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FEMOSTON CONTI 0.5MG/2.5MG FILM-COATED TABLETS

Active substance: ESTRADIOL

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Femoston-conti® 0.5mg/2.5mg film-coated tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

28 tablets, each containing 0.5 mg 17 -estradiol (as hemihydrate) and 2.5 mg dydrogesterone.

β

Excipient with known effect: lactose monohydrate 117.4 mg
For the full list of excipients, see section Error! Reference source not found..

3

PHARMACEUTICAL FORM
Film-coated tablet
A round, biconvex, marked 379 on one side
(7mm)
Yellow 0.5/2.5mg tablets

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Hormone replacement therapy (HRT) for oestrogen deficiency symptoms in
postmenopausal women at least 12 months since last menses.
The experience in treating women older than 65 years is limited.

4.2

Posology and method of administration
Femoston-conti 0.5mg/2.5mg film-coated tablets are a continuous combined
HRT for oral use.
The oestrogen and the progestogen are given every day without interruption.
The dosage is one tablet per day for a 28 day cycle.
Femoston-conti 0.5mg/2.5mg film-coated tablets should be taken continuously
without a break between packs.
For initiation and continuation of treatment of postmenopausal symptoms, the
lowest effective dose for the shortest duration (see also section 4.4) should be
used.
Continuous combined treatment may be started with Femoston-conti
0.5mg/2.5mg film-coated tablets depending on the time since menopause and
severity of symptoms. Women experiencing a natural menopause should

commence treatment with Femoston-conti 0.5mg/2.5mg film-coated tablets 12
months after their last natural menstrual bleed. For surgically induced
menopause, treatment may start immediately.
Depending on the clinical response, the dosage can subsequently be adjusted.
Patients changing from a continuous sequential or cyclical preparation should
complete the 28 day cycle and then change to Femoston-conti 0.5mg/2.5mg
film-coated tablets.
Patients changing from another continuous combined preparation may start
therapy at any time.
If a dose has been forgotten, it should be taken as soon as possible. If more
than 12 hours have elapsed, treatment should be continued with the next tablet
without taking the forgotten tablet. The likelihood of breakthrough bleeding or
spotting may be increased.
Femoston-conti 0.5mg/2.5mg film-coated tablets can be taken irrespectively of
food intake.
Paediatric population:
There is no relevant indication for the use of Femoston-conti 0.5mg/2.5mg
film-coated tablets in the paediatric population.

4.3











4.4

Contraindications
Known, past or suspected breast cancer
Known or suspected oestrogen-dependent malignant tumours (e.g. endometrial cancer)
Undiagnosed genital bleeding
Untreated endometrial hyperplasia
Previous or current venous thromboembolism (deep venous 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 infarction)
Acute liver disease, or a history of liver disease, as long as the liver function tests have
failed to return to normal
Porphyria
Known hypersensitivity to the active substances or to any of the excipients listed in
section 6.1
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 re-instituting 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 individual.
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-conti 0.5 mg/2.5 mg, 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 breast cancer
Hypertension
Liver disorders (e.g. liver adenoma)
Diabetes mellitus with or without vascular involvement
Cholelithiasis
Migraine or (severe) headache
Systemic lupus erythematosus
A history of endometrial hyperplasia (see below)
Epilepsy
Asthma
Otosclerosis
Meningioma

Reasons for immediate withdrawal of therapy
Therapy should be discontinued in case a contraindication is discovered and in the following
situations:





Jaundice or deterioration in liver function
Significant increase in blood pressure
New onset of migraine-type headache
Pregnancy

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 progestogen cyclically for at least 12 days per month /28 day cycle or
continuous combined oestrogen-progestogen therapy in non-hysterectomised women can
prevent 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.


Breast cancer
The overall evidence suggests an increased risk of breast cancer in women taking combined
oestrogen-progestogen 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 Women’s Health Initiative study (WHI), and
epidemiological studies are consistent in finding an increased risk of breast cancer in
women taking combined oestrogen-progestogen for HRT that becomes apparent after
about 3 years (see section 4.8).

Oestrogen-only therapy:
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 breast
cancer.
Ovarian cancer
Ovarian cancer is much rarer than breast cancer. Long-term (at least 5-10 years) use of
oestrogen-only HRT products has been associated with a slightly increased risk of ovarian
cancer (see section 4.8). Some studies, including the WHI trial suggest that the long-term use
of combined HRT may confer a similar, or slightly smaller, risk (see section 4.8).
Venous thromboembolism

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 later (see section 4.8).


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 age, major
surgery, prolonged immobilisation, 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 VTE.
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 completely mobilised.



