Duphaston®: composition and pharmaceutical form
Duphaston® comes as film-coated tablets. One tablet contains 10 mg of dydrogesterone.
If large doses are prescribed, the tablets are taken in equal parts, spread through the day. The composition includes lactose, so the medicine is not suitable for patients with the rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome.
How Duphaston® works
Dydrogesterone is a progestogen that is active when taken by mouth. It brings about the secretory transformation of the endometrium in a uterus on which oestrogen has previously acted, and thereby protects against the increased risk of hyperplasia and cancer of the endometrium associated with the isolated action of oestrogen.
The medicine is indicated in all cases of a lack of the body's own progesterone. At the same time dydrogesterone has no oestrogenic, androgenic, thermogenic, anabolic or corticosteroid action — in this it differs from a number of other progestogens.
Indications
The first group of indications are the conditions linked to a lack of progesterone: painful periods, endometriosis, secondary amenorrhoea, irregular menstrual cycles, abnormal uterine bleeding, premenstrual syndrome, threatened miscarriage, recurrent miscarriage and infertility associated with luteal insufficiency.
The second group is hormone replacement therapy. Here dydrogesterone is needed to counteract the influence of unopposed oestrogen on the lining of the uterus in women with an intact uterus in natural or surgical menopause.
Method of use and dosage
The dose, the scheme and the length of treatment are chosen according to the severity of the disorder and the clinical response. The day on which use begins and the number of days depend on the individual length of the cycle.
| Indication | Scheme of use |
|---|---|
| Painful periods | 10–20 mg a day from day 5 to day 25 of the cycle |
| Endometriosis | 10–30 mg a day from day 5 to day 25 of the cycle or continuously |
| Abnormal uterine bleeding | To stop the bleeding, 20–30 mg a day for up to 10 days; to prevent it, 10–20 mg a day in the second half of the cycle |
| Secondary amenorrhoea | 10–20 mg a day for 14 days of the second half of the expected cycle |
| Premenstrual syndrome | 10 mg twice a day from the second half of the cycle until the first day of the next |
| Irregular cycles | 10–20 mg a day from the second half of the cycle until the first day of the next |
| Threatened miscarriage | A starting dose of up to 40 mg as a single dose, then 20–30 mg a day until the symptoms disappear |
| Recurrent miscarriage | 10 mg twice a day up to the 12th week of pregnancy |
| Infertility due to luteal insufficiency | 10–20 mg a day from the second half of the cycle until the first day of the next, for at least 3 cycles in a row |
Hormone replacement therapy
In the continuous sequential scheme the oestrogen is taken continuously, and one 10 mg tablet of dydrogesterone a day is added to it in the last 14 days of each 28-day cycle. In the cyclical scheme the oestrogen is given in cycles — usually 21 days with a seven-day break — and dydrogesterone at a dose of 10 mg a day is added in the last 12–14 days of oestrogen use. Depending on the clinical response the dose can be increased to 20 mg a day. Replacement therapy is started only when the symptoms of the menopause worsen the quality of life, and the balance of benefit and risk is reviewed at least once a year.
Contraindications
Duphaston® is not prescribed in the following cases:
- hypersensitivity to dydrogesterone or to any excipient;
- established or reasonably suspected tumours that depend on progestogens, for example a meningioma;
- vaginal bleeding of unestablished cause;
- with concomitant use of an oestrogen — all the contraindications to oestrogens.
Special warnings and precautions
Before the treatment of abnormal vaginal bleeding begins, its cause is established. In the first months of therapy bleeding and spotting are possible; if they appear a long time after the start of treatment or persist after it has been stopped, an investigation is carried out, up to an endometrial biopsy, in order to rule out a malignant tumour.
