Femoston film-coated tablets 1 mg+1 mg/10 mg No. 56

Instructions for Femoston film-coated tablets 1 mg + 1 mg / 10 mg No. 56

Composition

estradiol tablet

active ingredient: estradiol;

1 tablet contains estradiol hemihydrate, micronized, equivalent to estradiol 1 mg or 2 mg;

excipients: lactose monohydrate; hypromellose (HPMC 2910), corn starch, colloidal anhydrous silica, magnesium stearate;

film coating: Opadry® Y-1-7000 white (hypromellose (HPMC 2910), polyethylene glycol 400, titanium dioxide (E 171)) – for tablets containing 1 mg of estradiol;

Opadry® OY-6957 pink (hypromellose (HPMC 2910), polyethylene glycol 400, talc, red iron oxide (E 172), black iron oxide (E 172), yellow iron oxide (E 172), titanium dioxide (E 171)) – for tablets containing 2 mg of estradiol;

estradiol and dydrogesterone tablet

active ingredients: estradiol; dydrogesterone;

1 tablet contains estradiol hemihydrate, micronized, equivalent to estradiol 1 mg or 2 mg; dydrogesterone, micronized 10 mg;

excipients: lactose monohydrate; hypromellose (HPMC 2910), corn starch, colloidal anhydrous silica, magnesium stearate;

film coating: Opadry® II gray 85F27664 (polyethylene glycol 3350, talc (E 553b), polyvinyl alcohol, black iron oxide (E 172), titanium dioxide (E 171)) – for tablets containing 1 mg of estradiol and 10 mg of dydrogesterone;

Opadry® OY-02B22764 yellow (hypromellose (HPMC 2910), polyethylene glycol 400, talc, iron oxide yellow (E 172), titanium dioxide (E 171)) – for tablets containing 2 mg of estradiol and 10 mg of dydrogesterone.

Dosage form

Film-coated tablets.

Main physicochemical properties:

tablet containing 1 mg of estradiol: round, biconvex, film-coated, white tablet marked "379" on one side; diameter 7 mm and tablet weight approximately 144 mg;

tablet containing 2 mg of estradiol: round, biconvex, film-coated, brick-red tablet marked "379" on one side; diameter 7 mm and tablet weight approximately 144 mg;

tablet containing 1 mg of estradiol and 10 mg of dydrogesterone: round, biconvex, film-coated, gray tablet marked "379" on one side; diameter 7 mm and tablet weight approximately 144 mg;

tablet containing 2 mg estradiol and 10 mg dydrogesterone: round, biconvex, film-coated, yellow tablet marked "379" on one side; diameter 7 mm and tablet weight approximately 144 mg.

Pharmacotherapeutic group

Preparations for the treatment of diseases of the genitourinary system and sex hormones. Combined preparations containing progestogens and estrogens for sequential use. ATX code G03F B08.

Pharmacological properties

Pharmacodynamics.

Estradiol

The active ingredient 17ß-estradiol is chemically and biologically similar to the natural female sex hormone estradiol. It replaces the loss of estrogen production in women during menopause and alleviates menopausal symptoms.

Estrogens prevent bone loss after menopause or oophorectomy.

Dydrogesterone

Dydrogesterone is an orally active progestogen whose effects are comparable to those of parenterally administered progesterone.

Because estrogens stimulate endometrial growth, if not used with a progestogen, they increase the risk of endometrial hyperplasia and carcinoma. The addition of a progestogen to therapy significantly reduces the estrogen-induced risk of endometrial hyperplasia in women with an intact uterus.

Clinical trial data

Reducing symptoms of estrogen deficiency and improving the bleeding profile.

A reduction in menopausal symptoms was observed during the first few weeks of treatment.

Regular withdrawal bleeding lasting an average of 5 days when using Femoston®, estradiol 2 mg + estradiol/dydrogesterone 2 mg/10 mg, was observed in 89% of women. Withdrawal bleeding usually began on day 28 of the cycle. Breakthrough uterine bleeding or spotting was recorded in 22% of women in the first 3 months of treatment and in 19% of women during the 10th-12th months of treatment. Amenorrhea (absence of bleeding or spotting) was observed in 12% of cycles during the first year of treatment.

