FEMOSTON 1/10 MG FILM-COATED TABLETS
Active substance(s): DYDROGESTERONE MICRONISED / ESTRADIOL HEMIHYDRATE MICRONISED / DYDROGESTERONE MICRONISED / ESTRADIOL HEMIHYDRATE MICRONISED / DYDROGESTERONE MICRONISED / ESTRADIOL HEMIHYDRATE MICRONISED
NAME OF THE MEDICINAL PRODUCT
Femoston 1/10mg film-coated tablets
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 1mg oestradiol (as hemihydrate) or a combination of 1mg
oestradiol (as hemihydrate) and 10mg dydrogesterone.
Excipient with known effect: lactose monohydrate
For the full list of excipients see 6.1.
Oestradiol only tablets: Round, biconvex, white film-coated tablets with
Oestradiol/dydrogesterone combination tablets: Round, biconvex, grey filmcoated tablets with inscription '379'.
Hormone replacement therapy (HRT) for oestrogen deficiency symptoms in
postmenopausal women at least 6 months since last menses.
Prevention of osteoporosis in postmenopausal women at high risk of future
fractures who are intolerant of, or contraindicated for, other medicinal
products approved for the prevention of osteoporosis. (See also section 4.4)
The experience in treating women older than 65 years is limited.
Posology and method of administration
Femoston 1/10 and Femoston 2/10, are continuous sequential hormone
For initiation and continuation of treatment of postmenopausal symptoms, the
lowest effective dose for the shortest duration (see also section 4.4) should be
In general, treatment should start with Femoston 1/10. Depending on the
clinical response, the dosage can afterwards be adjusted to individual need. If
the complaints linked to oestrogen deficiency are not ameliorated the dosage
can be increased by using Femoston 2/10
In women who are not taking hormone replacement therapy and who are
amenorrhoeic, or women who switch from a continuous combined hormone
replacement therapy, treatment may be started on any convenient day. In
women transferring from a cyclic or continuous sequential HRT regimen,
treatment should begin the day following completion of the prior regimen.
For the first 14 days during a 28-cycle, one tablet containing oestradiol is
taken daily; during the following 14 days one tablet containing oestradiol and
dydrogesterone is taken.
After a cycle of 28 days, on the 29th day, a new 28-day cycle begins. This
means that the treatment should be taken continuously without a break
between packs. Femoston can be taken with or without food.
The days of the week are printed on the back of the blister strips. Firstly, the
tablets from the part marked with arrow 1 should be taken, then all the tablets
from the part marked with arrow 2 should be taken.
If a dose has been forgotten, it should be taken as soon as possible. When
more than 12 hours have elapsed, it is recommended to continue with the next
dose without taking the forgotten tablet. The likelihood of breakthrough
bleeding or spotting may be increased.
There is no relevant indication for the use of Femoston in the paediatric
- Known, past or suspected breast cancer;
- Known or suspected oestrogen-dependent malignant tumours (e.g.
- Known or suspected progestogen-dependent neoplasms (e.g. meningioma)
- Undiagnosed genital bleeding;
- Untreated endometrial hyperplasia;
- Previous idiopathic or current venous thromboembolism (deep vein
thrombosis, pulmonary embolism);
- Known thrombophilic disorders (e.g. protein C, protein S, or antithrombin
deficiency, see section 4.4.);
- Active or recent arterial thromboembolic disease (e.g. angina, myocardial
- Acute liver disease or a history of liver disease as long as liver function
tests have failed to return to normal;
- Known hypersensitivity to the active substances or to any of the excipients.
Special warnings and precautions for use
For the treatment of postmenopausal symptoms, HRT should only be initiated for
symptoms that adversely affect quality of life. In all cases, a careful appraisal of the
risks and benefits should be undertaken at least annually and HRT should only be
continued as long as the benefit outweighs the risk.
