Visan

Visanne is a hormonal substance (progestogen) and a medicine used for diseases affecting the genital area. The active ingredient of the medicine is dienogest.

Dienogest is a derivative of nortestosterone, which exhibits a strong antiandrogenic effect. In general, this element accounts for 1/3 of the total activity of the cyproterone acetate component. Dienogest is able to influence endometriosis by reducing the internal production of estradiol. As a result, the trophic effect of estradiol on the endometrium is inhibited. [ 1 ]

Indications Visan

It is used in the treatment of endometriosis.

Release form

The drug is released in tablets - 14 pieces inside a cell plate. Inside the box - 2 such plates.

Pharmacodynamics

With continuous administration of dienogest, it creates a hypergestagenic and hypoestrogenic environment, in which decidualization of endometrial tissues first occurs, and later atrophy of areas affected by endometriosis occurs.

Dienogest is capable of synthesizing with progesterone endings located inside the uterus, but has only a 10% relative affinity. Although the active element of the drug has a weak affinity for progesterone endings, it has a powerful progestogenic effect in vivo. [ 2 ]

The drug has no significant mineralocorticoid, androgenic or GCS effects in vivo. Other effects, including antiangiogenic and immunological, help to slow down dienogest's effect on cell proliferation. [ 3 ]

Pharmacokinetics

Absorption.

When administered orally, dienogest is fully and rapidly absorbed. Serum Cmax values are observed after 90 minutes of single administration and are equal to 47 ng/ml. The bioavailability values of the drug are approximately 91%. The pharmacokinetic characteristics of dienogest are tied to the portion size in the dosage range of 1-8 mg.

Distribution processes.

Dienogest is synthesized with albumin, but not with globulin that synthesizes SHBG or with globulin that synthesizes GCS (GOK). Only 10% of the total dienogest values in the blood serum are in the form of free steroids, and 90% of the substance is non-specifically synthesized with albumin. The apparent distribution volume of the drug is 40 liters.

Exchange processes.

Dienogest is fully involved in metabolic processes – through steroid metabolism with the formation of metabolic elements that generally do not have endocrinological activity. In vitro and in vivo testing, CYP3A4 is the main enzyme involved in dienogest metabolic processes. Such metabolic elements are excreted from the plasma at a very high rate, leaving unchanged dienogest as the dominant intraplasmic metabolite.

The rate of intra-serum clearance is 64 ml per minute.

Excretion.

Intra-serum levels of dienogest decrease in 2 stages, with a half-life of 9-10 hours. Dienogest is excreted as metabolic components in urine and faeces (in a 3:1 ratio) after administration of a 0.1 mg/kg dose.

The half-life of metabolic components in urine is approximately 14 hours. After taking the drug, 86% of the dose is excreted within 6 days, with most of it being excreted within the first 24 hours, mainly in urine.

Dosing and administration

The medication should be taken once a day, at the same time of day. It is allowed to start using it on any day of the woman's menstrual cycle. There is no need to take a break between new packs of the medicine, use continues without any intervals, and without reference to the menstrual cycle.

If a tablet is missed or if the patient experiences diarrhea or vomiting, the effectiveness of the medication may be reduced.

If you miss a dose, take the pill as soon as possible and take a new one at its usual time. The dose cannot be increased; it is left unchanged. The same regimen is followed if you miss a dose due to diarrhea or vomiting.

• Application for children

The medication is not used for prescribing to girls who have not yet started their first menstruation.

Use Visan during pregnancy

Visanne is not used during pregnancy, because endometriosis therapy is not required during this period. However, pregnancy must be ruled out before the start of the treatment course.

If you need to take medication while breastfeeding, you should stop breastfeeding for the duration of therapy.

