Dydrogesterone
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Progestins, Therapy Class:
Synthetic hormone, Approved Countries
The United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Japan, India, Brazil and Mexico.
Dydrogesterone is a synthetic hormone agent belonging to the pharmacological class of progestins.
The FDA approves Dydrogesterone for the treatment of conditions related to women's health, including threatened or recurrent miscarriage and hormonal support during assisted reproductive techniques or in vitro fertilization (IVF) procedures.
Dydrogesterone absorbs rapidly through the oral route but slowly within 0.5-2.5 hours; it shows over 90% protein binding, undergoes hepatic metabolism, and promptly transforms it into 20α-dihydrodydrogesterone and excretes primarily via urine.
The most common side effects of Dydrogesterone include headache, nausea, vaginal bleeding, and breast pain.
Dydrogesterone is available as a tablet.
The molecule is available in the United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Japan, India, Brazil and Mexico.
Dydrogesterone is a synthetic hormone agent belonging to the pharmacological class of progestins.
It produces a complete secretory endometrium in a uterus primed by estrogen, thereby giving protection against the increased risk of endometrium hyperplasia and/or estrogen-induced carcinogenesis. Additionally, it lacks estrogenic, anabolic, androgenic, thermogenic, and corticoid characteristics.
Dydrogesterone is a progestogen that regulates the healthy growth and normal shedding of the womb lining by acting on progesterone receptors in the uterus.
The time required for Dydrogesterone to show its effect has yet to be clinically established.
The duration for which dydrogesterone remains effective in the body must be established.
The maximum plasma concentration (Cmax) of Dydrogesterone typically occurs within 1-2 hours (Tmax) after administration.
Dydrogesterone is available as a tablet.
Tablets: To be swallowed whole with water/liquid. Do not chew, crush or break it.
As the physician recommends, take the medication orally once daily. If the patient needs to take more than one tablet, then a proper time gap should be maintained between the two tablets. It can be taken with or without food as directed.
Dydrogesterone can be used for various health conditions:
- Female infertility
- Endometriosis
- Pain during menstruation
- Premenstrual syndrome (PMS)
- Hormone replacement therapy
- Prevention of Miscarriage
- Abnormal uterine bleeding
In Treatment of Female infertility
Dydrogesterone prepares the womb lining for pregnancy, aids in regulating menstrual periods, and prevents recurrent miscarriages. It enhances the likelihood of successful pregnancy in women with a history of repeated abortions.
In Treatment of Pain during menstruation
For menstrual pain relief, Dydrogesterone alleviates abdominal pain and cramps. Rest, stress reduction, and increased intake of warm fluids help mitigate the impact of a painful period on daily life.
In Treatment of Premenstrual syndrome (PMS)
Dydrogesterone alleviates premenstrual syndrome symptoms like bloating, swelling, tiredness, and mood swings. It also relieves associated pain, cramps, and headaches, improving overall comfort. Lifestyle changes like regular exercise, yoga, a healthy diet, and sufficient sleep can aid further.
In Treatment of Endometriosis
Dydrogesterone hinders the growth of endometrial tissue outside the uterus, alleviating symptoms such as lower stomach or back pain, menstrual discomfort, painful intercourse, constipation, diarrhoea, and fertility challenges associated with endometriosis.
In Treatment of Abnormal uterine bleeding
Dydrogesterone retards the growth of the womb lining pre-menstruation. It regulates and balances the menstrual cycle, reducing excessive or prolonged bleeding, enhancing regularity, and reinstating hormonal equilibrium within the uterus.
In Prevention of Miscarriage
Dydrogesterone aids in preventing miscarriage for women with prior complications. It enhances the thickness of the uterine lining and fosters the featus attachment to the uterus, avoiding abnormal contractions that could result in premature delivery. Dydrogesterone prevents threatened miscarriage by maintaining the hormonal environment crucial for pregnancy. With progesterone-like effects, it supports the uterus, ensuring favourable conditions for embryo implantation and development. It stabilizes the uterine lining, reducing the risk.
In Hormone replacement therapy
Dydrogesterone protects the uterus, relieves menopausal symptoms, regulates menstrual cycles, prevents estrogen-related complications, and supports fertility treatments.
Dydrogesterone effectively indicates potential as a treatment for a range of ailments. In female infertility treatment, it avoids recurrent miscarriages, controls menstrual cycles, and triggers the uterine lining for pregnancy. In addition to rest and stress relief, it actively reduces stomach discomfort associated with menstrual pain. When it comes to managing premenstrual syndrome (PMS), testosterone actively reduces symptoms and related pain; however, modifying one's lifestyle can further increase the hormone's effectiveness. It combats endometriosis by actively preventing the formation of aberrant tissue, which eases discomfort and problems with conception. It aggressively controls the menstrual cycle to minimize excessive bleeding in cases of abnormal uterine hemorrhage. In addition to promoting hormone replacement treatment and actively reducing menopausal symptoms while preserving uterine health, testosterone actively plays a critical role in preventing miscarriages.