Evidence regarding the risks associated with HRT in the treatment of premature
menopause is limited. Due to the low level of absolute risk in younger women,
however, the balance of benefits and risks for these women may be more favourable
than in older women.
Medical examination/follow up
Before initiating or reinstituting HRT, a complete personal and family medical history
should be taken. Physical (including pelvic and breast) examination should be guided
by this and by the contraindications and warnings for use. During treatment, periodic
check-ups are recommended of a frequency and nature adapted to the individual
woman. Women should be advised what changes in their breasts should be reported
to their doctor or nurse (see ‘Breast cancer’ below). Investigations, including
appropriate imaging tools, e.g. mammography, should be carried out in accordance
with currently accepted screening practices, modified to the clinical needs of the
Conditions which need supervision
If any of the following conditions are present, have occurred previously, and/or have
been aggravated during pregnancy or previous hormone treatment, the patient should
be closely supervised. It should be taken into account that these conditions may recur
or be aggravated during treatment with Femoston, in particular:
- Leiomyoma (uterine fibroids) or endometriosis
- Risk factors for thromboembolic disorders (see below)
- Risk factors for oestrogen dependent tumours, e.g. 1st degree heredity for
- Liver disorders (e.g. liver adenoma)
- Diabetes mellitus with or without vascular involvement
- Migraine or (severe) headache
- Systemic lupus erythematosus
- A history of endometrial hyperplasia (see below)
Reasons for immediate withdrawal of therapy:
Therapy should be discontinued in cases where a contra-indication is discovered and
in the following situations:
- Jaundice or deterioration in liver function
- Significant increase in blood pressure
- New onset of migraine-type headache
Endometrial hyperplasia and carcinoma
In women with an intact uterus the risk of endometrial hyperplasia and carcinoma is
increased when oestrogens are administered alone for prolonged periods. The
reported increase in endometrial cancer risk among oestrogen-only users varies from
2- to 12-fold greater compared with non-users, depending on the duration of
treatment and oestrogen dose (see section 4.8). After stopping treatment risk may
remain elevated for at least 10 years.
The addition of a progestagen cyclically for at least 12 days per month/28 day cycle
or continuous combined oestrogen-progestagen therapy in non-hysterectomised
women prevents the excess risk associated with oestrogen-only HRT.
Break-through bleeding and spotting may occur during the first months of treatment.
If break-through bleeding or spotting appears after some time on therapy, or
continues after treatment has been discontinued, the reason should be investigated,
which may include endometrial biopsy to exclude endometrial malignancy.
The overall evidence suggests an increased risk of breast cancer in women taking
combined oestrogen-progestagen and possibly also oestrogen-only HRT, that is
dependent on the duration of taking HRT.
Combined oestrogen-progestogen therapy
The randomised placebo-controlled trial, the Womens Health Initiative study (WHI)
and epidemiological studies are consistent in finding an increased risk of breast
cancer in women taking combined oestrogen-progestagen for HRT that becomes
apparent after about 3 years (see Section 4.8).The excess risk becomes apparent
within a few years of use but returns to baseline within a few (at most five) years after
HRT, especially oestrogen-progestagen combined treatment, increases the density of
mammographic images which may adversely affect the radiological detection of
The WHI trial found no increase in the risk of breast cancer in hysterectomised
women using oestrogen-only HRT. Observational studies have mostly reported a
small increase in risk of having breast cancer diagnosed that is substantially lower
than that found in users of oestrogen-progestogen combinations (see section 4.8).
The excess risk becomes apparent within a few years of use but returns to baseline
within a few (at most five) years after stopping treatment.
HRT, especially oestrogen-progestogen combined treatment, increases the density of
mammographic images which may adversely affect the radiological detection of
Ovarian cancer is much rarer than breast cancer. Epidemiological evidence from a
large meta-analysis suggests a slightly increased risk in women taking oestrogen-only
or combined oestrogen-progestagen HRT, which becomes apparent within 5 years of
use and diminishes over time after stopping. Some other studies including the WHI
trial suggest that use of combined HRTs may be associated with a similar or slightly
smaller risk (see Section 4.8).
