Delsia pills 3mg+0.03mg, 3 x 21pcs

Composition

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

Composition of the film shell:  opadray II yellow 31F82689 – 2.4 mg (hypromellose 2910-33%, lactose monohydrate-28%, titanium dioxide (E 171) – 22.5%, macrogol 6000-10%, talc-5%, iron oxide yellow dye (E 172) – 1.5%).

Pharmacological action

Combined monophasic hormonal contraceptive. The contraceptive effect is based on the interaction of various factors, the most important of which are the inhibition of ovulation, an increase in the viscosity of cervical secretions, as a result of which it becomes impervious to spermatozoa.

When used correctly, the Pearl index (a measure that reflects the number of pregnancies in 100 women using a contraceptive drug during the year) is less than 1. If you miss an appointment or use it incorrectly, the Pearl index may increase.

In a therapeutic dose, drospirenone also has antiandrogenic and weak antimineralocorticoid properties. Lacking estrogenic, glucocorticoid, and anti-glucocorticoid activity, drospirenone has a pharmacological profile similar to that of natural progesterone.

Having antiandrogenic activity, it helps to reduce the production of sebaceous gland secretions and improve the clinical course in women with acne (acne vulgaris).

This should be taken into account when choosing a contraceptive, especially for women with hormone-dependent fluid retention, as well as women with acne and seborrhea. In combination with ethinyl estradiol, it improves the lipid profile and increases the concentration of HDL.

The use of this combination regulates menstrual-like bleeding, helping to reduce the severity of pain and the volume of menstrual-like bleeding, reducing one of the risk factors for iron deficiency anemia.

Pharmacokinetics

When taken orally, drospirenone is rapidly and almost completely absorbed. After a single oral dose With_max in blood plasma is about 35 ng / ml, T_max in blood plasma 1-2 h. Bioavailability 76-85%. Food intake does not affect the bioavailability of drospirenone. It binds to plasma albumin and does not bind to sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin (CSG). The concentration of free drospirenone does not exceed 3-5% of the received dose.

Estradiol-induced increase in SHBG does not affect the binding of drospirenone to plasma proteins. The average apparent Vd is 3.7±1.2 l / kg. C_ss of drospirenone in blood plasma is reached between 7 and 14 days of treatment and is approximately 60 ng / ml. A further increase in the concentration is observed approximately between 1 and 6 cycles of use, and no subsequent increase in concentration is observed.

It is metabolized in the liver with almost no involvement of the cytochrome P450 system. Metabolites in blood plasma are mainly represented by acidic forms of drospirenone, formed as a result of lactic ring rupture, and 4,5-dihydro-drospirenone-3-sulfate.

It is almost completely metabolized. The metabolic clearance rate is 1.5±0.2 ml / min / kg. Metabolites are excreted through the intestines and kidneys in a ratio of 1.2: 1.4. T_1/2 of metabolites is about 40 hours.

When taken orally, ethinyl estradiol is rapidly and almost completely absorbed. After a single oral dose, C_max is 88-100 ng / ml, T_max 1-2 h. It is metabolized during absorption and during the” first pass ” through the liver.

Absolute oral bioavailability is 60%. Concomitant food intake reduces bioavailability in about 25% of volunteers. Binding to plasma proteins is about 98.5%. Ethinyl estradiol induces SHBG synthesis in the liver. The apparent Vd of ethinyl estradiol is about 5 l / kg. C_ss is achieved during the second half of the reception cycle.

Ethinyl estradiol in a small amount penetrates into breast milk (0.02% of the dose taken). About 50-60% of ethinyl estradiol undergoes presystemic conjugation in the mucosa of the small intestine and liver (the “first pass” effect).

The main pathway of metabolism is aromatic hydroxylation, resulting in the formation of hydroxylated and methylated metabolites, both free and in the form of conjugates with glucuronic and / or sulfuric acids. Part of the ethinyl estradiol conjugated with glucuronic acid is reabsorbed in the intestine after excretion with bile (enterohepatic recirculation).

It is completely metabolized (practically not excreted unchanged). The rate of metabolic clearance from blood plasma is 5 ml/min/kg. Metabolites of ethinyl estradiol are excreted by the kidneys and through the intestines in a ratio of 4: 6, T_1/2 is about 24 hours.

Indications

Contraception

Use during pregnancy and lactation

Contraindicated use during pregnancy and lactation (breastfeeding).

