Colpotrophin vaginal cream 1% tube 15 g

Instructions for use: Colpotrophin vaginal cream 1%, tube 15 g

Composition

active ingredient: promestrin;

1 g of cream contains 10 mg of promestrin;

excipients: sodium methylparaben (E 219), sodium propylparaben (E 217), a mixture of mono- and diglycerides of saturated fatty acids, polyglycol ether of saturated fatty alcohols, decyl oleate, medium chain triglycerides, glycerin, purified water.

Dosage form

Vaginal cream.

Main physicochemical properties: homogeneous white cream with a characteristic odor.

Pharmacotherapeutic group

Simple preparations of natural and semi-synthetic estrogens. ATX code G03C A09.

Pharmacological properties

Pharmacodynamics.

The drug is intended for intravaginal use. Promestrin has a local estrogenic effect on the vaginal mucosa, improving its trophism. Promestrin protects and restores the vaginal epithelium, promotes its proliferation. When administered intravaginally, it does not have a systemic effect, therefore it does not affect the endometrium, mammary glands and pituitary gland.

Pharmacokinetics.

When used intravaginally, the drug interacts with vaginal secretions, splits and its components are released. Promestrine does not accumulate in tissues, less than 1% of promestrin is absorbed, its half-life is 24 hours. When administered intravaginally, promestrin does not have a resorptive effect, and there are no systemic hormonal effects.

Indication

Vaginal atrophy caused by estrogen deficiency. Delayed healing of the vagina, cervix, and vulva after childbirth, surgery, or physical therapy.

Contraindication

Hypersensitivity to promestrin or to any component of the drug.

Breast cancer: established, suspected or history.

Known or suspected estrogen-dependent malignancies (e.g. endometrial cancer).

Untreated endometrial hyperplasia.

Genital bleeding of unknown etiology.

Severe nephropathy and heart disease.

Acute liver disease or history of liver disease until liver function tests return to normal.

Thrombophlebitis.

History of venous thromboembolism (deep vein thrombosis, pulmonary embolism).

Thrombophilic disorders (e.g. antithrombin, protein C, protein S deficiency, see section "Special warnings and precautions for use").

Active or recent arterial thromboembolic disease (e.g. angina pectoris, myocardial infarction).

Established or suspected pregnancy.

Breast-feeding.

Porphyria.

Interaction with other medicinal products and other types of interactions

Since systemic absorption of promestrin is minimal when administered vaginally, any clinically significant drug interactions are unlikely. However, interactions with other drugs used vaginally should be considered.

Spermicides

All drugs that are applied vaginally can inactivate topical spermicidal contraceptives.

Application features

During treatment, you should be under the supervision of a doctor.

If metrorrhagia occurs, it is necessary to determine the cause and provide supportive treatment.

In the treatment of postmenopausal symptoms, topical estrogen therapy is indicated only in cases where these symptoms negatively affect the quality of life. In each case, the benefit/risk ratio should be carefully assessed, at least once a year. It is recommended that therapy be continued only if the expected benefit of treatment outweighs the possible risks.

Data on the risks associated with HRT (hormone replacement therapy) in premature menopause are limited. Due to the low absolute risk, the benefit/risk balance for younger women may be more favourable than for older women.

Medical examination

Before starting or resuming local estrogen therapy, a detailed history of the patient and her family should be taken into account. In this case, together with the results of the examination (including examination of the breasts, pelvic organs), contraindications and existing risk factors should be taken into account. During treatment, it is recommended to conduct periodic medical examinations and examinations, the frequency and nature of which are individual for each patient. The woman should be warned about the need to inform the doctor about any changes in the breasts. Medical examinations, including mammography, should be carried out in accordance with modern diagnostic approaches and the individual clinical needs of the patient.

Caution should be exercised when prescribing promestrin to women with a family history of breast cancer and fibrocystic breast disease.

A Papanicolaou test should be performed to confirm or rule out dysplasia.

Conditions that require observation

If any of the following conditions are present, or have been previously or worsened during pregnancy or previous hormonal treatment, the patient should be closely monitored. These conditions may occur or worsen during treatment with promestrin, namely:

Leiomyoma (uterine fibroids) or endometriosis.

Risk of estrogen-dependent tumors, such as first-degree heredity for breast cancer.

Arterial hypertension.

