Usage
- Medical Conditions: Dydrogesterone + Estradiol is prescribed for hormone replacement therapy (HRT) in postmenopausal women experiencing symptoms such as hot flashes, night sweats, vaginal dryness, and sleep disturbances. It is also used to prevent osteoporosis in postmenopausal women. Additionally, some formulations are used for the treatment of vulvar and vaginal atrophy due to menopause and for dysfunctional uterine bleeding.
- Pharmacological Classification: Hormone replacement therapy (HRT), estrogen and progestogen combination.
- Mechanism of Action: Estradiol, a form of estrogen, replaces the declining estrogen levels in the body during menopause, alleviating menopausal symptoms. Dydrogesterone, a progestogen, counteracts the effects of estrogen on the uterine lining, reducing the risk of endometrial hyperplasia and cancer.
Alternate Names
- No commonly used alternate generic names.
- Brand Names: Femoston, Femoston Conti, Femoston-Mini. (Note: Brand names can vary by region.)
How It Works
- Pharmacodynamics: Estradiol binds to estrogen receptors throughout the body, producing estrogenic effects such as reducing menopausal symptoms and maintaining bone density. Dydrogesterone binds to progesterone receptors in the uterus, counteracting the proliferative effects of estrogen on the endometrium.
- Pharmacokinetics:
- Absorption: Both estradiol and dydrogesterone are well-absorbed orally. Estradiol reaches peak plasma concentration in 1.5-2 hours, while dydrogesterone reaches peak concentration in 0.5-2.5 hours. The main active metabolite of dydrogesterone, 20α-dihydrodydrogesterone (DHD), peaks at approximately 1.5 hours. Dydrogesterone has an absolute bioavailability of 28%.
- Distribution: Estradiol is widely distributed and has high concentrations in target organs. It also enters breast milk. Estradiol is 98-99% plasma protein bound, primarily to albumin and sex hormone binding globulin (SHBG). Dydrogesterone and its metabolite are >90% bound to plasma proteins.
- Metabolism: Estradiol is primarily metabolized in the liver to estrone and estriol, partly by CYP3A4 enzymes. It undergoes enterohepatic recirculation. Dydrogesterone is rapidly metabolized, primarily to DHD, its main active metabolite. Dydrogesterone metabolites retain the parent compound’s 4,6-diene-3-one configuration and lack 17α-hydroxylation, which explains its lack of estrogenic and androgenic effects. DHD reaches significantly higher plasma concentrations than dydrogesterone itself after oral administration.
- Elimination: The elimination pathways of both drugs and their metabolites are primarily through hepatic metabolism and subsequent renal excretion.
Dosage
Standard Dosage
Adults:
- Continuous Combined HRT: Estradiol 0.5 mg/Dydrogesterone 2.5 mg or Estradiol 1 mg/Dydrogesterone 5 mg, one tablet orally once daily, continuously without interruption.
- Continuous Sequential HRT: Estradiol 1 mg or 2 mg daily on days 1-14, followed by Estradiol 1 mg/Dydrogesterone 10 mg or Estradiol 2 mg/Dydrogesterone 10 mg daily on days 15-28. Repeat the cycle continuously.
- Osteoporosis Prophylaxis: Estradiol 1 mg/Dydrogesterone 5 mg, one tablet orally once daily, continuously.
- Dosage should be individualized based on patient response, starting with the lowest effective dose for the shortest duration.
Children: Not applicable; this medication is for postmenopausal women.
Special Cases:
- Elderly Patients: Standard adult dosing applies, but close monitoring is recommended.
- Patients with Renal Impairment: Caution is advised, especially in severe renal impairment. Dose adjustments may be needed.
- Patients with Hepatic Dysfunction: Contraindicated in active or chronic liver disease or a history of liver disease as long as liver function tests haven’t returned to normal.
- Patients with Comorbid Conditions: Caution in patients with hypertension, diabetes mellitus, cardiac dysfunction, asthma, uterine fibroids, endometriosis, migraine, epilepsy, and other conditions. Individualized assessment is required.
Clinical Use Cases These clinical use cases (Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use and Emergency Situations) are not relevant to Dydrogesterone/Estradiol. This is primarily indicated for hormone replacement therapy.
Dosage Adjustments
- Adjust dosage based on the clinical response and individual patient needs.
Side Effects
Common Side Effects
- Headache, abdominal pain, breast pain/tenderness, back pain, nausea, vomiting, flatulence, indigestion, nervousness, depressed mood, fatigue, vaginal bleeding or spotting, weight changes (gain or loss), dizziness.
Rare but Serious Side Effects
- Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism.
- Stroke, myocardial infarction.
- Hypersensitivity reactions (rash, pruritus, urticaria, angioedema, anaphylaxis).
Long-Term Effects
- Increased risk of breast cancer, endometrial cancer, and ovarian cancer with prolonged use, especially with higher doses.
Adverse Drug Reactions (ADR)
- Any signs of hypersensitivity or thromboembolic events require immediate medical attention.
Contraindications
- Known, past, or suspected breast cancer.
- Estrogen-dependent or progestogen-dependent neoplasms (e.g., endometrial cancer, meningioma).
