INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo LIVIFEM® (tablets)

        RU M1850.061.023

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

LIVIFEM® (tablets)

COMPOSITION
Each tablet contains 2,5 mg
tibolone, a steroidal compound.

PHARMACOLOGICAL CLASSIFICATION
A/21.5.4/Other combinations

PHARMACOLOGICAL ACTION
Livifem stabilises the hypothalamic-pituitary system after failure of the ovarian function in the climacteric, which leads to the occurrence of vasomotor complaints as a result of the involvement of the thermoregulatory centre in the hypothalamus. The therapeutic central effect of Livifem is due to the combined estrogenic, progestogenic and weak androgenic activities of the drug.
Livifem has a moderate gonadotrophin suppressing effect in post-menopausal women.
The peripheral effect of Livifem is the combination of hormonal activities that exerts a balanced effect and does not stimulate the endometrium in post-menopausal women.
Tibolone, the active ingredient of Livifem, is rapidly and extensively absorbed, appearing in the blood within 30 minutes of oral administration with peak levels between 1,5 and 4 hours. Tibolone is metabolised in the liver and converted to metabolites that are excreted mainly in the faeces and to a lesser extent in the urine. Some metabolites may contribute to the biological effects of the drug. The elimination half-life of tibolone and active metabolites is less than 2 days, justifying once-a-day administration.

INDICATIONS
- Symptomatic treatment of hot flushes and associated sweating resulting from the natural or surgical menopause.
- Prevention of postmenopausal osteoporosis.
- Improvement of bone-mineral density in patients with established post-menopausal osteoporosis.

CONTRA-INDICATIONS
- Pregnant and lactating women
- Known or suspected hormone-dependant tumours.
- Cardiovascular or cerebrovascular disorders, e.g. thrombophlebitis, thrombo-embolic processes or a history of these conditions.
- Vaginal bleeding of unknown etiology.
- Severe liver disease

WARNINGS
Livifem is not intended for contraceptive use.
The use of Livifem should be avoided until 12 months after the last natural menstrual bleed. If Livifem is taken sooner than this, the frequency of irregular bleeding may be increased.
Treatment should be discontinued if signs of thrombo-embolic processes occur, if results of liver function tests become abnormal or if cholestatic jaundice appears.
Vaginal bleeding may occur during Livifem therapy, because of an apparently stimulated endometrium due to some estrogen production. Normally such bleeding is of short duration. Bleedings commencing after three months of treatment, or recurrent or of longer duration should be investigated.
In women changing from another form of hormonal substitution therapy to Livifem therapy, it is always advisable to induce a withdrawal bleeding with a progestagen before starting Livifem.
Tibolone has been shown to be teratogenic in experimental animals, and should not be used in premenopausal women.
Periodic examinations must be done for endometrial hyperplasia, as well as possible signs of virilisation.

DOSAGE AND DIRECTIONS FOR USE
The dosage is one tablet per day. A missed dose should be taken as soon as remembered, unless it is more than 12 hours overdue. In the latter case, the missed dose should be skipped and the next dose should be taken at the normal time.
Improvement of symptoms generally occurs within a few weeks, but optimal results are obtained when therapy is continued for at least 3 months.
Administration: Livifem tablets should be swallowed whole with some water or other drink, preferably at the same time each day.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
The following adverse reactions have been observed: headache and migraine, oedema, increase in body mass, dizziness, seborrhoeic dermatosis (pruritus), rash, abdominal pain and depression. Vaginal bleeding or spotting may occur, mainly during the first months of treatment.
A higher dosage than the recommended may induce vaginal bleeding.
Safety of long-term administration has not been established.
QuickMarkQuickMarkPatients with the following conditions should be monitored frequently:
- Renal dysfunction, epilepsy or migraine or a history of these conditions, since the use of steroids with hormonal activity may induce fluid retention;
- impaired carbohydrate metabolism, since Livifem may diminish glucose tolerance and increase the need for insulin or other antidiabetic medicines.
- risk-benefit should be considered when any of the following medical conditions exist:
- liver disease or a history of this condition;
- hypercholesterolaemia, since during Livifem treatment changes in the serum lipid profile (lower values of lipid constituents of HDL-lipoprotein fraction) occur.

INTERACTION WITH OTHER MEDICAMENTS AND OTHER FORMS OF INTERACTION:
No examples of interactions between Livifem and other medicines have been reported in clinical practice. However, the following potential interactions should be considered on a theoretical basis:
- Enzyme-inducing compounds such as barbiturates, carbamazepine, hydantoins, and rifampicin may enhance the metabolism of tibolone and thus decrease its therapeutic effect.
- Since tibolone may increase blood fibrinolytic activity (lower fibrinogen levels; higher ATIII, plasminogen, and fibrinolytic activity values), it may enhance the effect of anticoagulants.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
In cases of acute overdose, nausea, vomiting and withdrawal bleeding in females may develop. No specific antidote is known. Symptomatic treatment can be given if necessary.

IDENTIFICATION
White round and flat tablets with bevelled edges, coded MK above 2 on the one side and Organon and a star on the reverse side.

PRESENTATION
Press-through strips of 28 tablets each containing 2,5 mg of tibolone.
Packs containing 1 strip.

STORAGE INSTRUCTIONS
Keep below 25°C. Protect from light and moisture.
Keep out of reach of children.

REGISTRATION NUMBER
V/21.5.4/55

NAME AND ADDRESS OF THE APPLICANT
Donmed Pharmaceuticals (Pty) Limited
Donmed House
Cambridge Place
cnr Kirkby & Oxford Roads
Bedfordview 2007

DATE OF PUBLICATION OF THIS PACKAGE INSERT
19 May 1999

Under license of NV Organon, The Netherlands

Updated on this site: September 2004
Source: Pharmaceutical Industry

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