Byzantine - instructions for use, analogs, reviews and release forms (2 mg tablets) of a hormonal drug for the treatment of endometriosis in women, including during pregnancy and lactation. Composition

In this article, you can read the instructions for using the drug Byzanne. Comments of visitors of the site - consumers of this medication, as well as opinions of doctors of specialists on the use of Byzantine in their practice are presented. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Byzantine in the presence of existing structural analogues. Use for the treatment of endometriosis in women, including during pregnancy and lactation.Composition of the hormonal drug.

Byzanne - is a derivative of nortestosterone, characterized by antiandrogenic activity, which is approximately one third of the activity of cyproterone acetate. Dienogest (the active substance of the drug Byzanne) binds to the receptors of Progesterone in the human uterus, possessing only 10% of the relative affinity of progesterone. Despite the low affinity for the receptors of progesterone, dienogest is characterized by a powerful progestagen effect. Dienogest does not have significant mineralocorticoid or glucocorticoid activity in vivo.

Byzanne acts on endometriosis by suppressing the trophic effects of estrogens against eutopic and ectopic endometrium, due to decreased estrogen production in the ovaries and a decrease in their plasma concentration.

With prolonged use causes initial decidualization of endometrial tissue with subsequent atrophy of endometriotic foci. Additional properties of dienogest, such as immunological and anti-angiogenic effects, seem to contribute to its suppressive effects on cell proliferation.

There was no decrease in bone mineral density (BMD), as well as a significant effect of the drug Byzanne on standard laboratory parameters, including general and biochemical parameters of blood, hepatic enzymes, lipids and HbA1C. Byzanne moderately reduces the production of estrogens in the ovaries.

Composition

Dienogest (micronized) + auxiliary substances.

Pharmacokinetics

After oral administration, Byzanne is quickly and almost completely absorbed. Bioavailability is about 91%. Dienogest binds to serum albumin and does not bind to sex hormone binding globulin (SHBG), nor to corticosteroid-binding globulin (CSG). 10% of the total concentration of the substance in the serum is in the form of a free steroid, while about 90% is non-specifically associated with albumin. The pharmacokinetics of dienogest does not depend on the level of SHBG. Dienogest is almost completely metabolized mainly by hydroxylation with the formation of several practically inactive metabolites. Metabolites are excreted very quickly, so the predominant fraction in the blood plasma is unchanged dienogest.After ingestion at a dose of 0.1 mg / kg, dienogest is excreted as metabolites, which are released through the kidneys and intestines in a ratio of approximately 3: 1. After oral administration, approximately 86% of the received dose is excreted within 6 days, with the major part excreted within the first 24 hours, mainly by the kidneys.

Indications

• treatment of endometriosis.

Forms of release

Tablets 2 mg.

Instructions for use and dosing regimen

The drug is prescribed for 6 months. The decision on further therapy is taken by the doctor depending on the clinical picture.

You can start taking pills any day of the menstrual cycle. Take 1 tablet a day without interruption, preferably at the same time each day, if necessary, washed down with water or another liquid. Tablets should be taken continuously, regardless of bleeding from the vagina. After the completion of taking the tablets from one package begin taking the pills from the next, without taking a break in taking the drug.

When skipping pills and in the case of vomiting and / or diarrhea (if it occurs within 3-4 hours after taking the pill), the effectiveness of the drug Byzanne may be reduced.In case of missing one or more tablets, a woman should take 1 tablet as soon as she remembers it, and then the next day continue taking the pills at the usual time. Instead of a pill that is not absorbed due to vomiting or diarrhea, you should also drink 1 tablet.