- patients in whom the conditions listed exist, existed before or worsened during a pregnancy or previous hormone therapy must be kept under observation;
- during treatment with dydrogesterone a relapse or worsening of porphyria, of depression and of abnormal liver tests in acute and chronic liver disease is possible — in such cases treatment may be interrupted;
- before the first start or a repeat start of hormone replacement therapy a detailed personal and family history is taken and an examination performed, including the pelvic organs and the breasts, in order to identify contraindications;
- during therapy periodic examinations are carried out, and the woman is asked to report any changes she notices in her breasts to the doctor;
- mammography and other imaging investigations are performed according to the current screening rules, taking individual needs into account;
- in women with an intact uterus, the prolonged use of oestrogens alone raises the risk of hyperplasia and cancer of the endometrium, so a progestogen is added for a minimum of 12 days of the 28-day cycle;
- the data on the risks of replacement therapy in premature menopause are scarce, but in young women the absolute risk is lower and the balance of benefit and risk may be more favourable than in older women.
Drug interactions
The main route of conversion of dydrogesterone into its principal active metabolite — 20α-dihydrodydrogesterone — is catalysed by aldo-keto reductase 1C in the cytosol. In addition, part of the conversion goes through cytochrome P450, mainly the isoenzyme CYP3A4, and the active metabolite itself is a substrate of it.
That is why the metabolism of dydrogesterone is accelerated by inducers of the cytochrome enzymes: the anticonvulsants — phenobarbital, phenytoin, carbamazepine; the anti-infective agents — rifampicin, rifabutin, nevirapine, efavirenz; and herbal preparations containing St John's wort, sage and ginkgo. Ritonavir and nelfinavir are known as strong enzyme inhibitors, but in combination with steroid hormones they show inducing properties. The clinical outcome of an accelerated metabolism is always the same — a reduction in the efficacy of the medicine.
Pregnancy and breastfeeding
It is estimated that more than 10 million women have been exposed to dydrogesterone during pregnancy, and to this day no data on a harmful influence have been obtained. There are reports in the literature linking some progestogens to an increased risk of hypospadias; however, because of the multitude of accompanying factors no unequivocal conclusions can be drawn, and clinical studies involving a limited number of women who received dydrogesterone in the early stages showed no increase in that risk.
The results of preclinical studies of embryo-foetal and postnatal development corresponded to the pharmacological profile of the substance: undesirable effects arose only at doses far exceeding the maximum ones for humans. Dydrogesterone may be prescribed to pregnant women where there is an indication. There are no data on the passage of dydrogesterone into breast milk.
Adverse effects
In the clinical studies of the indications without oestrogen, the most frequently noted were migraine, headache, nausea, disturbances of the menstrual cycle, and pain and increased sensitivity of the breasts.
- common — migraine and headache;
- common — nausea;
- common — disturbances of the menstrual cycle: uterine bleeding, heavy, scanty, painful, irregular periods or their absence;
- common — pain and increased sensitivity of the breasts;
- uncommon — low mood, dizziness, vomiting, weight gain;
- uncommon — impaired liver function with jaundice, weakness or malaise and abdominal pain;
- uncommon — allergic skin reactions: rash, itching, urticaria;
- rare — hypersensitivity reactions and angioedema, drowsiness, oedema, swelling of the breasts, haemolytic anaemia, enlargement of tumours that depend on progestogens, for example a meningioma.
According to spontaneous reports and the limited data from studies, the safety profile in adolescents is similar to that in adults. Separately one must remember the reactions linked to combined oestrogen and progestogen therapy: breast cancer, hyperplasia and cancer of the endometrium, ovarian cancer, venous thromboembolism, myocardial infarction, ischaemic heart disease and ischaemic stroke.
Overdose
There are few data on overdose in humans. Dydrogesterone was well tolerated when taken by mouth: the maximum daily dose taken by a person was 360 mg.
There are no specific antidotes and treatment should be symptomatic. This applies to overdose in children as well.
How to get a prescription for Duphaston® online
Dydrogesterone is dispensed on prescription: the scheme of use is strictly tied to the phase of the menstrual cycle and to the particular indication and, in replacement therapy, to the scheme of oestrogen use.
During the online consultation the doctor will go through the complaints, the results of the investigations and the length of your cycle, will choose the days of use and the dose and, if there are no contraindications, will issue an electronic prescription — the medicine can be collected from a pharmacy using its code.
