Tivion2.5 mg

Tivion is a synthetic steroid compound with tissue-selective estrogenic, progestogenic, and weak androgenic activity, used exclusively in postmenopausal women. Its evidence-based indications are:

Established/Approved Uses

• Treatment of estrogen-deficiency symptoms of the menopause (e.g., vasomotor symptoms such as hot flushes and night sweats, and vulvovaginal atrophy) in women who are more than 12 months past their last natural menstrual period, or in women after surgical menopause.
• Prevention of osteoporosis in postmenopausal women who are at high risk of future fractures and who are intolerant of, or have a contraindication to, other medicines approved for osteoporosis prevention.

Not Recommended As First-Line

Tivion is not recommended as a first-line treatment for osteoporosis prevention alone; it should be considered only when alternative therapies are unsuitable, given its safety profile (see Precautions and Warnings).

Tivion is used only in postmenopausal women and has no role in premenopausal women, men, or children.

Each tablet contains Tibolone 2.5 mg as the active ingredient, along with standard pharmaceutical excipients such as potato starch, magnesium stearate, colloidal silica, and ascorbyl palmitate.

Tivion is a synthetic steroid hormone that is structurally related to norethisterone and belongs to a class sometimes described as a Selective Tissue Estrogenic Activity Regulator (STEAR). After oral intake it is rapidly and extensively metabolized into three main metabolites that each act on different target tissues, giving Tivion a combined estrogenic, progestogenic, and androgenic profile. It is used to relieve menopausal symptoms and to help prevent postmenopausal osteoporosis in selected women.

Tivion belongs to the class of hormone replacement therapy (HRT) agents, specifically classified as a synthetic steroid with tissue-selective estrogenic, progestogenic, and androgenic activity (STEAR).

Tibolone itself has little intrinsic hormonal activity; after oral administration it is rapidly converted in the body into three active metabolites:

• The 3α-hydroxy and 3β-hydroxy metabolites, which have predominantly estrogenic activity and act mainly on the vasomotor center, vaginal epithelium, and bone.
• The Δ4-isomer, which has combined progestogenic and androgenic activity and acts mainly on the endometrium, helping to limit estrogen-driven endometrial proliferation.

This tissue-selective distribution of activity is why Tibolone can relieve estrogen-deficiency symptoms and support bone mineral density while having a different endometrial and breast-tissue effect profile compared with conventional combined hormone therapy, although endometrial and breast risks are still present and require monitoring (see Precautions and Warnings).

Tivion tablets are taken by mouth, once daily, with water, at approximately the same time each day, with or without food. Swallow the tablet whole; do not crush or chew unless directed by a physician.

The following clinically significant interactions have been reported with Tivion:

• CYP3A4 enzyme inducers (e.g., rifampicin, carbamazepine, phenytoin, barbiturates, and the herbal product St. John's Wort) may increase the metabolism of Tivion and reduce its therapeutic effect, potentially leading to breakthrough bleeding or reduced symptom control.
• Oral anticoagulants (e.g., warfarin): Tivion may enhance the anticoagulant effect. Coagulation parameters (e.g., INR) should be monitored more closely, especially when starting or stopping Tivion, and the anticoagulant dose adjusted if needed.
• Antidiabetic medicines: Tivion may affect glucose tolerance; blood glucose should be monitored in people with diabetes, particularly at the start of therapy.

Always inform your physician or pharmacist of all medicines, supplements, and herbal products you are taking before starting Tivion.

Possible side effects of Tivion include:

Common (≥1%)

• Lower abdominal pain
• Weight increase
• Abnormal (androgenic) hair growth and, less commonly, acne
• Vaginal discharge, irregular vaginal bleeding, or spotting
• Thickening of the endometrial lining
• Breast tenderness or discomfort

Uncommon/Rare

• Fluid retention (edema)
• Itching (pruritus)
• Dizziness, headache, or migraine
• Mood changes, including low mood
• Visual disturbances
• Changes in liver function tests

Serious Risks

Tivion is also associated with a serious increased risk of ischaemic stroke, venous thromboembolism (DVT/PE), and breast cancer recurrence (see Precautions and Warnings and Contraindications for full details); these are not routine "side effects" but important safety risks that should be discussed with your physician before and during treatment.

Tivion is contraindicated in pregnancy. It is intended solely for use in postmenopausal women; there is no indication for its use during pregnancy, and it must not be taken by anyone who is or may be pregnant. If pregnancy occurs or is suspected while taking Tivion, treatment should be stopped immediately and a physician consulted promptly.