- HRT is associated with a 1.3-3 fold risk of developing venous
thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism.
The occurrence of such an event is more likely in the first year of HRT than
Patients with known thrombophilic states have an increased risk of VTE and
HRT may add to this risk. HRT is therefore contraindicated in these patients
(see section 4.3)
Generally recognised risk factors for VTE include, use of oestrogens, older
ages, major surgery, prolonged immobilisation, severe obesity (BMI>30
kg/m2), pregnancy/postpartum period, systemic lupus erythematosus (SLE),
and cancer. There is no consensus about the possible role of varicose veins in
As in all postoperative patients, prophylactic measures need to be considered to
prevent VTE following surgery. If prolonged immobilisation is to follow
elective surgery temporarily stopping HRT 4 to 6 weeks earlier is
recommended. Treatment should not be restarted until the woman is
In women with no personal history of VTE but with a first degree relative with
a history of thrombosis at young age, screening may be offered after careful
counselling regarding its limitations (only a proportion of thrombophilic
defects are identified by screening).If a thrombophilic defect is identified
which segregates with thrombosis in family members or if the defect is ‘severe’
(e.g. antithrombin, protein S, or protein C deficiencies or a combination of
defects) HRT is contraindicated.
Women already on chronic anticoagulant treatment require careful
consideration of the benefit-risk use of HRT.
If VTE develops after initiating therapy, the drug should be discontinued.
Patients should be told to contact their doctors immediately when they are
aware of a potential thromboembolic symptom (e.g. painful swelling of a leg,
sudden pain in the chest, dyspnoea).
Coronary artery disease (CAD)
There is no evidence from randomised controlled trials of protection against
myocardial infarction in women with or without existing CAD who received
combined oestrogen-progestagen or oestrogen-only HRT.
Combined oestrogen-progestagen therapy
The relative risk of CAD during use of combined oestrogen+progestagen HRT is
slightly increased. As the baseline absolute risk of CAD is strongly dependent on age,
the number of extra cases of CAD due to oestrogen+progestagen use is very low in
healthy women close to menopause, but will rise with more advanced age.
Randomised controlled data found no increased risk of CAD in hysterectomised
women using oestrogen-only therapy.
Combined oestrogen-progestagen and oestrogen-only therapy are associated with an
up to 1.5-fold increase in risk of ischaemic stroke. The relative risk does not change
with age or time since menopause. However, as the baseline risk of stroke is strongly
age-dependent, the overall risk of stroke in women who use HRT will increase with
age (see section 4.8).
• Oestrogens may cause fluid retention, and therefore patients with cardiac or
renal dysfunction should be carefully observed. Women with pre-existing
hypertriglyceridemia should be followed closely during oestrogen replacement
or hormone replacement therapy, since rare cases of large increases of plasma
triglycerides leading to pancreatitis have been reported with oestrogen therapy
in this condition.
Oestrogens increase thyroid binding globulin (TBG), leading to increased
circulating total thyroid hormone, as measured by protein-bound iodine (PBI),
T4 levels (by column or by radio-immunoassay) or T3 levels (by radioimmunoassay). T3 resin uptake is decreased, reflecting the elevated TBG. Free
T4 and free T3 concentrations are unaltered. Other binding proteins may be
elevated in serum, i.e. corticoid binding globulin (CBG), sex- hormone-binding
globulin (SHBG) leading to increased circulating corticosteroids and sex
steroids, respectively. Free or biological active hormone concentrations are
unchanged. Other plasma proteins may be increased (angiotensinogen/renin
substrate, alpha-1-antitrypsin, ceruloplasmin).
HRT use does not improve cognitive function. There is some evidence of
increased risk of possible dementia in women who start using continuous
combined or oestrogen-only HRT after the age of 65.
