Dietycline - instructions for use, dose, side effects, contraindications

Composition of the tablet shell: opaglos 2 transparent 0.50 mg (carmellose sodium 270.80 μg maltodextrin 104.00 μg dextrose monohydrate 84.70 μg soy lecithin 30,50 μg sodium citrate dihydrate 10.00 μg).

Description:Round, biconvex tablets of white color. View on the cut: white or almost white tablets.

Pharmacotherapeutic group:Contraceptive combination (estrogen-gestagen).

ATX: & nbsp

G.03.A.A.16 Dienogest and ethinyl estradiol

Pharmacodynamics:

Dietycline® is a low-dose monophasic oral hormonal contraceptive. The contraceptive effect is based on the interaction of various factors, the most important of which is the inhibition of ovulation and a change in the viscosity of cervical mucus, as a result of which it becomes impenetrable for spermatozoa, the penetration of spermatozoa through the cervical canal is difficult. When used correctly, Perl's index (the indicator reflecting the number of pregnancies in 100 women who use the contraceptive during the year) is less than 1. When missing tablets or improperly used, the Pearl index may increase.

In addition to the contraceptive effect, it also has other concomitant positive properties. In women taking combined oral contraceptives, the cycle becomes more regular, the soreness, intensity and duration of menstrual bleeding decrease, which reduces the risk of iron deficiency anemia. There is also evidence of a reduced risk of endometrial and ovarian cancer.

The progestogen component of the drug dienogast is an active progestogen, is a derivative of nortestosterone with antiandrogenic activity and has a positive effect on the lipid profile, increasing the concentration of high-density lipoprotein (HDL).

Pharmacokinetics:

Ethinylestradiol

Suction: When ingested quickly and completely absorbed. The maximum concentration of estradiol in blood plasma (about 67 pg / ml) is achieved after 1.5-4 h. After absorption and the effect of "first passage" through the liver, ethinyl estradiol metabolized, its absolute bioavailability when administered orally is about 44%.

Distribution: Ethinylestradiol is largely associated with serum albumin (approximately 98%) and induces the synthesis of globulin, the hormone-binding hormone (SHGG), in the blood plasma. The volume of ethinyl estradiol distribution is about 2.8-8.6 l / kg.

Metabolism: Ethinylestradiol is subjected to presystemic conjugation both in the mucosa of the small intestine and in the liver. The main pathway of metabolism is aromatic hydroxylation with the formation of many hydroxylated and methylated derivatives in the form of free metabolites, metabolites of glucuronides and sulfates.The clearance rate from plasma is approximately 2.3-7 ml / min / kg.

Excretion from the body: Up to 30-50% of metabolites of ethinyl estradiol are excreted by the kidneys, 30-40% through the intestine. The half-life of estradiol (T1 / 2) does not exceed 10 hours after a single dose of 1 tablet and rises to 15 hours after 3 cycles of the drug.

The equilibrium concentration ethinyl estradiol in blood plasma with regular intake

is achieved in the second half of the cyclic administration of the drug

Dienogest

Suction: When ingested quickly and almost completely absorbed. The maximum concentration of dienogest in the blood serum (about 51 pg / ml) is achieved after 2.5 hours. The absolute bioavailability of the dienogest is 96%, the equilibrium concentration in blood plasma at constant reception is achieved after 4 days.

Distribution: 90% of the total concentration of dienogest in the blood plasma binds to serum albumin, but does not bind to SHBG, or corticosteroid-binding globulin. In unrelated form is 10% of the total concentration of dienogest in blood plasma. The volume of distribution of dienogest is about 37-45 liters.

Metabolism: Metabolized mainly by hydroxylation, but also by hydrogenation, conjugation and aromatization with the formation of inactive metabolites. After taking a single dose, the total clearance of the dienogest is about 3.6 l / h.

Excretion: After taking a dose of 0.1 mg / kg, the ratio of excretion of dienogest in the form of metabolites by the kidneys and through the intestine is 3: 1. Only a small amount of unchanged dienogest is excreted by the kidneys. The half-life period (T1 / 2) of dienogest is approximately 8.5-10.8 hours. After oral intake, 86% of the dose of dienogast taken is withdrawn within 6 days; a significant part of it is excreted in the first 24 hours after admission, mainly by the kidneys.

Equilibrium concentration. Induction with ethinylestradiol synthesis of globulin does not affect the pharmacokinetics of dienogest. With daily use of the drug, the concentration of dienogest in the serum increases by 1.5 times.

Indications:

Oral contraception.

Treatment of mild to moderate acne and seborrhea.