Orally: Dydrogesterone tablets are typically administered orally, with or without food. If a dose is missed, take it promptly. If over 12 hours have passed, proceed with the next dose without taking the missed tablet, possibly increasing the chance of breakthrough bleeding or spotting.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
Tablet: 10mg
Dydrogesterone is available in the form of tablets.
Dose Adjustment in Adult Patients:
The following dosage regimens are recommended for treatment with Dydrogesterone:
Endometriosis: 10–30 mg daily, or continuously, from day 5–25 of the cycle.
Recurrent miscarriage: 10 mg dose until the 12th or 20th week of pregnancy in cases linked to a confirmed progesterone insufficiency.
Threatened abortion: 10 milligrams twice a day until the 12th or 20th week of pregnancy in cases linked to demonstrable progesterone insufficiency.
Threatened stillbirth: When a progesterone deficit is established, in these cases, starting with a loading dose of up to 40 mg and reducing by 10 mg every eight hours until symptoms pass.
Lutein insufficiency-related infertility: 10 mg taken daily for at least six months, ranging from day 14 to day 25 of the cycle. Or 10 or 20 mg daily from the second part of the menstrual cycle to the first day of the subsequent month. Continue the regimen for three cycles minimum.
Menopause-related mild vasomotor symptoms: 10 mg per day for 14 days in a row throughout a 28-day cycle, in conjunction with continuous estrogen medication (continuous sequential therapy). In conjunction with cyclic treatment (cyclical estrogen therapy): 10 mg per day during the final 12–14 days of estrogen medication. Depending on the clinical response, doses may be changed to 20 mg daily (e.g. endometrial biopsy, ultrasound show).
Menopausal symptoms with mild vasomotor symptoms: 10 mg per day for 14 days in consecutive weeks throughout a 28-day cycle, in conjunction with continuous estrogen medication (continuous sequential therapy). In conjunction with cyclic treatment (cyclical estrogen therapy): 10 mg per day during the final 12–14 days of estrogen medication. Depending on the clinical response, doses may be changed to 20 mg daily (e.g. endometrial biopsy, ultrasound show).
Endometrial protection during menopausal hormonal replacement therapy: 10 mg per day for 14 days in consecutive weeks throughout a 28-day cycle, in conjunction with continuous estrogen medication (continuous sequential therapy). In combination with cyclic treatment (cyclical estrogen therapy): 10 mg per day during the final 12–14 days of estrogen medication. Depending on clinical response (such as endometrial tissue growth), doses may be changed to 20 mg daily.
Dysmenorrhoea: 10 or 20 mg daily, day 5–25 of the cycle.
Dysfunctional bleeding in the uterus: A 10 mg dose for 5-7 days is recommended to stop a bleeding episode. Alternatively, up to 10 days of 20 or 30 mg per day may be administered. For ongoing prevention, take 10 or 20 mg every day from cycle days 11 to 25. Different countries may have different treatment recommendations, with some suggesting the use of testosterone in addition to estrogen.
Secondary amenorrhoea: When combined with natural or exogenous oestrogen to sufficiently stimulate the endometrium between days 11 and 25 of the menstrual cycle, 10 or 20 mg per day.
Premenstrual syndrome: From day 11 to day 25 of the cycle, take 10 mg bid. Or 10 mg bid from the second half of the menstrual cycle to the first day of the subsequent cycle; the length of the individual cycle will determine the first treatment day and duration.
Irregular menstrual cycle: From cycle days 11 to 25, take 10 mg bid. Alternatively, 10 or 20 mg per day from the first day of the subsequent cycle to the second half of the menstrual cycle; the length of the individual cycle will determine the first treatment day and duration.
During assisted reproductive technology, oral luteal support: If pregnancy is confirmed, take 10 mg tid beginning on the day of oocyte retrieval and continuing for 10 weeks. When an abortion or miscarriage is diagnosed, stop the treatment.
Dydrogesterone doesn’t usually require dietary changes; however, maintaining a balanced diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats is crucial. Reduce consumption of triggering agents like caffeine, alcohol, and spicy foods known to induce hot flushes. Cease smoking to diminish hot flashes and lower the likelihood of heart disease, stroke, and cancer. Adherence to these dietary modifications and lifestyle changes supports overall well-being during Dydrogesterone use.
The dietary restriction should be individualized as per patient requirements.
