Dufaston pills 10mg, 20pcs

Composition

1 film-coated tablet contains: Active ingredient: didrogesterone-10.0 mg; Excipients: lactose monohydrate-111.1 mg, hypromellose-2.8 mg, corn starch-14 mg, colloidal silicon dioxide-1.4 mg, magnesium stearate-0.7 mg.

Shell composition:  opadray white Y-1-7000 (hypromellose, polyethylene glycol 400, titanium dioxide (E 171)) – 4 mg

Pharmacological action

Duphaston® (didrogesterone) is an orally active progestogen indicated in all cases of endogenous progesterone deficiency. Didrogesterone promotes the endometrial secretion phase, thereby reducing the risk of endometrial hyperplasia and/or estrogen-induced carcinogenesis.

It has no estrogenic, androgenic, anabolic or glucocorticoid activity.

Didrogesterone is not a contraceptive. The therapeutic effect of taking didrogesterone is achieved without suppressing ovulation.

Pharmacokinetics

Suction

After oral use, didrogesterone is rapidly absorbed. The time to reach_cmax for didrogesterone varies between 0.5 and 2.5 h. The absolute bioavailability of didrogesterone (a dose of 20 mg for oral use compared to intravenous use of 7.8 mg) is 28%.

The table shows the pharmacokinetic parameters of didrogesterone and 20α-dihydrodirogesterone (DHD) after a single dose of 10 mg of didrogesterone:

Distribution

After intravenous use_of didrogesterone, vd at steady state is about 1400 liters. More than 90% of didrogesterone and DHD are bound to plasma proteins.

Metabolism

After oral use, didrogesterone is rapidly metabolized to DHD. With_max the main metabolite of DHD is reached approximately 1.5 hours after taking the drug. The concentration of DHD in the blood plasma is significantly higher than the concentration of didrogesterone. The AUC and_{cmax ratios} of DHD to didrogesterone are about 40 and 25, respectively. The average T_1/2 of didrogesterone and DHD is from 5 to 7 and from 14 to 17 hours, respectively. A common property of all metabolites is the preservation of the 4,6-diene-3-oh configuration of the initial compound and the absence of a 17α-hydroxylation reaction. This explains the lack of estrogenic and androgenic effects of didrogesterone.

Deduction

After oral use of labeled didrogesterone, an average of 63% of the dose is excreted through the kidneys (in the urine). The total plasma clearance is 6.4 l/min. Didrogesterone is completely eliminated from the body after 72 hours. DHD is found in the urine mainly in the form of glucuronic acid conjugates.

Dependence of pharmacokinetic parameters on dose and time

The drug is characterized by linear pharmacokinetics with single and multiple oral use in the dose range from 2.5 mg to 10 mg.

When comparing the pharmacokinetic parameters for single and multiple oral use, it was found that the pharmacokinetics of didrogesterone and DHD do not change as a result of repeated use.

The state of equilibrium is reached 3 days after the start of treatment.

Indications

Conditions characterized by progesterone deficiency:

• endometriosis;
• infertility due to luteal phase insufficiency;
• threatened miscarriage;
• habitual miscarriage;
• premenstrual syndrome;
• dysmenorrhea;
• irregular menstruation;
• secondary amenorrhea;
• dysfunctional uterine bleeding;
• luteal phase support during assisted reproduction.

Hormone replacement therapy: to neutralize the proliferative effect of estrogens on the endometrium as part of HRT in women with disorders caused by natural or surgical menopause in an intact uterus.

Use during pregnancy and lactation

The drug can be used during pregnancy (see the section “Indications for use”).

Breastfeeding while taking Duphaston® is not recommended.

Contraindications

• Hypersensitivity to didrogesterone or other components of the drug.
• Diagnosed or suspected progestogen-dependent neoplasms (for example, meningioma).
• Vaginal bleeding of unclear etiology.
• Liver function disorders caused by acute or chronic liver diseases at the present time or in the anamnesis (before normalization of liver function tests).
• Currently or a history of malignant liver tumors.
• Galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.
• Breast-feeding period.
• Porphyria, currently or in history.
• Under 18 years of age, due to the lack of data on efficacy and safety in adolescent girls under 18 years of age.
• Spontaneous abortion (miscarriage) or failed miscarriage during luteal phase support in assisted reproductive technologies (ART).
• When combined with estrogens.
• When used as indicated, hormone replacement therapy (HRT).
• Untreated endometrial hyperplasia.
• Arterial and venous thrombosis, current or previous thromboembolism (including deep vein thrombosis, pulmonary embolism, myocardial infarction, thrombophlebitis, hemorrhagic and ischemic cerebrovascular disorders).
• Revealed predisposition to venous or arterial thrombosis (resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (cardiolipin antibodies, lupus anticoagulant).