Side effect

• bleeding from the vagina (including spotting, metrorrhagia, menorrhagia, irregular bleeding);
• headache;
• discomfort in the mammary glands;
• decreased mood;
• acne (pimples);
• anemia;
• increase in body weight;
• decreased body weight;
• increased appetite;
• migraine;
• low mood;
• sleep disturbance (including insomnia);
• nervousness;
• loss of libido;
• violation of attention;
• anxiety;
• depression;
• dry eyes;
• tinnitus;
• unspecified disorder of blood circulation;
• palpitation;
• arterial hypotension;
• dyspnea;
• nausea, vomiting;
• flatulence;
• diarrhea;
• constipation;
• discomfort in the abdomen;
• gingivitis;
• alopecia;
• dry skin;
• hyperhidrosis;
• onychoclasia;
• dandruff;
• dermatitis;
• back pain;
• pain in the bones;
• muscle spasms;
• pain in the limbs;
• feeling of heaviness in the limbs;
• ovarian cyst (including hemorrhagic cyst);
• candidiasis of the vagina;
• pelvic pain;
• atrophic vulvovaginitis;
• fibrocystic mastopathy;
• irritability;
• edema (including edema of the face).

Contraindications

• acute thrombophlebitis, venous thromboembolism at the present time;
• diseases of the heart and arteries, which are based on atherosclerotic vascular lesions (including IHD, myocardial infarction, stroke and transient ischemic attack) at present or in the anamnesis;
• diabetes mellitus with vascular complications;
• severe liver disease at present or in anamnesis (in the absence of normalization of functional liver samples);
• liver tumors (benign and malignant) at present or in the anamnesis;
• identified or suspected hormone-dependent malignant tumors, incl. mammary cancer;
• bleeding from the vagina of unknown origin;
• cholestatic jaundice of pregnant women in anamnesis;
• intolerance to galactose, deficiency of lactase, glucose-galactose malabsorption;
• children and adolescents under 18 years of age (efficacy and safety of use in adolescents not established);
• hypersensitivity to active substances or to any of the excipients.

Application in pregnancy and lactation

Data on the use of the drug Byzanne in pregnant women are limited. Data from studies in animals and data on the use of dienogest in women during pregnancy have not revealed a specific risk for pregnancy, fetal development, childbirth and child development after birth. The drug Byzanne should not be given to pregnant women due to the lack of the need for endometriosis treatment during pregnancy.

The use of the drug Byzanne during breastfeeding is not recommended, tk. Studies in animals indicate the isolation of dienogest with breast milk.

The decision to terminate breastfeeding or refuse to accept Bisanne is made based on an assessment of the relationship between the benefits of breastfeeding for a child and the benefits of treatment for a woman.

Application in elderly patients

Not applicable in postmenopausal women.

Use in children

Contraindicated in children and adolescents under 18 years (efficacy and safety of use in adolescents are not established).

special instructions

Before you start taking the drug, you need to exclude pregnancy. During the reception of the drug Byzanne, when contraception is needed, patients are advised to use non-hormonal contraceptive methods (eg, barrier).

Fertility

According to available data, during the reception of the drug Byzanne, most patients are suppressed ovulation. However, Byzantine is not a contraceptive.

According to available data, the physiological menstrual cycle is restored within 2 months after the discontinuation of the drug Byzanne.

The question of using the drug Byzanne in women with an ectopic pregnancy in history or with a violation of the function of the fallopian tubes should be decided only after a thorough assessment of the ratio of expected benefits and possible risks.

Since Byzantine is a preparation with only a progestational component, it can be assumed that special warnings and precautions when using other drugs of this type are also valid for the preparation of Byzanne, although not all of them have been confirmed in the course of clinical trials of the drug Byzanne.

In the presence or aggravation of any of the following conditions or risk factors, an individual assessment of the benefit-risk ratio should be undertaken before or during the start of the Bezanne drug.

Circulatory disorders

In the course of epidemiological studies, insufficient evidence has been obtained to confirm a link between the use of drugs with only a gestagen component and an increased risk of myocardial infarction or thromboembolism of cerebral vessels. The risk of cardiovascular episodes and disorders of cerebral circulation is more likely associated with an increase in age, arterial hypertension and smoking. The risk of stroke in women with arterial hypertension may slightly increase when taking drugs with only a progestational component.

