Tibofem

Approved Indications:

• Treatment of Menopausal Symptoms:
• Relief of moderate to severe vasomotor symptoms (e.g., hot flashes, night sweats).
• Alleviation of vulvovaginal atrophy symptoms (e.g., vaginal dryness, dyspareunia).
• Prevention of Postmenopausal Osteoporosis:
• In women at high risk of fractures who are intolerant of, or contraindicated for, other osteoporosis treatments.

Clinically Accepted Off-Label Uses:

• Improvement of Sexual Function: In postmenopausal women with hypoactive sexual desire disorder (HSDD).
• Mood Stabilization: Used in select postmenopausal women experiencing mood disturbances related to menopause.

Route of Administration: Oral

Standard Adult Dosage (Postmenopausal Women):

• 1.25 mg to 2.5 mg orally once daily (commonly 2.5 mg daily).
• Start treatment at least 12 months after the last natural menstrual period to minimize the risk of irregular vaginal bleeding.

Duration:

• Shortest duration necessary should be used.
• Reassess benefit-risk balance regularly, especially in long-term use beyond 5 years.

Pediatric Use:

• Not recommended for children or adolescents.

Elderly:

• No specific dose adjustment needed in healthy elderly postmenopausal women.

Renal Impairment:

• Use with caution; limited data available. No dose adjustment provided, but clinical monitoring is recommended.

Hepatic Impairment:

• Contraindicated in severe hepatic dysfunction. Avoid use due to extensive hepatic metabolism.

Tibolone is a synthetic steroid with tissue-selective estrogenic, progestogenic, and androgenic activities. After oral administration, it is rapidly metabolized into three active metabolites: the 3α- and 3β-hydroxy metabolites (estrogenic activity) and the Δ4-isomer (progestogenic and androgenic activity). These metabolites act on estrogen, progesterone, and androgen receptors depending on the target tissue. Tibolone mimics the beneficial effects of estrogen on bone and vaginal tissues while exerting minimal stimulatory effects on the endometrium and breast, thereby reducing the risks associated with conventional estrogen therapy.

• Absorption: Rapidly absorbed from the gastrointestinal tract.
• Bioavailability: Tibolone is not detectable in plasma due to rapid metabolism; active metabolites achieve therapeutic levels.
• Peak Plasma Levels: Reached within 1–2 hours after oral administration.
• Distribution: Widely distributed; lipophilic in nature.
• Metabolism: Extensive hepatic metabolism into 3α-hydroxy, 3β-hydroxy, and Δ4-isomer metabolites.
• Elimination Half-life: ~7.5 to 8 hours (metabolite-dependent).
• Excretion: Primarily excreted via urine (approx. 75%) and feces (approx. 25%) as inactive metabolites.

• Pregnancy: Contraindicated. Tibolone is not intended for use in premenopausal women. It has teratogenic potential in animal studies.
  FDA Pregnancy Category: X
• Lactation: Contraindicated during breastfeeding. It is unknown if tibolone or its metabolites are excreted in human breast milk, but due to hormonal activity, risk to the nursing infant cannot be excluded.

• Primary Class: Hormone Replacement Therapy (HRT)
• Subclass: Synthetic Steroid with Estrogenic, Progestogenic, and Androgenic Activity

• Known hypersensitivity to tibolone or any excipients
• Undiagnosed vaginal bleeding
• Active or history of breast cancer
• Known or suspected estrogen-dependent tumors
• Previous or current venous thromboembolism (VTE)
• Active or recent arterial thromboembolic disease (e.g., myocardial infarction, stroke)
• Severe hepatic impairment
• Pregnancy or breastfeeding

• Breast Cancer: Risk appears lower than with conventional HRT but still present; not recommended in women with a history of breast cancer.
• Endometrial Cancer: Though risk is lower than estrogen-only HRT, unexpected vaginal bleeding should always be investigated.
• Cardiovascular Risks: Increased risk of stroke, particularly in older postmenopausal women.
• Venous Thromboembolism: Caution in women with personal or strong family history of VTE.
• Liver Function: Avoid in liver dysfunction; monitor liver enzymes if needed.
• Cognitive Decline: Long-term HRT may increase risk of dementia in women over 65.
• Regular Monitoring: Recommended for breast, pelvic, and cardiovascular health during therapy.
• Discontinue Immediately: If signs of thromboembolic events, jaundice, or significant elevation of liver enzymes occur.

Common Side Effects:

• Gynecological: Vaginal bleeding or spotting (usually during initial months), breast tenderness, vaginal discharge
• CNS: Headache, dizziness, mood changes
• GI: Abdominal pain, bloating
• General: Weight gain, fluid retention

Less Common or Serious Side Effects:

• Breast cancer (risk increases with prolonged use)
• Stroke or thromboembolic events
• Endometrial hyperplasia or carcinoma
• Hepatic enzyme elevation
• Acne or hirsutism (due to androgenic activity)

Rare Effects:

• Visual disturbances
• Migraine exacerbation
• Cholestatic jaundice

• Anticoagulants (e.g., warfarin): Tibolone may reduce anticoagulant effect; monitor INR.
• Enzyme Inducers (e.g., rifampin, carbamazepine, phenytoin): May reduce effectiveness by increasing metabolism of tibolone.
• Enzyme Inhibitors (e.g., ketoconazole, erythromycin): May increase plasma concentrations of active metabolites.
• Hormonal Therapies: Concurrent use with other estrogens or progestins not recommended.
• CYP450 System: Tibolone and its metabolites are metabolized by hepatic CYP enzymes, though not primarily dependent on CYP3A4.

• EMA Advisory: Continues to recommend tibolone only after 12 months of amenorrhea due to bleeding risk.
• NICE Guidelines (UK): Recognize tibolone as an option for menopausal symptom management in women unable to take estrogen-progestogen HRT, especially with low libido.
• Label Update (EU): Warnings about increased risk of stroke, especially in women over 60, have been strengthened.

• Storage Temperature: Store below 25°C (77°F)
• Light Protection: Store in original packaging to protect from light
• Humidity: Keep container tightly closed to protect from moisture
• Handling: No specific precautions required beyond standard oral medication care
• Disposal: Dispose of unused or expired medication per local regulations for hormone-containing products