Femoston conti: composition and presentation
One tablet contains 1 mg of 17β-estradiol as estradiol hemihydrate and 5 mg of dydrogesterone. All 28 tablets in the pack are the same: both hormones are taken every day, with no break between packs. The regimen is called continuous combined, and by dose this pack sits in the middle of the continuous range — above the 0.5 mg with 2.5 mg one, but below the sequential packs with 10 mg of dydrogesterone.
The tablet contains lactose monohydrate, so in the rare hereditary galactose intolerance, Lapp lactase deficiency and glucose-galactose malabsorption syndrome the medicine is not prescribed. It is separately stated that this combination of an oestrogen and a progestogen has no contraceptive effect. On the ability to drive and to operate machinery the medicine has no or negligible influence.
How Femoston conti works
The active substance is synthetic 17β-estradiol, chemically and biologically identical to the estradiol produced in the human body. It makes up for the lack of the woman's own estradiol after the menopause and eases climacteric complaints, and beyond that oestrogens prevent the loss of bone mass after the menopause or removal of the ovaries. Dydrogesterone is a progestogen that is active when taken by mouth, and in strength of action it is comparable to progesterone given parenterally.
The second component is there not for the symptoms but to protect the uterus. Oestrogens stimulate growth of the endometrium, and unopposed oestrogen-only therapy increases the risk of endometrial hyperplasia and cancer. In women with an intact uterus adding a progestogen substantially reduces that oestrogen-dependent risk — which is why dydrogesterone is in every tablet rather than being taken on selected days of the cycle.
Indications
Hormone replacement therapy for the treatment of symptoms of oestrogen deficiency in postmenopausal women in whom at least 12 months have passed since the last period. That twelve-month interval is not a formality: before it the menopause is not regarded as confirmed, and the continuous regimen is designed precisely for the state in which the woman's own cycles have already ended.
The second indication is prevention of osteoporosis, and it is narrowly worded.
- it concerns postmenopausal women at high risk of fracture;
- who show signs of intolerance to other medicines used to treat osteoporosis, or in whom such medicines are contraindicated;
- replacement therapy is therefore not the first choice here, but an option for those for whom the usual drugs are unsuitable.
Method of use and dosage
The oestrogen and the progestogen are given every day without breaks: one tablet a day in a 28-day cycle, with the new pack following straight on from the previous one. When starting and when continuing treatment of postmenopausal symptoms, the lowest effective dose is used for the shortest possible time. The tablet may be taken with or without food.
| Situation | What is done |
| Starting continuous combined therapy | it may be started with a product containing 0.5 mg of estradiol and 2.5 mg of dydrogesterone, depending on how long it is since the last period and how severe the symptoms are; the dose is then adjusted to the clinical response |
| Switching from a continuous sequential or cyclic regimen | the 28-day cycle of the previous product is finished first, and only then is this one started |
| Switching from another continuous combined product | it may be started on any day |
| Missed dose, less than 12 hours have passed | take it as soon as possible |
| Missed dose, more than 12 hours have passed | the missed tablet is not taken and the next one is taken at the usual time; the likelihood of breakthrough bleeding or spotting then rises |
| Children and adolescents | the medicine is not indicated |
| Age over 65 | experience of treatment is limited |
The benefit-risk balance is assessed at least once a year, and treatment is continued exactly as long as the benefit outweighs the risk. Replacement therapy for menopausal symptoms is started at all only when those symptoms worsen quality of life. There is little data on the risks in premature menopause, but in younger women the absolute risk is lower, so the benefit-risk balance may turn out more favourable for them than for older women.
Contraindications
The oncological part of the list is wider than usual because the medicine contains two hormones. It covers breast cancer in the history or a well-founded suspicion of it; diagnosed or reasonably suspected malignant oestrogen-dependent tumours, for example endometrial cancer; and also tumours that depend on progestogens, for example meningioma — this last point is what distinguishes combined products from purely oestrogenic ones.
The remaining contraindications concern bleeding, the vessels and the liver.
- genital bleeding whose origin has not been established, and endometrial hyperplasia left untreated;
- venous thromboembolism, both that which occurred at some time and that present now: blockage of the deep veins or of the pulmonary artery;
- known clotting disorders of a thrombotic nature: lack of protein C, protein S or antithrombin;
- active or recently suffered arterial thromboembolic disorders, for example ischaemic heart disease or a heart attack;
- acute or previous liver disease, until the indices of its function return to normal; porphyria; established hypersensitivity to the active substances or to the excipients.
Special warnings and precautions
Before the first prescription or a repeat one, a full medical history is taken — the woman's own and her family's — and an examination is carried out, including the pelvic organs and the breasts, to confirm the indication and to find contraindications or states calling for caution. Periodic check-ups follow, their type and frequency set individually, and mammography is performed according to current screening rules. The woman is told which changes in the breasts call for a visit to a doctor or nurse. Under especially close observation are women in whom the states listed below exist now, existed in the past or worsened during pregnancy or earlier hormonal therapy: the medicine may bring them back or make them worse.
- uterine fibroids or endometriosis, endometrial hyperplasia in the history, risk factors for thromboembolic disorders and risk factors for oestrogen-dependent tumours such as breast cancer in first-degree relatives;
- arterial hypertension, liver disease such as adenoma, diabetes with or without vascular complications, gallstones, migraine or severe headaches, systemic lupus erythematosus, epilepsy, asthma, otosclerosis;
- grounds for stopping treatment are not only a contraindication that comes to light but also jaundice, worsening liver function, a marked rise in blood pressure, a migraine-type headache appearing for the first time, and pregnancy;
- because of fluid retention, women with impaired heart or kidney function are under particular supervision, and in those already known to have hypertriglyceridaemia isolated cases of pancreatitis have been described after a sharp rise in triglycerides during treatment.
