Duphaston 10mg 14 tablets — Made in Netherlands — Free Delivery

(Duphaston 10mg)
Duphaston 10mg 14 tablets  — Made in Netherlands — Free Delivery
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Abbott Biologicals B.V. Brand: Abbott Biologicals B.V.

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Description Duphaston 10mg 14 tablets — Made in Netherlands — Free Delivery

Pharmacological properties

Pharmacodynamics

Mechanism of action. Dydrogesterone is a selective progestogen that replaces some of the functions of progesterone. As a gestagen, dydrogesterone exclusively affects only the endometrium, vaginal mucosa and cervical canal.

Dydrogesterone does not inhibit ovulation. This means that the possibility of egg fertilization in non-pregnant women while taking dydrogesterone remains.

Dydrogesterone and its metabolites have no thermogenic properties. In postmenopausal women with a preserved uterus, estrogen replacement therapy is associated with an increased risk of endometrial hyperplasia and endometrial cancer. The addition of progestogens can prevent excessive risk.

Cyclic addition of dydrogesterone to women in whom the endometrium has been stimulated by estrogen puts it in the secretion phase.

Dydrogesterone has no virilizing or virilizing properties. Dydrogesterone has no anabolic or corticoid properties.

Clinical efficacy and safety

Luteal phase support with the use of assisted reproductive technologies (ART). A double-blind, double-masked, randomized multicenter study involving two parallel groups to compare the efficacy, safety and tolerability of oral dydrogesterone at a dose of 30 mg / day and intravaginal micronized progesterone in capsules at a dose of 600 mg / day to maintain the luteal phase in application of in vitro fertilization technologies (LOTUS I).

The main goal of the study - to demonstrate no less efficacy of oral dydrogesterone compared to intravaginal micronized progesterone in terms of the presence of heart contractions in the fetus at 12 weeks of gestation (10 weeks of gestation) - has been achieved.

In the study patient population, the pregnancy rate confirmed at 12 weeks of gestation (10 weeks of gestation) was 37.6% and 33.1% in the dydrogesterone and micronized progesterone groups, respectively. The difference in pregnancy rates between the two groups was 4.7 (95% confidence interval (CI) -1.2; 10.6).

In the safety assessment sample of subjects (1029 study subjects who received at least one dose of study preparation), the most frequently reported adverse events during therapy were identical in both study groups.

Due to the nature of the indications under study and the patient population under study, a certain number of early abortions / miscarriages is expected, especially before the 12th week of gestation (10th week of pregnancy), since the predicted rate of pregnancy during this period is about 35%.

The safety profile reported in this study was as expected given the established safety profile of dydrogesterone and the patient population and indication under study.

Pharmacokinetics. Unlike progesterone, dydrogesterone is not excreted in the urine as pregnandiol. Thus, it remains possible to determine the secretion of endogenous progesterone by excretion of pregnandiol.

With oral administration, an average of 63% of the dose is excreted in the urine. Complete excretion occurs after 72 hours. Its main metabolite is 20-alpha-dihydrodidrogesterone (DHD), which is excreted in the urine in a state associated with glucuronic acid. The common property of all metabolites is the preservation of the structure of the 4,6-dien-3-one of the original substance and the absence of 17-alpha-hydroxylation, which explains the absence of estrogenic and androgenic effects in dydrogesterone.

After oral administration of dydrogesterone, the plasma concentration of DHD is significantly higher than that of the parent substance. The AUC ratio is around 30.

Dydrogesterone is rapidly absorbed. Cmax of dydrogesterone and DHD is achieved after 0.5-2.5 hours.

Indications

Irregular menstrual cycles; endometriosis; dysmenorrhea; infertility caused by luteal insufficiency; support of the luteal phase with the use of vrt; threatening and habitual abortion associated with progesterone deficiency.

Dufaston can be used as a cyclic addition to estrogen therapy in women with an intact uterus:

  • to prevent endometrial hyperplasia during menopause;
  • with dysfunctional uterine bleeding;
  • with secondary amenorrhea.

Application

Doses, regimen and duration of treatment can be adjusted depending on the severity of the disorder and the individual clinical response of the patient.

Irregular menstrual cycles. A cycle duration of 28 days can be achieved by prescribing 1 Dufaston tablet per day from the 11th to the 25th day of the cycle.