Epidemiological studies indicate the possibility of a statistically insignificant increase in the risk of venous thromboembolism (deep vein thrombosis, pulmonary embolism) in connection with the use of drugs only with a gestagen component. The generally recognized risk factors for venous thromboembolism (VTE) include the corresponding family history (VTE in the brother,sisters or one of the parents at a relatively early age), age, obesity, prolonged immobilization, extensive surgery or massive trauma. In case of prolonged immobilization, it is recommended to stop taking the drug Byzanne (at the planned operation, at least four weeks before) and resume the use of the drug only two weeks after the complete recovery of motor ability.

An increased risk of thromboembolism in the postpartum period should be considered.

With the development or suspected development of arterial or venous thrombosis, the drug should be discontinued immediately.

Tumors

A meta-analysis of 54 epidemiological studies revealed a slight increase in the relative risk (RR = 1.24) of breast cancer in women who used oral contraceptives (PCs), primarily estrogen-progestogens, at the time of the study. This increased risk gradually disappears within 10 years after discontinuation of the use of combined oral contraceptives. Because breast cancer is rare in women younger than 40,a slight increase in the number of such diagnoses in women taking combined oral contraceptives at the moment or using combined oral contraceptives earlier is small relative to the overall risk of breast cancer. The risk of detecting breast cancer in women using hormonal contraceptives with only a progestational component may be similar in magnitude to the corresponding risk associated with the use of combined oral contraceptives. However, the facts relating to preparations with only a progestational component are based on much smaller populations of women using them and are therefore less convincing than data on combined oral contraceptives. Establish a causal relationship based on these studies is not possible. The revealed pattern of increased risk may be due to earlier diagnosis of breast cancer in women taking PC, biological effects of PC or a combination of both. Malignant breast tumors, which are diagnosed in women who have ever used a PC,are less pronounced than in women who have never used hormonal contraception.

In rare cases, against the background of the use of hormonal substances, similar to that contained in the preparation of Byzantine, benign, and even less often, malignant liver tumors were noted. In some cases, these tumors led to a life-threatening intra-abdominal bleeding. If the woman taking the drug Byzanne has severe pain in the upper abdomen, the liver is enlarged or there are signs of intra-abdominal bleeding, then in case of differential diagnosis, the probability of having a hepatic tumor should be taken into account.

Changing the nature of bleeding

In most women, taking the drug Byzanne affects the character of menstrual bleeding.

Against the background of the use of the drug Byzanne, uterine bleeding can increase, for example, in women with adenomyosis or uterine leiomyoma. Abundant and prolonged bleeding time can lead to anemia (in some cases, severe). In such cases, consideration should be given to the cancellation of the drug Byzanne.

Other states

Patients with a history of depression need careful monitoring. If depression recurs in serious form, the drug should be discontinued.

In general, Byzanne, apparently, does not affect BP in women with normal blood pressure. However, if against the background of taking the drug Byzanne there is persistent clinically significant arterial hypertension, it is recommended to cancel the drug and prescribe antihypertensive treatment.

In case of recurrence of cholestatic jaundice and / or cholestatic pruritus, which first appeared on the background of pregnancy or previous application of sex steroids, the drug Byzanne should be canceled.

Byzanne may have little effect on peripheral insulin resistance and glucose tolerance. Women suffering from diabetes, especially in the presence of diabetes mellitus pregnant in the anamnesis, during the reception of the drug Byzanne need careful monitoring.

In some cases, there may be a chloasma, especially in women with a history of pregnant women with chloasma. Women, prone to the development of chloasma, during the period of taking the drug Byzanne should avoid exposure to the sun or ultraviolet radiation.

During the application of the drug Byzanne, persistent ovarian follicles (often called functional ovarian cysts) may appear. Most of these follicles are asymptomatic, although some may be accompanied by pain in the pelvic region.

Lactose

In 1 tablet of the drug Byzanne contains 63 mg of lactose monohydrate. On a lactose-free diet, patients with rare hereditary disorders, such as galactose intolerance, lactase deficiency lapp or glucose-galactose malabsorption, should consider the amount of lactose contained in the Byzantine preparation.