Regular withdrawal bleeding lasting an average of 5 days when using Femoston®, estradiol 1 mg + estradiol/dydrogesterone 1 mg/10 mg, was observed in 76% of women. Withdrawal bleeding usually began on the last day of the progestogen phase (on average on day 28 of the cycle). Breakthrough uterine bleeding or spotting was recorded in approximately 23% of women in the first 3 months of treatment and in 15% of women during the 10th-12th month of treatment. Amenorrhea (absence of bleeding or spotting) was observed in 21% of cycles during the first year of treatment.

Osteoporosis prevention

Data from the Women's Health Initiative (WHI) trial and meta-analyses of other studies suggest that the use of HRT in predominantly healthy women, either as estrogen monotherapy or in combination with a progestogen, reduces the risk of hip, vertebral, and other types of fractures due to osteoporosis. HRT may also prevent fractures in women with low bone density and/or known osteoporosis, but the data on this are limited.

After two years of treatment with Femoston®, estradiol 2 mg + estradiol/dydrogesterone 2 mg/10 mg, bone density (BDD) in the lumbar spine increased by 6.7 ± 3.9% (mean ± standard deviation). Bone density in the lumbar spine increased or remained unchanged in 94.5% of women.

In women taking Femoston®, estradiol 1 mg + estradiol/dydrogesterone 1 mg/10 mg, bone density in the lumbar spine increased by 5.2 + 3.8% (mean ± standard deviation). Bone density in the lumbar spine increased or remained unchanged in 93.0% of women.

Femoston® also affected the GCT of the femur.

After two years of treatment with Femoston®, estradiol 2 mg + estradiol/dydrogesterone 2 mg/10 mg, GFR increased by 2.6 ± 5.0% (mean ± standard deviation) at the femoral neck, by 3.5 ± 5.0% (mean ± standard deviation) at the trochanteric zone and by 4.1 ± 7.4% (mean ± standard deviation) at the triangle of Ward. GFR in the three femoral zones increased or remained unchanged after treatment with Femoston®, estradiol 2 mg + estradiol/dydrogesterone 2 mg/10 mg, in 71–88% of women.

After two years of treatment with Femoston®, estradiol 1 mg + estradiol/dydrogesterone 1 mg/10 mg, the GCT in the femoral neck increased by 2.7 ± 4.2% (mean ± standard deviation), in the trochanteric zone by 3.5 ± 5.0% (mean ± standard deviation) and in the triangle of Ward by 2.7 ± 6.7% (mean ± standard deviation). GCT in the three femoral zones increased or remained unchanged after treatment with Femoston®, estradiol 1 mg + estradiol/dydrogesterone 1 mg/10 mg, in 67–78% of women.

Pharmacokinetics.

Estradiol

Absorption

The absorption of estradiol depends on particle size: micronized estradiol is rapidly absorbed from the gastrointestinal tract.

Table 1 presents the mean steady-state pharmacokinetic parameters of estradiol (E2), estrone (E1), and estrone sulfate (E1S) for each dose of micronized estradiol.

Data are presented as mean (SD).

Table 1

Estradiol 1 mg

Estradiol 2 mg

Distribution

Estrogens are determined in an unbound or bound state. About 98–99% of the estradiol dose binds to plasma proteins, of which 30–52% to albumin and about 46–69% to sex hormone binding globulin (SHBG).

Biotransformation

After oral administration, estradiol is extensively metabolized. The major unconjugated and conjugated metabolites are estrone and estrone sulfate. These metabolites may contribute to estrogenic activity directly or after conversion to estradiol. Estrone sulfate may undergo enterohepatic circulation.

Breeding

In urine, the main compounds are glucuronides of estrone and estradiol. The half-life is from 10 to 16 hours. Estrogens are secreted into breast milk.

Dose and time dependence

With daily oral administration of Femoston®, estradiol concentrations reach steady state after approximately five days. In most cases, steady state concentrations are reached between the 8th and 11th day of administration.

Dydrogesterone

Absorption

After oral administration, dydrogesterone is rapidly absorbed with a Tmax of 0.5–1.5 hours.

Table 2 presents the mean steady-state pharmacokinetic parameters of dydrogesterone (D) and dihydrodydrogesterone (DH).

Data are presented as mean (SD).

Table 2

Dydrogesterone 10 mg

After a single dose, food delays the peak plasma concentration of dydrogesterone by approximately 1 hour, resulting in a decrease in peak plasma concentrations of dydrogesterone by approximately 20%, without affecting the extent of exposure to dydrogesterone and DHD.

After oral administration of dydrogesterone, the apparent volume of distribution is significant and is approximately 22,000 L. Dydrogesterone and DHD are more than 90% bound to plasma proteins.