Endometriosis From 1 to 3 Dufaston tablets per day from the 5th to the 25th day of the cycle or during the entire cycle. Doses in multiples of 10 mg / day should be distributed evenly throughout the day. It is recommended to prescribe the maximum dose at the initial stage of treatment.

Dysmenorrhea. From 1 to 2 Dufaston tablets per day from the 5th to the 25th day of the cycle. Doses in multiples of 10 mg / day should be distributed evenly throughout the day. It is recommended to prescribe the maximum dose at the initial stage of treatment.

Infertility caused by luteal insufficiency. 1 tablet Dufaston per day from the 14th to the 25th day of the cycle. This treatment should be continued for a minimum of 6 consecutive cycles. It is recommended to continue treatment during the first months of pregnancy at the same doses as for a routine abortion.

Support of the luteal phase with the use of ART. 1 tablet Dufaston 3 times a day (30 mg / day). Treatment begins on the day of oocyte collection and continues for 10 weeks if pregnancy is confirmed.

Risk of miscarriage. Initial dose: 4 tablets of Dufaston at once, then 1 tablet of Dufaston every 8 hours. Doses, multiples of 10 mg / day, should be evenly distributed throughout the day. It is recommended to prescribe the maximum dose at the initial stage of treatment.

If symptoms persist or reappear during treatment, the dose should be increased by 1 tablet of Dufaston every 8 hours.

After the symptoms disappear, the effective dose must be maintained for 1 week, then it can be gradually reduced. If symptoms reappear, treatment should be reinstated immediately at the established effective dosage.

Habitual miscarriage. Treatment must be started before conception. 1 tablet Dufaston per day until the 20th week of pregnancy, after which you can gradually reduce the dose.

If symptoms of threatened abortion appear during treatment, then therapy should be continued as described in the case of threatened abortion.

Dysfunctional uterine bleeding. 2 tablets Dufaston for 5-7 days in combination with estrogen.

A few days after the end of such treatment, withdrawal bleeding will appear.

In order to prevent further bleeding, Dufaston is prescribed 1 tablet per day from the 11th to the 25th day of the cycle.

In the case of cystic hemorrhagic metropathy, 1 tablet of Dufaston is prescribed per day from the 11th to the 25th day of the cycle.

In some cases, it may be necessary to prescribe estrogen during the first half of the cycle. A few days after stopping such treatment, withdrawal bleeding will appear.

This treatment should be continued for several cycles.

Secondary amenorrhea. For treatment, estrogen must be prescribed at the same time. Estrogen is prescribed from the 1st to the 25th day of the cycle, from the 11th to the 25th day in combination with 1 tablet of Dufaston per day.

To create the prerequisites for subsequent cycles, therapy begins on the 5th day after the onset of bleeding by prescribing estrogens (from the 5th to the 25th day). Dufaston 10 mg is prescribed from the 11th to the 25th day.

To prevent endometrial hyperplasia during menopause. During each 28-day cycle of estrogen therapy, only estrogen is taken for the first 14 days, and for the next 14 days, 1 or 2 tablets containing 10 mg of dydrogesterone are taken in addition to estrogen therapy. In the case of dosing 10 mg of dydrogesterone 2 times a day, the tablets should be distributed throughout the day. Withdrawal bleeding usually occurs with the use of dydrogesterone.

The use of combination therapy with estrogen and progestogen in postmenopausal women should be limited to the minimum effective dose and the minimum time to achieve the therapeutic goal, and the risks for each woman should be periodically reviewed (see SPECIAL INSTRUCTIONS).

Mode of application. For oral administration. When using high doses, the tablets should be evenly distributed for administration throughout the day.

Children. Due to the lack of data on the safety and efficacy of Dufaston in children, it is not recommended to prescribe the preparation to this category of patients.

Contraindications

Undiagnosed vaginal bleeding; the presence of serious liver disease or the presence of severe liver disease in the past, if the liver function indicators have not returned to normal; should consider contraindications to the use of estrogens when they are used in combination with progestogens such as dydrogesterone; established hypersensitivity to the active substance or any other component of the preparation; established or suspected progestogen-dependent neoplasms (eg meningioma).

Treatment to support the luteal phase with ART should be discontinued if abortion / miscarriage is diagnosed.

Side effects

When dydrogesterone was used in clinical studies as indicated without estrogen treatment, the following adverse reactions were most often reported: migraine / headache, nausea, menstrual irregularities, and breast pain / sensitivity.

