When deciding on the use of the drug Melleva® It is necessary to take into account the associated individual risk factors, especially risk factors for VTE. Besides, the risk of VTE when using Melleva® should be compared with the risk of VTE when using other hormonal contraceptives.
If any of the conditions, diseases and risk factors identified below are present, careful consideration should be given to the potential risk and expected benefit of the Melleva drug 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 or risk factors, a woman should consult a 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 involving sin 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 ethinylestradiol) is 2-3 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 in the form of deep vein thrombosis or pulmonary embolism may develop 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 along the vein on the lower extremity, pain and discomfort in the lower extremity only in the vertical position or walking, local increase in temperature 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; a 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 can 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 linden, 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, swelling and weak blueing of the limbs; "sharp" abdomen.
Symptoms of myocardial infarction: pain, discomfort, pressure, heaviness, a feeling of squeezing or raspiraniya in the chest or behind the breastbone with irradiation in the back, jaw, larynx, left arm, 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, the use of the drug Melleva is contraindicated.
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 at a relatively young age). In the case of hereditary predisposition, a woman should be examined by an appropriate specialist to decide on the possibility of taking the drug;
prolonged immobilization, extensive surgical intervention, any operation on the lower extremities or extensive trauma.In these situations, the Melleva® drug should be discontinued (in the case of a planned operation, at least 4 weeks before it) and does not resume admission within two weeks after immobilization is complete. Temporary immobilization (for example, air travel lasting more than 4 hours) is also a risk factor for the development of VTE, especially if there are other risk factors:
- dyslipoproteinemia;
- arterial hypertension;
- migraine;
- heart valve flaws;
- atrial fibrillation.
The question of the possible role of varicose veins and superficial thrombophlebitis in the development of VTE remains controversial.
An increased risk of thromboembolism in the postpartum period should be considered. Violations of the peripheral circulation can also occur in diabetes mellitus, systemic lupus erythematosus, hemolytic-uremic syndrome, chronic inflammatory bowel diseases (Crohn's disease, 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 reason for the immediate discontinuation of these medications.
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 oral contraceptives (<0.05 mg 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. Due to the fact that breast cancer is rarely seen in women giving birth until the age of 40, the increase in the number of diagnoses of breast cancer in women who are currently taking COCs or who are taking it 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 the result of an earlier diagnosis of breast cancer in women taking COC, the biological effects of COCs, or a combination of these factors. Women who have ever used COC have earlier stages of breast cancer than women who have never used them.
In rare cases, with the use of COC, benign, and in very rare cases, malignant liver tumors, which in some cases led to life-threatening intraperitoneal bleeding, was observed.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
In women with hypertriglyceridemia (or in 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 COC, these drugs should be discontinued and the 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 relationship with COCs has not been proven: cholestatic jaundice and / or itching,associated with cholestasis; formation of stones in the gallbladder; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes during pregnancy in anamnesis; loss of hearing, 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, the use of estrogens may cause or worsen the symptoms of angioedema.
Acute or chronic liver dysfunction may require cancellation of the COC until the functional liver 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 COCs.
Although COCs may have an effect on insulin resistance and glucose tolerance, dose adjustment for hypoglycemic drugs in patients with diabetes is generally not required. 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 Melleva should avoid prolonged exposure to the sun and exposure to ultraviolet radiation.
Preclinical safety data
Preclinical data obtained from standard toxicity studies with multiple doses of the drug, as well as genotoxicity, carcinogenicity and reproductive toxicity, do not indicate a particular risk to humans. Nevertheless, it should be remembered that sex steroids can promote the growth of some hormone-dependent tissues and tumors.
Laboratory Tests
The administration of COC can influence the results of some laboratory tests, including liver, kidney, thyroid, adrenal, traffic protein in plasma (eg, corticosteroid-binding globulin), lipid / lipoprotein fractions, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond the limits of normal values.
Decreased efficiency
The effectiveness of the drug Melleva® can be reduced in the following cases: when skipping tablets,gastrointestinal disorders (vomiting and diarrhea) or as a result of drug interactions.
Effect on the character of menstrual bleeding
On the background of taking COC, 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 assessed only after an adaptation period of approximately 3 cycles.
If irregular menstrual bleeding repeats or develops after previous regular cycles, a thorough examination should be performed to exclude malignant neoplasms or pregnancy.
In some women during the intermission of pills may develop a bleeding "cancellation". If Melleva® 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 can not be continued until exclusion of pregnancy.
Medical examinations
Before the start or resumption of the drug Melleva should be thoroughly acquainted with the history of life, a family history of a woman, to conduct a thorough general medical and gynecological examination, to 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 (but at least every 6 months). Typically, the examination includes measuring blood pressure, heart rate; determination of body mass index; assessment of the condition of the mammary glands, abdominal and pelvic organs, including cytological examination of the cervical epithelium (Papanicolaou test).
It is necessary to bear in mind, that the drug Melleva® does not protect against HIV infection (AIDS) and other sexually transmitted diseases!