Contraindications:

- hypersensitivity to any of the components of the drug;

- thrombosis (venous and arterial) and thromboembolism now or in the anamnesis (including, deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke,cerebrovascular disorders);

- conditions preceding thrombosis (including, transient ischemic attacks, angina pectoris) at present or in the anamnesis;

- Multiple or expressed risk factors for venous or arterial thrombosis, including complicated heart valve disease, atrial fibrillation, cerebrovascular or coronary artery disease; uncontrolled arterial hypertension, voluminous surgical intervention with prolonged immobilization, smoking over the age of 35, obesity with a body mass index> 30 kg / m2;

- diabetes mellitus with diabetic angiopathy;

- identified predisposition to venous or arterial thrombosis, including resistance to activated protein C, deficiency of antithrombin III, deficiency of protein C, deficiency of protein S, hyperhomocysteinemia, antibodies to phospholipids, lupus antigen;

- severe liver disease (before the restoration and normalization of laboratory indicators of liver function);

- Benign or malignant tumors of the liver, incl. in the anamnesis;

- severe forms of arterial hypertension with blood pressure> 160/100 mm Hg;

- identified hormone-dependent malignant diseases of genital organs or mammary glands or suspected of them, incl. in the anamnesis;

- bleeding from the vagina of unknown origin;

- Migraine with focal neurologic symptoms at present or in the anamnesis;

- Pancreatitis accompanied by severe hypertriglyceridemia at present or in anamnesis;

- severe and / or acute renal failure;

- pregnancy or suspected of it;

- lactation period;

- hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome, or hypersensitivity to peanuts or soybeans (due to the presence of lactose and soy lecithin in the formulation);

Carefully:

Risk factors for thrombosis and thromboembolism: obesity, smoking, dyslipoproteinemia, arterial hypertension, migraine without focal neurological symptoms, heart valve defects, prolonged immobilization, serious surgery, extensive trauma, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident in young age at any of the next of kin).

Other diseases in which peripheral circulation disorders may occur include: diabetes mellitus without diabetic angiopathy, surface venous phlebitis, systemic lupus erythematosus (SLE), hemolytic-uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia.

Diseases that first appeared or worsened during pregnancy or against the background of previous reception of sex hormones, such as jaundice and / or pruritus against cholestasis, gall bladder disease, porphyria, Sydenham's chorea, history of herpes during pregnancy, hearing loss (associated with otosclerosis ).

Endogenous depression, epilepsy; hereditary angioedema; hypertriglyceridemia; liver disease; the postpartum period.

Pregnancy and lactation:The drug is contraindicated during pregnancy. If pregnancy is detected, stop taking oral contraceptives immediately. If it is necessary to use the drug during lactation, it is necessary to solve the problem of stopping breastfeeding.

Dosing and Administration:Inside, daily, preferably at the same time, in the order indicated on the package, with a small amount of water. Take 1 tablet a day continuously for 21 days.The taking of tablets from each next package begins after a 7-day break, during which bleeding "cancellation" (menstrual-like bleeding) is observed. It usually starts 2-3 days after taking the last pill and may continue until the pill is taken from the new package. In the absence of taking any hormonal contraceptives in the previous month, the drug begins on the first day of the menstrual cycle (on the first day of menstrual bleeding). It is acceptable to start taking the menstrual cycle for 2-5 days, 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. When changing from the preceding reception of other combined oral contraceptives preferably taking this medication on the day after the last active tablet from the previous package, but not later than the day after the usual 7-day free interval (for formulations containing 21 tablet) or after the last inactive tablets (for preparations containing 28 tablets in a package).

When moving from the vaginal ring, the transdermal patch, it is preferable to start taking the drug on the day of removal of the ring or patch, but no later than the day when a new ring is to be inserted or a new patch is stuck.

When switching from contraceptives containing only gestagens ("mini-pili", injection forms, implant), the drug is taken: from the "mini-pili" - any day (without interruption), from the implant - on the day of its removal, from the injection form -when the next injection was to be made. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets.

After abortion in the first trimester of pregnancy, you can start taking it immediately. If this condition is met, there is no need for additional contraceptive protection.

After childbirth or abortion in the second trimester of pregnancy, it is recommended to start taking the drug on days 21-28 after giving birth or abortion. If the intake 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 has already lived a sexual life, pregnancy should be excluded before the beginning of taking medications or it is necessary to wait for the first menstruation.