The following adverse reactions were observed with the following frequency in clinical studies of the use of dydrogesterone (n = 3483) for indications without estrogen treatment and for spontaneous reports: often (≥1 / 100, 1/10); infrequently (≥1 / 1000, 1/100); rarely (≥1 / 10,000, 1/1000).

Neoplasms are benign, malignant and indeterminate (including cysts and polyps): rarely - an increase in the size of progestogen-dependent neoplasms (for example, meningiomas) *.

Blood and lymphatic system: rarely - hemolytic anemia *.

Mental disorders: infrequently - depressed mood.

Immune system: rarely - hypersensitivity reactions.

Nervous system: often - headache and migraine; infrequently - dizziness; rarely, drowsiness.

Digestive tract: often - nausea; infrequently - vomiting.

Hepatobiliary system: infrequently - abnormal liver function, accompanied by weakness, malaise, jaundice and abdominal pain.

Skin and subcutaneous tissues: infrequently - allergic dermatitis (eg rash, itching and urticaria); rarely - angioedema *.

Reproductive system and mammary glands: often - menstrual irregularities (including metrorrhagia, menorrhagia, oligo- / amenorrhea, dysmenorrhea and irregular menstruation), breast pain / breast tenderness; rarely - swelling of the mammary glands.

General symptoms and local reactions: rarely - edema.

Examination: infrequently - an increase in body weight.

* Adverse reactions from spontaneous messages not observed in clinical trials are included in the column "rare" on the basis that the upper limit of the 95% CI frequency is estimated not higher than 3 / x, where x = 3483 (total number of subjects of observation in clinical trials) ...

The LOTUS I study to support the luteal phase with ART (see PHARMACOLOGICAL PROPERTIES, Pharmacodynamics): the most commonly reported adverse events were vaginal bleeding, nausea, pain during procedures, headache, abdominal pain and biochemical pregnancy. The only adverse event that occurred during therapy and was observed in both groups was vaginal bleeding, reported in ≥2% of subjects.

Adverse reactions associated with estrogen-progestogen treatment (see SPECIAL INSTRUCTIONS and instructions for medical use of estrogen preparations):

breast cancer, endometrial hyperplasia and carcinoma, ovarian cancer **;

venous thromboembolism;

myocardial infarction, ischemic heart disease, ischemic stroke.

** The use of estrogen monotherapy or combined estrogen-progestogen hormone replacement therapy (HRT) was associated with a slightly increased risk of diagnosing ovarian cancer (see SPECIAL INDICATIONS). A meta-analysis of 52 epidemiological studies showed an increased risk of ovarian cancer in women who received HRT compared with women who never used HRT (RR 1.43; 95% CI 1.31–1.56). In women aged 50–54 years who used HRT for 5 years, the result showed one additional case in 2000 patients. About 2 out of 2,000 women aged 50–54 who have not used HRT have been diagnosed with ovarian cancer within a 5-year period.

Special instructions

Before starting the use of dydrogesterone for the treatment of pathological bleeding, an organic cause of bleeding should be excluded.

Breakthrough bleeding or spotting may occur in the first months of treatment. If breakthrough bleeding or spotting occurs after some time of treatment or continues after the end of treatment, the cause should be established, including, if necessary, exclude endometrial malignancy by performing an endometrial biopsy.

If any of the following disorders occurs for the first time or worsens with the use of the preparation, discontinuation of treatment should be considered:

very severe headache, migraine, or symptoms that may indicate cerebral ischemia;

significant increase in blood pressure;

the appearance of venous thromboembolism.

In the case of habitual or threatened abortion, the viability of the fetus must be determined and monitored during treatment to ensure that the pregnancy continues and the embryo is alive.

Conditions requiring control. It is known that the following rare cases can be influenced by sex hormones, and therefore, during pregnancy or with the use of sex hormones, it can develop or worsen: cholestatic jaundice, herpes of pregnancy, severe itching, otosclerosis, porphyria, depression and abnormal liver function indicators caused by acute or chronic liver disease. If any of these conditions are present or have appeared earlier and / or worsened during pregnancy or previous hormone treatment, the patient should be closely monitored. It must be borne in mind that these conditions may recur or worsen during therapy with dydrogesterone, therefore, discontinuation of therapy in such cases should be considered.

Patients with a history of depression should be closely monitored. If severe depression recurs, dydrogesterone treatment should be discontinued.