With caution: depression, currently or in the anamnesis; conditions that previously appeared or worsened during a previous pregnancy or previous use of sex hormones, such as: cholestatic jaundice, herpes during pregnancy, severe itching of the skin, otosclerosis. When using didrogesterone in combination with estrogens, caution should be exercised if there are risk factors for developing thromboembolic conditions, such as angina pectoris, prolonged immobilization, severe forms of obesity (body mass index more than 30 kg/m2), elderly age, extensive surgical interventions, systemic lupus erythematosus, cancer, in patients receiving anticoagulant therapy; with endometriosis, uterine fibroids; with a history of endometrial hyperplasia; liver adenoma; diabetes mellitus with or without vascular complications; arterial hypertension; bronchial asthma; epilepsy; migraine or severe headache in the anamnesis; cholelithiasis; chronic renal failure; in the presence of a history of risk factors for the development of estrogen-dependent tumors (for example, relatives of the 1st line of kinship with breast cancer).

Side effects

In clinical studies, the following symptoms were most common in patients treated with didrogesterone alone: headache/migraine, nausea, menstrual irregularities, and breast tenderness/sensitivity.

In clinical studies, as well as during post-marketing use (spontaneous reports), the following adverse effects were observed with the use of didrogesterone alone, with the frequency indicated below (number of reported cases/number of patients): often (≥1/100 to <1/10); infrequently (≥1/1000 to <1/100); rarely (≥1/10,000 to

From the hematopoietic system:  rarely-hemolytic anemia.

Mental disorders:  infrequently – depression.

From the immune system:  rarely – hypersensitivity reactions.

Nervous system disorders:  often-migraine/headache; infrequently-dizziness; rarely-drowsiness.

From the gastrointestinal tract:  often – nausea; infrequently-vomiting.

Liver and biliary tract disorders:  infrequently-liver function disorders (with jaundice, asthenia or malaise, abdominal pain).

Skin and subcutaneous tissue disorders:  infrequently-allergic dermatitis (for example, rash, pruritus, urticaria); rarely – angioedema.

From the genitals and breast:  often – menstrual disorders (including metrorrhagia, menorrhagia, oligo – / amenorrhea, dysmenorrhea and irregular menstrual cycle); soreness/sensitivity of the mammary glands; rarely-swelling of the mammary glands.

Neoplasms:  rarely-an increase in the size of progestogen-dependent neoplasms (for example, meningioma).

Other services:  rarely-edema; infrequently-weight gain.

When using some progestogens in combination with estrogens as part of hormone replacement therapy, the following undesirable effects were noted: : breast cancer, endometrial hyperplasia, endometrial cancer, ovarian cancer; venous thromboembolism; myocardial infarction, coronary heart disease, ischemic stroke.

In a randomized double-blind study with two parallel groups to study the oral use of didrogesterone in comparison with intravaginal use of micronized progesterone to support the luteal phase during the use of assisted reproduction methods, it was shown that the incidence of the most frequent adverse events that occurred during treatment was comparable in both groups. Most frequently encountered (at least 5% in one of the treatment groups, regardless of the drug): vaginal bleeding, nausea, pain during the procedure, headache, abdominal pain, biochemical pregnancy. The only adverse event that occurred during treatment, with a frequency of ≥2% of patients in each of the groups, was vaginal bleeding.

Termination of pregnancy is possible at an early stage (especially before the 10th week of pregnancy) – the frequency of pregnancy during ART procedures is on average about 35%.

The safety profile observed in this study is consistent with that expected, given the well-studied safety profile of didrogesterone and the patient population.

Interaction

The metabolism of didrogesterone and DHD can be accelerated by the combined use of substances that are inducers of cytochrome 450 enzymes, such as anticonvulsants (for example, phenobarbital, phenytoin, carbamazepine), antibacterial and antiviral drugs (for example, rifampicin, rifabutin, nevirapine, efavirenz) and herbal preparations containing, for example, St. John’s wort.

Ritonavir and nelfinavir, known as strong inhibitors of cytochrome P450 enzymes, have enzyme-reducing properties when co-administered with steroids.