Biotransformation

After oral administration, dydrogesterone is rapidly metabolized to DHD. The levels of the main active metabolite 20α-dihydrodydrogesterone (DHD) peak at the same time as dydrogesterone. DHD plasma levels are significantly higher than those of the parent compound. The AUC and Cmax ratios of DHD to dydrogesterone are approximately 25 and 20, respectively. The mean terminal half-life of dydrogesterone and DHD is approximately 15 hours. A common feature of all metabolites is the retention of the 4,6-dien-3-one configuration of the parent compound and the absence of 17α-hydroxylation. This explains the absence of estrogenic and androgenic effects of dydrogesterone.

Breeding

After oral administration of labeled dydrogesterone, an average of 63% of the dose is excreted in the urine. The apparent total plasma clearance of dydrogesterone in the body is high and is approximately 20 l/min. Complete excretion occurs within 72 hours. DHD is present in the urine mainly as a glucuronic acid conjugate.

Dose and time dependence

The pharmacokinetics of single and multiple doses are linear in the oral dose range of 2.5 to 20 mg. Comparison of single and multiple dose kinetics shows that the pharmacokinetics of dydrogesterone and DHD do not change with repeated administration. Steady-state conditions are usually reached after 3 days of treatment.

Indication

Hormone replacement therapy (HRT) to eliminate symptoms caused by estrogen deficiency in menopausal women no earlier than 6 months after the last menstruation.

Prevention of osteoporosis in postmenopausal women at high risk of fractures. Femoston® should be used in patients only in case of intolerance or contraindications to the use of other drugs for the prevention of osteoporosis (see section "Special instructions").

Experience in treating women over 65 years of age is limited.

Contraindication

- Past diagnosed, current or suspected breast cancer;

- established or suspected estrogen-sensitive tumors (e.g. endometrial cancer);

- established or suspected progestogen-sensitive tumors (e.g. meningioma);

- vaginal bleeding of unknown origin;

- untreated endometrial hyperplasia;

- venous thromboembolism, present or in history (deep vein thrombosis, pulmonary embolism);

- presence of thrombophilic disorders (e.g. protein C, protein S or antithrombin deficiency, see section "Special precautions for use");

- acute or recent thromboembolic arterial disease (e.g. angina pectoris, myocardial infarction);

- acute liver disease or a history of liver disease if liver function tests have not returned to normal;

- known hypersensitivity to the active substances or to any of the excipients of the medicinal product;

- porphyria.

Interaction with other medicinal products and other types of interactions

Drug interaction studies have not been conducted.

The effectiveness of estrogens and progestogens may be impaired

– The metabolism of estrogens (and progestogens) may be enhanced by concomitant use of substances that can induce enzymes involved in drug metabolism. This applies in particular to the P450 enzymes 2B6, 3A4, 3A5, 3A7. Such substances include anticonvulsants (phenobarbital, carbamazepine, phenytoin) and antibacterial/antiviral agents (e.g. rifampicin, rifabutin, nevirapine, efavirenz).

– Although ritonavir and nelfinavir are known to be potent inhibitors of CYP450 3A4, A5, A7, they actually have an inducing effect when used concomitantly with steroid hormones.

– Herbal preparations containing St. John's wort (Hypericum perforatum) may also enhance the metabolism of estrogens (and progestogens) when metabolized by CYP450 3A4.

– Clinically, increased metabolism of estrogens and progestogens may manifest as decreased efficacy and changes in bleeding profile.

Pharmacodynamic interactions

In clinical trials of hepatitis C virus (HCV) treatment with ombitasvir/paritaprevir/ritonavir with or without dasabuvir, alanine aminotransferase (ALT) elevations greater than 5 times the upper limit of normal were significantly more common in women using ethinyl estradiol-containing medicinal products, such as combined hormonal contraceptives (CHCs). In women using medicinal products containing estrogens other than ethinyl estradiol, such as estradiol, the extent of ALT elevations was similar to that in women not taking any estrogens; however, due to the limited number of women taking other estrogens, caution should be exercised when using this drug concomitantly with ombitasvir/paritaprevir/ritonavir combination therapy with or without dasabuvir, as well as with glecaprevir/pibrentasvir therapy (see section 4.4).

Estrogens may inhibit CYP450 enzymes involved in drug metabolism by competitive inhibition. This should be considered especially for drugs with a narrow therapeutic index, such as:

- tacrolimus and cyclosporine A (CYP450 3A4, 3A3);

- fentanyl (CYP450 3A4);

- theophylline (CYP450 1A2).