Liver dysfunction (e.g., liver adenoma).

Diabetes mellitus with or without vascular disorders (if a woman has diabetes, appropriate precautions should be taken, as estrogens may reduce glucose tolerance).

Gallstone disease.

Migraine or headache (severe).

Systemic lupus erythematosus.

History of endometrial hyperplasia (see below).

Epilepsy.

Bronchial asthma.

Otosclerosis.

Heart disease.

Nephropathy.

Current or history of major depression.

Systemic absorption of promestrin during local vaginal administration is minimal (see section "Pharmacological properties"), therefore recurrence or worsening of the above conditions is less likely than during systemic estrogen treatment.

Reasons for immediate discontinuation of treatment

Treatment must be discontinued if one of the contraindications is detected or if the following conditions occur:

Jaundice or liver dysfunction, cholestatic jaundice, especially in patients with a history of jaundice.

Significant increase in blood pressure.

New cases of migraine.

Pregnancy.

First signs of thrombotic or embolic disorders.

First signs of hypercalcemia in women with breast cancer.

The following risks are associated with systemic hormone replacement therapy and are less relevant to vaginal estrogen preparations, the systemic exposure of which remains within normal limits after menopause. However, these risks should be considered with repeated or prolonged use of this medicinal product.

Endometrial hyperplasia and carcinoma

In women with an intact uterus, the risk of endometrial hyperplasia and carcinoma increases when systemic estrogens are used as monotherapy for long periods of time.

The addition of a progestogen to vaginal estrogen preparations where systemic estrogen exposure remains within the normal range for the postmenopausal period is not recommended.

The safety of long-term (more than one year) or repeated use of topical vaginal estrogen for the endometrium has not been established. Therefore, treatment should be reviewed at least annually when re-initiated.

Estrogen stimulation may lead to malignant or premalignant transformation in foci of residual endometriosis. Therefore, it is recommended to use this drug with caution in women after hysterectomy for endometriosis, especially if residual endometriosis is diagnosed.

If vaginal bleeding or spotting occurs during therapy, the cause should be determined, for example by performing an endometrial biopsy to exclude endometrial malignancy.

The following risks have been associated with systemic HRT and are less relevant to topical estrogens when systemic estrogen exposure remains within the normal range for the postmenopausal period. However, these risks should be considered with prolonged or repeated use of Colpotrophin.

Breast, uterine and ovarian cancer

Systemic estrogen treatment increases the risk of some cancers, particularly of the uterus, ovaries and breast. No increased risk of cancer is expected with promestrin, which has minimal systemic absorption when administered locally vaginally.

Breast cancer

Overall evidence suggests an increased risk of breast cancer in women taking combined estrogen-progestogen or estrogen-only systemic HRT, which depends on the duration of HRT.

The risk of breast cancer increases within several years of use, but returns to baseline within several (maximum five) years after stopping treatment.

Ovarian cancer

Ovarian cancer is much less common than breast cancer.

Epidemiological evidence from a large meta-analysis suggests a slightly increased risk in women taking oestrogen-only systemic HRT. This risk becomes apparent within 5 years of use and decreases over time after discontinuation of therapy.

Venous thromboembolism

Systemic HRT is associated with a 1.3- to 3-fold increased risk of venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. Thrombosis is more likely to occur during the first year of HRT than later.

Patients with thrombophilic states are at increased risk of VTE, and HRT increases this risk. Therefore, HRT is contraindicated in such patients (see section 4.3).

Risk factors for venous thromboembolism include: use of systemic estrogens, advanced age, major surgery, prolonged immobility, obesity (BMI > 30 kg/m2), pregnancy/postpartum period, systemic lupus erythematosus, and cancer. There is no consensus on the possible role of varicose veins in the occurrence of venous thromboembolism.

Women without a history of VTE but with close relatives who have had thrombosis at a young age may be offered screening. The patient should be informed that only a fraction of thrombophilic defects are detected by screening.

If a thrombophilic defect associated with thrombosis is identified in family members, or the defect is severe (e.g. antithrombin, protein S or protein C deficiency, or a combination of defects), HRT is contraindicated.

For women already receiving ongoing anticoagulant therapy, the benefits and risks of HRT should be carefully weighed.

