Adult: Continuous combined HRT regimen: Estradiol 0.5 mg and dydrogesterone 2.5 mg tab Estradiol 1 mg and dydrogesterone 5 mg tab
1 tab once daily without interruption for a 28-day cycle. Repeat continuously without a break between packs. Use the lowest effective dose for the shortest possible duration. Treatment initiation depends on the time since menopause, severity of symptoms, or when changing from another HRT regimen (refer to the detailed individual product guidelines).
Continuous sequential HRT regimen: Estradiol 1 mg and dydrogesterone 10 mg tab Estradiol 2 mg and dydrogesterone 10 mg tab
An estradiol tab is co-packaged with the estradiol/dydrogesterone combination tab in the blister pack. Initially, 1 tab (estradiol 1 mg) once daily on days 1 to 14, followed by 1 tab (estradiol 1 mg/dydrogesterone 10 mg) once daily on days 15 to 28. Repeat the sequence continuously without a break on a 28-day cycle. If needed, doses may be increased to 1 tab (estradiol 2 mg) once daily on days 1 to 14, followed by 1 tab (estradiol 2 mg/dydrogesterone 10 mg) once daily on days 15 to 28. Dosage must be individualised based on the patient's response. Use the lowest effective dose for the shortest possible duration. Treatment initiation depends on the symptoms or when changing from another HRT regimen (refer to the detailed individual product guidelines).
Oral Prophylaxis of osteoporosis in postmenopausal women
Adult: Continuous combined HRT regimen: Estradiol 1 mg and dydrogesterone 5 mg tab
1 tab once daily without interruption for a 28-day cycle. Repeat continuously without a break between packs. Treatment initiation depends on the time since menopause, severity of symptoms, or when changing from another HRT regimen (refer to the detailed individual product guidelines).
Continuous sequential HRT regimen: Estradiol 1 mg and dydrogesterone 10 mg tab Estradiol 2 mg and dydrogesterone 10 mg tab
An estradiol tab is co-packaged with the estradiol/dydrogesterone combination tab in the blister pack. Initially, 1 tab (estradiol 1 mg) once daily on days 1 to 14, followed by 1 tab (estradiol 1 mg/dydrogesterone 10 mg) once daily on days 15 to 28. Repeat the sequence continuously without a break on a 28-day cycle. If needed, doses may be increased to 1 tab (estradiol 2 mg) once daily on days 1 to 14, followed by 1 tab (estradiol 2 mg/dydrogesterone 10 mg) once daily on days 15 to 28. Dosage must be individualised based on the patient's response. Treatment initiation depends on the symptoms or when changing from another HRT regimen (refer to the detailed individual product guidelines).
Hepatic Impairment
Contraindicated.
Contraindications
History, suspected, or known breast cancer; known or suspected estrogen-dependent malignant tumours (e.g. endometrial cancer) and progestogen-dependent neoplasms (e.g. meningioma); undiagnosed genital bleeding, untreated endometrial hyperplasia; previous idiopathic or current venous thromboembolism (e.g. DVT, pulmonary embolism); recent or active arterial thromboembolic events (e.g. angina, MI), cerebrovascular event (e.g. stroke); thrombophilic disorders (e.g. protein C and S or antithrombin deficiency); porphyria; acute liver disease, history of liver disease with persistent abnormal LFTs. Pregnancy and lactation.
Special Precautions
Patient with risk factors for estrogen-dependent tumours (e.g. 1st-degree heredity for breast cancer), history of endometrial hyperplasia; risk factors for VTE (e.g. obesity [BMI >30 kg/m2], prolonged immobilisation, SLE); hypertension, cardiac dysfunction, asthma, diabetes mellitus, hypothyroidism, hypoparathyroidism, hypertriglyceridaemia, uterine fibroids, endometriosis, hereditary angioedema, migraine or severe headache, epilepsy, chorea minor, otosclerosis, cholelithiasis, hepatic haemangiomas. Patients undergoing surgery or receiving chronic anticoagulant therapy. Not indicated for contraception or the prevention of dementia and CV disease. Concomitant use with ombitasvir/paritaprevir/ritonavir combination regimen with or without dasabuvir and glecaprevir/pibrentasvir. Renal impairment. Elderly.
Adverse Reactions
Significant: Increased risk of breast or ovarian cancers and endometrial hyperplasia or carcinoma; breakthrough bleeding and spotting; increased risk of VTE (e.g. DVT, pulmonary embolism), ischaemic stroke, and CAD; hypertension, fluid retention, increased HDL-cholesterol, decreased LDL-cholesterol, increased plasma triglycerides (which may lead to pancreatitis), jaundice, abnormal LFT, increased thyroid binding globulin levels, hypocalcaemia, retinal vascular thrombosis; increased risk of possible dementia (in women ≥65 years old), enlargement of uterine fibroids; exacerbation of hereditary or acquired angioedema symptoms, SLE, epilepsy, asthma, chorea minor, gallbladder disease, endometriosis, migraine, otosclerosis, and porphyria. Cardiac disorders: Rarely, MI. Gastrointestinal disorders: Nausea, vomiting, abdominal pain or distension, flatulence, dyspepsia. General disorders and administration site conditions: Asthenia, fatigue, malaise, peripheral oedema. Investigations: Weight gain or loss. Musculoskeletal and connective tissue disorders: Back pain. Nervous system disorders: Headache, dizziness. Psychiatric disorders: Depression, nervousness, influence on libido. Renal and urinary disorders: Urinary incontinence, cystitis-like symptoms. Reproductive system and breast disorders: Breast pain, tenderness, or enlargement; metrorrhagia, menorrhagia, oligomenorrhoea, amenorrhoea, irregular menstruation, dysmenorrhoea, pelvic pain, cervical discharge, vaginal candidiasis. Skin and subcutaneous tissue disorders: Rash, urticaria, pruritus, erythema multiforme. Vascular disorders: Peripheral vascular disease, varicose vein.
