Local treatment, vaginal dryness in women, menopause with atrophy, vaginal

BLISSEL 50 micrograms / g, vaginal gel is a drug-based estrogen alone used vaginally

It must be inserted into the vagina using a dosing applicator according to the instructions in the package leaflet

One dose of applicator (filled applicator up to the ring used as a marker) contains 1 g of vaginal gel, ie 50 micrograms of estriol.
To initiate and continue treatment of postmenopausal symptoms, this drug should be prescribed at the lowest effective dose for the shortest possible period of time (see also Warnings and Precautions for Use)

Initial treatment: one dose of applicator per day for 3 weeks (preferably at bedtime).
For maintenance treatment, it is advisable to prescribe an applicator dose twice a week (preferably at bedtime). Continuation of treatment should be reconsidered by the doctor after 12 weeks of treatment.

If the patient has forgotten to apply a dose, the forgotten dose should be applied as soon as possible within 12 hours of the usual time of application. After 12 hours, the forgotten dose should not be applied and the patient should continue the usual dosage regimen.
Gel homogeneous, colorless, clear, slightly translucent

Class: Pharmacotherapeutic: Estrogens, Code: ATC: G03CA04

BLISSEL 50 micrograms / g vaginal gel contains synthetic estriol, which is chemically and biologically identical to human estriol. Estriol exerts its biological and pharmacological effects by acting on estrogen receptors (ER). It has a relatively high binding affinity for estrogen receptors (ER) present in vaginal and bladder tissues, and a relatively low binding affinity for those present in mammary and endometrial tissues. Thus, estriol binding to endometrial estrogen receptors is not strong enough to cause true proliferation with a single daily administration of estriol, while its binding to estrogen vaginal receptors is sufficient to To exercise a trophic effect, maximal vaginal by using only a very small dose of estriol.
Estriol may be used in the treatment of vaginal conditions and symptoms (vaginal dryness, itching, discomfort and dyspareunia) associated with deficiency, estrogenic of menopause (whether natural or surgically induced)

A randomized, placebo-controlled clinical trial showed that vaginal application of a low dose of estriol (50 micrograms per application) significantly improved the maturation index of the vaginal epithelium, vaginal pH, and vaginal pH; Symptoms of vaginal atrophy such as the fragility, dryness and paleness of the mucous membrane and the flattening of the folds. Analysis of responses by symptom (secondary endpoint) showed statistical significance, vaginal dryness, but not dyspareunia, vaginal pruritus, burns and dysuria after 12 weeks of Treatment.

BLISSEL 50 micrograms / g, vaginal gel has no effect on the ability to drive and use machines

· Hypersensitivity to the active substance or to any of the excipients.
· Known or suspected breast cancer or a history of breast cancer

Estrogen-dependent malignant tumors known or suspected (eg endometrial cancer).

· Undiagnosed genital haemorrhage

· Untreated endometrial hyperplasia.

History of venous thromboembolic disease, idiopathic or presence of thromboembolic disease, venous (deep vein thrombosis, pulmonary embolism)

· Recent or evolving arterial thromboembolic events (eg angina, myocardial infarction).
Acute liver disease or history of liver disease, normalization of liver tests

· Porphyria.

In the indication of the treatment of postmenopausal symptoms, local estrogen therapy should be introduced only if the disorders are perceived by the patient as impairing her quality of life. As with any estrogen-based product, a thorough evaluation of the ratio, benefit / risk should be performed at least once a year. Estrogen therapy may be continued as long as the benefit is greater than the risk incurred.

BLISSEL 50 micrograms / g vaginal gel should not be combined with estrogen-containing preparations for systemic treatment because there are no studies on the safety and risks of estrogen concentrations in treatment combined .

The vaginal applicator may cause minor local trauma, especially in women suffering from severe vaginal atrophy

Excipients

BLISSEL 50 micrograms / g vaginal gel contains sodium methyl parahydroxybenzoate (E 219) and sodium propyl parahydroxybenzoate (E 217), which may cause allergic reactions (possibly delayed).

Clinical examination / surveillance

Before beginning or resuming treatment with estriol, it is essential to collect the patient's personal and family medical history. A complete clinical and gynecological examination (with mammary and pelvic examination) should be performed, taking into account the patient's medical history and contraindications and warnings regarding treatment. >

Throughout the duration of the treatment it is advisable to carry out regular examinations, the nature and frequency of which will be adapted to each woman. Women should be informed of the type of breast abnormalities to be reported to their doctor or nurse.

It is recommended that examinations, including mammography, be performed according to the recommendations in force and adapted to each patient.