Contraindications

Main contraindications:

• severe intolerance associated with elements of the drug;
• venous thromboembolism;
• diseases of cardiovascular or arterial nature (including cardiac ischemia, myocardial infarction and cerebrovascular pathologies);
• diabetes mellitus, which is accompanied by vascular diseases;
• severe stages of liver diseases (this includes neoplasms of any etiology);
• neoplasms, the development of which is associated with gonadosteroids;
• vaginal bleeding of unknown origin;
• lactose intolerance.

When using the medication, you need to use barrier contraception, because during the specified period it is prohibited to take hormonal contraceptives.

Side effects Visan

When administering the drug, some side effects may be observed (especially during the first months of the course). During therapy, these disorders disappear. Among the noted manifestations: discomfort in the mammary glands, acne, headaches and depression.

If other negative symptoms develop while using Visanne, you should consult your doctor regarding a possible change in your treatment regimen.

Interactions with other drugs

Effects of other drugs relative to Visanne.

Progestogens, including dienogest, participate in metabolic processes mainly through the structure of the hemoprotein P450 ZA4 (CYP3A4), which is located inside the liver and intestinal mucosa. Because of this, agents that induce or slow down the action of CYP3A4 can affect the metabolic processes of progestogen. An increase in the level of gonadosteroid clearance due to enzyme induction can weaken the therapeutic activity of Visanne and cause the appearance of negative symptoms (for example, a change in the nature of menstrual bleeding).

A decrease in gonadosteroid clearance rates due to enzyme inhibition may reduce the therapeutic effect of the drug and cause the appearance of side effects.

Elements that increase the clearance of gonadosteroids (weakening the effect through enzyme induction).

These include barbiturates with carbamazepine, phenytoin, rifampicin and primidone, and in addition, possibly felbamate and oxcarbazepine with griseofulvin and topiramate, as well as substances containing St. John's wort.

Enzyme induction may be observed after several days of treatment. Maximum enzymatic induction develops after several weeks. Enzymatic induction may last up to 1 month after the end of treatment.

The effect of rifampicin (an inducer of CYP 3A4 action) was studied in healthy postmenopausal women. Co-administration of rifampicin with dienogest/estradiol valerate tablets resulted in a significant decrease in the steady-state values and systemic exposure to estradiol with dienogest. The overall effect of estradiol and dienogest (at steady-state values calculated from AUC (0-24 h)) was reduced by 44% and 83%.

Medicines that have different effects on the level of gonadosteroid clearance.

The combined use of gonadosteroids and a large number of combinations of HIV protease inhibitors and non-nucleoside type inhibitors of reverse transcriptase activity, together with combinations of hepatitis C virus inhibitors, may decrease or increase plasma progestin levels. The combined effect of these changes may be clinically significant in certain situations.

Medicines that reduce the level of gonadosteroid clearance (enzyme inhibitors).

Dienogest is a substrate of the hemoprotein P450 (CYP) 3A4. Administration together with strong inhibitors of the CYP3A4 component may increase the plasma level of the substance.

Use in combination with ketoconazole, a potent inhibitor of the CYP3A4 enzyme, causes an increase in dienogest AUC values (0-24 hour range) by 2.9 times at steady state.

Combination with erythromycin (moderate inhibitor) caused an increase in dienogest AUC (0-24 hours) by 1.6 times at steady state values.

Laboratory tests.

Progestogen use may alter the results of certain laboratory tests, including liver or thyroid biochemistry, renal and adrenal function, plasma protein (carrier) values (including, for example, GOC and lipoprotein/lipid fractions), fibrinolysis and coagulation values, and carbohydrate metabolism properties. Such changes are often within laboratory normal limits.

Storage conditions

Visanne should be stored in a place closed to small children. Temperature indicators - no more than 30°C.

Shelf life

Visanne can be used for a period of 5 years from the date of manufacture of the pharmaceutical product.

Analogues

Analogues of the drug are the following medications: Sofiti, Zhastinda with Denovel 30, Yulidora and Klimodien with Dinoret, and also Luvina, Janine, Silhouette with Klayra and Naadin.