Delsia - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate 60 mg, corn starch 12.77 mg, silicon dioxide colloid 0.8 mg, hypromellose-2910 1.6 mg, talc 1.2 mg, magnesium stearate 0.6 mg;

film sheath: Opapray II yellow 31F82689 2.4 mg (hypromellose-2910 33%, lactose monohydrate 28%, titanium dioxide (E171) 22.5%, macrogol-6000 10%, talc 5%, ferric oxide yellow oxide (E172) 1.5%).

Description:

Round, biconvex tablets, covered with a film coating of yellow color, engraved "647" on one side and smooth on the other.

On the cross-section: the core is from white to almost white and the film shell is yellow.

Pharmacotherapeutic group:Contraceptive agent combined (estrogen + progestogen)

ATX: & nbsp

G.03.A.A.12 Drospirenone and ethinylestradiol

Pharmacodynamics:

Delsia is a low-dose combined monophasic oral hormonal contraceptive containing ethinyl estradiol and drospirenone. The contraceptive effect of Delsia is mainly due to suppression of ovulation, increased viscosity of the secretion of the cervix and changes in the endometrium.

When used correctly, the Perl index (an indicator that reflects the number pregnancies in 100 women who use contraceptive during the year) is less than 1. When missing tablets or improperly used, the Pearl index may increase.

In women taking combined oral contraceptives (COCs), the menstrual cycle becomes more regular, less painful menstruation,the intensity of menstrual bleeding decreases, resulting in a reduced risk of iron deficiency anemia. In addition, there is evidence that. which reduces the risk of developing endometrial cancer and ovarian cancer.

Drospirenone, contained in the preparation of Delsia, has an antimineralocorticoid action and prevents an increase in body weight and peripheral edema associated with estrogen-dependent fluid retention.

Drospirenone also has anti-androgenic activity and helps reduce acne (acne), oiliness of the skin and hair. This action of drospirenone is similar to the action of natural progesterone, produced in the female body. This should be considered when choosing a contraceptive drug, especially for women with hormone-dependent fluid retention, as well as women with acne and seborrhea.

Pharmacokinetics:

Drospirenone

Absorption

When ingested drospirenone quickly and almost completely absorbed. After a single dose, the maximum concentration (Cmah) of drospirenone in blood plasma, equal to 38 ng / ml, is achieved in 1-2 hours. Eating does not affect bioavailability, which ranges from 76 to 85%.

Distribution

Drospirenone binds to plasma albumin and does not bind to sex hormone binding globulin (SHBG), or corticosteroid-binding globulin (CSG). Only 3-5% of the total concentration of the substance in the blood plasma is present as a free hormone. 95-97% of the substance binds non-specifically to plasma albumin. The increase in SHBG induced by ethinyl estradiol does not affect the binding of drospirenone with plasma proteins. The average apparent volume of distribution is 3.7 ± 1.2 l / kg.

Metabolism

After oral administration, drospirenone is completely metabolized. Most metabolites in the blood plasma are represented by acid forms of drospirenone.

Drospirenone is also a substrate for oxidative metabolism catalyzed by the isoenzyme CYP3A4. The metabolic clearance rate of drospirenone from plasma is 1.5 ± 0.2 ml / min / kg.

Excretion

The concentration of drospirenone in the blood plasma is reduced biphasic. The second, final phase has a half-life (T1 / 2) of about 31 hours. In unmodified form, drospirenone is excreted in trace amounts. Its metabolites are excreted through the gastrointestinal tract and the kidneys in a ratio of approximately 1.2: 1.4.The half-life of the metabolites of drospirenone is approximately 40 hours.

The equilibrium concentration

The concentration of SHBG does not affect the pharmacokinetics of drospirenone. During the cycle of taking the drug, the concentration of drospirenone in the blood plasma increases 2-3 times, the equilibrium concentration is reached after 8 days of taking the drug.

