TIBOLONE

What it is

APO-Tibolone is a tablet containing 2.5 mg tibolone. APO-Tibolone 2.5 mg are white to off white, circular tablets with flat face beveled edge, debossed with 'TO' above '2' on one side and plain on the other side. Tibolone is rapidly metabolised into three compounds which all contribute to its pharmacological effects. Two metabolites have predominantly estrogenic activity, whilst a third metabolite and the parent compound have predominantly progestagenic and androgenic activities.

Approved indications

— Short-term treatment of symptoms resulting from the natural or surgical menopause in postmenopausal women. — Second line therapy for the prevention of bone mineral density loss in postmenopausal women at high risk of future osteoporotic fractures who are intolerant of, or contraindicated for, other medicinal products approved for the prevention of bone mineral density loss.

Dosing overview

The recommended dose is 2.5 mg once daily for both treatment of menopausal symptoms and prevention of postmenopausal bone mineral density loss. No dose adjustment is necessary for the elderly. The tablets should be swallowed with some water or other drink, preferably at the same time of day. Improvement of symptoms generally occurs within a few weeks, but optimal results are obtained when therapy is continued for at least 3 months.

Key safety warnings

APO-Tibolone should be prescribed for the shortest duration consistent with treatment goals. The need for continuation of treatment should be reviewed after 6 months, taking into account the risk–benefit ratio for the individual user at that moment including cardiovascular disease and breast cancer. APO-Tibolone should only be continued for as long as the benefit outweighs the risks. Tibolone increased the risk of breast cancer recurrence in a placebo-controlled trial, and known, past or suspected breast cancer is a contraindication. The Million Women Study identified a significant increase in the risk of breast cancer in association with use of the 2.5 mg dose. This risk became apparent within a few years of use and increased with duration of intake, returning to baseline within a few (at most five) years after stopping treatment. Women who are prescribed tibolone in normal clinical practice are at an increased risk of having endometrial cancer diagnosed, with risk increasing with increasing duration of use. Tibolone increases endometrial wall thickness, as measured by transvaginal ultrasound. Women should be advised to report any breakthrough bleeding or spotting if it is still present after 6 months of treatment, if it starts beyond that time or if it continues after treatment has been discontinued. The woman should be referred for gynaecological investigation, which is likely to include endometrial biopsy to exclude endometrial malignancy. Tibolone increases the risk of ischaemic stroke from the first year of treatment. The baseline risk of stroke is strongly age-dependent and so the effect of tibolone is greater with older age. A 2.9 year randomised controlled study estimated a 2.2-fold increase in the risk of stroke in women (mean age 68 years) who used 1.25 mg tibolone compared with placebo. The majority (80%) of strokes were ischaemic.

Contraindications

Contraindications include pregnancy and lactation; known, past or suspected breast cancer; known or suspected oestrogen-dependent malignant tumours such as endometrial cancer; undiagnosed genital bleeding; untreated endometrial hyperplasia; previous or current venous thromboembolism; known thrombophilic disorders such as protein C, protein S, or antithrombin deficiency; any history of arterial thromboembolic disease such as angina, myocardial infarction, stroke or TIA; acute liver disease or a history of liver disease as long as liver function tests have failed to return to normal; known hypersensitivity to the active substance or excipients; and porphyria.

PBS listing

No PBS listing information is provided in the source documents.

Regulatory history

APO-Tibolone tibolone 2.5 mg tablet was first listed on the ARTG on 4 April 2018.