LIVIAL
Tibolone 2.5mg tablets
Presentation
Tibolone 2.5mg tablet is a white, round, flat tablet with bevelled edges, coded MK above 2 on one side and Organon and a star on the reverse side, and containing 2.5mg tibolone. Average diameter 6mm, average weight 100mg.
Uses
Actions
After oral administration tibolone is rapidly metabolized into three compounds which contribute to the pharmacological effects of LIVIAL. Two of these metabolites have predominantly oestrogenic activity, a third metabolite and the parent compound have predominantly progestagenic activity.
LIVIAL has an oestrogen-like effect on hot flushes and other climacteric complaints. In addition, oestrogen-like effects are exerted on the vagina and bone. Due to its progestagenic effects LIVIAL does not stimulate the endometrium. Therefore, if bleeding occurs, this usually results from an atrophic endometrium. Finally, LIVIAL has effects on certain metabolic and haematological parameters such as a decrease in plasma high density lipoprotein cholesterol, triglycerides, lipoprotein(a), and an increase in blood fibrinolytic activity.
Pharmacokinetics
After oral administration, tibolone is rapidly and extensively absorbed. Due to rapid metabolism the plasma levels of tibolone are very low. Pharmacokinetic data indicate linear kinetics. Peak plasma levels are reached after 1-4 hours and accumulation does not occur. Excretion of tibolone is mainly in the form of polar and very polar metabolites. A small amount of the administered compound is excreted in the urine, but most is eliminated via the bile and the faeces.
Indications
Complaints resulting from the natural or surgical menopause.
Prevention of postmenopausal osteoporosis.
Dosage And Administration
Dosage
The dosage is one tablet per day. The tablets should be swallowed with some water or other drink, preferably at the same time each 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, LIVIAL may be used without interruption for longer periods.
Administration
The first tablet that is taken from the starting zone (the boxed upper row of the pack) is the tablet marked with the day on which the user begins to take LIVIAL. Following the direction of the arrows, tablet taking is continued with the outermost tablets. One tablet is taken each day until the pack is empty.
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.
Contraindications
• Pregnancy and lactation.
• Known or suspected hormone-dependent tumours.
• Cardiovascular or cerebrovascular disorders.
• Active deep vein thrombosis, thromboembolic disorders, or a documented history of these conditions.
• Vaginal bleeding of unknown etiology.
• Severe liver disorders.
Warnings And Precautions
• LIVIAL is not intended for contraceptive use.
• The use of LIVIAL should be avoided until 12 months after the last natural menstrual bleed. If LIVIAL is taken sooner than this, the frequency of irregular bleeding may be increased.
• If changing from another hormone replacement preparation, induction of a withdrawal bleed with a progestagen is advisable before starting LIVIAL.
• As for all steroids with hormonal activity, annual medical examination is advisable.
• The occurrence of vaginal bleeding or spotting soon after starting treatment with LIVIAL may be due to the residual effects of endogenous or exogenous oestrogens. Bleeding commencing after three months of treatment, or recurrent or persistent bleeding, should be investigated.
• Epidemiological studies have suggested that conventional hormone replacement therapy (HRT) is associated with a 2-3 fold increase in the risk of venous thromboembolism (VTE). It is not yet known whether LIVIAL changes the risk of VTE.
• Treatment should also be discontinued if results of liver function tests become abnormal or if cholestatic jaundice appears.
• Conventional HRT has been associated with a small increase in the relative risk of breast cancer. The effects of tibolone on breast tissue appear to be predominantly progestagenic and it is not certain whether there is the same increased risk of having breast cancer as with conventional HRT. Human data suggest that LIVIAL causes less increase in breast density and less breast pain and tenderness than conventional HRT. In women receiving LIVIAL long-term, any subsequent examination of the breast and/or mammography should be carried out in accordance with current accepted practices for the well-woman, modified according to the clinical needs of the individual.
Patients with any of the following conditions should be monitored:
- renal dysfunction, epilepsy or migraine or a history of these conditions, since the use of steroids with hormonal activity may occasionally induce fluid retention;
- hypercholesterolaemia, since during LIVIAL treatment changes in the serum lipid profile have been observed;
- impaired carbohydrate metabolism, since LIVIAL may diminish glucose tolerance and increase the need for insulin or other antidiabetic agents;
Pregnancy And Lactation
LIVIAL is contraindicated in pregnant and lactating women.
Effects On Ability To Drive And Use Machines
As far as is known LIVIAL has no effect on alertness and concentration.
Adverse Reactions
Occasionally, vaginal bleeding or spotting may occur, mainly during the first months of treatment. Other adverse events that have been occasionally observed include: headache and migraine, oedema, dizziness, pruritus, increase in body weight, nausea, abdominal pain, rash, and depression.
Interactions
No examples of interactions between LIVIAL 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 AT III, plasminogen, and fibrinolytic activity values), it may enhance the effect of anticoagulants.
Overdosage
The acute toxicity of tibolone in animals is very low. Therefore, toxic symptoms are not expected to occur if several tablets are taken simultaneously. 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.
Pharmaceutical Precautions
The shelf-life of LIVIAL tablets is 2 years if stored in the dark under dry conditions at 2-25°C.
Medicine Classification
Prescription Medicine.
Package Quantities
Press-through strips of 28 tablets; packs containing one strip or three strips.
Further Information
List Of Excipients
LIVIAL tablets 2.5mg contain potato starch, magnesium stearate, ascorbyl palmitate and lactose.