Patients with rare hereditary problems of galactose intolerance, the Lapp
lactase deficiency or glucose-galactose malabsorption should not take this
Women who may be at risk of pregnancy should be advised to adhere to nonhormonal contraceptive methods.
Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
The efficacy of oestrogens and progestogens might be impaired:
The metabolism of oestrogens and progestagens may be increased by
concomitant use of substances known to induce drug-metabolising enzymes,
specifically the P450 enzymes 2B6, 3A4, 3A5, 3A7, such as anticonvulsants
(e.g. phenobarbital, phenytoin, carbamezapin) and anti-infectives (e.g.
rifampicin, rifabutin, nevirapine, efavirenz).
Ritonavir and nelfinavir, although known as strong inhibitors of CYP450 3A4,
A5, A7, by contrast exhibit inducing properties when used concomitantly with
Herbal preparations containing St John’s Wort (Hypericum perforatum) may
induce the metabolism of oestrogens and progestagens via the CYP450 3A4
Clinically an increased metabolism of oestrogens and progestagens may lead
to decreased effect and changes in the uterine bleeding profile.
Oestrogens might interfere with the metabolism of other drugs:
Oestrogens per se may inhibit CYP450 drug-metabolising enzymes via
competitive inhibition. This is in particular to be considered for substrates with
a narrow therapeutic index, such as:
- tacrolimus and cyclosporine A (CYP450 3A4, 3A3)
- fentanyl (CYP450 3A4)
- theophylline (CYP450 1A2).
Clinically this may lead to an increased plasma level of the affected substances
up to toxic concentrations. Thus, careful drug monitoring for an extended
period of time might be indicated and a dosage decrease of tacrolimus,
fentanyl, cyclosporin A and theophylline may be necessary.
Pregnancy and lactation
Femoston is not indicated during pregnancy. If pregnancy occurs during
medication with Femoston, treatment should be withdrawn immediately.
The results of most epidemiological studies to date relevant to inadvertent
foetal exposure to combinations of oestrogens and progestagens indicate no
teratogenic or foetotoxic effect.
There are no adequate data from the use of oestradiol/dydrogesterone in
Femoston is not indicated during lactation.
Effects on ability to drive and use machines
Femoston does not affect the ability to drive and use machines.
The most commonly reported adverse drug reactions of patients treated with
oestradiol/dydrogesterone in clinical trials are headache, abdominal pain,
breast pain/tenderness and back pain.
The following undesirable effects have been observed with the frequencies
indicated below during clinical trials (n=4929):
Increase in size
Breast Cancer risk
• An up to 2-fold increased risk of having breast cancer diagnosed is
reported in women taking combined oestrogen-progestagen therapy for
more than 5 years.
• Any increased risk in users of oestrogen-only therapy is substantially
lower than that seen in users of oestrogen-progestagen combinations.
• The level of risk is dependent on the duration of use (see section 4.4).
• Results of the largest randomised placebo-controlled trial (WHI-study) and
largest epidemiological study (MWS) are presented.
Million Women study– Estimated additional risk of breast cancer after 5
Risk ratio & Additional cases per 1000
Age range Additional cases per 1000
HRT users over 5 years
never-users of HRT over a 5 95%CI#
Oestrogen only HRT
#Overall risk ratio. The risk ratio is not constant but will increase with increasing
duration on use
Note: Since the background incidence of breast cancer differs by EU country, the
number of additional cases of breast cancer will also change proportionately.
Taken from baseline incidence rates in developed countries
US WHI studies - additional risk of breast cancer after 5 years’ use
Age range Incidence per 1000
Risk ratio & Additional cases per 1000
women in placebo arm
HRT users over 5 years
over 5 years
0.8 (0.7 –
-4 (-6 – 0)*2
CEE+MPA oestrogen & progestagen‡
1.2 (1.0 –
+4 (0 – 9)
WHI study in women with no uterus, which did not show an increase in risk of
‡When the analysis was restricted to women who had not used HRT prior to
the study there was no increased risk apparent during the first 5 years of
treatment: after 5 years the risk was higher than in non-users.