Dydrogesterone may be contraindicated in the following conditions:-
- Known hypersensitivity to dydrogesterone or any of the excipients.
- Known or suspected sex hormone-dependent malignancies. (e.g. meningioma).
- Contraindications for use of oestrogens in combination with progestogens such as dydrogesterone in combined therapy.
- Undiagnosed irregular vaginal bleeding.
- The existence of severe liver diseases or a history of severe liver diseases until the point at which the liver function results have stabilized.
Before use, a healthcare provider should evaluate the patient's medical history, including any past or existing conditions and concurrent medications, to mitigate potential risks.
Patients with a history of liver disorders or those currently experiencing liver dysfunction should exercise caution. During treatment, regular liver function tests may be advisable to monitor for any adverse effects.
Careful monitoring is necessary for individuals with a history of depression, as dydrogesterone may exacerbate this condition.
During the treatment course, immediate medical consultation is essential in case of sudden, unexplained abdominal pain, liver dysfunction symptoms (e.g., jaundice), severe headaches, visual disturbances, or thromboembolic events such as deep vein thrombosis or pulmonary embolism.
Dydrogesterone might interact with other medications; thus, consultation with a healthcare professional before initiating any new medicines alongside dydrogesterone is crucial.
The use of dydrogesterone during pregnancy should be under strict medical supervision and should be avoided during breastfeeding unless recommended by a healthcare provider.
Patients should carefully follow prescribed dosages and adhere strictly to the treatment plan. Any concerns or unusual symptoms during treatment should be promptly reported to a healthcare professional for evaluation and guidance.
Alcohol Warning
It is unsafe to consume alcohol.
Breast Feeding Warning
It is not recommended for use during breastfeeding.
Pregnancy Warning
It can be safely to use during pregnancy.
Food Warning
Maintain a balanced diet; limit triggers like caffeine, alcohol, and spicy foods. Quit smoking.
The adverse reactions related to Dydrogesterone can be categorized as
- Common Adverse Effects: Headaches, dizziness, breast tenderness, and gastrointestinal disturbances such as nausea, bloating, or abdominal discomfort.
- Less Common Adverse Effects: Mood changes, alterations in libido, skin reactions like rash, or fluid retention resulting in swelling.
- Rare Adverse Effects: Hypersensitivity reactions leading to severe skin manifestations, allergic reactions, or hepatic disorders such as jaundice or dysfunction.
The clinically relevant drug interactions of Dydrogesterone are briefly summarized here.
Drug-Drug Interactions: This medication may interact with specific herbal remedies (e.g., Ginkgo Biloba), anticonvulsants (e.g., acetazolamide, carbamazepine), and anti-infectives (e.g., metronidazole, clindamycin).
Drug-Food Interactions: Grapefruit, grapefruit juice, and St. John's wort (a plant used to treat depression) may interact with Dydrogesterone.
Drug-Disease Interactions: Dydrogesterone may interact with several medical conditions, such as cancer of the breast, liver disease, thromboembolism, depression, oedema, fluid retention, glucose intolerance, thyroid disease, high cholesterol (hyperlipidemia), ovarian cysts, uterine bleeding, and weight gain (obesity).
The common side effects of Dydrogesterone include: -
Bloating
Vaginal discharge
Joint pain
Headache
Abdominal pain
Fatigue or extreme tiredness
Somnolence or sleepiness
Vaginal haemorrhage
Pruritus (severe itching of the skin)
Nausea
Hot flushes
Weight Gain
Dizziness
Rash
Breast Tenderness
- Pregnancy
Pregnancy Category B (FDA): Could be acceptable. Either no danger has been shown by animal research, but human studies have yet to be conducted, or some risk has been shown by animal studies but not by human studies.
Over 9 million women have used dydrogesterone during pregnancy with no evident harmful effects. Some studies suggest a potential risk of hypospadias with progestogen use, but this hasn't been confirmed conclusively.
Limited clinical trials haven't shown increased risk, but more epidemiological data are needed. Non-clinical studies on embryo-fetal and postnatal development matched the pharmacological profile, with adverse effects observed only at significantly higher exposures than human maximums. Dydrogesterone use during pregnancy is permissible if medically indicated.
- Fertility
The impact of dydrogesterone on fertility is not well-documented.
- Nursing Mothers
The excretion of dydrogesterone in breast milk is unknown. The excretion of dydrogesterone in breast milk has not been studied. Other progestogen interactions show breast milk contains trace amounts of progestogens and metabolites. The youngster may be at risk, but this is unknown. Therefore, it is not recommended to utilize dydrogesterone during nursing.
- Pediatric Use
As per FDA, the safety and efficacy of Dydrogesterone in pediatric patients have yet to be extensively studied or established.