In case of impaired renal function

Studies have shown that the concentration of drospirenone in the blood plasma of women with mild impairment of renal function (creatinine clearance (CK) - 50-80 ml / min) when reaching an equilibrium state and in women with a preserved kidney function (KC - more than 80 ml / min) is comparable . Nevertheless, in women with moderate renal dysfunction (CK - 30-50 ml / min), the average concentration of drospirenone in the blood plasma was 37% higher than in patients with preserved kidney function. There was no change in the concentration of potassium in blood plasma with drospirenone.

When a violation of liver function

In women with moderate impaired liver function (class B on the Child-Pugh scale), the area under the concentration-time curve (AUC) is comparable with the corresponding index in healthy women with close values of Cmah in the absorption and distribution phase.T1 / 2 drospirenone in patients with moderate impaired liver function was 1.8 times higher than in healthy volunteers.

In patients with moderate impairment of liver function, a decrease in clearance of drospirenone by approximately 50% compared with healthy women was noted, and there was no difference in the potassium concentration in the blood plasma in the study groups. In the detection of diabetes mellitus and concomitant use of spironolactone (both conditions are regarded as factors predisposing to the development of hyperkalemia), an increase in the concentration of potassium in blood plasma has not been established. Thus, it is possible conclude that tolerability of drospirenone in women with mild and moderate a violation of liver function is good (class B on the Child-Pugh scale).

Ethnicity

There is no evidence of the influence of ethnicity (the study was conducted on cohorts of women of the Caucasian and Japanese women) on the parameters of the pharmacokinetics of drospirenone and ethinylestradiol.

Ethinylestradiol

Absorption

After ingestion ethinyl estradiol quickly and completely absorbed. FROMmah - 100 mg / ml is achieved within 1-2 hours.During suction and "first pass" through the liver ethinyl estradiol is metabolized. as a result of which its bioavailability when taken orally averages about 45% with a high interindividual variability - from 20 to 65%. Simultaneous food intake in some cases is accompanied by a decrease in bioavailability of ethinyl estradiol by 25%.

Distribution

Ethinyl estradiol, non-specifically, but firmly binds to blood plasma albumin (about 98%) and induces an increase in the concentration in the plasma of SHBG. The estimated volume of distribution is 5 l / kg.

Metabolism

Ethinyl estradiol undergoes significant primary metabolism in the intestine and liver. Ethinylestradiol and its oxidative metabolites are primarily conjugated to glucuronides or sulfate. The metabolic clearance rate of ethinylestradiol is about 5 ml / min / kg.

Excretion

Reduction in the concentration of ethinyl estradiol in blood plasma is biphasic; the first phase is characterized by a half-life of about 1 hour, the second - 20 hours. Ethinylestradiol almost not output in unmodified form.Metabolites of ethinyl estradiol are excreted by the kidneys and through the intestine in a ratio of 4: 6. The half-life of metabolites is approximately 24 hours.

The equilibrium concentration

The equilibrium state is reached in the second half of the cycle, when the concentration of ethinyl estradiol in the blood plasma increases by 40-110% compared with the use of a single dose.

Indications:

Contraception.

Contraindications:

- Thrombosis (venous and arterial) at present or in anamnesis (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);

- conditions preceding thrombosis (including transient ischemic attacks, atrial fibrillation, angina pectoris) at the present time or in the anamnesis:

- a predisposed predisposition to venous or arterial thrombosis, including resistance to activated protein C, anthrombin III deficiency, protein C deficiency, protein deficiency S, hyperhomocysteinemia. antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant);

- migraine with focal neurologic symptoms at present or in anamnesis;

- Diabetes mellitus with diabetic angiopathy;

- Multiple or expressed risk factors for venous or arterial thrombosis (including complicated heart valve valvular defects, atrial fibrillation, cerebrovascular or coronary artery disease, uncontrolled arterial hypertension, prolonged immobilization, volumetric surgical intervention, operative interventions on the lower extremities, in the pelvis, neurosurgery, extensive injuries, smoking over the age of 35, obesity with a body mass index of more than 30 kg / m²; severe dyslipoproteinemia; airfare lasting more than 4 hours);