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 anticoagulant treatment require careful consideration of the benefitrisk of 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 oestrogenprogestogen or oestrogen-only HRT.
Combined oestrogen-progestogen therapy:
The relative risk of CAD during use of combined oestrogen-progestogen 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-progestogen use is very low in healthy women close to
menopause, but will rise with more advanced age.
Oestrogen-only:
Randomised controlled data found no increased risk of CAD in hysterectomised women using
oestrogen-only therapy.
Ischaemic Stroke
Combined oestrogen-progestogen 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).
Other conditions
• Oestrogens may cause fluid retention, and therefore patients with cardiac or renal
dysfunction should be carefully observed.
• Women with pre-existing hypertriglyceridaemia 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 radio-immunoassay). 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), sexhormone-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 probable 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, Lapp lactase deficiency or
glucose-galactose malabsorption should not take this medicine.

This oestrogen-progestogen combination treatment is not a contraceptive.

4.5

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 progestogens may be increased by
concomitant use of substances known to induce drug-metabolising
enzymes, specifically P450 enzymes, such as anticonvulsants (e.g.
phenobarbital, carbamazepin, phenytoin) and anti-infectives (e.g.
rifampicin, rifabutin, nevirapine, efavirenz).
• Ritonavir and nelfinavir, although known as strong inhibitors, by contrast
exhibit inducing properties when used concomitantly with steroid
hormones.
• Herbal preparations containing St. John’s Wort (Hypericum perforatum)
may induce the metabolism of oestrogens and progestogens. Clinically, an
increased metabolism of oestrogens and progestogens may lead to
decreased effect and changes in the uterine bleeding profile.

4.6

Pregnancy and lactation

Pregnancy
Femoston-conti 0.5 mg/2.5 mg is not indicated during pregnancy. If pregnancy occurs during
medication with Femoston-conti 0.5 mg/2.5 mg treatment should be withdrawn immediately.
There are no adequate data from the use of estradiol/dydrogesterone in pregnant women.The
results of most epidemiological studies to date relevant to inadvertent fetal exposure to
combinations of oestrogens and progestogens indicate no teratogenic or foetotoxic effect.
Lactation
Femoston-conti 0.5 mg/2.5 mg is not indicated during lactation.

4.7

Effects on ability to drive and use machines
Femoston-conti 0.5mg/2.5mg film-coated tablets have no or negligible
influence on the ability to drive and/or to use machines.

4.8

Undesirable effects

The most commonly reported adverse drug reactions of patients treated with
estradiol/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).
*Undesirable effects from spontaneous reporting not observed in clinical trials have been
attributed to the frequency “rare”:



Vaginal
candidiasis

Neoplasms
benign, malignant
and unspecified
Blood and the
lymphatic system
disorders
Immune system
disorders
Psychiatric
disorders
Nervous system
disorders



Infections and
infestations

Common
1/100 to <1/10

Uncommon
1/1,000 to
<1/100
Cystitis- like
symptoms



Very common
1/10

Increase in size of
leiomyoma
Haemolytic
anaemia*
Hypersensitivity
Depression,
nervousness
Headache

Influence on
libido,

Migraine,
dizziness

Meningioma*

Eye disorders

Cardiac disorders
Vascular disorders

Gastrointestinal
disorders
Hepatobiliary
disorders

Skin and
subcutaneous
tissue disorders

Rare
1/10,000 to
<1/1,000



MedDRA system
organ class

Abdominal pain

Nausea, vomiting
, flatulence

Venous
thromboembolism*
, hypertension,
peripheral vascular
disease, varicose
vein
Dyspepsia

Steepening of
corneal
curvature*,
contact lenses
intolerance*
Myocardial
infarction
Stroke*

Abnormal hepatic
function
occasionally with
jaundice asthenia
or malaise, and
abdominal pain.
gallbladder
disorders
Allergic skin
reactions (e.g.
rash, urticaria,
pruritus)

Angioedema,
vascular purpura,
erythema
nodosum*,
Chloasma or
melasma, which
may persist when
drug is
discontinued*

Back pain

Investigations



General disorders
and administration
site reactions

Breast
pain/tenderness

Uncommon
1/1,000 to
<1/100

Menstrual
disorders
(including
postmenopausal
spotting,
metrorrhagia,
menorrhagia,
oligo/amenorrhoea,
irregular
menstruation,
dysmenorrhoea),
pelvic pain,
cervical discharge

Breast
enlargement,
premenstrual
syndrome



Musculoskeletal
and connective
tissue disorders
Reproductive
system and breast
disorders