Postmenopausal women

Not applicable in this category of patients.

Patients with renal insufficiency

There are no data indicating the need for dose adjustment in patients with kidney disease.

Medical examination

Before starting or resuming the use of the drug, Bezanne should thoroughly familiarize himself with the patient's medical history and conduct a physical and gynecological examination. The frequency and nature of such surveys should be based on existing norms of medical practice, with the necessary consideration of the individual characteristics of each patient (but notless than 1 time in 3-6 months) and should include measurement of blood pressure, assessment of the condition of the mammary glands, abdominal cavity and pelvic organs, including cytological examination of the cervical epithelium.

Impact on the ability to drive vehicles and manage mechanisms

As a rule, the drug Byzanne does not affect the ability to drive and work with mechanisms, but patients who are marked by attention deficit disorders should be careful.

Drug Interactions

Individual inducers or inhibitors of enzymes (isoenzyme CYP3A)

Gestagens, incl. dienogest, are metabolized predominantly with the participation of CYP3A4, located both in the intestinal mucosa and in the liver. Therefore, inducers or inhibitors of CYP3A4 can influence the metabolism of progestational drugs.

The increased clearance of sex hormones due to induction of enzymes can lead to a decrease in the therapeutic effect of the drug Byzanne, and also cause side effects, for example, a change in the character of uterine bleeding.

Reducing the clearance of sex hormones due to the inhibition of enzymes can increase the exposure of the dienogest and cause side effects.

Substances that can induce enzymes

Interactions may occur with drugs that induce microsomal enzymes (for example, cytochrome P450 systems), resulting in increased clearance of sex hormones (such drugs include phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate , nevirapine, griseofulvin, as well as preparations containing St. John's wort).

The maximum induction of enzymes is usually observed not earlier than in 2-3 weeks, but can then persist for at least 4 weeks after discontinuation of therapy.

The effect of the inducer CYP3A4 rifampicin was studied in healthy postmenopausal women. With the simultaneous administration of rifampicin with estradiol valerate / dienogest, there was a significant decrease in the equilibrium concentration and systemic exposure of the dienogest. Systemic exposure of dienogest at equilibrium concentration, determined by the value of AUC (0-24 h), was reduced by 83%.

Substances that can inhibit enzymes

Known CYP3A4 inhibitors, such as azole antifungal agents (eg, ketoconazole, itraconazole, fluconazole), cimetidine, verapamil,macrolides (eg erythromycin, Clarithromycin and roxithromycin), diltiazem, protease inhibitors (eg, ritonavir, saquinavir, indinavir, nelfinavir), antidepressants (for example, nefazodone, fluvoxamine, fluoxetine) and grapefruit juice, can increase the concentration of progestogens in the blood plasma and cause side effects.

Influence of dienogest on other medicinal substances

Based on data from in vitro inhibition studies, the clinically significant interaction between the preparation of Byzanne and the mediated enzymes of the cytochrome P450 system by the metabolism of other drugs is unlikely.

Note: for the identification of possible interactions, you should read the instructions for concomitant medications.

Interaction with food products

Food intake with a high fat content did not affect the bioavailability of the drug Byzanne.

Other types of interaction

The use of gestagens can influence the results of some laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney functions, plasma concentrations of proteins (carriers), for example, lipid / lipoprotein fractions, parameters of carbohydrate metabolism and coagulation parameters.

Analogues of the drug Byzanne

The medicine has no structural analogs for the active substance.

Analogues on the curative effect (remedies for the treatment of endometriosis):

• Buserelin;
• Buserelin depot;
• Buserelin Long FS;
• Vero Danazol;
• Danoval;
• Dianodiol;
• Danol;
• Decapeptil;
• Decapeptil depot;
• Derinat;
• Diferelin;
• Duphaston;
• Zoladex;
• Indinol;
• Lucrin Depot;
• Nemestran;
• Norkolut;
• Omnadren 250;
• Organometr;
• Prim is Nor;
• The prostate;
• Epigallate.

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