- pancreatitis with severe hypertriglyceridemia at present or in the anamnesis;

- liver failure and severe liver disease (before the normalization of functional liver tests and within three months after returning these indicators to normal);

- Liver tumors (benign or malignant) at present or in the anamnesis;

- severe renal failure and / or acute renal failure:

- identified hormone-dependent malignant diseases (incl.genitals or mammary glands) or suspicion of them:

bleeding from the vagina of unknown origin;

- Pregnancy or suspicion of it;

- the period of breastfeeding;

- hypersensitivity to the components of the drug;

- hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

In case of detection or development of any of the above diseases / conditions or risk factors for the first time against the background of the drug, Delsia should be stopped immediately.

Carefully:

The ratio of potential risk and the expected benefit of using Delsia in each individual case should be assessed in the presence of the following diseases / conditions and risk factors:

- Risk factors for thrombosis and thromboembolism: smoking, obesity with body mass index less than 30 kg / m², dyslipoproteinemia, controlled arterial hypertension, migraine without focal neurologic symptoms, uncomplicated defects of the valvular apparatus of the heart, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or impaired cerebral circulation at a young age in any of the next of kin), age over 35 years in nonsmoking women;

- other diseases, which may occur when the peripheral circulatory disorders: diabetes without diabetic angiopathy, systemic lupus erythematosus (SLE), hemolytic uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, phlebitis superficial veins;

- hereditary angioedema;

- hypertriglyceridemia;

- liver disease, not related to contraindications (see "Contraindications");

- the disease first appeared or worsen during pregnancy, or on the background of the previous use of sex hormones (eg, jaundice and / or pruritus related to cholestasis, cholelithiasis otosclerosis with hearing impairment, porphyria, herpes during a previous pregnancy, Sydenham's chorea, chloasma). ;

- Postpartum period.

Pregnancy and lactation:

Pregnancy.

Dalsia is contraindicated during pregnancy. If pregnancy is detected during the administration of Delsia, the drug should be stopped immediately. Conducted epidemiological studies are not revealed an increased risk of developmental defects in children born to women who received sex hormones before pregnancy,or teratogenicity in cases where sex hormones were taken by negligence in the early stages of pregnancy. Experimental studies in animals have shown adverse effects of the drug during pregnancy and lactation in animals. Based on these data can not exclude the possibility of adverse effects of the drug on the fetus or newborn in humans.

The available data on the results of taking Delsia during pregnancy are limited, which does not allow us to draw any conclusions about the negative effect of the drug on pregnancy, the health of the fetus and the newborn. Currently, there are no significant epidemiological data.

Breastfeeding period.

The use of the drug Delsia is contraindicated in the period of breastfeeding. COCs can reduce the amount of breast milk and change its composition, so their use is not recommended until the end of breastfeeding. A small amount of sex hormones and / or their metabolites can penetrate into breast milk.

Dosing and Administration:

Tablets should be taken orally in the order given on the package,every day at about the same time, with a small amount of water. Take 1 tablet continuously for 21 days. The taking of tablets from the next package begins after a 7-day break, during which menstrual-like bleeding (bleeding "cancellation") is usually observed. As a rule, it begins on the 2-3 day after the last pill and may not end before taking the tablets from the new package.

The beginning of the drug Delsia. In the absence of taking any hormonal contraceptives in the previous month, taking Delsia begins on the 1st day of the menstrual cycle (that is, on the 1st day of menstrual bleeding). It is allowed to start taking the menstrual cycle on the 2nd-5th day, but in this case it is recommended to use the barrier method of contraception during the first 7 days of taking the tablets from the first package.

