Drug Interaction:
Tibolone activity may be reduced in women taking rifampicin or anticonvulasants such as phenytoin, phenabarbitone, or carbamazepine. During tibolone usage sensitivity to anticoagulants may be increased. In diabetics, the requirement for insulin or other hypoglycemic agents may be increased with concomittant tibolone therapy.
Indication:
Menopausal symptoms- Prevention of postmenopausal osteoporosis-
New Drugs Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
Tibolone Treatment of Complaints 16-10-1996
resulting from natural
or surgical menopause
Adverse Reaction:
The drug has been well tolerated. Weight gain, dizziness, acneiform rash, seborrheic dermatitis, headache,
GI symptoms, facial hair growth, and pretibial edema have been reported with tiboline. None of these occured significantly more often than in placibo group.
Vaginal bleeding may occur during treatment, if endometrrial proliferation is already present because of the recent use of other hormone replacement regimens or because of the residual endogenous hormone production in women within 1 year of menopause.
Contra-Indications:
Hormone dependent tumors, uninvestigated vaginal bleeding, H/O cardiovascular or cerebrovascular disease, severe liver disease, pregnancy and lactation.
Special precautions: Patients with renal dysfunction, migraine, epilepsy, and hypercholesterolemia, should be monitored during tiboline therapy.
Discontinue treatment in the event of development of thromboembolic disorders or abnormal liver function tests.
Sensitivity to anticoagulants during tiboline therapy, Caution is required during concomittant therapy.
Should not be used in premenopausal women or women within 1 yr of menopause.
Dosages/ Overdosage Etc:
Menopausal symptoms- Prevention of postmenopausal osteoporosis- Menopausal symptoms-
Dosage-
1 tablet daily for minimum 3 months.
A separate progestogen should not be used Prevention of postmenopausal osteoporosis- 1 tablet daily for 5 to 10 years
Children - not applicable The drug should not be given to women within 1 yr of menopause.(may cause irregular bleeding).
Other Information:
EVIDENCE BASED MEDICINE (April 2003)
Premenstrual sydrome
Comparative effectiveness of various intreventions
Beneficial
Overall Premenstrual Syndrome Symptoms
1. Prostagalndin inhibitors (e.g. Indomethicin)
2. Selective serotonin Reuptake Inhibitors (e.g. Fluoxetine, Seratinine, Fluvoxamine)
Breast symptoms only
1. Leuteal phase control
2. Bromocriptine
Bloatedness and Swelling
1. Spironolactone/ diuretics
Likely to be beneficial
1. Tobolone
2. Oestrogen
3. Vitamin B-6
4. Evening primrose B-6
Trade-off between Benefits and Harms
1. Danazol
2. Gonodotropin-releasing hormone (GnRH analogues)
3. Non-SSRI antidepressants/ anxiolytics
4. Hysterectomy with/without oophorectomy
Unknown effectiveness
1. Progesterone
2. Progestogens
3. Oral contraceotives
4. Cognitive behaviour treatment
5. Dietary supplements
6. Relaxation treatment
7. Endometrial ablation
8. Laproscipic bilateral oophorectomy
KEY POINTS
1. Trials have found that SSRIs and prostagalndin inhibitors relieve premenstrual symptoms. Antidepressants and ovulation suppression with danazol and GnRH analoges are also effective but have significant adverse effects, including the masculanising effects of danazol and the menopausal effects of GnHR analogues.
2. There is a limited evidence suggesting that oestrogen, viatmin-B6 , evening Primrose Oil and excercise may also be beneficial
3. Trials have found that bromocriptine is effective for breast symptoms and diuretics are effective for bloatedness and swelling. Both can have adverse efects.
4. There is no good evidence to support the use of progesterone or oral contraceptives
5. Few treatments have been adequately validated in trials.
Pharmacology/ Pharmacokinetics:
Pharmacology
Tiboline posseses estrogenic, progestrogenic & weak androgenic properties & is related struturally to the progestrones norethisterone & norethynodrel. Tibolone restore plasma-endorphin levels in post-menopausal women and also acts centraly the thermo-regulatory system. These actions are likely to account for the improvement of mood and reduction in hot flushes & night sweats following tibolone therapy.
Pharmacokinetics:
Studies with "C" labelled tibolone have shown that radioactivity appears in plasma 30 min after oral administration & peak levels are attained after 1.5 to 4 hrs. The plasma elimination half-life of total radioactivity, after administration of "C" labelled tibolone is 45hrs. Plasma protein binding is 96.3%. Excretion of tibolone occurs mainly via the fecal route (app 60%), the balance through urinary excretion.
Manufacturer Details