Brand
name : TIBOFEM ( Tibolone)
Gynaecological Products
Tibofem :
Tibolone Tablets
Composition
Each uncoated tablet contains
Tibolone ............................. 2.5 mg
Dosage form TIBOFEM ( Tibolone)
Oral tablet :
Description:
Tibolone is a selective tissue estrogenic activity regulator (STEAR),
as it regulates estrogenic activity in a tissue selective manner,
resulting in desired estrogenic effects on tissues like brain,
bone and vagina, while avoiding undesired estrogenic effects on
endometrium and breast. Tibolone is rapidly converted to three
key metabolites: 3alpha-hydroxy tibolone, 3beta-hydroxy tibolone
and the delta4-isomer of tibolone. Most of the activity of tibolone
is derived from these three metabolites.
Clinical pharmacology
Pharmacodynamics
Following oral administration, tibolone is rapidly metabolized
into three compounds which all contribute to its pharmacological
effects. Two of these metabolites (3a-OH-tibolone and 3ß-OH-tibolone)
have oestrogen-like activity, whereas the third metabolite (?4-isomer
of tibolone) has progestagenic and androgenic-like activities.
Tibolone substitutes for the loss of oestrogen production in postmenopausal
women, and alleviates menopausal symptoms.
Tibolone prevents bone loss following menopause or ovariectomy.
Benefits of tibolone in reducing bone resorption in postmenopausal
women may be secondary to reduced urinary calcium excretion via
an increase in renal tubular reabsorption of calcium; this would
result in increases in serum calcium levels and decreased parathyroid
hormone secretion.
It also has effects on certain metabolic and haematological parameter
such as a decrease in plasma high density lipoprotein cholesterol,
triglycerides and lipoprotein (a), and an increase in blood fibrinolytic
activity. Finally, tibolone has favourable effects on mood and
libido.
Pharmacokinetics
Following oral administration tibolone is rapidly and extensively
absorbed. The consumption of food has no significant effects
on the extent of absorption. Due to rapid metabolism the plasma
levels of tibolone are very low. The plasma levels of the ?4-isomer
of tibolone are also very low. Therefore some of the pharmacokinetic
parameters could not be determined. Peak plasma levels of the
3a-OH and the 3ß-OH metabolites are higher but accumulation
does not occur.
Excretion of tibolone is mainly in the form of conjugated (mostly
sulfated) metabolites. Part of the administered compound is excreted
in the urine, but most is eliminated via the faeces . The pharmacokinetic
parameters for tibolone and its metabolites were found to be independent
of renal function.
In estrogen deficiency states for the treatment of vasomotor symptoms
(such as hot flushes and sweating), depressed mood, decreased libido
and prevention of osteoporosis in women at risk of developing fractures
Dosage and Administration
The dosage is 2.5 mg per day. The tablet should be swallowed with
some water or other drink, preferably at the same time of day.
Improvement of symptoms generally occurs within a few weeks, but
optimal results are obtained when therapy is continued for at least
3 months. At the recommended dosage, Tibofem may be used uninterrupted
for longer periods.
Starting Tibofem
Women experiencing a natural menopause should commence treatment
with Tibofem, 12 months after their last natural bleed. If Tibofem
is taken sooner than this, irregular menstrual bleeding may occur.
In the case of artificial menopause, treatment with Tibofem may
commence immediately. Women being treated with gonodotrophin
releasing hormone (GnRH) analogues, for example, for endometriosis,
may commence treatment with Tibofem immediately.
Switching from conventional hormone replacement therapy (HRT)
In changing from another HRT preparation the endometrium may already
be stimulated, so induction of a withdrawal bleed with a progestogen
is advisable.
Missed tablets
A missed dose should be taken as soon as remembered, unless it
is more that 12 hours overdue. In the latter case, the missed dose
should be skipped and the next dose should be taken at the normal
time. Missing a dose may increase the likelihood of breakthrough
bleeding and spotting.
Contraindications
* Pregnancy & Lactation
* Known or suspected hormone - dependent tumours
* Cardiovascular or cerebrovascular disorders e.g.
thrombophlebitis, thrombo -embolic processes or a history of these conditions
* Undiagnosed vaginal bleeding
* Severe liver disorders, thromboembolic disorders, thrombophlebitis
* Allergic to one or any of its ingredients
Warnings and Precautions
Drug interactions
Since Tibofem may increase blood fibrinolytic activity, it may
enhance the effect of anticoagulants. This effect has been reported
with warfarin
Medicines that may reduce the blood level of tibolone, making
it less effective are,
Rifampicin, antiepileptic medicines such as carbamazepine, phenytoin,
Phenobarbital, primidone and barbiturates such as amobarbital (amylobarbitone).
Women with diabetes may need an increase in the dose of their antidiabetic
medicine (insulin or oral antidiabetic medicine) while taking Tibofem
.
Pregnancy:
Tibofem is contraindicated in pregnancy.
Lactation:
Tibofem is contraindicated during lactation
General:
Tibofem is not intended for contraceptive use
Risk - benefit should be considered when any of the following
medical conditions exist:-
a. Liver disorders or a history of this condition
b. Disturbances of the lipid and Lipoprotein profile
Treatment should be discontinued if signs of thromboembolic processes
occur, if results of liver function tests become abnormal, or if
cholestatic jaundice appears.
The occurrence of vaginal bleeding or spotting soon after starting
treatment with Tibofem may be due to the residual effects of endogenous
or exogenous estrogens. Bleeding commencing after three months
of treatment or persistent bleeding should be appropriately investigated.
In most cases no apparent cause of bleeding is found.
As with all steroids with hormonal activity, yearly medical examination
is advisable
Side effects TIBOFEM ( Tibolone)
Occasionally, vaginal bleeding or spotting, vaginal discharge,
breast pain or abdominal pain may occur, mainly during the first
months of treatment. Other adverse events that have been observed
occasionally include: headache or migraine, oedema, dizziness,
pruritis , increase in body weight, nausea, rash, hirsutism, visual
disturbances and depression, d isturbances of the gut such as diarrhoea,
constipation, nausea, vomiting or abdominal pain , alteration in
results of liver function tests, pain in the muscles and joints,
seborrhoeic dermatitis
Overdosage
The acute toxicity of Tibofem in animals is very low. Therefore,
toxic symptoms are not expected to occur, even when several tablets
are taken simultaneously. In case of acute overdose, nausea, vomiting
and vaginal bleeding in females may occur. No specific antidote
is known. Symptomatic treatment can be given if necessary.
Storage
Store in a cool dry place. Protect form light & moisture.