Transition from other combined hormonal contraceptive drugs (COC, vaginal ring or transdermal patch). It is preferable to start taking Dalsia on the day after taking the last tablet containing hormones,but in no case no later than the next day after an ordinary 7-day break (for preparations containing 21 tablets) or after taking the latter tablets from the previous package (for preparations containing 28 tablets). Reception Delsia should be started on the day of removal of the vaginal ring or plaster, but no later than the day when a new ring is to be inserted or a new adhesive is stuck.

Transition from contraceptives containing only gestagens ("mini-drank", injectable form, implant or intrauterine system (IUD) with a controlled release of progestogen). You can go from "mini-drills" to taking Delsia in any day (without interruption), with an implant or IUD - on the day of their removal, with an injection contraceptive - the day the next injection is to be made. In all cases It is necessary to use an additional barrier method of contraception during the first 7 days of taking pills.

After abortion in the first trimester of pregnancy. You can start taking the drug immediately - on the day of abortion. If this condition is met, the woman does not need additional methods of contraception.

After childbirth or abortion in the second trimester. It is recommended to start taking the drug on days 21-28 after giving birth (if there is no breastfeeding) or abortion in the second trimester. If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets. However, if a woman already had a sex life, pregnancy should be ruled out before the beginning of taking Delsia or it is necessary to wait for the first menstruation.

Acceptance of missed tablets. If the delay in taking the drug is less than 12 hours, the contraceptive protection is not reduced. A woman should take the pill as soon as possible, the next pill is taken at the usual time.

If the delay in taking the drug is more than 12 hours, contraceptive protection can be reduced. The more pills are missed and the closer the pass to the 7-day break in taking pills, the more likely it is to become pregnant.

In this case, you can follow the following two basic rules:

- taking the drug should never be interrupted for more than 7 days;

- to achieve adequate suppression of the hypothalamic-pituitary-ovarian system, 7 days of continuous intake of tablets are required.

Accordingly, if the delay in taking the tablets was more than 12 hours (the interval from the time of taking the last tablet is more than 36 hours), you can recommend the following:

The first week of taking the drug. It is necessary to take the last missed pill as soon as possible, as soon as a woman remembers it (even if you need to take two tablets at the same time). The next tablet is taken in the usual time. In addition, barrier method of contraception should be used (eg, a condom) for the next 7 days. If the sexual contact took place in During the week before passing the pill, it is necessary to take into account the probability of pregnancy.

The second week of taking the drug. It is necessary to take the last missed pill as soon as possible, as soon as a woman remembers it (even if you need to take two tablets at the same time). The next tablet is taken at the usual time. Provided that the woman took the pill correctly for 7 days preceding the first missed pill, there is no need to use additional contraceptive measures.Otherwise, as well as when two or more tablets are missed, barrier methods of contraception (for example, a condom) should be used additionally within 7 days.

The third week of taking the drug. The risk of pregnancy is increased because of the upcoming pause in taking pills. A woman should strictly adhere to one of the following two options. If, during the 7 days preceding the first missed tablet, all the pills were taken correctly, there is no need to use additional contraceptive methods. Otherwise it is necessary to use the first of the following schemes and additionally use the barrier method of contraception (for example, a condom) for 7 days.

1. It is necessary to take the last missed pill as soon as possible, as soon as a woman remembers it (even if you need to take two tablets at the same time). The following tablets are taken at the usual time, until the tablets in the current packaging run out. The next package should be started immediately without interruption. Bleeding "cancellation" is unlikely until the tablets in the second package run out, but "smearing" bleeding and "breakthrough" bleeding may be noted during taking the tablets.

2.You can also interrupt the taking of tablets from the current package, thus starting a 7-day break (including the day of skipping the tablets), and then start taking the tablets from the new package.

If a woman misses taking pills, and then during a break in admission she does not have a bleeding "withdrawal", it is necessary to exclude pregnancy.

Recommendations in case of occurrence of disorders from the gastrointestinal tract (GIT). In the case of severe gastrointestinal disorders (vomiting, diarrhea), absorption may be incomplete, therefore, additional methods of contraception. If within 4 hours after taking the pill there will be vomiting, it is necessary to be guided by the recommendations when missing tablets.