Clinically, this may result in increased plasma levels of such substances to toxic concentrations. Thus, careful monitoring of drug levels over a long period of time may be required, as well as dose reduction of tacrolimus, fentanyl, cyclosporine A, and theophylline.

Application features

For the treatment of estrogen deficiency symptoms in postmenopausal women, HRT should only be initiated if these symptoms significantly impair quality of life. The benefits and risks of HRT should be carefully assessed regularly, at least annually, and treatment should only be continued if the benefits outweigh the risks.

Data on the risks associated with HRT in the treatment of premature menopause are limited. However, due to the low absolute risk in younger women, the benefit-risk ratio is more favourable in these women than in older women.

Medical examination/follow-up

Before starting HRT or when restarting HRT after a break, a complete medical history (including family history) should be taken. A physical examination (including gynaecological and breast examination) should be performed, taking into account the history, contraindications and precautions for use. Regular check-ups are recommended during treatment, the frequency and extent of which should be determined individually. Women should be informed of any changes in the breasts that should be reported to their doctor or nurse (see section below on Breast cancer). Examination, including appropriate imaging techniques such as mammography, should be carried out in accordance with current screening practices, modified according to individual clinical needs.

Diseases in which it is necessary to monitor the condition of patients

Patients with any of the following conditions, present or past, and/or aggravated during pregnancy or previous hormonal therapy, should be closely monitored. It should be borne in mind that these conditions may recur or worsen during treatment with Femoston®. These include:

leiomyoma (uterine fibroids) or endometriosis;

risk factors for thromboembolic diseases (see below);

risk factors for estrogen-sensitive tumors, such as a first-degree hereditary predisposition to breast cancer;

arterial hypertension;

liver disease (hepatic adenoma);

diabetes mellitus with or without vascular symptoms;

gallstone disease;

migraine or (severe) headache;

systemic lupus erythematosus;

history of endometrial hyperplasia (see below);

epilepsy;

bronchial asthma;

otosclerosis;

meningioma.

Reasons for immediate discontinuation of therapy

Hormone replacement therapy should be discontinued immediately if a contraindication is identified, as well as in the following situations:

the appearance of jaundice or impaired liver function;

significant increase in blood pressure;

the appearance of a migraine-like headache for the first time;

pregnancy.

Endometrial hyperplasia and carcinoma

In women with an intact uterus, the risk of endometrial hyperplasia and carcinoma is increased with prolonged use of estrogen-only HRT. The observed increased risk of endometrial cancer in women taking estrogen-only HRT ranges from 2- to 12-fold compared with those not taking estrogen, depending on the duration of treatment and the dose of estrogen (see section 4.8). After stopping treatment, the risk may remain elevated for at least 10 years.

Cyclical combination of estrogen and progestogen for at least 12 days per month/per 28-day cycle or continuous combined estrogen-progestogen therapy in women with a preserved uterus avoids the excess risk associated with estrogen-only use.

Breakthrough uterine bleeding or spotting may occur during the first months of treatment. If they occur some time after the start of treatment or persist after discontinuation of therapy, their cause should be investigated, including by performing an endometrial biopsy to exclude malignancy.

Breast cancer

All available evidence suggests an increased risk of breast cancer in women taking combined oestrogen-progestogen HRT or oestrogen-only HRT. This risk depends on the duration of use.

Combined estrogen-progestogen therapy

Both the randomised placebo-controlled trial, the Women's Health Initiative Study (WHI), and a meta-analysis of prospective epidemiological studies have consistently shown an increased risk of breast cancer in women using combined oestrogen-progestagen HRT. The increased risk becomes apparent after approximately 3 (1-4) years (see section 4.8).

The WHI trial did not find an increased risk of breast cancer in hysterectomised women taking oestrogen-only HRT. Pilot studies have mostly reported a small increased risk of breast cancer, which is significantly lower than in patients taking combinations of oestrogens and progestogens (see section 4.8).

The results of a large meta-analysis showed that after stopping treatment, the increased risk will decrease over time, and the time taken to return to baseline depends on the duration of previous HRT use. In cases where HRT has been used for more than 5 years, the risk may persist for 10 years or longer. Hormone replacement therapy, especially combined estrogen-progestagen therapy, increases the density of mammographic images, which may adversely affect the radiological detection of breast cancer.