- Undiagnosed genital bleeding.
- Untreated endometrial hyperplasia.
- Active or recent arterial or venous thromboembolism.
- Thrombophilic disorders.
- Active liver disease or a history of liver disease with abnormal liver function tests.
- Porphyria.
- Hypersensitivity to estradiol, dydrogesterone, or any component of the formulation.
- Pregnancy.
Drug Interactions
- CYP450 enzyme inducers (e.g., phenobarbital, phenytoin, carbamazepine, rifampicin, rifabutin, nevirapine, efavirenz) can increase the metabolism and reduce the efficacy of estradiol and dydrogesterone.
- Ritonavir and nelfinavir, despite being CYP3A4 inhibitors, can exhibit inducing properties with steroid hormones.
- St. John’s wort can induce metabolism.
- Estradiol can increase plasma levels of certain drugs metabolized by CYP3A4, including tacrolimus, ciclosporin, fentanyl, and theophylline.
- Alcohol can increase the risk of breast cancer.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated in pregnancy. If pregnancy occurs during treatment, discontinue immediately. May cause fetal harm.
- Breastfeeding: Contraindicated during breastfeeding. Excreted in breast milk and may affect the infant.
Drug Profile Summary
- Mechanism of Action: Estradiol replaces declining estrogen levels, while dydrogesterone provides endometrial protection.
- Side Effects: Common: headache, breast tenderness, abdominal pain, nausea. Serious: VTE, stroke, myocardial infarction.
- Contraindications: Breast cancer, endometrial cancer, undiagnosed genital bleeding, VTE, liver disease, pregnancy, breastfeeding.
- Drug Interactions: CYP450 inducers, St. John’s wort, certain medications metabolized by CYP3A4.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Varies based on indication and formulation; individualize to the lowest effective dose.
- Monitoring Parameters: Blood pressure, breast examination, pelvic exam, endometrial assessment, bone mineral density, liver function tests, lipid profile, blood glucose.
Popular Combinations
- No other drugs are typically combined in the same tablet with estradiol and dydrogesterone. However, other medications might be prescribed concurrently to manage co-existing conditions or other menopausal symptoms not adequately controlled by HRT alone.
Precautions
- General Precautions: Thorough medical history, including personal and family history of breast cancer, thromboembolic events, and liver disease. Perform baseline and periodic physical examinations, including breast and pelvic exams, mammography, and Pap smear.
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Contraindicated.
- Children & Elderly: Not applicable for children. For the elderly, monitor closely and adjust dose as needed.
- Menstruating Individuals: Not applicable; used in postmenopausal women.
- Lifestyle Considerations: Avoid alcohol.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dydrogesterone + Estradiol?
A: The dosage varies based on the formulation and indication. For HRT, commonly used dosages include estradiol 0.5 mg/dydrogesterone 2.5 mg or estradiol 1 mg/dydrogesterone 5 mg daily in a continuous combined regimen, or estradiol 1 mg or 2 mg on days 1-14 followed by estradiol/dydrogesterone 10 mg on days 15-28 in a continuous sequential regimen. Individualize the dosage to the lowest effective dose.
Q2: What are the common side effects of Dydrogesterone + Estradiol?
A: Common side effects include headache, breast tenderness, abdominal pain, nausea, vaginal bleeding, and weight changes.
Q3: What are the serious side effects of Dydrogesterone + Estradiol?
A: Serious side effects include venous thromboembolism, stroke, myocardial infarction, and endometrial cancer. Immediate medical attention is required if any of these occur.
Q4: Who should not take Dydrogesterone + Estradiol?
A: Contraindicated in women with current or past breast cancer, estrogen-dependent neoplasia, undiagnosed genital bleeding, untreated endometrial hyperplasia, active or recent thromboembolic disorders, liver disease, or during pregnancy.
Q5: Can Dydrogesterone + Estradiol be used during pregnancy?
A: No, it is contraindicated during pregnancy. Discontinue the drug immediately if pregnancy occurs.
Q6: Does Dydrogesterone + Estradiol protect against osteoporosis?
A: Yes, it can help prevent osteoporosis in postmenopausal women. The Estradiol 1 mg/Dydrogesterone 5 mg continuous combined regimen is specifically indicated for osteoporosis prophylaxis.
Q7: What should patients be monitored for when taking Dydrogesterone + Estradiol?
A: Patients should be monitored for blood pressure changes, breakthrough bleeding, signs of thromboembolic events, breast changes, endometrial changes, bone mineral density, and liver function.
Q8: How long can a patient take Dydrogesterone + Estradiol?
A: HRT should be used for the shortest duration necessary to control symptoms. The risks and benefits should be reassessed annually.
Q9: Can Dydrogesterone + Estradiol interact with other medications?
A: Yes, it can interact with certain medications such as CYP450 inducers (e.g., some anticonvulsants, antibiotics), St. John’s wort, and certain drugs metabolized by CYP3A4.
Q10: What lifestyle changes should be considered while taking Dydrogesterone + Estradiol?
A: Patients should avoid alcohol consumption, as it can increase the risk of breast cancer.