Change in the day of menstrual bleeding. In order to delay the onset of menstrual bleeding, it is necessary to continue taking the tablets from a new package of Delsia without a 7-day break. Tablets from a new package can be taken for as long as necessary, including until the packaging is finished. Against the background of taking the drug from the second package, it is possible "smearing" spotting from the vagina or "breakthrough" uterine bleeding.To resume the regular reception of Delsia from the regular package follows the usual 7-day break. In order to transfer the onset of menstrual bleeding to another day of the week, the woman should shorten the nearest break in taking the tablets for the desired number of days. The shorter the interval, the higher the risk that it will not have the bleeding of the "cancellation", and later "spotting" excretions and "breakthrough" bleedings will be observed during taking the tablets from the second package (as well as in case she would like delay the onset of menstrual bleeding).

Additional information for specific patient categories

Use in children. The efficacy and safety of the drug as a contraceptive is studied in women of reproductive age. The use of the drug before menarche is not indicated. It is assumed that the efficacy and safety of the drug in post-pubertal age under 18 years are similar to those in women after 18 years of age. The available data do not imply dose adjustment in this age group.

Application in the elderly. After the onset of menopause, the use of Delsia is not indicated.

Application for violations of the liver. Contraindicated use of the drug in the presence of currently severe liver disease (before the normalization of functional liver tests and within three months after the return of these indicators in the norm).

Use in cases of impaired renal function. Contraindicated use of the drug in acute renal failure and severe renal failure.

Side effects:

Organ Class System	Frequency of adverse reactions
Organ Class System	Often (≥1 / 100 and <1/10)	Infrequently (≥1 / 1000 and <1/100)	Rarely (≥1 / 10000 and <1/1000)
Immune system disorders			Hypersensitivity reactions, bronchial asthma
Disorders of the psyche	Depressive states	Changing libido
Disturbances from the nervous system	Headache, migraine
Hearing impairment and labyrinthine disorders			Hearing loss
Vascular disorders		Increased blood pressure, lower blood pressure	Venous or arterial thromboembolism *
Disorders from the gastrointestinal tract	Nausea	Vomiting, diarrhea
Disturbances from the skin and subcutaneous tissues		Acne, eczema, itching, alopecia	Nodular erythema, erythema multiforme
Disorders from the reproductive system and mammary glands	Violations of the menstrual cycle, acyclic bleeding, pain in the mammary glands, tenderness of the mammary glands, leucorrhoea, vaginal candidiasis	Mammary gland enlargement, vaginitis	Discharge from the mammary glands
General disorders and disorders at the site of administration		Fluid retention, change in body weight

* Venous or arterial thromboembolism includes the following nosological forms: peripheral deep vein occlusion, thrombosis and thromboembolism / pulmonary vascular occlusion, thrombosis, thromboembolism and myocardial infarction / cerebral infarction and stroke.

The following adverse reactions were reported the women using COC with a very rare incidence or with delayed symptoms that, it is believed, can be associated with the reception of COCs:

- breast cancer (see section "Special instructions");

- liver tumors (benign and malignant);

- increase in blood pressure:

- Pancreatitis in women with hypertriglyceridemia;

- the appearance or deterioration of conditions, the relationship of which with the administration of COC has not been fully established: porphyria. epilepsy, uterine myoma, systemic lupus erythematosus (SLE), herpes during pregnancy, Sydenham's chorea, hemolytic-uremic syndrome, cholestatic jaundice and / or itching associated with cholestasis: cholelithiasis; otosclerosis with hearing impairment;

- abnormal liver function;

- change in glucose tolerance and development of insulin resistance:

- Chloasma;

- Crohn's disease, ulcerative colitis.

In women with hereditary angioedema, estrogen use may cause or aggravate its symptoms.

Overdose:

No serious violations were reported in case of an overdose. Based on the generalized experience of using COCs symptoms, which can be noted during an overdose: nausea, vomiting, "smearing" spotting from the vagina or metrorrhagia.