The following warnings concern the use of Dufaston for indications "for the prevention of endometrial hyperplasia during menopause." See also warnings in the directions for use of estrogen preparations.

For the relief of postmenopausal symptoms, HRT should be used only in cases where the symptoms negatively affect the quality of life. In all cases, it is necessary to carefully assess the benefits and risks of HRT at least once a year. HRT should only be continued if the benefits outweigh the risks.

Evidence regarding the risks associated with HRT for treating premature menopause is limited. Due to the low level of absolute risk in young women, the balance between benefits and risks in this group may be more favorable than in older women.

Medical examination / further medical supervision. Before starting HRT or when recovering from a break, it is necessary to collect a complete personal and family history. Taking into account the history data, as well as contraindications and warnings for taking the preparation, an objective examination of the patient should be carried out (including examination of the pelvic organs and examination of the mammary glands). During treatment, it is recommended to carry out periodic examinations, the frequency and nature of which depend on the individual characteristics of the patient. Women should be informed about what changes in the mammary glands they should report to their doctor or nurse (see Breast Cancer below). Breast exams, including appropriate imaging techniques such as mammography, should be performed in accordance with current screening practice, taking into account the individual clinical needs of the patient.

Endometrial hyperplasia and carcinoma. In women with an intact uterus, the risk of endometrial hyperplasia and carcinoma increases with prolonged estrogen monotherapy. Depending on the duration of treatment and the dose of estrogen, the risk can be 2 to 12 times higher than in women who are not taking estrogen. After stopping estrogen therapy, this risk persists for at least 10 years. The addition of progestogens, such as dydrogesterone, cyclically for at least 12 days per month / 28-day cycle or as continuous combined estrogen-progestogen therapy in women with a preserved uterus may prevent the excessive risk associated with estrogen-only HRT.

Breakthrough bleeding and spotting may occur during the first months of treatment. If breakthrough bleeding or spotting occurs after the appointment of therapy for some time, or if they continue after the end of treatment, further examination is indicated. This may mean that an endometrial biopsy is needed to rule out malignancy.

Mammary cancer. All available data indicate an increased risk of breast cancer in women taking combined estrogen-progestogen therapy, and possibly even with estrogen-only HRT. This risk depends on the duration of HRT use.

Combined estrogen-progestogen therapy: The Women’s Health Initiative's (WHI) randomized placebo-controlled trial and epidemiological studies have shown an increased risk of breast cancer in women taking estrogen-progestogen HRT for 3 years or more. After stopping treatment, this increased risk persists for at least 5 years. HRT, especially estrogen-progestogen combination therapy, increases mammographic imaging density, which can negatively affect radiologic detection of breast cancer.

Ovarian cancer. Ovarian cancer occurs much less frequently than breast cancer. Epidemiological data obtained from a broad meta-analysis showed a slightly increased risk in women taking estrogen monotherapy or a combination of estrogen and progestogen as HRT; this risk manifests itself within 5 years of use and decreases over time after discontinuation of therapy. Several other studies, including the WHI, have shown that the use of combined HRT may be associated with the same or slightly lower risk (see SIDE EFFECTS).

Venous thromboembolism. HRT is associated with a 1.3–3-fold increased risk of venous thromboembolism, that is, deep vein thrombosis or pulmonary embolism. The occurrence of such an event is more likely in the first year of HRT than later.

Patients with known thrombophilic conditions have an increased risk of developing venous thromboembolism, and HRT may increase this risk. Therefore, HRT is contraindicated in this group of patients.

Commonly recognized risk factors for venous thromboembolism are estrogen use, advanced age, major surgery, prolonged immobilization, obesity (body mass index 30 kg / m2), pregnancy / puerperium, systemic lupus erythematosus, and cancer. There is no consensus regarding the possible role of varicose veins in the occurrence of venous thromboembolism.

As with all postoperative patients, preventive measures should be considered to prevent venous thromboembolism after surgery. If planned surgery requires further prolonged immobilization, it is recommended to temporarily discontinue HRT 4–6 weeks before surgery. Until the woman regains full mobility, treatment should not be resumed.

Women without a personal history of venous thromboembolism, but with a history of first-degree thrombosis at a young age in relatives, can be offered screening after a thorough discussion of its limitations (only a part of thrombophilic defects can be detected during screening). If an established thrombophilic defect is associated with thrombosis in family members or the defect is associated with a serious abnormality (for example, a lack of antithrombin, protein S, or protein C, or a combination of defects), HRT is contraindicated.