Ovarian cancer

Ovarian cancer is much less common than breast cancer. Epidemiological data from a large meta-analysis have shown a slightly increased risk in women using oestrogen-only or combined oestrogen-progestagen hormone replacement therapy; this risk becomes apparent within 5 years of use and decreases over time after discontinuation of therapy. Some other studies, including the WHI study, suggest that the use of combined HRT may be associated with the same or slightly lower risk (see section 4.8).

Venous thromboembolism

HRT is associated with a 1.3- to 3-fold increased risk of venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. This is most likely to occur during the first year of HRT use (see section 4.8).

Patients with known thrombophilic conditions are at increased risk of VTE, and HRT may further increase this risk. Therefore, hormone replacement therapy is contraindicated in this group of patients (see section 4.3).

Generally recognized risk factors for VTE include estrogen use, older age, major surgery, prolonged immobilization, obesity (BMI > 30 kg/m2), pregnancy/postpartum period, systemic lupus erythematosus (SLE), and cancer. There is no consensus on the role of varicose veins in the development of VTE.

As with all postoperative patients, precautions should be taken to prevent VTE after surgery. If prolonged immobilization is expected after elective surgery, it is recommended that HRT be temporarily discontinued 4-6 weeks before surgery. Treatment should not be resumed until the woman has regained full mobility.

Women without a history of VTE but with a first-degree relative who has had thrombosis at a young age may be offered screening after careful discussion of its limitations (screening only detects a subset of thrombophilic disorders).

If a congenital thrombophilic disorder is identified, accompanied by a family history of thrombosis, or if the disorder is severe (e.g., antithrombin, protein S, or protein C deficiency, or a combination of disorders), HRT is contraindicated.

In women already taking regular anticoagulant therapy, the benefits and risks of HRT should be carefully weighed.

If VTE develops after initiation of therapy, the drug should be discontinued immediately. Patients should be advised to seek immediate medical attention if they develop potential symptoms of thromboembolism (e.g. painful swelling of a leg, sudden chest pain, shortness of breath).

Coronary heart disease (CHD)

There is no evidence from randomized controlled trials of protection against myocardial infarction in women with or without coronary heart disease who took combined estrogen-progestogen HRT or estrogen-only HRT.

Combined estrogen-progestogen therapy

The relative risk of CHD with combined estrogen-progestogen HRT is slightly increased. Since the baseline absolute risk of CHD is largely age-dependent, the number of additional cases of CHD due to estrogen and progestogen use is very small in healthy women close to menopause, but will increase with age.

Estrogen monotherapy

Data from randomized controlled trials have not shown an increased risk of CHD in hysterectomized women taking estrogen monotherapy.

Ischemic stroke

Combined estrogen-progestogen therapy and estrogen monotherapy are associated with an increased risk of ischemic stroke of up to 1.5 times. The relative risk does not change with age or time since menopause. However, as the baseline absolute risk of stroke is largely age-dependent, the overall risk of stroke in women taking HRT will increase with age (see section 4.8).

Other states

Estrogens may cause fluid retention, and therefore patients with impaired cardiac or renal function should be carefully monitored.

Exogenous estrogens may induce or exacerbate symptoms of hereditary and acquired angioedema.

Estrogens increase thyroxine-binding globulin (TBG), leading to increased circulating thyroid hormones as measured by protein-bound iodine (PBI), T4 levels (by column assay or radioimmunoassay), or T3 levels (by radioimmunoassay). Triiodothyronine (T3) uptake is reduced as a result of increased TGB levels. Free triiodothyronine (T3) and thyroxine (T4) concentrations are not altered. Other serum binding proteins, corticoid-binding globulin (CBG) and sex hormone-binding globulin (SHBG), may be increased, leading to increased serum concentrations of corticosteroids and sex hormones. Free and/or biologically active hormone concentrations are not altered. Concentrations of other plasma proteins (angiotensin-renin substrate, alpha-I-antitrypsin, ceruloplasmin) may increase.

HRT does not improve cognitive function. There has been some evidence of an increased risk of developing possible dementia in women who start long-term combined or oestrogen-only HRT after the age of 65.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Femoston® is not a contraceptive.