Monitoring Parameters
Obtain a complete personal and family medical history prior to treatment initiation and periodically during therapy. Routinely perform a physical examination, including blood pressure monitoring, breast examination (e.g. mammogram), and Papanicolaou smear. Monitor glycaemic control (in diabetic patients), lipid profile (in patients with hyperlipidaemia), thyroid function (in patients on thyroid HRT), and BMD (for prevention of osteoporosis). Perform an adequate diagnostic procedure (e.g. endometrial sampling) to rule out malignancy for all cases of undiagnosed vaginal bleeding. Assess for signs and symptoms of endometrial cancer, thromboembolic disorders, menopausal symptoms, and migraine.
Metabolism may be increased by CYP450 enzyme inducers (e.g. phenobarbital, phenytoin, carbamazepine, rifampicin, nevirapine, efavirenz). Ritonavir and nelfinavir (although known as strong CYP3A4 inhibitors) may exhibit inducing effects when given with estradiol + dydrogesterone.
Estradiol: May increase the plasma levels of tacrolimus, ciclosporin, fentanyl, and theophylline. May cause ALT elevations when concomitantly used with ombitasvir/paritaprevir/ritonavir combination regimen with or without dasabuvir and glecaprevir/pibrentasvir.
Food Interaction
Metabolism may be increased by St. John's wort.
Lab Interference
May interfere with results of tests for coagulation factors, lipids, glucose tolerance and binding proteins. May decrease response to metyrapone test.
Action
Description: Mechanism of Action: Estradiol is a synthetic preparation that is biologically and chemically similar to endogenous human estradiol. In menopausal women, it substitutes for estrogen production loss and alleviates menopausal symptoms. Estradiol also prevents bone loss after menopause or ovariectomy.
Dydrogesterone, an orally active progestogen, is a synthetic retroisomer that is structurally similar to progesterone. It induces secretory changes in the endometrium and reduces the risk of estradiol-induced endometrial hyperplasia in non-hysterectomised women. Dydrogesterone lacks androgenic, estrogenic, anabolic, corticoid, and thermogenic properties. Pharmacokinetics: Absorption: Estradiol: Well absorbed from the gastrointestinal tract. Time to peak plasma concentration: 1.5-2 hours.
Dydrogesterone: Rapidly absorbed. Absolute bioavailability: 28%. Time to peak plasma concentration: 0.5-2.5 hours (dydrogesterone); approx 1.5 hours (20α-dihydrodydrogesterone [DHD]). Distribution: Estradiol: Widely distributed, with high concentrations in the sex hormone target organs. Enters breast milk. Plasma protein binding: 98-99% (30-52% to albumin, 46-69% to sex hormone binding globulin [SHBG]).
Dydrogesterone: Plasma protein binding: >90% (dydrogesterone and DHD). Metabolism: Estradiol: Extensively metabolised in the liver into estrone and estriol; partially metabolised by CYP3A4 enzymes; undergoes enterohepatic recirculation.
Dydrogesterone: Rapidly metabolised mainly to DHD (main active metabolite). Excretion: Estradiol: Mainly via urine (as estradiol, estrone, estriol, and its glucuronide and sulfate conjugates). Elimination half-life: 10-16 hours.
Dydrogesterone: Via urine (63% as metabolites). Terminal elimination half-life: 5-7 hours (dydrogesterone); 14-17 hours (DHD).
Chemical Structure
Estradiol Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5757, Estradiol. https://pubchem.ncbi.nlm.nih.gov/compound/Estradiol. Accessed Nov. 23, 2023.
Dydrogesterone Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 9051, Dydrogesterone. https://pubchem.ncbi.nlm.nih.gov/compound/Dydrogesterone. Accessed Nov. 23, 2023.
G03FA14 - dydrogesterone and estrogen ; Belongs to the class of progestogens and estrogens in fixed combinations. G03FB08 - dydrogesterone and estrogen ; Belongs to the class of progestogens and estrogens in sequential preparations.
References
Anon. Dydrogesterone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 19/10/2023.Anon. Estradiol (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 19/10/2023.Anon. Estradiol and Dydrogesterone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 14/11/2023.Buckingham R (ed). Dydrogesterone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 19/10/2023.Buckingham R (ed). Estradiol. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 19/10/2023.Femoston 1 mg/10 mg Film-coated Tablets (Mylan Products Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 14/11/2023.Femoston 2 mg/10 mg Film-coated Tablets (Abbott Laboratories [M] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 19/10/2023.Femoston 2 mg/10 mg Film-coated Tablets (Mylan Products Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 19/10/2023.Femoston-conti 0.5 mg/2.5 mg Film-coated Tablets (Mylan Products Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 19/10/2023.Femoston-conti 1 mg/5 mg Film-coated Tablets (Abbott Laboratories [M] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 19/10/2023.Femoston-conti 1 mg/5 mg Film-coated Tablets (Mylan Products Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 14/11/2023.Joint Formulary Committee. Estradiol with Dydrogesterone. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 19/10/2023.
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