Postmenopausal women with a uterus
The endometrial cancer risk is about 5 in every 1000 women with a uterus not
In women with a uterus, use of oestrogen-only HRT is not recommended because
it increases the risk of endometrial cancer (see section 4.4). Depending on the
duration of oestrogen-only use and oestrogen dose, the increase in risk of
endometrial cancer in epidemiology studies varied from between 5 and 55 extra
cases diagnosed in every 1000 between the ages of 50 and 65.
Adding a progestagen to oestrogen-only therapy for at least 12 days per cycle can
prevent this increased risk. In the Million Women Study the use of five years of
combined (sequential or continuous) HRT did not increase risk of endometrial
cancer (R.R of 1 .0 (0.8-1.2)).
Use of oestrogen-only or combined oestrogen-progestagen HRT has been
associated with a slightly increased risk of having ovarian cancer diagnosed (see
A meta-analysis from 52 epidemiological studies reported an increased risk of
ovarian cancer in women currently using HRT compared to women who have
never used HRT (RR 1.43, 95% CI 1.31-1.56). For women aged 50 to 54 years
taking 5 years of HRT, this results in about 1 extra case per 2000 users. In
women aged 50 to 54 who are not taking HRT, about 2 women in 2000 will be
diagnosed with ovarian cancer over a 5-year period.
Risk of venous thromboembolism
HRT is associated with a 1.3-3-fold increased relative risk of developing venous
thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. The
occurrence of such an event is more likely in the first year of using HT (see
section 4.4.). Results of the WHI studies are presented:
WHI Studies - Additional risk of VTE over 5 years’ use
Incidence per 1000 women in Risk ratio
placebo arm over 5 years
Oral combined oestrogen-progestagen
2.3 (1.2 –
Study in women with no uterus
Additional cases per
1000 HRT users
1 (-3 – 10)
5 (1 - 13)
Risk of coronary artery disease
• The risk of coronary artery disease is slightly increased in users of
combined oestrogen-progestagen HRT over the age of 60 (see section 4.4).
Risk of ischaemic stroke
• The use of oestrogen-only and oestrogen + progestagen therapy is
associated with an up to 1.5 fold increased relative risk of ischaemic stroke.
The risk of haemorrhagic stroke is not increased during use of HRT.
• This relative risk is not dependent on age or on duration of use, but as the
baseline risk is strongly age-dependent, the overall risk of stroke in women
who use HRT will increase with age, see section 4.4.
WHI studies combined - Additional risk of ischaemic stroke*4 over 5 years’
Incidence per 1000 women
Additional cases per
in placebo arm over 5 years and 95%CI
1000 HRT users
No differentiation was made between ischaemic and haemorrhagic stroke
Other adverse reactions have been reported in association with
oestrogen/progestogen treatment (including oestradiol/dydrogesterone):
Neoplasms benign, malignant and unspecified:
Oestrogen dependent neoplasms both benign and malignant, e.g. endometrial
cancer, ovarian cancer. Increase in size of progestogen dependent neoplasms, e.g.
Blood and lymphatic system disorders:
Immune system disorders:
Systemic lupus erythematosus
Metabolism and nutrition disorders:
Nervous system disorders:
Probable dementia over the age of 65 (see section 4.4), chorea, exacerbation of
Steepening of corneal curvature, contact lenses intolerance
Pancreatitis (in women with pre-existing hypertriglyceridemia)
Skin and subcutaneous tissue disorders:
Erythema multiforme, erythema nodosum, chloasma or melasma, which may
persist when drug is discontinued.
Musculoskeletal and connective tissue disorders:
Renal and urinary disorders:
Reproductive system and breast disorders:
Fibrocystic breast disease, uterine cervical erosion
Congenital, familial and genetic disorders:
Total thyroid hormones increased
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal
product is important. It allows continued monitoring of the benefit/risk balance of
the medicinal product. Healthcare professionals are asked to report any suspected
adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Both oestradiol and dydrogesterone are substances with low toxicity.