If VTE develops after initiation of therapy, Colpotrophin should be discontinued. Patients should be advised to seek immediate medical attention if they experience possible thromboembolic symptoms (such as painful leg swelling, sudden chest pain, shortness of breath).

Coronary heart disease (CHD)

Estrogen monotherapy

Randomized controlled trials have not found an increased risk of CHD in women after hysterectomy who used systemic estrogen monotherapy.

Ischemic stroke

Systemic estrogen monotherapy is associated with a 1.5-fold increased risk of ischemic stroke. The relative risk does not change with age or time since menopause. However, because the baseline risk of stroke is largely age-dependent, the overall risk of stroke in women taking HRT increases with age.

Other states

Estrogens can cause fluid retention, so patients with cardiac and renal dysfunction should be carefully monitored.

Women with hypertriglyceridemia should be closely monitored during estrogen replacement therapy or hormone replacement therapy, as rare cases of significant increases in plasma triglycerides during estrogen therapy in such patients, leading to pancreatitis, have been reported.

Estrogens increase the level of thyroxine-binding globulin (TBG), which leads to an increase in total circulating thyroid hormone. The concentration of free T4 and T3 remains unchanged. The serum level of other binding proteins, namely corticosteroid-binding globulin (CBG), sex hormone-binding globulin (SHBG), may be increased, leading to an increase in the amount of circulating corticosteroids and sex steroids. The concentration of active free or biological hormone remains unchanged. The level of other plasma proteins may increase (renin/angiotensin substrate, alpha-I-antitrypsin, ceruloplasmin).

Systemic absorption of promestrin during local vaginal administration is minimal (see section "Pharmacological properties"), therefore no effect on plasma protein binding is expected.

In case of concomitant vaginal infection, the use of special medications or anti-inflammatory drugs is recommended.

Use of the drug, especially long-term, may cause sensitization. In this case, treatment should be discontinued and appropriate therapy should be initiated.

To avoid prolonged stimulation of effector organs, it is advisable to administer Colpotrophin in cycles interspersed with an adequate washout period. In the case of long-term therapy, accurate tests should be performed every 6 months (including endometrial biopsy).

Topical estrogen-containing preparations may cause discharge, vulvovaginal candidiasis, cervical changes; exacerbation of endometriosis, mastodynia, breast enlargement or discharge, cholestatic jaundice, exacerbation of a previous allergic rash, or pruritus.

HRT does not improve cognitive function. There is some evidence of an increased risk of dementia if long-term combined HRT or estrogen monotherapy is started in women over 65 years of age.

This medicine contains sodium methylparaben (E 219) and sodium propylparaben (E 217) and may cause allergic reactions (which sometimes occur some time after starting use).

The onset of metrorrhagia requires a thorough examination, including a biopsy, to rule out the presence of uterine malignancy.

Use during pregnancy or breastfeeding

Colpotrophin is contraindicated for use during pregnancy. If pregnancy occurs during the use of promestrin, treatment should be discontinued immediately.

The results of most epidemiological studies on the effects of estrogens on the fetus, conducted recently, do not contain data on their teratogenic or fetotoxic effects.

Breast-feeding

Promestrine is contraindicated during breastfeeding.

Breastfeeding women need to decide whether to stop breastfeeding their baby or continue breastfeeding without taking the medicine.

Ability to influence reaction speed when driving vehicles or other mechanisms

Colpotrophin does not affect the ability to drive a car or other vehicles.

Method of administration and doses

Apply the cream 1-2 times a day every 2-3 days.

Children.

Do not apply.

Overdose

Given the route of administration and the very low absorption of promestrin (see section "Pharmacological properties"), systemic overdose is unlikely. However, excessive use may lead to an exacerbation of local side effects such as irritation, itching and burns of the vulva.

Side effects

The frequency of adverse reactions is classified as follows: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1000 to <1/100), rare (≥ 1/10,000 to <1/1000), very rare (<1/10,000), frequency unknown (cannot be estimated from the available data).

On the part of the immune system

Rare: hypersensitivity (including rash, eczema, anaphylactic reactions).

Skin and subcutaneous tissue disorders

Frequency unknown: mild vulvovaginal burning accompanied by redness, especially after prolonged use in the most sensitive patients.

Reproductive system and mammary gland disorders

Rare: vulvovaginal itching, frequency unknown: vulvovaginal pain, discomfort and burning sensation, vaginal discharge.

