Sign Out
Pharmacology: Pharmacodynamics: Following oral administration, tibolone is rapidly metabolized into three compounds, which all contribute to the pharmacodynamic profile of Livial. Two of the metabolites (3α-OH-tibolone and 3β-OH-tibolone) have estrogenic-like activities, whereas the third metabolite (Δ4-isomer of tibolone) has progestogenic and androgenic-like activities.
Livial substitutes for the loss of estrogen production in postmenopausal women and alleviates menopausal symptoms. Livial prevents bone loss following menopause or ovariectomy.
Clinical trial information of Livial: Relief of estrogen-deficiency symptoms: Relief of menopausal symptoms generally occurs during the first few weeks of treatment.
Effects on the endometrium and bleeding patterns: There have been reports of endometrial hyperplasia and endometrial cancer in patients treated with Livial (see Precautions and Adverse Reactions).
Amenorrhea has been reported in 88% of women using Livial 2.5 mg after 12 months of treatment. Breakthrough bleeding and/or spotting has been reported in 32.6% of women during the first 3 months of treatment, and in 11.6% of women after 11-12 months of use.
Prevention of osteoporosis: Estrogen deficiency at menopause is associated with an increasing bone turnover and decline in bone mass. 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 untreated women.
In the LIFT study, Livial reduced the number of women (mean age 68 years) with new vertebral fractures compared to placebo during the 3 years of treatment (ITT: Livial to placebo odds ratio 0.57; 95% CI [0.42, 0.78]).
After 2 years of treatment with Livial (2.5 mg), the increase in lumbar spine bone mineral density (BMD) was 2.6±3.8%. The percentage of women who maintained or gained BMD in lumbar zone during treatment was 76%. A second study confirmed these results.
Livial (2.5 mg) also had an effect on hip BMD. In one study, the increase after 2 years was 0.7±3.9% at the femoral neck and 1.7±3.0% at the total hip. The percentage of women who maintained or gained BMD in the hip region during treatment was 72.5%. A second study showed that the increase after 2 years was 1.3±5.1% at the femoral neck and 2.9±3.4% at the total hip. The percentage of women who maintained or gained BMD in the hip region during treatment was 84.7%.
Effects on the breast: In clinical studies mammographic density is not increased in women treated with Livial compared to placebo.
Pharmacokinetics: Following oral administration, tibolone is rapidly and extensively absorbed. Due to rapid metabolism, the plasma levels of tibolone are very low. The plasma levels of the Δ4-isomer of tibolone are also very low. Therefore some of the pharmacokinetic parameters could not be determined. Peak plasma levels of the 3α-OH and the 3β-OH metabolites are higher but accumulation does not occur. (See Table 1.)
Click on icon to see table/diagram/imageExcretion 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 feces.
The consumption of food has no significant effects on the extent of absorption.
The pharmacokinetic parameters for tibolone and its metabolites were found to be independent of renal function.
Toxicology: Preclinical safety data: In animal studies, tibolone had anti-fertility and embryotoxic activities by virtue of its hormonal properties. Tibolone was not teratogenic in mice and rats. It displayed teratogenic potential in the rabbit at near-abortive dosages (see Use in Pregnancy & Lactation). Tibolone is not genotoxic under in vivo conditions. Although a carcinogenic effect was seen in certain strains of rat (hepatic tumors) and mouse (bladder tumors), the clinical relevance of this is uncertain.
