Tibolone


Generic Medicine Info
Indications and Dosage
Oral
Estrogen deficiency symptoms in postmenopausal women
Adult: 1 tab (2.5 mg) daily. Initiate treatment ≥1 year following last natural bleed, or immediately in cases of surgical menopause or for those undergoing treatment with gonadotrophin releasing hormone (GnRH) analogues. Refer to individual product guideline on how to manage missed doses and for detailed dosing instructions.

Oral
Prophylaxis of osteoporosis in postmenopausal women
Adult: In women at high risk of future fractures who are intolerant of, or contraindicated for, other osteoporosis-preventing therapies: 1 tab (2.5 mg) daily. Initiate treatment ≥1 year following last natural bleed, or immediately in cases of surgical menopause or for those undergoing treatment with gonadotrophin releasing hormone (GnRH) analogues. Refer to individual product guideline on how to manage missed doses and for detailed dosing instructions.
Administration
May be taken with or without food.
Contraindications
Known, previous, or suspected breast cancer, current or suspected estrogen-dependent malignant tumours (e.g. endometrial cancer), undiagnosed abnormal genital bleeding, untreated endometrial hyperplasia, active or history of venous thromboembolism (e.g. DVT, pulmonary embolism) or active thrombophlebitis, known thrombophilic disorders (e.g. protein C, protein S, antithrombin deficiency), previous arterial thromboembolic disease (e.g. angina, MI, stroke, TIA, CHD). Acute liver disease or a history of liver disease wherein LFTs have failed to return to normal; porphyria. Pregnancy and lactation.
Special Precautions
Patient with leiomyoma (uterine fibroids) or endometriosis; risk factors for thromboembolic disorder; risk factors for venous thromboembolism (e.g. family history, obesity [BMI >30 kg/m2], SLE, prolonged immobilisation, major surgery, postpartum period, cancer); risk factor for estrogen-dependent tumours (e.g. 1st degree heredity); diseases which may be exacerbated by fluid retention (e.g. CV disease); hypertension, diabetes mellitus (with or without vascular involvement), cholelithiasis, pre-existing hypertriglyceridaemia, migraine or severe headache, history of endometrial hyperplasia, epilepsy, asthma, otosclerosis, gallstones, hereditary angioedema; metabolic or endocrine disease, abnormal Ca and phosphorus metabolism. Used only for women with an intact uterus. Not intended for combined therapy; should not add a separate progestogen to the therapy. Not intended for contraceptive use. Patient undergoing surgery; consider discontinuation of therapy 4-6 weeks before operation and restart only when the patient becomes fully mobile. Renal and hepatic impairment. Elderly.
Adverse Reactions
Significant: Increased risk of endometrial, breast, or ovarian cancer; endometrial hyperplasia, breakthrough bleeding and spotting; increased risk of venous thromboembolism (e.g. DVT, pulmonary embolism), ischaemic stroke, dementia; increased endometrial wall thickness; fluid retention; decreased HDL cholesterol, total triglyceride, lipoprotein, total cholesterol and VLDL-C; decreased (very minor) thyroid-binding globulin, total thyroxine, sex hormone-binding globulin (SHBG). Rarely, hypertriglyceridaemia resulting in pancreatitis.
Eye disorders: Visual disturbances (e.g. blurred vision).
Gastrointestinal disorders: Lower abdominal pain, abdominal discomfort.
General disorders and administration site conditions: Oedema.
Investigations: Increased weight, abnormal cervical smear, changes in liver function parameters.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia.
Nervous system disorders: Dizziness, headache, migraine.
Psychiatric disorders: Depression.
Reproductive system and breast disorders: Breast tenderness, discomfort; vaginal discharge, candidiasis, haemorrhage; endometrial wall thickening, postmenopausal haemorrhage, pelvic pain, cervical dysplasia, vulvovaginitis; genital pruritus, discharge, amenorrhoea.
Skin and subcutaneous tissue disorders: Abnormal hair growth, acne, rash, seborrheic dermatosis.
Monitoring Parameters
Obtain a complete personal and family medical history prior to therapy; baseline mammography, blood glucose, serum Ca, triglycerides and cholesterol levels, LFTs. Perform routine physical examination that includes blood pressure, breast and pelvic exam, including a Papanicolaou smear; adequate diagnostic measures (e.g. endometrial sampling), if indicated. Monitor glycaemic control in diabetics, lipid profiles in patients with hyperlipidaemia, and thyroid function in patients undergoing thyroid hormone replacement therapy. Assess for signs of endometrial cancer in female patients with a uterus; signs and symptoms of thromboembolic disorders. Evaluate the need for continuation of therapy.
Overdosage
Symptoms: Nausea, vomiting, vaginal bleeding. Management: Symptomatic treatment.
Drug Interactions
Enhanced effect of anticoagulants (e.g. warfarin). May increase metabolism with CYP3A4 inducers (e.g. barbiturates, carbamazepine, hydantoins, rifampicin).
Food Interaction
May induce metabolism with St. John's wort.
Lab Interference
May impair coagulation, lipid, glucose tolerance, corticoid binding globulin, sex hormone-binding globulin, and thyroid function tests.
Action
Description: Tibolone is a steroid that is rapidly converted into 3 active metabolites following administration which possess estrogenic, progestogenic, and androgenic properties. It substitutes for estrogen loss in postmenopausal women, reduces vasomotor symptoms of menopause, and prevents bone loss after menopause or ovariectomy.
Pharmacokinetics:
Absorption: Rapidly and extensively absorbed. Time to peak plasma concentration: 1-2 hours (tibolone and active metabolites).
Metabolism: Rapidly converted in the gastrointestinal tract and liver into 3 active metabolites, with 2 (3α-OH-tibolone, 3β-OH-tibolone) having predominantly estrogenic property and 1 (delta-4-isomer of tibolone) with progestogenic and androgenic property.
Excretion: Mainly via faeces (as metabolites); partly via urine (as metabolites). Elimination half-life: 6-8 hours (3α-OH-tibolone, 3β-OH-tibolone).
Chemical Structure

Chemical Structure Image
Tibolone

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 444008, Tibolone. https://pubchem.ncbi.nlm.nih.gov/compound/Tibolone. Accessed July 26, 2021.

Storage
Store below 25°C. Protect from light and moisture.
MIMS Class
Oestrogens, Progesterones & Related Synthetic Drugs
ATC Classification
G03CX01 - tibolone ; Belongs to the class of other estrogens. Used in the treatment of menopausal symptoms.
References
Anon. Tibolone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 20/04/2021.

Buckingham R (ed). Tibolone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/04/2021.

Joint Formulary Committee. Tibolone. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/04/2021.

Livial 2.5 mg Tablets (Merck Sharp & Dohme [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 20/04/2021.

Livial 2.5 mg Tablets (Organon Pharma [UK] Limited). MHRA. https://products.mhra.gov.uk. Accessed 20/04/2021.

Organon New Zealand Limited. Livial 2.5 mg Tablets data sheet 1 December 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 20/04/2021.

Tibolone 2.5 mg Tablets (Gedeon Richter Plc.). MHRA. https://products.mhra.gov.uk. Accessed 20/04/2021.

Disclaimer: This information is independently developed by MIMS based on Tibolone from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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