General disorders and administration site conditions

Frequency unknown: irritation at the injection site.

Effects associated with systemic HRT that are specific to this class of drugs

The following risks have been associated with systemic HRT and are less relevant to vaginal estrogen preparations, in which systemic estrogen exposure remains within the normal range for the postmenopausal period.

Risk of developing breast cancer

The risk of breast cancer was almost doubled in women who took combined estrogen-progestogen therapy for more than 5 years.

The risk is significantly lower in patients taking estrogen monotherapy than in women taking estrogen-progestogen combinations.

The level of risk depends on the duration of use of the drug (see section "Special instructions for use").

Below are the results of the largest randomized placebo-controlled trial (WHI trial) and the largest epidemiological study (MWS).

Table 1

Million Women Study: Breast Cancer Risk After 5 Years of Treatment

*Based on baseline incidence rates in developed countries.

#Overall risk factor. The risk factor is not a constant value, it increases with increasing duration of use.

Note: As the baseline incidence of breast cancer varies in each EU country, the number of additional cases of breast cancer varies proportionally in each EU country.

Table 2

WHI study in the US: additional risk of developing breast cancer after 5 years of treatment

*WHI study in women with a uterus removed, which did not show an increased risk of breast cancer.

Ovarian cancer

The use of systemic HRT has been associated with a small increased risk of ovarian cancer (see section "Special warnings and precautions for use").

A meta-analysis of 52 epidemiological studies showed an increased risk of ovarian cancer in women who were currently taking systemic HRT compared with women who had never taken HRT (relative risk (RR) 1.43, 95% confidence interval (CI) 1.31–1.56). In women aged 50–54 years who have been taking HRT for 5 years, the risk of ovarian cancer increases by about 1 case per 2000. In women aged 50–54 years who do not use HRT, about 2 women in 2000 will be diagnosed with ovarian cancer within 5 years.

Risk of developing venous thromboembolism

The relative risk of venous thromboembolism (VTE), such as deep vein thrombosis or pulmonary embolism, is increased 1.3-3-fold with systemic HRT. Thrombosis is most likely to occur during the first year of hormone therapy (see section 4.4). The data from the WHI studies are presented below.

Table 3

WHI study: additional risk of VTE over 5 years of treatment

*Study in women with a removed uterus.

The use of systemic HRT is associated with a 1.5-fold increased relative risk of ischemic stroke. The risk of hemorrhagic stroke is not increased with HRT use. This relative risk is independent of age or duration of use. However, because the baseline risk is largely age-dependent, the overall risk of stroke increases with increasing age in women using HRT (see section 4.4).

Table 4

Combined WHI studies: additional risk of ischemic stroke* over 5 years of treatment

*Differentiation between ischemic and hemorrhagic stroke was not performed.

Other adverse reactions have been reported with estrogen-based treatment (risk estimates were made based on systemic use and it is not known how they can be extrapolated to topical treatment):

benign and malignant neoplasms related to estrogen, such as endometrial cancer and breast cancer (see also sections "Contraindications" and "Special instructions for use");

Venous embolism, i.e. deep vein thrombosis in the leg or pelvis, and pulmonary embolism; more common in patients using hormone replacement therapy. See sections "Contraindications" and "Special instructions for use";

myocardial infarction and stroke;

gallbladder disease;

Skin and subcutaneous tissue disorders: chloasma, erythema multiforme, erythema nodosum, vascular purpura;

dementia in women aged 65 years and over (see section "Special warnings and precautions for use").

Treatment should be discontinued immediately at the first signs of thrombotic or embolic disorders, hypertension, hypercalcemia in women with breast cancer, cholestatic jaundice in patients with a history of gravidarum jaundice.

Topical estrogen-containing preparations may cause discharge, vulvovaginal candidiasis, cervical changes; exacerbation of endometriosis, mastodynia, breast enlargement or discharge, cholestatic jaundice, exacerbation of a previous allergic rash, or pruritus.

Expiration date

5 years.

Storage conditions

The medicine does not require any special storage conditions. Keep out of the reach of children.

Packaging

15 g of cream in a tube, 1 tube in a box.

Vacation category

According to the recipe.

Producer

SHEMINO Laboratory.

Location of the manufacturer and address of its place of business.

Rue de Monnet 93, 37210 Vouvray, France.