Contraindications

Thrombosis (venous and arterial) in the present or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders); state prior thrombosis (including transient ischemic attack, atrial fibrillation, angina) at present or in history; the presence of multiple or severe risk factors for venous or arterial thrombosis, including the complicated lesions of valvular apparatus of the heart, atrial fibrillation, vascular diseases of the brain or coronary arteries; uncontrolled hypertension, prolonged immobilization, body surgery surgery on the lower extremities, extensive trauma, Smoking at the age of 35 years, obesity with BMI more than 30 kg/m 2; hereditary or acquired predisposition for venous or arterial thrombosis, such as resistance to activated protein C (APS), a deficiency, antithrombin III deficiency protein C, protein S deficiency, hyperhomocysteinemia and the presence of antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant); migraine with focal neurological symptoms currently or in history; diabetes mellitus with diabetic angiopathy; liver failure and severe liver disease (up to normalization of the functional tests of the liver and for 3 months after the return of these parameters to normal); liver tumor (benign or malignant) at present or in history; severe or acute renal failure was diagnosed of hormone-dependent cancers (including genitalia or mammary glands) or suspicion of them; vaginal bleeding of unknown origin; pregnancy or suspicion of it; lactation (breastfeeding); pancreatitis with severe hypertriglyceridemia present or in the anamnesis; hypersensitivity to the components of the combination.

If any of the above diseases or conditions develop for the first time while using a drug containing this combination, then it should be immediately discontinued.

Caution

risk Factors for development of thrombosis and thromboembolism: Smoking, obesity with BMI less than 30 kg/m 2, dislipoproteinemia, controlled hypertension, migraine without focal neurologic symptoms, uncomplicated cardiac valve diseases of the heart, the presence of thrombosis and thromboembolism in family history (thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the next of kin); age over 35 years of non-Smoking women.

Diseases that may cause peripheral circulatory disorders: diabetes mellitus without vascular disorders, SLE, hemolytic-uremic syndrome, Crohn’s disease, ulcerative colitis, sickle cell anemia, superficial venous phlebitis.

Hereditary angioedema.

Hypertriglyceridemia;

Mild to moderate liver disease.

Jaundice and / or pruritus associated with cholestasis, cholelithiasis, otosclerosis with hearing loss, porphyria, a history of herpes simplex during pregnancy, Syndenham’s chorea, chloasma, and the postpartum period.

Side effects

From the immune system:  rarely – bronchial asthma, hypersensitivity reactions.

Nervous system disorders:  often – headache.

Mental disorders:  often – a depressive state; infrequently-a change in libido.

From the side of the hearing organ:  rarely-hearing loss.

From the cardiovascular system:  often-migraine; infrequently-increased blood pressure, decreased blood pressure; rarely-thromboembolism.

From the digestive system:  often – nausea; infrequently-vomiting, diarrhea.

Skin and subcutaneous tissue disorders:  infrequently – acne, eczema, pruritus; rarely-erythema nodosum, erythema multiforme.

From the side of the reproductive system and breast: often – menstrual disorders, acyclic bleeding, breast tenderness, hypersensitivity of the breast, leucorrhoea, candida vulvovaginitis; infrequently-breast enlargement, vaginitis; rarely-discharge from the mammary glands.

Other services: infrequently-fluid retention, changes in body weight.

Interaction

Long-term treatment with inducers of microsomal liver enzymes, which increases the clearance of sex hormones, may lead to a decrease in contraceptive effectiveness. These drugs include: phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine, rifampicin, rifabutin, topiramate, felbamate, griseofulvin and preparations containing St. John’s wort.

HIV protease inhibitors (ritonavir), non-nucleoside reverse transcriptase inhibitors (nevirapine) and their combinations also have the potential to affect hepatic metabolism.

Maximum enzyme induction is usually achieved approximately 10 days after starting these medications, but may persist for at least 4 weeks after they are discontinued.

When taking drugs that affect the induction of microsomal liver enzymes at the same time and within 28 days after their withdrawal, it is necessary to temporarily use a barrier method of contraception.

Contraceptive protection decreases against the background of taking penicillin and tetracycline antibiotics due to a decrease in the intrahepatic circulation of estrogens, and as a result, a decrease in the concentration of ethinyl estradiol. During the use of these antibiotics and for 7 days after their withdrawal, it is necessary to additionally use a barrier method of contraception.