Recommendations in case of irregular intake of the drug

In case of admission to the drug, if the delay in taking the tablet is less than 12 hours, the contraceptive protection is not reduced. It is necessary to take the pill as soon as possible, the next tablet is taken at the usual time. If the delay in taking the tablet is more than 12 hours, the contraceptive protection may be reduced. In the first 2 weeks of taking the drug, if the interval from the last tablet is more than 36 hours: the last missed tablet should be taken as soon as possible (even if it means taking 2 tablets at a time ). The next tablet is taken at the usual time. In addition, a barrier method of contraception (condom) should be used for the next 7 days. If there was a sexual intercourse within 1 week before passing the pill, it is necessary to take into account the probability of pregnancy. The more pills are missed and the closer this pass to the 7-day break in taking the drug, the higher the risk of pregnancy. At the 3rd week of taking the drug, if the interval from the time of taking the last tablet is more than 36 hours: it is necessary to take the last missed tablet as soon as possible (even if it means taking 2 tablets simultaneously).The next tablet is taken at the usual time. In addition, a barrier method of contraception (condom) should be used for the next 7 days. In addition, taking a pill from a new package should be started as soon as the current package is finished, i. E. without a break Most likely, bleeding "cancellation" will not be until the end of taking the tablets from the second package, but there may be "smearing" discharge or uterine bleeding "breakthrough" on the days of taking the tablets.

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

In case of gastrointestinal disorders:

If a woman has vomiting or diarrhea within 3 to 4 hours after taking the drug, absorption may be incomplete. In this case it is necessary to be guided by the recommendations concerning the admission of the tablet. If a woman does not want to change the normal mode of taking the drug, she must take an extra pill from the spare package if necessary.

Change in the day of menstrual bleeding

To delay the onset of menstrual bleeding it is necessary to continue taking the tablets from the new package immediately after all the pills from the previous one have been taken,without a break in admission. Tablets from a new package can be taken until the packaging is finished. Against the background of taking the drug from the second package, a woman may have "spotting" discharge or uterine bleeding "breakthrough". Resume the drug from the new pack should be after an ordinary 7-day break.

In order to transfer the day of the onset of menstrual bleeding to another day of the week, it is necessary to shorten the nearest break in taking the tablets for as many days as the day of menstrual bleeding should be rescheduled. The shorter the interval, the higher the risk of no bleeding of the "cancellation" and the appearance in future of "smearing" excretions and bleeding of the "breakthrough" during the taking of the tablets from the second package (as well as in the case of a delay in the onset of menstrual bleeding).

Side effects:

To determine the incidence of side effects of the drug used

the following classification:

Often (> 1/10)

Often (> 1/100 and <1/10)

Infrequently (> 1/1000 and <1/100)

Rarely (>1/10 000 and <1/1000)

Rarely (> 1/10 000).

System of organs	Frequency of occurrence of undesirable phenomena
System of organs	Often	Infrequently	Rarely	Frequency unknown
Disturbances from the nervous system	Headache	Migraine, dizziness	Ischemic stroke, cerebrovascular disorders, dystonia, irritability
Mental disorders		Decreased Mood	Depression, Mental violations, insomnia, sleep disturbance, aggression,	Change mood, decline libido, rise libido
Disturbances on the part of the organ of sight			Dry eye mucosa, irritation	Intolerance of contact
			mucous membrane of the eye, oscilloscopy, visual impairment,	lenses
Hearing disorders			Sudden hearing loss, tinnitus, hearing loss
Infringements from cardiovascular systems		Increase or decrease in blood pressure	Tachycardia, impaired heart function Thrombophlebitis, thrombosis / pulmonary embolism, orgostatic dystonia, blood tides, varicose veins, pain along the veins
Violations of the blood and lymphatic system			Anemia
Disturbances from the respiratory system, chest and mediastinal organs			Bronchial asthma, hyperventilation lungs
Disorders from the gastrointestinal tract		Abdominal pain, discomfort in belly, swelling abdomen, nausea, vomiting, diarrhea	Gastritis, enteritis
Infringements from skin and subcutaneous fabrics		Acne, alopecia, rash, including macule; itching, including generalized	Allergic dermatitis, neurodermatitis, eczema, psoriasis, hyperhidrosis, chloasma, pigmentation disorder / hyperpigmentation, seborrhea, dandruff, hirsutism, skin diseases, cellulitis, "vascular" asterisks	Hives, erythema nodosum, erythema multiforme
Infringements from support- impellent apparatus and connective tissue			Backache, discomfort in muscles and bones, myalgia, pain in limbs
Infringements from reproductive system and dairy glands	Painful- or pain in dairy glands, roughing dairy glands	Change duration and volume menstrual-like bleeding, including menorrhagia, hypomenorrhoea, oligomenorrhoea and amenorrhea; Acyclic bleeding, including, bleeding from the vagina and metrorrhagia; increase in size mammary glands, swelling and mummification of the mammary glands; Swelling of the mammary glands; Dimenorrhea, discharge from the genital tract / discharge from the vagina, ovarian cysts	Cysts of milk glaucoma, fibro- cystic mastopathy, dyspareunia.	Allocations from dairy glands
From the endocrine system			Virilism
From the immune system			Allergic reactions
Metabolism		Increased appetite	Anorexia
Benign and malignant tumors			Myoma of the uterus, breast lipoma
Infectious and parasitic diseases		Vaginitis / vulvovaginitis, vaginal candidiasis or others fungal vulvovaginLinear infection	Salpingoophoritis, urinary tract infection, cystitis, mastitis, cervicitis, fungal infection, candidiasis, herpetic defeat oral cavity, influenza, bronchitis, sinusitis, infection of the upper respiratory ways, viral infection
General disorders		Increased fatigue, asthenia, bad well-being, change body weight	Pain in the chest, peripheral edema, influenza-like state, rise body temperature
results laboratory surveys			Increase concentrations triglycerides in blood, hypercholesterolemianemia

In women with congenital angioneurotic edema, estrogens can induce or aggravate the symptoms of angioedema.

Overdose:

Possible symptoms of drug overdose: nausea, vomiting, irregular bloody discharge, absence of menstrual bleeding. If necessary, symptomatic therapy is performed.

Interaction:

Some drugs can increase the rate of metabolic clearance of sex hormones and lead to severe bleeding or a decrease in the contraceptive effect of the drug. Similar effects are typical for drugs inducing microsomal enzymes of the liver: hydantoin, barbiturates, primidon, carbamazepine and rifampicin. There are also suggestions for rifabutin, efavirenz, nevirapine, oxcarbazepine, topiramate, felbamate, ritonavir, nelvinaphyr, griseofulvin, and also medicines containing St. John's wort (Hypericum perforatum).

Some antibiotics that reduce the intestinal hepatic circulation of estrogens (such as ampicillin or tetracycline), reduce the effectiveness of combined oral contraceptives.

Women taking short courses (maximum 1 week) of the above medicines should resort to additional contraceptive measures (for example, the barrier method) during the simultaneous use of drugs and in the next 7 days.

When using oral contraceptives with reefs, the use of additional contraceptive measures (for example, the barrier method) should be resorted to during the simultaneous use of drugs and in the next 4 weeks after discontinuation of treatment. If the package of oral contraceptives ends before the completion of the course of use of other drugs, the tablets from the next package of the drug should be taken without interruption.

It is necessary to increase the dose of contraceptives with a long-term course of treatment with drugs that induce microsomal enzymes of the liver. In case of side effects (eg, irregular menstruation) or inefficiency of the drug, other non-hormonal contraceptives should be used additionally. Oral contraceptives can affect the metabolism of some other drugs. Accordingly, this can lead to an increase (ciclosporin) or decrease (lamotrigine) of their concentration in plasma or tissues.

Dienogest is the substrate of cytochrome P450 (CYP3A4). Known inhibitors of CYP3A4, such as antifungal agents (eg, ketoconazole), cimetidine, verapamil, macrolides (for example, erythromycin), diltiazem, antidepressants and grapefruit juice, can increase the concentration of dienogest in the blood plasma.

Special instructions:

Irregular reception can lead to acyclic bleeding and reduce the contraceptive effectiveness of the drug.

Before starting or resuming the use of the drug, it is recommended to conduct a thorough general medical and gynecological examination (including breast examination and cytology of cervical scraping), to exclude pregnancy. In addition, violations of the blood coagulation system should be avoided. When using the drug, it is necessary to conduct preventive check-ups at least once every 6 months.

The drug does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Diseases of the cardiovascular system

Possible occurrence of venous thromboembolism (VTE) in the form of deep vein thrombosis and / or pulmonary embolism with the use of hormonal contraceptives. The approximate frequency of VTE in women taking oral contraceptives with a low estrogen dose (less than 50 μg 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. However, the frequency of VTE developing with combined oral contraceptives is less than the frequency of VTE associated with pregnancy (6 per 10,000 pregnant women per year).

Women who take combined oral contraceptives describe extremely rare cases of thrombosis of other blood vessels, for example, liver, mesenteric, renal arteries and veins or veins and arteries of the retina. The relationship of these cases with the use of combined oral contraceptives has not been proven. A woman should stop taking the drug and consult a doctor if symptoms of venous or arterial thrombosis develop, which may include unilateral pain in the lower limb and / or swelling; sudden severe pain in the chest; with irradiation or without in the left hand; sudden shortness of breath; sudden coughing attacks; any unusual, strong,prolonged headache; increased frequency and severity of migraine; sudden partial or complete loss of vision; Diplomacy; slurred speech or aphasia; dizziness; collapse with or without partial seizure; weakness or very significant loss of sensitivity, suddenly appeared on one side or in one part of the body; motor disorders; "sharp" abdomen.

The risk of thrombosis (venous and / or arterial) and thromboembolism increases: with age, smokers (with an increase in the number of smoked cigarettes or an increase in age, the risk further increases, especially in women older than 35 years), with a family history (ie, venous or arterial thromboembolism ever at close relatives or parents at a relatively young age), obesity of dyslipoproteinemia, arterial hypertension, heart valve disease, prolonged immobilization, extensive surgical intervention, any operation on the lower extremities or extensive trauma, atrial fibrillation. With prolonged immobilization, in case of serious surgical intervention, any foot surgery or extensive trauma, it is desirable to stop the use of the drug (in the case of a planned operation, at least,for 4 weeks before it) and not to resume reception within 2 weeks after the end of immobilization. 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.

Disturbances of microcirculation can also occur in diabetes mellitus, SLE, hemolytic-uremic syndrome, Crohn's disease, ulcerative colitis and sickle-cell anemia.

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 long-term use of combined oral contraceptives. However, the association with the use of combined oral contraceptives has not been proven. The possibility of interrelation of these data with screening of diseases of the cervix uteri and with the peculiarities of sexual behavior (a rare use 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 taking combined oral contraceptives now (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, the increase in the number of diagnoses of breast cancer in women taking combined oral contraceptives now or recently, is insignificant in relation to the overall risk of this disease. The relationship between the development of breast cancer and the use of combined oral contraceptives 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 combined oral contraceptives. Women who have ever used combined oral contraceptives are diagnosed with earlier stages of breast cancer than women who have never used them.

In rare cases, combined with the use of combined oral contraceptives, development of benign,and in extremely rare - malignant liver tumors, which in some cases led to life-threatening intraabdominal hemorrhage. In the event 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

Women with hypertriglyceridemia or family history may have an increased risk of developing pancreatitis when taking combined oral contraceptives.

Although a small increase in blood pressure (BP) has been reported in many women taking combined oral contraceptives, clinically significant increases were rare. The relationship between taking combined oral contraceptives and increasing blood pressure is not established. However, if persistent, clinically significant arterial hypertension develops during their administration, it is advisable to cancel combined oral contraceptives and treat hypertension. Reception of combined oral contraceptives can be continued if normal blood pressure values are achieved with the help of antihypertensive therapy.

Effects on the menstrual cycle

Against the background of the use of combined oral contraceptives, irregular (acyclic) bleeding ("spotting" bleeding or "breakthrough" bleeding) can occur, 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 reception of combined oral contraceptives was carried out in accordance with the instructions, then pregnancy is unlikely. However, if before the reception of combined oral contraceptives was conducted irregularly, or if there are no consecutive two bleeding "cancellations", then the continuation of the drug should be excluded from pregnancy.

Impact on laboratory test scores

The use of oral combination therapies may affect the results of somelaboratory tests, including biochemical blood tests (liver, thyroid, kidney and adrenal function, transport protein concentrations in plasma (such as SHBG), carbohydrate metabolism, lipid / lipoprotein fractions), and coagulation and fibrinolysis parameters. Nevertheless, the changes in these indicators remain within the framework of normal values.

Effect on the ability to drive transp. cf. and fur:Data on the negative effect of Dietecylen® on the ability to drive vehicles and engage in potentially dangerous activities that require increased concentration and speed of psychomotor reactions are not.

Form release / dosage:Tablets, film-coated 2.0 mg + 0.03 mg.

Packaging:For 21 tablets are placed in A1 / PVC / P VDH blister. For 1 or 3 blisters are placed in a cardboard box together with instructions for medical use.

Storage conditions:At a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001494

Date of registration:10.02.2012

Date of cancellation:2017-02-10

The owner of the registration certificate:BBC FARMA BV BBC FARMA BV Netherlands

Manufacturer: & nbsp

Laboratorios LEON FARMA, S.A. Spain

Representation: & nbspBBC FARMA BV BBC FARMA BV Netherlands

Information update date: & nbsp30.01.2016

Illustrated instructions

Instructions

Dicycylene® (Dieciklen®)