Symptoms such as nausea, vomiting, breast tenderness, dizziness, abdominal
pain, drowsiness/fatigue, and withdrawal bleeding could occur in cases of
overdosing. It is unlikely that any specific or symptomatic treatment will be
Aforementioned information is applicable for overdosing by children also.
The ATC code is G03FB08. (Oestrogens: urogenital system and sex
Sequential hormone replacement therapy (combined oestradiol and
The active ingredient, synthetic 17β-oestradiol, is chemically and biologically
identical to endogenous human oestradiol. It substitutes for the loss of
oestrogen production in menopausal women, and alleviates menopausal
symptoms. Oestrogens prevent bone loss following menopause or
Dydrogesterone is an orally-active progestagen having an activity comparable
to parenterally administered progesterone. As oestrogens promote the growth
of the endometrium, unopposed oestrogens increase the risk of endometrial
hyperplasia and cancer. The addition of a progestagen greatly reduces the
oestrogen-induced risk of endometrial hyperplasia in non-hysterectomised
Clinical trial information
Relief of oestrogen-deficiency symptoms and bleeding patterns.
- Relief of menopausal symptoms was achieved during the first few weeks of
- Regular withdrawal bleeding with Femoston 1/10 occurred in
approximately 75-80% of women with a mean duration of 5 days.
Withdrawal bleeding usually started on the day of the last pill of the
progestagen phase. Break-through bleeding and/or spotting occurred in
approximately 10% of the women; amenorrhoea (no bleeding or spotting)
occurred in 21-25% of the women for months 10 to 12 of treatment.
- With Femoston 2/10, approximately 90% of women had regular
withdrawal bleeding. The start day and duration of bleeding, and the
number of women with intermittent bleeding was the same as with
Femoston 1/10, amenorrhoea occurred in 7-11% of the women for months
10 to 12 of treatment.
Prevention of osteoporosis
- Oestrogen deficiency at menopause is associated with an increasing bone
turnover and decline in bone mass.
- The effect of oestrogens on the bone mineral density is dose-dependent.
Protection appears to be effective for as long as treatment is continued.
After discontinuation of HRT, bone mass is lost at a rate similar to that in
- Evidence from the WHI trial and meta-analysed trials shows that current
use of HRT, alone or in combination with a progestagen – given to
predominantly healthy women – reduces the risk of hip, vertebral, and
other osteoporotic fractures. HRT may also prevent fractures in women
with low bone density and/or established osteoporosis, but the evidence for
that is limited.
- After two years of treatment with Femoston 2/10, the increase in lumbar
spine bone mineral density (BMD) was 6.7% ± 3.9% (mean ± SD). The
percentage of women who maintained or gained BMD in lumbar zone
during treatment was 94.5%. For Femoston 1/10 the increase in lumbar
spine BMD was 5.2% ± 3.8% (mean ± SD), and the percentage of women
with no change or an increase in lumbar spine BMD was 93%.
- Femoston also had an effect on hip BMD. The increase after two years of
treatment with 1mg oestradiol was 2.7% ± 4.2% (mean ± SD) at femoral
neck, 3.5% ± 5.0% (mean ± SD) at trochanter and 2.7%± 6.7% (mean ±
SD) at Wards triangle. After two years of treatment with 2mg oestradiol
these figures were respectively, 2.6% ± 5.0%; 4.6% ± 5.0% and 4.1% ±
7.4%. The percentage of women who maintained or gained BMD in the 3
hip areas after treatment with 1mg oestradiol was 67-78% and 71-88% after
treatment with 2mg oestradiol.
Absorption of oestradiol is dependent on the particle size: micronized
oestradiol is readily absorbed from the gastrointestinal tract.
