Duphaston

Duphaston is a drug that contains synthetic progesterone called dydrogesterone. It is widely used in gynecology for a number of different indications, including the treatment of some forms of luteal phase deficiency, endometriosis, abortment and other menstrual disorders. Dydrogesterone, like natural progesterone, affects estrogen-dependent processes in the body, which makes it an important component in regulating hormonal balance in women.

Indications Duphaston

1. Luteal phase deficiency.
2. Endometriosis.
3. Preventing threatened miscarriages.
4. Resolution of functional uterine cysts.
5. Combination hormonal therapy in the case of short-term therapy against the background of estrogen deficiency.

Release form

Duphaston is usually available in the form of tablets for oral (oral) use.

Pharmacodynamics

1. Progestogenic action:

   • Effect on the endometrium: Dydrogesterone causes secretory transformation of the proliferative endometrium, which helps prepare it for the possible implantation of a fertilized egg. This action is similar to the physiological effect of endogenous progesterone in the luteal phase of the menstrual cycle.
   • Pregnancy support: Dydrogesterone maintains the condition of the endometrium, which promotes the continuation of pregnancy, and prevents miscarriages associated with progesterone deficiency.

2. Antiestrogen action:

   • Regulation of hormonal balance: Dydrogesterone counteracts endometrial hyperplasia and other hyperplastic changes caused by excessive exposure to estrogen. This is important in the treatment of conditions associated with hyperestrogenism, such as dysfunctional uterine bleeding and endometriosis.

3. Lack of androgenic activity:

   • Unlike some other synthetic progestogens, dydrogesterone does not have androgenic activity. This means that it does not cause side effects associated with skin, hair and lipid metabolism, such as acne, hirsutism or changes in blood lipid levels.

4. Lack of estrogenic activity:

   • Dydrogesterone does not exhibit estrogenic activity, which reduces the risk of estrogen-related side effects, such as an increased risk of thromboembolism and breast cancer.

5. Lack of glucocorticoid and anabolic activity:

   • Dydrogesterone does not affect glucose metabolism and does not cause anabolic effects, which makes it safe for patients with disorders of glucose metabolism and metabolism.

Clinical effects:

• Regulation of the menstrual cycle: Dydrogesterone is effectively used to normalize the menstrual cycle in case of dysfunctional uterine bleeding and secondary amenorrhea.
• Treatment of endometriosis: By reducing the proliferative activity of endometrioid tissue and reducing pain.
• Pregnancy support: Used for threatened and habitual miscarriages associated with progesterone deficiency.
• Hormone replacement therapy (HRT): Used as part of HRT to prevent endometrial hyperplasia in menopausal women receiving estrogens.

Pharmacokinetics

Suction:

• Oral absorption: Dydrogesterone is rapidly absorbed from the gastrointestinal tract after oral administration.
• Maximum concentration: The maximum concentration (Cmax) in blood plasma is reached approximately 2 hours after dosing.

Distribution:

• Distribution in the body: Dydrogesterone and its metabolites are widely distributed throughout the tissues of the body.
• Protein binding: High degree of binding to plasma proteins, which contributes to the effective distribution of the active substance.

Metabolism:

• Hepatic metabolism: Dydrogesterone is actively metabolized in the liver. The main metabolite is 20α-dihydrodydrogesterone (DHD), which also has progestogenic activity.
• Pharmacologically active metabolites: DHD, the main metabolite, reaches maximum plasma concentrations 1.5 hours after taking dydrogesterone. The ratio of Cmax DHD to dydrogesterone is approximately 1.7.

Withdrawal:

• Half-life: The half-life of dydrogesterone is about 5-7 hours, and its metabolite DHD is about 14-17 hours.
• Urine excretion: Dydrogesterone and its metabolites are excreted primarily in the urine. About 63% of the dose taken is excreted in the urine within 72 hours.
• Complete elimination: Complete elimination of dydrogesterone and its metabolites from the body occurs within approximately 72 hours.

Special instructions:

• Pharmacokinetics in the elderly: There are no specific data on the effect of age on the pharmacokinetics of dydrogesterone, however, given the overall safety profile, dose adjustment in the elderly is usually not required.
• Renal failure: Dose adjustment is usually not required for mild to moderate renal failure, but individual patient characteristics must be taken into account.
• Liver impairment: Patients with severe hepatic impairment may require special monitoring due to changes in drug metabolism.

Dosing and administration

The following are basic recommendations for use and dosage for various indications.

1. Dysfunctional uterine bleeding

• Acute therapy: 10 mg twice daily for 5-7 days to stop bleeding.
• Prophylaxis: 10 mg twice a day from the 11th to the 25th day of the cycle.

2. Secondary amenorrhea

• Combination therapy with estrogens: 10 mg twice a day from the 11th to the 25th day of the cycle.

3. Endometriosis

• Dose: 10 mg two to three times a day from the 5th to the 25th day of the cycle or continuously.

4. Premenstrual syndrome (PMS)

• Dose: 10 mg twice a day from the 11th to the 25th day of the cycle.

5. Dysmenorrhea

• Dose: 10 mg twice a day from the 5th to the 25th day of the cycle.

6. Irregular menstruation

• Dose: 10 mg twice a day from the 11th to the 25th day of the cycle.

7. Threatened miscarriage

• Initial dose: 40 mg once, then 10 mg every 8 hours until symptoms disappear.