Since the main metabolites of drospirenone in human plasma are formed without the participation of the cytochrome P450 system, inhibitors of this enzyme system do not affect the metabolism of drospirenone.

Oral combined estrogen-progestogen contraceptives can affect the metabolism of other drugs, which leads to an increase (cyclosporine), or a decrease (lamotrigine) in their concentration in plasma and tissues.

How to take, course of use and dosage

Take inside 1 time/day according to a special scheme.

Special instructions

Before starting the use of drugs containing this combination, pregnancy should be excluded and it is recommended to undergo a thorough general medical and gynecological examination, including breast examination and cytological examination of the cervix.

In addition, a violation of the blood coagulation system should be excluded. In case of long-term use, preventive control examinations should be performed at least once every 6 months.

A number of epidemiological studies have revealed an increase in the incidence of venous and arterial thrombosis and thromboembolism when taking COCs.

The greatest risk of developing these complications exists in the first year of taking the drug (especially in the first 3 months) or resuming taking it after a 4-week break. The use of any COC may be complicated by the development of venous thromboembolism (VTE), which manifests itself as deep vein thrombosis and pulmonary embolism.

The approximate incidence of VTE in women taking low-dose oral contraceptives (less than 50 micrograms of ethinyl estradiol) is up to 4 per 10,000 women per year, compared to 0.5-3 per 10,000 women who do not use oral contraceptives.

The risk of thrombosis (venous and/or arterial) and thromboembolism is increased: with age, Smoking (with increasing number of cigarettes smoked or the increasing age the risk further increases, especially in women older than 35 years), in the presence of a family history (i. e. venous or arterial thromboembolism ever in close relatives or parents at a relatively young age), obesity (BMI more than 30 kg/m 2); dyslipoproteinemia, hypertension, diseases of the heart valves, atrial fibrillation; prolonged immobilization; temporary immobilization, including travel for more than 4 h; major surgery; any operations on the lower extremities or extensive injuries in these situations, it is necessary to stop taking the drug; in the case of planned surgical intervention for 4 weeks prior to it and not to renew the appointment for 2 weeks after immobilization.

Peripheral circulatory disorders can also occur with diabetes mellitus, SLE, hemolytic-uremic syndrome, chronic inflammatory bowel diseases (Crohn’s disease or ulcerative colitis) and sickle cell anemia.

An increase in the frequency and severity of migraines during the use of COCs (which may precede cerebrovascular disorders) may be a reason for immediate discontinuation of these medications.

In rare cases, the development of liver tumors was observed against the background of the use of COCs. If there is severe abdominal pain, enlarged liver, or signs of intra-abdominal bleeding, this should be taken into account when making a differential diagnosis.

Recurrent cholestatic jaundice, which develops for the first time during pregnancy or during a previous intake of sex hormones, requires discontinuation of COCs.

Women with hypertriglyceridemia or a family history have an increased risk of developing pancreatitis while taking COCs.

Although a small increase in blood pressure has been reported in many women taking COCs, clinically significant increases have rarely been observed. The relationship between the use of COCs and clinically significant increase in blood pressure has not been established. However, if a persistent, clinically significant increase in blood pressure develops while taking COCs, discontinuation of the drug and treatment of arterial hypertension is necessary. The use of COCs can be continued after consulting a doctor, if blood pressure has returned to normal with the help of antihypertensive therapy.

Although COCs may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using COCs. However, women with diabetes should be carefully monitored while taking COCs.

Women with a tendency to chloasma should avoid prolonged exposure to the sun and UV radiation while taking COCs.

Due to its antimineralocorticoid activity, drospirenone increases plasma renin and aldosterone concentrations.

While taking COCs, the course of endogenous depression and epilepsy may worsen.

While taking COCs, irregular bleeding (spotting spotting or “breakthrough” bleeding) may occur, especially during the first months of use. Therefore, the assessment of any irregular bleeding is significant only after 3-4 months of contraception.

If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be performed to rule out malignancies or pregnancy.

Some women may not develop “withdrawal” bleeding during the pill break. If the COC was taken as directed, pregnancy is unlikely. However, if the use of COCs has been irregular before, or if there are no consecutive “withdrawal” bleeds, then pregnancy should be excluded before continuing to take the drug.

Active ingredient

Drospirenone, Ethinyl Estradiol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets