Duphaston® - (IR): composition and pharmaceutical form
One film-coated tablet contains 10 mg of dydrogesterone. This is the only strength of the medicine, and higher daily doses are made up from several tablets.
When a large daily dose is prescribed, it is divided into equal parts and spread through the day. The tablets contain lactose and are therefore not suitable in hereditary galactose intolerance, Lapp lactase deficiency and glucose-galactose malabsorption syndrome.
How Duphaston® - (IR) works
Dydrogesterone is a progestogen that retains its activity when taken by mouth. In a uterus that has previously been under the action of oestrogen it brings about the secretory transformation of the endometrium. It is precisely this reorganisation that protects the lining from the increased risk of hyperplasia and cancer of the endometrium that oestrogen produces without progestogen cover.
The medicine is used in any deficiency of the body's own progesterone. An important feature: dydrogesterone has no oestrogenic, androgenic, thermogenic, anabolic or corticosteroid action, so the side effects characteristic of some progestogens are not expected from it.
Indications
Progesterone deficiency is the main field of use: painful periods, endometriosis, secondary amenorrhoea, irregular cycles, abnormal uterine bleeding, premenstrual syndrome, threatened miscarriage, recurrent miscarriage and infertility due to luteal insufficiency.
A separate indication is hormone replacement therapy in women with an intact uterus in natural or surgical menopause. Here dydrogesterone is added to oestrogen in order to balance its influence on the lining of the uterus.
Method of use and dosage
The scheme depends on the indication, the severity of the disorder and the response to treatment, and the day on which use begins and the number of days depend on the length of the particular cycle. A withdrawal bleed occurs if the growth of the endometrium has previously been sufficiently stimulated by the body's own or by administered oestrogen.
| Indication | Dose and days of use |
|---|---|
| Painful periods | 10–20 mg a day, days 5 to 25 of the cycle |
| Endometriosis | 10–30 mg a day, days 5 to 25 of the cycle or continuously |
| Abnormal uterine bleeding | 20–30 mg a day for up to 10 days to stop it; 10–20 mg a day in the second half of the cycle to prevent it |
| Secondary amenorrhoea | 10–20 mg a day for 14 days in the second half of the expected cycle |
| Premenstrual syndrome and irregular cycles | 10–20 mg a day from the second half of the cycle until the first day of the next |
| Threatened miscarriage | 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 in the second half of the cycle, for at least 3 cycles in a row |
Schemes of replacement therapy
In the continuous sequential scheme the oestrogen is taken without breaks, and dydrogesterone 10 mg a day is added in the last 14 days of each 28-day cycle. In the cyclical scheme the oestrogen is given for 21 days with a seven-day break, and dydrogesterone 10 mg a day in the last 12–14 days of oestrogen use. With an insufficient clinical response the dose is increased to 20 mg a day. Replacement therapy is prescribed only when the symptoms of the menopause worsen the quality of life, and is continued exactly as long as the benefit outweighs the risk; that balance is reviewed at least once a year.
Contraindications
The medicine is not used in the following cases:
- hypersensitivity to dydrogesterone or to any excipient;
- confirmed or reasonably suspected tumours that depend on progestogens — for example a meningioma;
- vaginal bleeding of unestablished origin;
- all the contraindications to oestrogens, if dydrogesterone is used together with an oestrogen.
Special warnings and precautions
Before abnormal vaginal bleeding is treated, its cause is established. Bleeding and spotting in the first months of therapy are usual, but if they appear after a long period of treatment or do not stop once it has ended, an investigation is needed — up to an endometrial biopsy, in order to rule out a malignant tumour.
- special monitoring is required for women in whom the conditions listed below exist now, existed before or worsened during a pregnancy or previous hormone therapy;
- during use a worsening of porphyria and of depression is possible, as are abnormal liver tests in acute and chronic liver disease — these situations may make it necessary to stop treatment;
- before starting or resuming replacement therapy the personal and family history is taken and an examination performed, including the pelvic organs and the breasts;
- thereafter the examinations are repeated periodically, and the woman reports any changes she notices in her breasts to the doctor;
- mammography and other imaging investigations are carried out according to the current screening rules;
- in women with an intact uterus, the prolonged use of oestrogens alone raises the risk of hyperplasia and cancer of the endometrium — a progestogen is added for no fewer than 12 days of the 28-day cycle;
- in premature menopause the data on the risks of replacement therapy are scarce; however, in young women the absolute risk is lower and the balance of benefit and risk may be better than in older women.
Drug interactions
The main active metabolite of dydrogesterone — 20α-dihydrodydrogesterone — is formed with the participation of aldo-keto reductase 1C in the cytosol, and part of the conversion goes through cytochrome P450, above all the isoenzyme CYP3A4; the metabolite itself is also a substrate of that enzyme.
Because of this, inducers of the cytochrome enzymes speed up the metabolism of dydrogesterone and reduce its efficacy. They include the anticonvulsants — phenobarbital, phenytoin, carbamazepine — the anti-infective agents — rifampicin, rifabutin, nevirapine, efavirenz — and also herbal preparations containing St John's wort, sage and ginkgo. Ritonavir and nelfinavir, known as strong enzyme inhibitors, in combination with steroid hormones on the contrary show inducing properties.
Pregnancy and breastfeeding
It is estimated that more than 10 million women have been exposed to dydrogesterone during pregnancy, and no data on a harmful influence have been obtained. Publications link some progestogens to an increased risk of hypospadias, but because of the multitude of accompanying factors no unequivocal conclusions can be drawn, and studies involving women who took dydrogesterone in the early stages showed no rise in that risk.
Preclinical studies of embryo-foetal and postnatal development corresponded to the pharmacological profile of the substance, and undesirable effects arose only at doses far exceeding the maximum ones for humans. That is why, where there is an indication, the medicine may be prescribed to a pregnant woman. There are no data on the passage of dydrogesterone into breast milk.
Adverse effects
According to the results of clinical studies, in the indications without oestrogen the most frequent were migraine, headache, nausea, disturbances of the menstrual cycle and breast tenderness.
- common — migraine, headache, nausea;
- common — disturbances of the menstrual cycle: uterine bleeding, heavy, scanty, painful or irregular periods, absence of periods;
- common — pain and increased sensitivity of the breasts;
- uncommon — low mood, dizziness, vomiting;
- uncommon — impaired liver function accompanied by jaundice, weakness or malaise and abdominal pain;
- uncommon — allergic skin reactions and weight gain;
- rare — hypersensitivity reactions, angioedema, drowsiness, oedema and swelling of the breasts;
- rare — haemolytic anaemia and enlargement of tumours that depend on progestogens.
In adolescents the safety profile, judging by spontaneous reports and by the limited data from studies, is close to that in adults. With combined oestrogen and progestogen therapy the risk of breast cancer, of hyperplasia and cancer of the endometrium, of ovarian cancer, of venous thromboembolism, of myocardial infarction, of ischaemic heart disease and of ischaemic stroke are taken into account separately.
Overdose
There is little information about overdose in humans. Taken by mouth, dydrogesterone was well tolerated: the maximum daily dose a person has taken was 360 mg.
There is no specific antidote and treatment is symptomatic — this also applies to cases of overdose in children.
How to get a prescription for Duphaston® - (IR) online
Dydrogesterone is dispensed on prescription: the dose and the days of use depend on the indication and on the length of the cycle and, in replacement therapy, also on the scheme of oestrogen use.
During the online consultation the doctor will go through the symptoms and the results of the investigations, will work out the days of use for your cycle and, if there are no contraindications, will issue an electronic prescription — the medicine can be collected from a pharmacy using its code.