Any vaginal infection should be treated before starting treatment with BLISSEL 50 micrograms / g, vaginal gel.
Conditions requiring monitoring

If any of the following conditions occur, has occurred previously, and / or has worsened during pregnancy or previous hormonal treatment, the patient should be closely monitored. The following conditions may reappear or worsen during treatment with BLISSEL 50 micrograms / g, vaginal gel, in particular

· Leiomyoma (uterine fibroid) or endometriosis

• antecedent or presence of risk factors • thromboembolic (see section "Accidents, venous thromboembolism" below)

· Risk factors for estrogen-dependent tumors, eg: 1st degree of heredity for breast cancer

· High blood pressure

· Liver problems (eg, adenoma, hepatic)

· Diabetes with or without vascular involvement

· Biliary lithiasis

· Migraines or severe headache

· Systemic lupus erythematosus (SLE)

· A history of endometrial hyperplasia (see section "endometrial hyperplasia")

· Epilepsy

· Asthma

· Otospongiosis.

Stop, immediate processing

The treatment shall be discontinued immediately in the event of contraindication or in the following cases:

· Jaundice or impairment of liver function

· Significant increase in blood pressure

· Unusual migraine headache

· Pregnancy.

Endometrial hyperplasia

In the case of estrogen alone, the risk of endometrial and endometrial hyperplasia depends both on the duration of use and on the dose of estrogen used. The risk of endometrial hyperplasia or of cancer of the uterus does not increase with the administration of vaginal estriol.However, in case of prolonged administration, it is recommended to carry out regular examinations, By paying particular attention to symptoms suggestive of endometrial or tumor hyperplasia, malignant of the endometrium

The occurrence of metrorrhagia or "spottings" during the course of treatment should seek an underlying pathology. This procedure may require an endometrial biopsy in order to eliminate a malignant pathology.

Non-compensated estrogen stimulation may lead to transformation, premaligned residual foci, endometriosis. This drug should therefore be prescribed with caution in women who have undergone hysterectomy following endometriosis, especially in those with endometriosis:

Cancer of the ovary, uterus, or breast

Systemic treatment with estrogen may increase the risk of certain types of cancer, especially breast, ovary and uterus BLISSEL 50 micrograms / g, vaginal gel for local application, which contains a low Dose of estriol, does not appear to increase the risk of cancer

Venous thromboembolic events, stroke and coronary heart disease

Hormone replacement therapy with systemically active formulations increases the risk of venous thromboembolism (VTE), stroke, cerebral and coronary heart disease. BLISSEL 50 micrograms / g vaginal gel for local application containing a low dose of estriol does not appear to increase the risk of VTE, stroke and coronary heart disease

Risk factors for VTE include personal or family history, severe obesity (BMI> 30 kg / m2), and systemic lupus erythematosus (SLE). In contrast, there is no consensus on the possible role of varicose veins on venous thromboembolic risk. It is recommended to closely monitor patients with these risk factors

Other precautions for use

Patients with renal or cardiac insufficiency or a pre-existing hypertriglyceridemia should be monitored closely during the first few Weeks of treatment. BLISSEL 50 micrograms / g vaginal gel for local application containing a low dose of estriol is unlikely to have systemic effects

Patients with severe renal insufficiency should be monitored closely because of the increase in possible circulating levels of estriol.


Without object.

The toxicity of estriol is very low. Overdose with BLISSEL 50 micrograms / g, vaginal gel is very unlikely after vaginal application. Accidental ingestion of a large amount of gel can cause nausea, vomiting and vaginal bleeding in women. There is no specific antidote. If necessary, symptomatic treatment should be introduced.
Pregnancy

BLISSEL 50 micrograms / g, vaginal gel has no indication during pregnancy.
The discovery of a pregnancy during treatment with BLISSEL 50 micrograms / g, vaginal gel, requires immediate cessation of treatment.

No clinical data on pregnancies exposed to estriol are available.

To date, most epidemiological studies have not demonstrated teratogenic or fetotoxic effects, and in pregnant women who have been exposed, involuntarily
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Breastfeeding

BLISSEL 50 micrograms / g, vaginal gel has no indication during breastfeeding

Adverse effects of estriol are usually seen in 3 to 10% of patients treated. They are generally transient and of light intensity.

At the onset of treatment, when the vaginal mucosa is still atrophic, local irritation may develop as a sensation of heat and / or itching.
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The adverse effects encountered in clinical trials conducted on BLISSEL 50 micrograms / g vaginal gel were classified by frequency

Class of organ

Common (³ 1/100,