Dose Adjustment in Kidney Impairment Patients:
There is no sufficient scientific evidence regarding the use and safety of Dydrogesterone in kidney impairment patients.
Dose Adjustment in Hepatic Impairment Patients:
Dydrogesterone should be used with caution in patients with liver disease. A dose adjustment of Dydrogesterone may be needed.
Not recommended in patients with severe liver disease.
The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Dydrogesterone.
Signs and Symptoms
Overconsumption of Dydrogesterone could lead to nausea, vomiting, and abdominal discomfort.
Management
There is no specific antidote or treatment for excessive Dydrogesterone, so treatment typically involves symptomatic and supportive measures. If ingestion is recent, gastric lavage or activated charcoal might limit absorption.
Nausea, vomiting, and abdominal discomfort can be managed symptomatically. If severe symptoms persist or worsen, or in case of significant ingestion, seeking immediate medical attention is recommended. Close vital sign monitoring is crucial, emphasizing timely medical intervention to mitigate potential risks from Dydrogesterone overdose.
Pharmacodynamics:
An estrogen-primed uterus produces a whole secretory endometrium when dydrogesterone, an orally active progestogen, acts directly on the uterus. Since dydrogesterone does not impede or interfere with ovulation or the corpus luteum, it has no contraceptive effect when used at therapeutic levels. In addition, testosterone is not excreted as pregnanediol and is neither androgenic, estrogenic, corticoid, nor anabolic. Dydrogesterone aids in controlling the uterine lining's regular growth and shedding. Consequently, it might help treat menstrual diseases such as endometriosis, premenstrual syndrome, infertility, and absent, irregular or painful menstrual cycles.
Pharmacokinetics:
Absorption
Dydrogesterone demonstrates rapid absorption, reaching peak plasma concentration within 0.5 to 2.5 hours for dydrogesterone itself and approximately 1.5 hours for 20α-dihydrodydrogesterone (DHD).
Bioavailability stands at 28%.
Distribution
Both dydrogesterone and its metabolite DHD exhibit high plasma protein binding, surpassing 90%.
Metabolism
Metabolism occurs swiftly, primarily converting dydrogesterone into 20α-dihydro dydrogesterone (DHD).
Elimination
Elimination predominantly occurs through urine, with around 63% excreted as metabolites. The terminal elimination half-life spans 5 to 7 hours for dydrogesterone and extends to 14 to 17 hours for its metabolite DHD.
- Griesinger G, Blockeel C, Kahler E, Pexman-Fieth C, Olofsson JI, Driessen S, Tournaye H. Dydrogesterone as an oral alternative to vaginal progesterone for IVF luteal phase support: A systematic review and individual participant data meta-analysis. PLoS One. 2020 Nov 4;15(11):e0241044. doi: 10.1371/journal.pone.0241044. PMID: 33147288; PMCID: PMC7641447.
- Carp H. A systematic review of dydrogesterone for the treatment of threatened miscarriage. Gynecol Endocrinol. 2012 Dec;28(12):983-90. doi: 10.3109/09513590.2012.702875. Epub 2012 Jul 16. PMID: 22794306; PMCID: PMC3518297.
- Mirza FG, Patki A, Pexman-Fieth C. Dydrogesterone use in early pregnancy. Gynecol Endocrinol. 2016;32(2):97-106. doi: 10.3109/09513590.2015.1121982. Epub 2016 Jan 22. PMID: 26800266.
- Griesinger G, Blockeel C, Kahler E, Pexman-Fieth C, Olofsson JI, Driessen S, Tournaye H. Dydrogesterone as an oral alternative to vaginal progesterone for IVF luteal phase support: A systematic review and individual participant data meta-analysis. PLoS One. 2020 Nov 4;15(11):e0241044. doi: 10.1371/journal.pone.0241044. PMID: 33147288; PMCID: PMC7641447.
- Stute P. Dydrogesterone indications beyond menopausal hormone therapy: an evidence review and woman's journey. Gynecol Endocrinol. 2021 Aug;37(8):683-688. doi: 10.1080/09513590.2021.1908252. Epub 2021 Apr 19. PMID: 33866898.
- Health Products Regulatory Authority (HPRA) [Internet]. Dublin. Ireland; Package leaflet information for the user; Duphaston (dydrogesterone)
- http://www.hpra.ie/img/uploaded/swedocuments/Licence_PA2010-010-001_21092021144738.pdf
- https://www1.ndmctsgh.edu.tw/pharm/pic/medinsert/005DUP05E.pdf
- https://www.lybrate.com/medicine/dydrogesterone
Published on: 5 Dec 2023 5:25 AM GMT