The risk figures are known and are given in the leaflet. The risk of endometrial cancer with long-term oestrogen-only use in women with an intact uterus is 2–12 times higher, depends on the duration of treatment and the dose, and stays raised for at least 10 years after it ends; continuous combined therapy does not produce that rise. The risk of breast cancer with combined therapy increases after roughly 3 years of treatment, and the therapy itself increases tissue density on mammograms, which makes radiological detection of a tumour harder. Venous thromboembolism occurs 1.3–3 times more often, most likely in the first year; before planned surgery followed by prolonged immobilisation the therapy should be interrupted 4–6 weeks beforehand and not resumed until full activity has returned. The risk of ischaemic stroke rises by up to half as much again, and replacement therapy has no preventive effect on heart attack. Finally, it does not improve cognitive function, and there is evidence of an increased risk of probable dementia in women who start it after the age of 65.
Interactions with other medicines
No specific interaction studies have been carried out, but two directions are known. The first: the metabolism of oestrogens and progestogens is accelerated by the concomitant use of substances that induce the enzymes involved in drug metabolism, above all the cytochrome P450 isoenzymes 2B6, 3A4, 3A5 and 3A7. These include anticonvulsants such as phenobarbital, carbamazepine and phenytoin, and anti-infectives: rifampicin, rifabutin, nevirapine, efavirenz. Ritonavir and nelfinavir are known as strong inhibitors of 3A4, 3A5 and 3A7, yet together with steroid hormones they show inducing properties. Preparations of St John's wort enhance the metabolism of both hormones through 3A4. Clinically, accelerated metabolism means a weaker effect of the medicine and a change in the pattern of genital bleeding.
There is an influence in the opposite direction as well: oestrogens themselves slow the breakdown of other medicines by competing with them for cytochrome P450 enzymes.
- tacrolimus and ciclosporin A — through 3A4 and 3A3;
- fentanyl — through 3A4;
- theophylline — through 1A2;
- these substances have a narrow therapeutic index, so their plasma concentration may reach toxic values; long-term monitoring of those concentrations and a reduction in the doses of tacrolimus, fentanyl, ciclosporin A and theophylline may be needed.
Pregnancy and breastfeeding
In pregnancy the medicine is not indicated; if pregnancy occurs during treatment, it is stopped at once. Most published epidemiological studies of inadvertent exposure of the fetus to oestrogens with progestogens have shown no teratogenic or toxic effect.
There is not enough data on the use of estradiol with dydrogesterone in pregnant women. Animal studies showed reproductive toxicity, and the possible risk to humans is unknown. During breastfeeding the medicine is likewise not indicated.
Adverse reactions
The commonest complaints of women taking this combination in clinical trials were headache, abdominal pain, breast pain and tenderness on pressure, and low back pain — those four are the ones classed as very common. The rest is distributed as follows.
- common: vaginal candidiasis, depression, nervousness, migraine, dizziness, nausea, vomiting, bloating, allergic skin reactions — rash, urticaria, itching — menstrual disorders including postmenopausal spotting, acyclic periods with prolonged bleeding, heavy, infrequent or absent periods, irregular and painful periods, pelvic pain, vaginal discharge, states of fatigue;
- uncommon: an increase in the size of a fibroid, hypersensitivity reactions, change in libido, venous thromboembolic disease, liver function disorders sometimes with jaundice, weakness or malaise and abdominal pain, gallbladder disease, breast enlargement, premenstrual syndrome;
- rare: heart attack, angioneurotic oedema, vascular purpura.
Bleeding deserves a separate mention. Transient bleeding and mid-cycle spotting during the first months of treatment are to be expected. What is worrying is something else: bleeding that starts later or does not stop after the medicine is withdrawn. Investigations are then arranged, with endometrial biopsy if necessary, to find the cause and rule out a tumour.
Overdose
Both oestrogens and dydrogesterone are substances of low toxicity, so an overdose is rarely dangerous.
In overdose nausea, vomiting, breast tenderness on pressure, dizziness, abdominal pain, drowsiness and fatigue may occur, as well as bleeding after the medicine is withdrawn. These usually require no symptomatic treatment. The same applies to cases of overdose in children.
How to get a Femoston conti prescription online
The medicine is available on prescription, and the first thing the doctor will establish is how long it is since the last period: the continuous regimen is intended for women in whom at least 12 months have passed. The second question is what exactly is being treated — climacteric symptoms or prevention of osteoporosis — because in the second case it must be explained why the usual osteoporosis medicines were not suitable.
For the online consultation prepare the information that decides whether replacement therapy is permissible: breast cancer and other hormone-dependent tumours in yourself and in close female relatives, genital bleeding of unclear origin, thromboses and embolisms, clotting disorders, ischaemic heart disease and heart attack, liver disease and porphyria. Mention separately hypertension, diabetes, migraine, epilepsy, asthma, gallstones, fibroids and endometriosis, the date of your last mammogram and all the medicines you take — especially anticonvulsants, rifampicin, anti-HIV drugs, St John's wort, and also tacrolimus, ciclosporin, fentanyl and theophylline, whose doses sometimes have to be reduced alongside oestrogens. The doctor will assess these circumstances and, if there are no contraindications, will issue an electronic prescription.
