol (which may precede cerebrovascular disorders) is the basis for the immediate withdrawal of this drug.
Biochemical indicators indicating a 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, antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant).
When assessing the risk-benefit ratio, 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 COCs (<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. There are contradictions concerning The extent to which these data are associated with screening for cervical pathology or with peculiarities of sexual behavior (a more rare use of barrier methods of contraception).
A meta-analysis of 54 epidemiological studies showed that there is a slightly elevated the 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 rare in women under 40 years of age, an increase in the number of diagnoses of breast cancer in women,taking COCs now or recently, 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 a consequence of an earlier diagnosis of breast cancer in women using COCs; and can also be due to the biological effect of sex hormones or a combination of these two factors. 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 case of severe pain in the abdominal region, enlarged liver, 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), 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. 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. 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 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 can affect 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 monitored while taking COC.
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 Dienogest + Ethinylestradiol should avoid prolonged exposure to sunlight and exposure to ultraviolet radiation.
Preclinical safety data
Preclinical data obtained during standard studies for the detection of toxicity with multiple doses of the drug, as well as genotoxicity,carcinogenic potential and toxicity for the reproductive system, do not indicate the existence of a special 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 Dienogest + Ethinylestradiol can influence the results of some laboratory tests, including liver, kidney, thyroid, adrenal, traffic protein in plasma, carbohydrate metabolism, blood clotting parameters and fibrinolysis. Changes usually do not go beyond the limits of normal values.
Decreased efficiency
Effectiveness of the drug Dienogest + Ethinylestradiol can be reduced in the following cases: when a tablet is missed, gastrointestinal disorders or as a result of drug interaction.
Frequency and severity of menstrual bleeding
Against the background of taking the drug Dienogest + Ethinylestradiol there may be irregular bleeding (spotting spotting and / or breakthrough uterine bleeding), 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.
The absence of another menstrual bleeding
Some women during the break in taking pills may not develop a bleeding "cancellation". If the drug Dienogest + Ethinylestradiol was taken according to recommendations, it is unlikely that a woman is pregnant. However, if the drug has been used irregularly or if there are no consecutive "bleeding" consecutive bleeds, the drug can not be taken until the pregnancy is excluded.
Medical examinations
Before starting or resuming the use of the drug Dienogest + Ethinylestradiol It is necessary to familiarize with the anamnesis of life, family
medical history, conduct a thorough general medical (including measurement blood pressure, heart rate,determination of body mass index) and gynecological examination, including breast examination and cervical cytology (Papanicolaou test), to exclude pregnancy. When you resume taking the drug Dienogest + Ethinylestradiol the amount of additional studies and the frequency of follow-up visits are determined individually, but not less than once every 6 months.
It should be borne in mind that the drug Dienogest + Ethinylestradiol does not protect against HIV infection (AIDS) and other sexually transmitted diseases!
When to consult a doctor:
- with any changes in health, especially any conditions / diseases / risk factors listed in this manual (see also "Contraindications" and "Precautions");
- with local compaction in the mammary gland;
- if you intend to use other medications (see also section "Interaction with other drugs");
- if prolonged immobility is expected (for example, gypsum is applied to the lower limb), hospitalization or surgery is planned (consult a doctor at least 4-6 weeks before);
- when an unusual strong vaginal bleeding occurs;
- if you forgot to take the pill in the first week of taking the package and there was sexual contact 7 or less days before;
- if you have not had another menstrual bleeding twice in a row or you suspect that you are pregnant (do not start taking the next package until you consult a doctor).
Stop taking pills and consult a doctor immediately if you notice possible signs of thrombosis, first arising: an unusual cough; unusually severe pain behind the sternum, giving to the left hand; unexpectedly arisen; unusual, severe or 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 faintness; 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.