Tivion is contraindicated during breastfeeding. It is not intended for use in women who are lactating, as its indications apply only to the postmenopausal population.

Before starting Tivion, and periodically during treatment, a full medical and family history should be taken, including a physical and gynecological/breast examination, guided by individual risk factors.

Stroke Risk

Tivion increases the risk of ischaemic stroke, with an increased risk observed from the first year of treatment. This risk should be discussed with your physician, particularly if you have other stroke risk factors.

Breast Cancer

Use of Tivion has been associated with an increased risk of breast cancer, and it is contraindicated in women with current or past breast cancer due to a risk of recurrence/stimulation of hormone-sensitive tissue (see Contraindications).

Venous Thromboembolism (VTE)

Tivion is associated with an increased risk of venous thromboembolism (DVT/PE), particularly in the first year of use. Risk factors such as personal/family history of VTE, obesity, prolonged immobilization, or major surgery should be assessed and managed appropriately; therapy should be stopped temporarily before planned surgery associated with prolonged immobilization.

Endometrial Effects

Endometrial thickening and an increased risk of endometrial abnormalities, including endometrial cancer, have been reported with Tivion. Any unexpected or persistent vaginal bleeding during treatment should be promptly evaluated by a physician.

General Principle

Tivion should be used at the lowest effective dose for the shortest duration necessary, with regular reassessment of the benefits and risks (at least annually). It should be used with caution in women with risk factors for the conditions above, or with a history of hepatic, renal, or cardiovascular disease, migraine, epilepsy, diabetes, or gallbladder disease. Treatment should be discontinued immediately if jaundice, marked deterioration in liver function, significant blood pressure rise, new-onset migraine-type headache, or signs of thromboembolism occur.

The acute toxicity of Tivion is reported to be low. In case of overdose, symptoms that may occur include nausea, vomiting, and vaginal bleeding/spotting. There is no specific antidote.

If an overdose of Tivion is suspected, seek immediate medical attention or contact a poison control center/emergency services right away. Treatment is generally supportive and symptomatic, and should only be given under professional medical supervision.

Store below 25°C, away from light and moisture, in the original package. Do not refrigerate. Keep out of reach of children.

Elderly

Tivion is not typically initiated in significantly elderly women (e.g., many years after menopause) due to a less favorable benefit-risk profile with increasing age and time since menopause; no specific dose adjustment is required based on age alone when use is appropriate.

Renal Impairment

Data on the use of Tivion in patients with renal impairment are limited; use with caution and under close medical supervision.

Hepatic Impairment

Tivion is contraindicated in acute liver disease or in patients with a history of liver disease in which liver function tests have not normalized (see Contraindications).

Pediatric Use

Tivion is not indicated for use in children or adolescents. Its indications are limited to postmenopausal women, and safety and efficacy in the pediatric population have not been established.

Men

Tivion is not indicated for use in men.

Tivion should be used for the shortest duration consistent with the treatment goals, at the lowest effective dose. The need for continued treatment should be reassessed by a physician periodically, generally at least once a year, weighing ongoing symptom relief or fracture-risk reduction against the cumulative risks of stroke, venous thromboembolism, and breast/endometrial effects described in Precautions and Warnings.

Tibolone is classified as a synthetic steroid / Selective Tissue Estrogenic Activity Regulator (STEAR), functionally grouped with hormone replacement therapy (HRT) agents used in postmenopausal women.

Tibolone is rapidly metabolized after oral intake into three main active metabolites with distinct tissue-selective actions:

• Two metabolites with predominantly estrogenic activity act on the hypothalamic vasomotor center, vaginal tissue, and bone, relieving vasomotor symptoms, improving vaginal atrophy, and helping maintain bone mineral density.
• A third metabolite with combined progestogenic and androgenic activity acts mainly at the endometrium, which is thought to limit unopposed estrogenic stimulation of the endometrium compared with estrogen-only therapy, and also contributes mild androgenic effects (e.g., on libido and mood in some women).

This selective, tissue-specific pattern of action distinguishes Tibolone from conventional estrogen-only or combined estrogen-progestogen hormone therapies, although it does not eliminate the associated cardiovascular, cerebrovascular, and oncological risks, which still require careful monitoring.

Tivion is not indicated for use in children or adolescents. It is approved only for postmenopausal women, and there is no pediatric dosing information. Safety and efficacy of Tivion in patients under 18 years of age have not been established, and it should never be given to children.