Usage
Tibolone is a synthetic steroid medication prescribed for the relief of menopausal symptoms in postmenopausal women, typically starting at least one year after the last natural menstrual bleed. It is also used in the prevention of osteoporosis (weakening of the bones) in postmenopausal women at high risk of fractures who cannot tolerate or are contraindicated for other osteoporosis medications. It has estrogenic, androgenic, and progestogenic properties, meaning it acts like a combination of these hormones in the body. Pharmacologically, it is classified as a Hormone Replacement Therapy (HRT) or more specifically as a “tissue selective estrogen complex” (TSEC). It’s not a true HRT but has some similar effects. Tibolone isn’t technically classified under a single pharmacological category like antibiotic or analgesic. It is a unique medication that modulates estrogen, progesterone, and androgen receptors in a tissue-specific manner.
Alternate Names
Tibolone is often marketed under the brand name Livial. There are no widely recognized international variations for “Tibolone.”
How It Works
Pharmacodynamics: Tibolone itself is inactive. However, it is quickly metabolized into three compounds: 3α-hydroxytibolone, 3β-hydroxytibolone, and Δ4-isomer. These metabolites have distinct effects on different tissues. 3α-hydroxytibolone and Δ4-isomer have estrogenic effects on bone and the brain, reducing the risk of osteoporosis and alleviating menopausal symptoms like hot flushes and vaginal dryness. The 3β-hydroxytibolone metabolite exerts androgenic effects. Δ4-isomer has progestogenic effects on the endometrium (uterine lining), reducing the risk of endometrial hyperplasia (thickening) that can occur with estrogen-only HRT.
Pharmacokinetics: Tibolone is well-absorbed after oral administration. Peak plasma concentrations are reached within one to two hours. It is extensively metabolized in the liver via CYP3A4, with the metabolites displaying varying elimination half-lives. Primarily excreted in the urine (mainly as sulfates and glucuronides) with a small amount in feces.
Mechanism of Action: Tibolone’s metabolites exert tissue-specific effects by binding to estrogen, androgen, and progesterone receptors in different organs. This selective modulation of receptor activity leads to its unique clinical profile.
Elimination Pathways: Predominantly renal excretion with minor hepatic contribution.
Dosage
Standard Dosage
Adults:
The standard dose is 2.5 mg (one tablet) taken orally once daily, preferably at the same time each day. Treatment is typically initiated one year after the last natural menstrual period. In cases of surgical menopause (removal of ovaries), treatment can begin immediately.
Children:
Tibolone is not indicated for use in children.
Special Cases:
- Elderly Patients: No dose adjustment is generally necessary in elderly patients, but data on those over 65 is limited.
- Patients with Renal Impairment: Caution is advised. Monitor closely for fluid retention, as estrogens can exacerbate this.
- Patients with Hepatic Dysfunction: Contraindicated in patients with acute liver disease or a history of liver disease where liver function tests have not returned to normal.
- Patients with Comorbid Conditions: Tibolone should be used with caution in women with conditions including uncontrolled hypertension, active or past venous thromboembolism, diabetes with vascular complications, gallbladder disease, migraine, and certain types of cancer (endometrial, ovarian, breast cancer history).
Clinical Use Cases
Tibolone is not indicated for:
- Intubation
- Surgical Procedures (consider discontinuing 4-6 weeks before elective surgery)
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations (e.g., status epilepticus, cardiac arrest)
Dosage Adjustments
Dose adjustments based on renal/hepatic impairment are not routinely made but require careful clinical monitoring, with particular caution in patients with renal dysfunction, as fluid retention can occur.
Side Effects
Common Side Effects
- Vaginal bleeding or spotting
- Abdominal pain
- Breast pain or tenderness
- Weight gain
- Acne
- Headache
- Dizziness
Rare but Serious Side Effects
- Venous thromboembolism (blood clots), including deep vein thrombosis and pulmonary embolism
- Stroke
- Myocardial infarction (heart attack)
- Breast cancer
- Liver dysfunction (jaundice)
Long-Term Effects
- Increased risk of breast cancer, stroke and venous thromboembolism with long-term use.