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

If venous thromboembolism develops after starting therapy, the preparation should be discontinued. Patients should be advised to see a doctor immediately if potential thromboembolic symptoms occur (eg, painful leg swelling, sudden chest pain, shortness of breath).

Ischemic heart disease. In randomized controlled trials, there was no evidence of protection against myocardial infarction in women with or without coronary artery disease receiving combined estrogen-progestogen therapy or HRT only with estrogens.

Combined estrogen-progestogen therapy: the relative risk of coronary artery disease with HRT is slightly increased. Since the baseline absolute risk of coronary artery disease largely depends on age, the number of additional cases of coronary artery disease due to the use of estrogen-progestogens is very small in healthy women at the time of menopause, but will increase at an older age.

Ischemic stroke. Combined estrogen-progestogen therapy and estrogen monotherapy is associated with a 1–1.5-fold increased risk of ischemic stroke. The relative risk does not change with age or time since menopause. However, since the baseline risk of stroke is highly dependent on age, the overall risk of stroke in women taking HRT increases with age.

Excipients. This medicinal product contains lactose monohydrate. Patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not use this preparation.

Use during pregnancy and lactation

Pregnancy. More than 9 million pregnant women were estimated to have taken dydrogesterone. So far, no evidence has been identified for the harmful effects of dydrogesterone when used during pregnancy.

A study has been reported in the literature showing that the use of certain progestogens may be associated with an increased risk of hypospadias. But since this has not yet been confirmed in other studies, it is impossible to finally determine the role of progestogens in the development of hypospadias. Clinical studies in which a limited number of women were treated with dydrogesterone early in pregnancy did not show an increased risk. No other epidemiological data are available yet.

In preclinical studies of embryofetal and postnatal development, the effects were consistent with the pharmacological profile. Side effects occurred only when the effect of the preparation significantly exceeded the maximum effect on humans.

Dydrogesterone can be used during pregnancy for clear indications.

Breastfeeding period. There is no data on the penetration of dydrogesterone into breast milk. Studies on the penetration of dydrogesterone into breast milk have not been conducted.

Experience with other progestogens shows that progestogens and their metabolites pass into breast milk in small amounts. It is not known if there is a risk to the baby, so dydrogesterone should not be used while breastfeeding.

Fertility There is no evidence that therapeutic doses of dydrogesterone reduce fertility.

The ability to influence the reaction rate when driving or driving other mechanisms. Duphaston insignificantly affects the ability to drive a car and work with machines and mechanisms.

Infrequently, dydrogesterone may cause mild drowsiness and / or dizziness, especially in the first few hours after oral administration. Therefore, it is necessary to drive a car or work with equipment with care.

Interactions

Data from in vitro studies show that the main metabolic pathway that forms the main pharmacologically active metabolite, DHD, is catalyzed by aldoketo reductase 1c (akr 1c) in the human cytosol. Along with cytosolic metabolism, metabolic transformations are carried out by cytochrome p450 (cyp) isoenzymes, almost exclusively by cyp 3a4 isoenzymes, which leads to the formation of several minor metabolites. the main active metabolite, DHD, is a substrate for the metabolic conversion of cyp 3a4. therefore, the metabolism of dydrogesterone and DHD can be accelerated by the simultaneous use of substances that induce cytochrome p450 enzymes, such as anticonvulsants (for example, phenobarbital, phenytoin, carbamazepine), antimicrobial preparations (for example, rifampicin, rifabutin, nevirazin, phytoprepaviren) or ginkgo biloba.

Ritonavir and nelfinavir, both known to be potent inhibitors of cytochrome enzymes, exhibit enzyme inducing properties when used concomitantly with steroid hormones. A clinically increased metabolism of dydrogesterone may lead to a decrease in the effect.

In vitro studies have shown that dydrogesterone and DHD at clinically significant concentrations do not inhibit or induce cytochrome P450 enzymes involved in preparation metabolism.

Overdose

Symptoms Dydrogesterone is a very low toxicity preparation. Symptoms that theoretically can occur in case of an overdose are nausea, vomiting, drowsiness and dizziness. there are cases when an overdose of dydrogesterone led to harmful consequences (the maximum daily dose taken by a person was 360 mg).

Care. No special treatment is required. In case of overdose, symptomatic treatment may be considered.

Storage conditions

Does not require special storage conditions.


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