Estradiol + Dydrogesterone


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Menopausal hormone replacement therapy Continuous combined therapy: Each tab contains estradiol 0.5 mg and dydrogesterone 2.5 mg or estradiol 1 mg and dydrogesterone 5 mg: 1 tab/day without interruption. Continuous sequential therapy: Each tab contains estradiol 1 mg and dydrogesterone 10 mg or estradiol 2 mg and dydrogesterone 10 mg: 1 tab/day from pack, as directed. Prophylaxis of postmenopausal osteoporosis Continuous combined therapy: Each tab contains estradiol 1 mg and dydrogesterone 5 mg: 1 tab/day without interruption. Continuous sequential therapy: Each tab contains estradiol 1 mg and dydrogesterone 10 mg or estradiol 2 mg and dydrogesterone 10 mg: 1 tab/day from pack, as directed.
Dosage Details
Oral
Menopausal hormone replacement therapy
Adult: Continuous combined therapy
Estradiol 0.5 mg and dydrogesterone 2.5 mg tab
Estradiol 1 mg and dydrogesterone 5 mg tab
1 tab once daily without interruption, preferably at the same time each day.

Continuous sequential therapy
Estradiol 1 mg and dydrogesterone 10 mg tab
Estradiol 2 mg and dydrogesterone 10 mg tab
1 tab once daily from pack, as directed.

Oral
Prophylaxis of postmenopausal osteoporosis
Adult: Continuous combined therapy
Estradiol 1 mg and dydrogesterone 5 mg tab
1 tab once daily without interruption, preferably at the same time each day.

Continuous sequential therapy
Estradiol 1 mg and dydrogesterone 10 mg tab
Estradiol 2 mg and dydrogesterone 10 mg tab
1 tab once daily from pack, as directed.
Hepatic Impairment
Contraindicated.
Contraindications
History of or suspected breast cancer, oestrogen-dependent malignant tumours (e.g. endometrial cancer), progestogen-dependent neoplasms (e.g. meningioma). Venous and arterial thromboembolism (e.g. DVT, MI), CVA, thrombophilic disorders (e.g. protein C or S deficiency), untreated endometrial hyperplasia. Undiagnosed genital bleeding. Porphyria. Hepatic impairment (active or chronic, including history of liver disease). Pregnancy and lactation.
Special Precautions
Patient with history of endometrial hyperplasia, risk factors for oestrogen-dependent tumours and for venous and arterial thromboembolism (e.g. family history, BMI >30 kg/m2, during postpartum period); cardiac impairment, hypertension, diabetes mellitus, asthma, cholelithiasis, uterine fibroids, endometriosis, migraine, epilepsy, SLE, otosclerosis, hypertriglyceridaemia. Patient who underwent hysterectomy, surgery. Smokers. Renal impairment. Elderly.
Adverse Reactions
Significant: May increase risk of breast, endometrial and ovarian cancers; may increase risk of dementia; VTE, pulmonary emboli, MI, stroke, hypertension, gall bladder disease, endometrial hyperplasia, migraine, jaundice, abnormal LFT, increased thyroid binding globulin levels. Rarely, visual abnormalities (e.g. partial or complete vision loss, proptosis, diplopia).
Gastrointestinal disorders: Abdominal pain, nausea, vomiting, flatulence.
General disorders and administration site conditions: Fatigue, asthenia, malaise.
Investigations: Increased or decreased weight.
Metabolism and nutrition disorders: Peripheral oedema.
Nervous system disorders: Headache, migraine, dizziness.
Psychiatric disorders: Depression, nervousness.
Reproductive system and breast disorders: Breast pain or tenderness, menstrual disorders (e.g. postmenopausal spotting, oligo-/amenorrhoea, metrorrhagia, menorrhagia, irregular menstruation, dysmenorrhea), pelvic pain, vaginal discharge, vaginal candidiasis.
Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria.
MonitoringParameters
Assess personal and family medical history prior to start of treatment and at regular intervals thereafter. Include blood pressure and breast, abdominal and pelvic examinations including mammography. Periodically evaluate the need to continue treatment.
Overdosage
Symptoms: Nausea, vomiting, abdominal pain, dizziness, drowsiness, fatigue, breast tenderness, withdrawal bleeding. Management: Symptomatic treatment.
Drug Interactions
Decreased effect with CYP enzyme system inducers (e.g. phenobarbital, rifampicin, nevirapine). May increase toxicity of substrates of CYP enzyme system (e.g. theophylline, tacrolimus, fentanyl).
Food Interaction
Decreased effect with St John’s Wort.
Action
Description: Estradiol is a synthetic sex hormone similar to endogenous oestrogen. During menopause, estradiol substitutes for oestrogen production and alleviates its symptoms. Estradiol also prevents bone loss following menopause or ovariectomy.
Dydrogesterone is a synthetic sex hormone similar to progestogen. It reduces the estradiol-induced risk of endometrial hyperplasia in non-hysterectomised women.
Pharmacokinetics:
Absorption: Estradiol: Well absorbed from the gastrointestinal tract. Time to peak plasma concentration: 1.5-2 hours.
Dydrogesterone: Rapidly absorbed from the gastrointestinal tract. Absolute bioavailability: 28%. Time to peak plasma concentration: 0.5-2.5 hours.
Distribution: Estradiol: 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%.
Metabolism: Estradiol: Extensively metabolised in the liver mainly to estrone and estrone sulfate.
Dydrogesterone: Rapidly metabolised mainly to dihydrodydrogesterone (DHD).
Excretion: Estradiol: Mainly via urine as estradiol, estrone, estriol and its glucuronide and sulfate conjugates; faeces as unconjugated metabolites. Elimination half-life: 10-16 hours.
Dydrogesterone: Mainly via urine (63%). Terminal elimination half-life: 5-7 hours (dydrogesterone), 14-17 hours (DHD).
Chemical Structure

Chemical Structure Image
Estradiol

Source: National Center for Biotechnology Information. PubChem Database. Estradiol, CID=5757, https://pubchem.ncbi.nlm.nih.gov/compound/Estradiol (accessed on Jan. 22, 2020)


Chemical Structure Image

Source: National Center for Biotechnology Information. PubChem Database. Dydrogesterone, CID=9051, https://pubchem.ncbi.nlm.nih.gov/compound/Dydrogesterone (accessed on Jan. 21, 2020)

Storage
Store below 30°C.
ATC Classification
G03CA53 - estradiol, combinations ; Belongs to the class of natural and semisynthetic estrogens used in estrogenic hormone preparations.
References
Anon. Estradiol (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 01/02/2018.

Buckingham R (ed). Dydrogesterone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.new.medicinescomplete.com. Accessed 01/02/2018.

Buckingham R (ed). Estradiol. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/02/2018.

Joint Formulary Committee. Estradiol with Dydrogesterone. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/02/2018.

Disclaimer: This information is independently developed by MIMS based on Estradiol + Dydrogesterone from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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