Adverse Drug Reactions (ADR)
- Angioedema (swelling of the face, lips, tongue)
- Hypersensitivity reactions (rash, itching, hives)
Contraindications
- Known, past, or suspected breast cancer
- Estrogen-dependent neoplasia
- Undiagnosed vaginal bleeding
- Untreated endometrial hyperplasia
- Venous thromboembolism (history)
- Arterial thromboembolic disease (history)
- Liver disease
- Pregnancy
- Breastfeeding
Drug Interactions
Tibolone is metabolized by CYP3A4. Concomitant use with CYP3A4 inducers like rifampicin, phenobarbital, carbamazepine, phenytoin, and St. John’s wort may decrease tibolone’s effectiveness. Conversely, inhibitors of CYP3A4 might increase tibolone levels. Tibolone can also potentiate the effects of anticoagulants like warfarin. Interactions with other medications metabolized by CYP3A4 are possible.
Pregnancy and Breastfeeding
Tibolone is contraindicated during pregnancy and breastfeeding.
Drug Profile Summary
- Mechanism of Action: Tissue-selective estrogenic, androgenic, and progestogenic effects through active metabolites.
- Side Effects: Vaginal bleeding, abdominal pain, breast pain, weight gain, acne, headache, dizziness. Serious effects include VTE, stroke, myocardial infarction, and breast cancer.
- Contraindications: Breast cancer, estrogen-dependent tumors, undiagnosed vaginal bleeding, VTE history, pregnancy, breastfeeding, liver disease.
- Drug Interactions: CYP3A4 inducers/inhibitors, warfarin.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 2.5 mg orally once daily.
- Monitoring Parameters: Monitor for vaginal bleeding, breast changes, signs of thromboembolism, and liver function tests.
Popular Combinations
Tibolone is typically used as monotherapy. Combining it with other HRTs is not recommended. Supplementation with calcium and vitamin D may be advised for osteoporosis prevention.
Precautions
- Use the lowest effective dose for the shortest duration.
- Evaluate individual risk-benefit, especially in women over 60.
- Regularly re-assess for continued need for therapy.
- Pre-screening for relevant contraindications and risk factors is crucial.
- Monitor closely in patients with specific conditions like renal/hepatic impairment, cardiovascular disease, and diabetes.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Tibolone?
A: The standard recommended dose is 2.5mg once daily. No dose adjustment is typically needed for elderly patients. It is not used in children.
Q2: When should Tibolone therapy be initiated after menopause?
A: Generally, it is started at least one year after the last natural menstrual period.
Q3: Can Tibolone be used in women with a history of breast cancer?
A: No. Tibolone is contraindicated in women with current, past, or suspected breast cancer.
Q4: What are the most common side effects of Tibolone?
A: Vaginal bleeding or spotting, abdominal or breast pain, headaches, dizziness, and weight gain.
Q5: Does Tibolone interact with any other medications?
A: Yes, Tibolone interacts with CYP3A4 inducers and inhibitors. It also can interact with anticoagulants like warfarin.
Q6: Can Tibolone be used during pregnancy or breastfeeding?
A: No, Tibolone is contraindicated during pregnancy and breastfeeding.
Q7: How long should a patient continue Tibolone therapy?
A: Treatment duration depends on the individual patient’s symptoms and risk-benefit assessment. Regular reviews with a doctor are necessary, usually every 6-12 months, to assess the need for continued therapy.
Q8: What should be done if a patient misses a dose of Tibolone?
A: If a dose is missed, take it as soon as remembered, unless it’s almost time for the next dose. In that case, skip the missed dose and continue with the regular schedule. Do not double the dose.
Q9: What are the serious side effects to be aware of with Tibolone?
A: Blood clots (venous thromboembolism), stroke, heart attack, liver problems, and an increased risk of breast cancer with long-term use.
Q10: What type of monitoring is recommended for patients taking Tibolone?
A: Patients should be monitored for persistent vaginal bleeding, breast changes, signs of blood clots (leg pain, swelling, chest pain, shortness of breath), and liver dysfunction. Regular gynaecological check-ups, including breast and pelvic examinations are advised, along with mammograms as per national screening guidelines.