Common
1/100 to <1/10

Asthenic
conditions
(asthenia, fatigue,
malaise),
peripheral oedema
Increased weight



Very common
1/10

Rare
1/10,000 to
<1/1,000
Leg cramps*



MedDRA system
organ class

Decreased weight

Breast cancer risk
• An up to 2-fold increased risk of having breast cancer diagnosed is reported in women
taking combined oestrogen-progestogen 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-progestogen 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 years’ use
Additional cases
per 1000 neverAge
Additional cases per 1000 HRT users over 5 years
users of HRT
Risk ratio #
range
(95%CI)
over a 5 year
(years)
period1
Oestrogen only HRT
50 - 65
9 - 12
1.2
1 - 2 (0 - 3)
Combined oestrogen-progestogen
50 - 65
9 - 12
1.7
6 (5 - 7)
#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.

1

Taken from baseline incidence rates in developed countries

US WHI studies - additional risk of breast cancer after 5 years’ use
Age
Incidence per 1000 women
Additional cases per 1000 HRT
range
in placebo arm over 5 years Risk ratio & 95%CI
users over 5 years (95%CI)
(yrs)
CEE oestrogen-only
50 - 79
21
0.8 (0.7 – 1.0)
-4 (-6 – 0)2
CEE+MPA oestrogen & progestogen‡
50 - 79
17
1.2 (1.0 – 1.5)
+4 (0 – 9)
‡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.
Endometrial cancer risk
Postmenopausal women with a uterus:
The endometrial cancer risk is about 5 in every 1000 women with a uterus not using HRT.
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 women between the ages of 50 and 65.
Adding a progestogen 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 the risk of endometrial cancer (RR of 1.0 (0.8-1.2)).
Ovarian cancer
Long-term use of oestrogen-only and combined oestrogen-progestogen HRT has been
associated with a slightly increased risk of ovarian cancer. In the Million Women Study 5
years of HRT resulted in 1 extra case per 2500 users.
Risk of venous thromboembolism
HRT is associated with a 1.3- to 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 HRT (see section 4.4). Results of the
WHI studies are presented:

WHI Studies - Additional risk of VTE over 5 years’ use
Age range (years) Incidence per 1000
Risk ratio and
women in placebo arm
95%CI
over 5 years
Oral oestrogen-only3
50 - 59
7
1.2 (0.6-2.4)
Oral combined oestrogen-progestogen
50 - 59
4
2.3 (1.2 – 4.3)

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 oestrogenprogestogen HRT over the age of 60 (see section 4.4).
2
3

WHI study in women with no uterus, which did not show an increase in risk of breast cancer
Study in women with no uterus

Risk of ischaemic stroke
The use of oestrogen-only and oestrogen+progestogen therapy is associated with an up to 1.5fold 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 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 stroke4 over 5 years’ use
Age range (years)
Incidence
Risk ratio and
Additional cases per
per 1000 women in
95%CI
1000
placebo arm over 5
HRT users over 5
years
years
50 - 59
8
1.3 (1.1 - 1.6)
3 (1 - 5)
Other adverse reactions have been reported in association with oestrogen/progestogen
treatment
Neoplasms benign, malignant and unspecified:
Oestrogen- dependent neoplasms both benign and malignant, e.g. endometrial cancer,
ovarian cancer. Increase in size of meningioma.
Immune system disorders:
Systemic lupus erythematosus
Metabolism and nutrition disorders:
Hypertriglyceridemia
Nervous system disorders:
Probable dementia, chorea, exacerbation of epilepsy
Vascular disorders:
Arterial thromboembolism
Gastrointestinal disorders:
Pancreatitis (in women with pre-existing hypertriglyceridemia)
Skin and subcutaneous tissue disorders:
Erythema multiforme
Renal and urinary disorders:
Urinary incontinence
Reproductive system and breast disorders:
Fibrocystic breast disease, uterine cervical erosion
Congenital, familial and genetic disorders:
Aggravated porphyria
Investigations:

4

no differentiation was made between ischaemic and haemorrhagic stroke.

Total thyroid hormones increased

4.9

Overdose

Both estradiol 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 necessary.
Aforementioned information is also applicable for overdosing in children.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Genito urinary system and sex hormones, progestogens and
oestrogens, fixed combinations.
ATC code: G03FA14.
Estradiol
The active ingredient, synthetic 17 -estradiol, is chemically and biologically identical to
endogenous human estradiol. It substitutes for the loss of oestrogen production in menopausal
women, and alleviates menopausal symptoms.