From a clinical point of view, increased metabolism of didrogesterone may reduce its effectiveness.

The results of in vitro studies show that didrogesterone and DHD in clinically significant concentrations do not inhibit or induce cytochrome P450 enzymes that metabolize drugs.

How to take, course of use and dosage

The drug is taken orally. Endometriosis: 10 mg 2-3 times a day from the 5th to the 25th day of the menstrual cycle or continuously. Infertility (due to luteal phase insufficiency): 10 mg per day from the 14th to the 25th day of the cycle. Treatment should be carried out continuously for at least 6 consecutive cycles. In the first months of pregnancy, it is recommended to continue treatment according to the scheme described in the usual miscarriage. Threatened miscarriage: 40 mg once, then 10 mg every 8 hours until symptoms disappear. Habitual miscarriage: 10 mg 2 times a day until the 20th week of pregnancy, followed by a gradual reduction in the dose. Premenstrual syndrome: 10 mg 2 times a day from the 11th to the 25th day of the menstrual cycle. Dysmenorrhea: 10 mg 2 times a day from the 5th to the 25th day of the menstrual cycle. Irregular menstruation: 10 mg 2 times a day from the 11th to the 25th day of the menstrual cycle. Secondary amenorrhea: estrogenic drug 1 time a day from the 1st to the 25th day of the cycle together with 10 mg of Duphaston® 2 times a day from the 11th to the 25th day of the menstrual cycle. Dysfunctional uterine bleeding (to stop the bleeding): take 10 mg 2 times a day for 5 or 7 days. Dysfunctional uterine bleeding (to prevent bleeding): 10 mg 2 times a day from the 11th to the 25th day of the menstrual cycle. HRT combined with estrogens: 

• With a continuous sequential regimen – 10 mg of didrogesterone per day for 14 consecutive days within a 28-day cycle.
• With a cyclic therapy scheme (when estrogens are used in 21-day courses with 7-day breaks) – 10 mg of didrogesterone per day for the last 12-14 days of taking estrogens.

If a biopsy or ultrasound examination indicates an insufficient response to a progestogen drug, the daily dose of didrogesterone should be increased to 20 mg. If the patient missed taking the pill, it should be taken as early as possible, within 12 hours after the usual intake time. If more than 12 hours have passed, the missed pill should not be taken, and the next day it should be taken at the usual time. Skipping the drug may increase the likelihood of “breakthrough” bleeding or “spotting” spotting. Support of the luteal phase in the process of using assisted reproduction methods: 10 mg 3 times a day, starting from the day of egg collection and up to the 10th week of pregnancy (if pregnancy is confirmed). If the patient missed taking a pill, this pill should be taken as early as possible and consult a doctor. The use of didrogesterone before menarche is not indicated. The safety and efficacy of didrogesterone in adolescent girls aged 12-18 years have not been established. Currently available limited data do not allow us to make recommendations on the dosage regimen in patients of this age group.

Overdose

Data on drug overdose cases are limited. Theoretically, clinical manifestations of drug overdose are possible: nausea, vomiting, dizziness and drowsiness. There is no specific antidote, and treatment should be symptomatic.

Description

Round biconvex tablets of white color, with beveled edges, film-coated, with a risk on one side, engraved “155” on both sides of the risk.

Special instructions

Before starting treatment with Duphaston® for abnormal uterine bleeding, it is necessary to determine the cause of bleeding.

With prolonged use of the drug, periodic examinations of a gynecologist are recommended, the frequency of which is set individually, but at least once every six months.

In the first months of treatment for abnormal uterine bleeding, “breakthrough” bleeding or “smearing” spotting may occur.

If “breakthrough” bleeding or” spotting ” spotting occurs after a certain period of taking the drug or continues after a course of treatment, you should contact your doctor and conduct an appropriate additional examination, if necessary, do an endometrial biopsy to exclude neoplasms in the endometrium.

When prescribing didrogesterone in combination with estrogens for the purpose of hormone replacement therapy (HRT), you should carefully read the contraindications and special instructions related to the use of estrogens.

Form of production

Coated tablets.

Storage conditions

In a dry place, at a temperature not exceeding 30 °C, in the original packaging

Shelf life

5 years

Active ingredient

Didrogesterone

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For postmenopausal women, For women of childbearing age, For women in the menopausal period, For women, For women planning pregnancy

Indications

Premenstrual syndrome, Menstrual Disorders, Threatened Miscarriage, Menopause