The following table provides the mean steady state pharmacokinetic
parameters of oestradiol (E2), estrone (E1) and estrone sulphate (E1S) for each
dose of micronized oestradiol. Data is presented as mean (SD).
Oestrogens can be found either unbound or bound. About 98-99% of the
oestradiol dose binds to plasma proteins, from which about 30-52% to albumin
and about 46-69% to the sex hormone-binding globulin (SHBG).
Following oral administration, oestradiol is extensively metabolised. The
major unconjugated and conjugated metabolites are estrone and estrone
sulphate. These metabolites can contribute to the oestrogen activity, either
directly or after conversion to oestradiol. Estrone sulphate may undergo
In urine, the major compounds are the glucuronides of estrone and oestradiol.
The elimination half-life is between 10-16 h.
Oestrogens are secreted in the milk of nursing mothers.
• Dose and time dependencies
Following daily oral administration of Femoston, oestradiol concentrations
reached a steady-state after about five days.
Generally, steady state concentrations appeared to be reached for within 8 to
11 days of dosing.
Following oral administration, dydrogesterone is rapidly absorbed with a Tmax
between 0.5 and 2.5 hours. The absolute bioavailability of dydrogesterone
(oral 20mg dose versus 7.8mg intravenous infusion) is 28%.
The following table provide the mean steady state pharmacokinetic parameters
of dydrogesterone (D) and dihydrodydrogesterone (DHD). Data is presented
as mean (SD).
After intravenous administration of dydrogesterone the steady-state volume of
distribution is approximately 1400 L. Dydrogesterone and DHD are more than
90% bound to plasma proteins.
Following oral administration, dydrogesterone is rapidly metabolised to DHD.
The levels of the main active metabolite 20 α-dihydrodydrogesterone (DHD)
peak about 1.5 hours post dose. The plasma levels of DHD are substantially
higher as compared to the parent drug. The AUC and Cmax ratios of DHD to
dydrogesterone are in the order of 40 and 25, respectively. Mean terminal halflives of dydrogesterone and DHD vary between 5 to 7 and 14 to 17 hours,
respectively. A common feature of all metabolites characterised is the
retention of the 4,6 diene-3-one configuration of the parent compound and the
absence of 17α- hydroxylation. This explains the lack of oestrogenic and
androgenic effects of dydrogesterone.
After oral administration of labelled dydrogesterone, on average 63% of the
dose is excreted into the urine. Total plasma clearance is 6.4 L/min. Within 72
hours excretion is complete. DHD is present in the urine predominantly as the
glucuronic acid conjugate.
• Dose and time dependencies
The single and multiple dose pharmacokinetics are linear in the oral dose
range 2.5 to 10mg. Comparison of the single and multiple dose kinetics shows
that the pharmacokinetics of dydrogesterone and DHD are not changed as a
result of repeated dosing. Steady state was reached after 3 days of treatment.
Preclinical safety data
There are no preclinical safety data of relevance to the prescriber in the target
population that are additional to those already included in other sections of the
Summary of Product Characteristics (SmPC).
List of excipients
Oestradiol only tablets:
colloidal anhydrous silica,
Opadry Y-l-7000 white:
polyethylene glycol 400,
titanium dioxide (E171)
colloidal anhydrous silica,
Opadry II grey 85F27664: polyvinyl alcohol,
iron oxide black (E172)
Special precautions for storage
This medicinal product does not require any special storage conditions.
Nature and contents of container
PVC film with a covering aluminium foil.
Blister packs: 28 film-coated tablets
84 film-coated tablets
Not all pack sizes may be marketed.
Special precautions for disposal
Any unused product or waste material should be disposed of in accordance
with local requirements.
MARKETING AUTHORISATION HOLDER
Mylan Products Ltd.
20 Station Close
MARKETING AUTHORISATION NUMBER(S)
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
DATE OF REVISION OF THE TEXT
Source: Medicines and Healthcare Products Regulatory Agency
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