β

Dydrogesterone
Dydrogesterone is an orally-active progestogen 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 progestogen greatly reduces the
oestrogen-induced risk of endometrial hyperplasia in non-hysterectomised women.
Clinical trial information
• Relief of oestrogen-deficiency symptoms and bleeding patterns
• Relief of menopausal symptoms was achieved during the first few weeks of
treatment.

With Femoston conti 0.5 mg/2.5 mg the reduction of moderate to severe hot flushes was
statistically significant versus placebo from week 4 onward. The number of moderate to
severe hot flushes decreased further until end of treatment period in week 13.
In two studies amenorrhoea (no bleeding or spotting) was seen in 91% and in 88% of the
women respectively during months 10-12 of treatment. Irregular bleeding and or spotting
appeared in 10% and 21% of the women during the first 3 months of treatment and in 9% and
in 12% during months 10-12 of treatment.

5.2

Pharmacokinetic properties

Estradiol

Absorption:
Absorption of estradiol is dependent on the particle size: micronized estradiol is readily
absorbed from the gastrointestinal tract.

The following table provides the mean steady state pharmacokinetic parameters of estradiol
(E2), estrone (E1) and estrone sulphate (E1S) for each dose of micronized estradiol. Data is
presented as mean (SD).

Estradiol 0.5 mg
Parameters
Cmax (pg/mL)
Cmin (pg/mL)
Cav (pg/mL)
AUC0-τ
(pg.h/mL)

E2
34.8 (30.4)
21.5 (16.0)
516 (383)

E1
182 (110)
2959 (2135)

Parameters
Cmax (ng/mL)
AUC0-τ
(ng.h/mL)

E1S
6.98 (3.32)
82.0 (42.6)


Distribution:
Oestrogens can be found either unbound or bound. About 98- 99% of the estradiol dose binds
to plasma proteins, from which about 30-52% to albumin and about 46-69% to the sex
hormone-binding globulin (SHBG).


Metabolism:
Following oral administration, estradiol 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 estradiol. Estrone sulphate may
undergo enterohepatic circulation.

Elimination:
In urine, the major compounds are the glucuronides of estrone and estradiol. 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, estradiol concentrations reached a steadystate after about five days.
Generally, steady state concentrations appeared to be reached for within 8 to 11 days of
dosing.

Dydrogesterone

Absorption:
Following oral administration, dydrogesterone is rapidly absorbed with a Tmax between 0.5
and 2.5 hours. The absolute bioavailability of dydrogesterone (oral 20 mg dose versus 7.8 mg
intravenous infusion) is 28 %.
The following table provides the mean steady state pharmacokinetic parameters of
dydrogesterone (D) and dihydrodydrogesterone (DHD). Data is presented as mean (SD).

Dydrogesterone 2.5 mg
Parameters
Cmax (ng/mL)
Cmin (ng/mL)
Cav (ng/mL)
AUC0-τ (ng.h/mL)

D
0.759 (0.313)
0.0309 (0.0209)
0.117 (0.0455)
2.81 (1.09)

DHD
18.9 (7.22)
90.4 (44.1)



Distribution:
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.

Metabolism:
Following oral administration, dydrogesterone is rapidly metabolised to DHD. The levels of
the main active metabolite 20 -dihydrodydrogesterone (DHD) peak about 1.5 hours
postdose. 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 half lives 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
17 -hydroxylation. This explains the lack of oestrogenic and androgenic effects of
dydrogesterone.

α

α


Elimination:
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 10 mg.
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.

5.3

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).

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Core:
Lactose monohydrate

Hypromellose
Maize starch
Colloidal anhydrous silica
Magnesium stearate
Film-coating:
Macrogol 3350
Polyvinyl alcohol
Talc
Titanium dioxide (E171)
Iron oxide yellow (E172)

6.2

Incompatibilities
Not applicable

6.3

Shelf life
Femoston-conti® 0.5 mg/2.5 mg: 48 months

6.4

Special precautions for storage
This medicinal product does not require any special storage conditions.

6.5

Nature and contents of container
PVC/Aluminium blister strips in a printed carton.
Blister packs: 28 film-coated tablets
84 film-coated tablets
280 (10 x 28) film-coated tablets
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
Any unused product or waste material should be disposed of in accordance
with local requirements.

7

MARKETING AUTHORISATION HOLDER
Abbott Healthcare Products Ltd.
Mansbridge Road
Southampton
SO18 3JD

8

MARKETING AUTHORISATION NUMBER(S)
PL 00512/0397

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
28/05/2010

10

DATE OF REVISION OF THE TEXT
27/12/2013

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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