Elevated ALT levels

In clinical trials in patients treated for hepatitis C virus (HCV) infection with ombitasvir/paritaprevir/ritonavir with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal were significantly more common in women using ethinyl estradiol-containing medicinal products, such as combined hormonal contraceptives (CHCs). In addition, ALT elevations were also observed in women using ethinyl estradiol-containing medicinal products, such as CHCs, also in patients treated with glecaprevir/pibrentasvir. In women using medicinal products containing estrogens other than ethinyl estradiol, such as estradiol, the extent of ALT elevations was similar to that in women not taking any estrogens; however, due to the limited number of women taking other estrogens, caution should be exercised when using this drug concomitantly with ombitasvir/paritaprevir/ritonavir combination therapy with or without dasabuvir, as well as with glecaprevir/pibrentasvir therapy (see section 4.5).

Use during pregnancy or breastfeeding

Pregnancy

Femoston® is not indicated for use during pregnancy. If pregnancy occurs during treatment with Femoston®, the drug should be discontinued immediately.

There are no adequate data on the use of estradiol/dydrogesterone in women during pregnancy.

The scientific literature has reported that the use of some progestogens has been associated with an increased risk of hypospadias. However, due to confounding factors during pregnancy, it is not possible to definitively determine whether progestogens contribute to the development of hypospadias.

To date, the results of most epidemiological studies on accidental fetal exposure to combinations of estrogens and progestogens indicate no teratogenic or toxic risk to the fetus.

Breast-feeding

Femoston® is not indicated for use during breastfeeding.

Impact on the ability to get pregnant.

Femoston® is not indicated for use in women of childbearing age.

Ability to influence reaction speed when driving vehicles or other mechanisms

Femoston® has no or negligible influence on the ability to drive or use machines.

Method of administration and doses

Femoston® is administered orally daily according to a continuous sequential regimen as described below.

Treatment begins with taking one tablet containing 1 mg or 2 mg of estradiol, once a day, every day for the first 14 days of a 28-day cycle.

After that, for the next 14 days, take 1 tablet containing 1 mg or 2 mg of estradiol and 10 mg of dydrogesterone, once a day, as indicated on the 28-day calendar pack.

After the end of the 28-day cycle, on day 29, a new 28-day cycle should be started immediately.

The treatment cycles follow each other and are continuous.

For the treatment of estrogen deficiency in postmenopausal women, the lowest effective dose should be used as initial and maintenance doses, and the duration of treatment should be as short as possible (see also section "Special warnings and precautions for use").

In general, sequential combination treatment should begin with Femoston®, estradiol 1 mg + estradiol/dydrogesterone 1 mg/10 mg.

In women not using HRT or in women switching from continuous combined HRT, treatment can be started on any convenient day. In women switching from cyclic or continuous sequential HRT, treatment should be started immediately on the day after the end of the previous cycle.

If a tablet is missed, it is recommended to continue with the next tablet without taking the missed tablet. If a tablet is missed, the likelihood of breakthrough bleeding or spotting may increase.

Femoston® can be taken regardless of meals.

Children

There is no appropriateness of using the drug Femoston® for this category of patients.

Overdose

Both estradiol and dydrogesterone are substances of low toxicity. Symptoms of overdose may include nausea, vomiting, breast tenderness, dizziness, abdominal pain, drowsiness/fatigue, and withdrawal bleeding. It is unlikely that any specific or symptomatic treatment will be required in the event of overdose.

The information described above also applies to overdose in children.

Adverse reactions

The most common adverse reactions in patients treated with estradiol/dydrogesterone during clinical trials were headache, abdominal pain, breast pain/tenderness, and back pain.

During clinical trials (n = 5108), the adverse reactions listed in Table 3 were observed with the following frequencies:

Table 3

Reviews

There are no reviews for this product.

+ Add review

Write a review

Femoston film-coated tablets 1 mg+1 mg/10 mg No. 56

My mark:

Continue

There are no reviews for this product, be the first to leave your review.

new

Cochleaton capsules 300 mg No. 30

In stock

0

1 328.29 грн.

Add to Cart

new

Rose essential oil 10 ml

In stock

0

453.53 грн.

Add to Cart

new

Nimesulide powder for oral suspension 100 mg/2 g sachet 2 g No. 30

In stock

0

614.55 грн.

Add to Cart

new

Visiox Junior capsules 500 mg No. 30

In stock

0

545.87 грн.

Add to Cart

new

Benzyl benzoate Grindex ointment 200 mg/g tube 30 g

In stock

0

395.73 грн.

Add to Cart

new

Canpol babies 31/200 non-spill mug pink 250 ml

In stock

0

348.55 грн.

Add to Cart

new

Amitriptyline hydrochloride tablets 25 mg blister No. 50

In stock

0

61.94 грн.

Add to Cart