Treatment: conduct symptomatic therapy. There is no specific antidote.

Interaction:

The interaction of COC with other drugs can lead to "breakthrough" bleeding and / or a decrease in contraceptive reliability.Women taking these drugs should temporarily use barrier methods of contraception in addition to the drug Delsia or choose another method of contraception.

Interactions, leading to a decrease in the effectiveness of the drug Delsia

Influence on hepatic metabolism. The use of drugs that induce microsomal enzymes of the liver can lead to an increase in the clearance of sex hormones, which, in turn, can lead to "breakthrough" bleeding or a decrease in the reliability of contraception. Such medicines include phenytoin, barbiturates, primidon. carbamazepine, rifampicin, rifabutin, perhaps also oxcarbazepine, topiramate, felbamate, griseofulvin and preparations containing St. John's wort.

When combined with Delsia, many HIV protease inhibitors and hepatitis C virus, as well as non-nucleoside reverse transcriptase inhibitors, can both increase and decrease the concentration of estrogens or progestogens in blood plasma. In some cases, this effect can be clinically significant.

During the administration of drugs that affect microsomal enzymes of the liver, and within 28 days after their withdrawal, the barrier method of contraception should be used additionally.

Effect on intestinal hepatic recirculation. Some antibiotics (eg, penicillins and tetracyclines) can reduce the intestinal hepatic circulation of estrogens, thereby lowering the concentration of ethinyl estradiol.

During the reception of antibiotics (such as penicillins and tetracyclines) and within 7 days after their withdrawal, the barrier method of contraception should be used additionally. If the period of use of the barrier method of protection ends later than the tablets in the package, you need to switch to taking the tablets from the next package of the Delsia preparation without the usual break in taking the tablets.

Other interactions

Strong and moderate inhibitors CYP3A4. such as azole antimycotics (eg, itraconazole, voriconazole, fluconazole), verapamil. macrolides (for example, clarithromycin, erythromycin), diltiazem and grapefruit juice can increase plasma concentrations of estrogen or progestin, or both.

It was shown that etorikoksib in doses of 60 and 120 mg / day when taken together with COC containing 0.035 mg of ethinylestradiol. increases the concentration of ethinyl estradiol in blood plasma by 1.4 and 1.6 times, respectively.

In vitro Drospirenone is able to weakly or moderately inhibit cytochrome P450 enzymes CYP1A1, CYP2C9, CYP2C19 and CYP3A4.

Based on interaction studies in vivo women volunteers who took omeprazole, simvastatin or midazolam as marker substrates, it can be concluded that the clinically significant effect of 3 mg of drospirenone on the metabolism of medications mediated by cytochrome P450 enzymes is unlikely. In vitro ethinyl estradiol is a reversible inhibitor CYP2C19, CYP1A1 and CYP1A2, as well as an irreversible inhibitor CYP3A4/5, CYP2C8 and CYP2J2. In clinical trials, the appointment of a hormonal contraceptive containing ethinyl estradiol, not led to any increase or resulted only in a slight increase in the concentrations of substrates CYP3A4 in plasma of blood (for example, midazolam), while plasma concentrations of substrates CYP1A2 may grow weakly (for example, theophylline) or moderately (for example, melatonin and tizanidine).

COCs can affect the metabolism of other drugs, leading to an increase (for example, ciclosporin) or decrease (for example, lamotrigine) of their concentration in plasma and tissues.

There is a theoretical possibility of increasing the concentration of potassium in the blood plasma in women receiving the drug Delsia at the same time as other drugs that can increase the concentration of potassium in the blood plasma. These drugs include angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, certain anti-inflammatory drugs, potassium-sparing diuretics and aldosterone antagonists. However, studies investigating the interaction of drospirenone with ACE inhibitors or indomethacin did not reveal a significant difference between the potassium concentration in plasma compared with placebo. Nevertheless, in women taking drugs that increase the concentration of potassium in the blood plasma, it is recommended to determine this index during the first cycle of taking Delsia.