8. Habitual miscarriage

• Dose: 10 mg twice daily until the 20th week of pregnancy, then gradually reduce the dose.

9. Hormone replacement therapy (HRT)

• In combination with estrogens in cyclic or sequential therapy: 10 mg once daily for the last 12-14 days of each 28-day cycle.

10. Luteal deficiency, including infertility

• Dose: 10 mg twice a day from the 14th to the 25th day of the cycle, continue treatment continuously for at least 6 cycles, as well as in the first months of pregnancy.

General recommendations:

• Application: Tablets should be taken orally with a sufficient amount of water. Can be taken with or without food.
• Missing a dose: If you miss a pill, take it as soon as possible. If it is almost time for your next dose, do not double the dose, just continue taking it as usual.
• Discontinuation: It is not recommended to suddenly stop taking the drug without consulting your doctor, especially if the drug is used to support pregnancy or for HRT.

Important notes:

• Treatment monitoring: Regular consultations with a doctor are necessary to assess the effectiveness and safety of therapy.
• Tests and monitoring: In some cases, monitoring of hormone levels and endometrial condition may be necessary.

Use Duphaston during pregnancy

1. Use in threatened miscarriage: A systematic review showed that dydrogesterone significantly reduces the risk of miscarriage in women with threatened miscarriage. In a study of 660 women, dydrogesterone was found to reduce the rate of miscarriage from 24% to 13% compared with the control group (Carp, 2012).
2. Use in recurrent miscarriages: Another systematic review of 509 women found that dydrogesterone reduced the rate of recurrent miscarriage from 23.5% to 10.5% compared with the control group. This supports the effectiveness of dydrogesterone in reducing the risk of miscarriage in women with a history of recurrent miscarriages (Carp, 2015).
3. Luteal phase support: A study comparing oral dydrogesterone with vaginal progesterone for luteal phase support in in vitro fertilization (IVF) found that both drugs were similarly effective in increasing the chance of pregnancy. However, dydrogesterone was better tolerated and caused fewer side effects (Tomić et al., 2015).
4. Modulation of the immune response: Dydrogesterone may positively influence the immune response in women with recurrent miscarriages. Studies show that dydrogesterone treatment is associated with an increase in progesterone-blocking factors and a shift from Th1 to Th2 cytokines, which contributes to successful pregnancy (Walch et al., 2005).
5. Prevention of risks after amniocentesis: A study showed that dydrogesterone use reduced the risk of complications after amniocentesis, such as amniotic fluid leakage and uterine contractions, compared to the control group (Korczyński, 2000).

Contraindications

1. Transfer of previously occurring allergic reactions to dydrogesterone or other components of the drug.
2. Thrombosis and thromboembolic disorders (including history).
3. Liver problems such as acute or chronic hepatitis, severe liver dysfunction.
4. If you have or are predisposed to the formation of hormone-sensitive tumors, such as breast tumors or cancer of estrogen-dependent organs.
5. Uncontrolled arterial hypertension.
6. Prolactin-dependent tumors (for example, pituitary prolactinoma).
7. Impaired kidney or cardiovascular function.
8. Congenital or acquired angioedema.
9. Severe diabetes mellitus, true or diabetic migraine, as well as obvious first signs of venous or arterial thrombosis (for example, thrombophlebitis, venous thromboembolism syndrome, stroke, myocardial infarction).

Side effects Duphaston

1. Headaches.
2. Dizziness or fatigue.
3. Pain in the mammary glands.
4. Gastrointestinal problems such as nausea, vomiting, diarrhea, or constipation.
5. Swelling (usually soft tissue).
6. Mood changes.
7. Menstrual bleeding or spotting during the non-menstrual period.
8. Weight gain.

Overdose

• Nausea.
• Vomiting.
• Dizziness.
• Stomach pain.
• Drowsiness.
• Vaginal bleeding.

Interactions with other drugs

1. Drugs affecting liver enzymes:

   • Liver enzyme inducers (for example, rifampicin, phenytoin, carbamazepine, barbiturates):
     • These drugs may increase the metabolism of dydrogesterone by the liver, which may reduce its effectiveness.
   • Liver enzyme inhibitors (eg, ketoconazole, erythromycin):
     • These drugs may slow the metabolism of dydrogesterone, which may increase dydrogesterone levels in the blood and increase the risk of side effects.

2. Hormonal drugs:

   • Other progestogens and estrogens:
     • When used simultaneously with other hormonal drugs, dydrogesterone can enhance or weaken their effects. It is important to adjust the dosage under the supervision of a physician.

3. Antibacterial and antifungal agents:

   • Some antibiotics and antifungal drugs may alter the metabolism of dydrogesterone. For example, rifampicin (an antibiotic) and griseofulvin (an antifungal agent) may reduce its effectiveness.

4. Antidepressants and antipsychotics:

   • Some interactions may occur when used concomitantly with antidepressants and antipsychotics, requiring patient monitoring for possible changes in effects and side effects.

5. Anticoagulants:

   • When used concomitantly with anticoagulants (for example, warfarin), careful monitoring of blood clotting parameters may be required, as dydrogesterone may alter their effectiveness.

6. Antidiabetic drugs:

   • Hormonal medications can affect glucose metabolism, so dosages of antidiabetic medications may need to be adjusted in patients with diabetes.