Despite the fact that the administration of COC affects insulin resistance and glucose tolerance, correction of the dose of hypoglycemic drugs during COC administration is not required.

Special instructions:

Medical examinations

Before starting or resuming the use of Delsia, you need to familiarize yourself with the history of life,(including blood pressure, heart rate, body mass index) and gynecological examination, including breast examination and cervical scraping (Papanicolaou test), 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 informed that the drug Delsia does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

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 application of COCs in each individual case and discuss it with a woman before she decides to start taking the drug. With weighting, strengthening, or with the first manifestation of risk factors, it may be necessary 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 disease. 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 women taking low-dose COCs (containing less than 50 μg ethinylestradiol) is 2-3 times higher than in non-pregnant women who do not take COC, however, this risk remains lower compared to the risk of VTE in pregnancy and childbirth. VTE can lead to death (in 1-2% of cases).

According to some data, preparations containing drospirenone have a higher risk of developing thromboembolic complications compared to drugs containing levonorgestrel, norgestimate or norethisterone.

VTE, manifested as deep vein thrombosis or pulmonary embolism (PE), can 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. 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 unilateral edema lower limb or along veins of 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 PE are as follows: shortness of breath or rapid breathing; sudden cough, incl. with hemopoiesis; acute pain in the chest, which can deep inspiration; sense of anxiety; severe dizziness; rapid or irregular heartbeat. Some of these symptoms (eg, dyspnea, cough) are nonspecific and may be misinterpreted as symptoms of other more or less severe events (eg, respiratory tract infection).

Arterial thromboembolism can lead to stroke, vascular occlusion or myocardial infarction. Symptoms of a stroke: sudden weakness or loss 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 slight blueing of the extremities, sharp abdomen.

Symptoms of myocardial infarction include: pain; discomfort; feeling of pressure, heaviness, a feeling of squeezing or bursting in the chest,in the arm or behind the breastbone; discomfort in the left half of the chest with irradiation in the back, cheekbone, larynx, arm, epigastric region; cold sweat, nausea, vomiting, dizziness, severe weakness, anxiety, shortness of breath; a feeling of rapid or irregular heartbeat.

Arterial thromboembolism can be life threatening or fatal.

In women with a combination of several risk factors for arterial and venous thrombosis and thromboembolism, or the high severity of one of them, one should consider the possibility of their mutual amplification. In such cases, the total value of the available risk factors is increased. In this case, taking Delsia is contraindicated (see the section "Contraindications").

The risk of developing thrombosis (venous and / or arterial) and thromboembolism increases:

- with age;

- for smokers (with an increase in the number of cigarettes or an increase in the age, the risk increases, especially in women over 35 years of age);

in the presence of:

- obesity (body mass index more than 30 kg / m²);

- family history (eg, thrombosis or thromboembolism in first-degree relatives under the age of 50 years).In the case of a hereditary or acquired predisposition, a woman should be examined by an appropriate specialist to decide on the possibility of taking COC;

- prolonged immobilization, serious surgery on the lower extremities, pelvic area, neurosurgical operations or extensive trauma. In these situations, it is necessary to stop the use of COCs (in the case of a planned operation, at least four weeks before) and not to 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 the development of VTE. especially if there are other risk factors;

- severe 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.

An increased risk of thromboembolism in the postpartum period should be considered. Violations of the peripheral circulation can also occur in diabetes mellitus, SLE,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 attacks during the use of COCs (which may precede cerebrovascular disorders) is the basis for the immediate discontinuation of these medications.

Biochemical indicators indicating a hereditary or acquired predisposition to venous or arterial thrombosis include: resistance to activated protein C, hyperhomocysteinemia. deficiency of antithrombin III, deficiency of protein C, deficiency of protein S, presence of antibodies to phospholipids (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 (containing less than 50 μg 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. Controversial data remain regarding the extent to which these data are associated with screening for the diagnosis of cervical pathology or with features of sexual behavior (the more rare use of barrier methods of contraception).

There is also evidence of a reduced risk of developing endometrial and ovarian cancer when taking COCs.

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 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. The relationship between the development of breast cancer and 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. earlier stages of breast cancer are revealed than in women who 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. Tumors can endanger life or lead to death.

Other states

Clinical studies showed no effect of drospirenone on the potassium concentration in blood plasma in women with mild and moderate renal insufficiency. Theoretically, there is a risk of developing hyperkalemia in women with impaired renal function and the initial concentration of potassium in the blood plasma at the upper limit of the norm or against the background of taking medications,leading to a delay in potassium in the body.

In women with hypertriglyceridemia (or in the presence of this condition in the family history) may increase the risk of developing pancreatitis during the COC. Despite the fact that a small increase in blood pressure was described in many women taking COC, clinically significant hypertension was rare. 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 COCs. but their connection with the administration of COC is not proved: jaundice and / or itching associated with cholestasis; formation of stones in the gallbladder: porphyria; SLE: hemolytic-uremic syndrome; Sydengam's chorea: herpes during pregnancy; hearing loss associated with otosclerosis. Cases of Crohn's disease or ulcerative colitis are also described against the background of COC use.

When using the drug, the development of chloasma is possible, especially in women with a history of pregnant chloasma. Women with a tendency to chloasma while taking COC should avoid prolonged exposure to the sun and exposure to ultraviolet radiation.

In women with hereditary forms of angioedema, exogenous estrogens can cause or worsen symptoms of angioedema.

In acute or chronic violations of liver function, it may be necessary to cancel the drug until the parameters of the functional liver samples return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or during the previous intake of sex hormones, requires the cessation of COCs.

Although COCs can affect insulin resistance and glucose tolerance, there is no need to change the dosage regimen for hypoglycemic agents in women with diabetes using low-dose COCs (containing less than 50 μg ethinyl estradiol). Nevertheless, women with diabetes require careful monitoring of blood glucose concentrations during the use of the drug.

Decreased efficiency

The effectiveness of COCs can be reduced by missing tablets, vomiting and diarrhea, or as a result of drug interactions.

Effects on the menstrual cycle

Against the background of the use of COC may be observed irregular (acyclic) bleeding ("smearing" bleeding or "breakthrough" bleeding), especially during the first months of use. Therefore, any irregular bleeding should be assessed only 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.

Some women during the break in taking pills may not develop a bleeding "cancellation". If the COC was administered in accordance with the directions, pregnancy is unlikely. Nevertheless, if before the reception of the COC was performed irregularly, or if there are no consecutive two bleeding "cancellations", then before continuing with the drug should be excluded pregnancy.

Impact on laboratory test scores

Admission COC can affect the results of some laboratory tests, including indicators of liver function, kidney function, thyroid gland, adrenal gland, transport protein concentration in blood plasma, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond the limits of normal values. Drospirenone increases the concentration of renin and aldosterone in the blood plasma, which is due to its antimineralocorticoid effect.

Effect on the ability to drive transp. cf. and fur:No effect on the ability to drive vehicles and mechanisms has been identified.

Form release / dosage:

Tablets, film-coated, 3 mg + 0.03 mg.

Packaging:

For 21 tablets in a blister of PVC / aluminum foil.

One blister, along with a pocket for wearing a blister and instructions for use, is placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004240

Date of registration:12.04.2017

Expiration Date:12.04.2022

The owner of the registration certificate:San Pharmaceutical Industries Co., Ltd.San Pharmaceutical Industries Co., Ltd. India

Manufacturer: & nbsp

Sun Pharmaceutical Industries, Ltd. India

Representation: & nbspSAN PHARMACEUTICAL INDUSTRIES LTD. SAN PHARMACEUTICAL INDUSTRIES LTD. India

Information update date: & nbsp23.04.2017

Illustrated instructions

Instructions

Delsia (Delsya)