Issues for surgery
Potential for menopausal symptoms if discontinued.
Reduced protection against osteoporosis if discontinued for prolonged period.
Risk of venous thromboembolism (VTE) if continued (see Further information).
Advice in the perioperative period
Elective surgery
Minor surgery
Continue unless there is a risk of prolonged immobilisation – see Major surgery.
Major surgery
Consider stopping 4-6 weeks before surgery where prolonged immobilisation is likely (e.g. abdominal surgery or orthopaedic lower limb surgery). See Further information.
Except:
Where tibolone is being used for short-term management of oestrogen-deficiency in women also being treated with gonadotrophin releasing hormone analogues for gynaecological issues for which they are awaiting surgery. Consideration should be given to the risk: benefit of stopping tibolone treatment and return of symptoms prior to surgery versus the risk of VTE. A discussion with the patient and their gynaecology team may be required.
Consider other risk factors that the patient may have that further increase the risk of VTE, e.g. age, weight, previous history of VTE.
Please note, if doses are missed, it may result in breakthrough bleeding.
If continuing, ensure adequate thromboprophylaxis.
Emergency surgery
Ensure adequate thromboprophylaxis to reduce risk of VTE.
If prolonged immobilisation anticipated consider discontinuing on admission.
Please note, if doses are missed, it may result in breakthrough bleeding.
Patients admitted with gallstones (cholelithiasis)
Use of tibolone can aggravate gallstones in patients who have a previous history of this condition; bear this in mind for patients admitted with gallstones who are on this medication.
Post-operative advice
If discontinued pre-operatively, restart when fully mobile.
Patients undergoing gynaecological surgery
Review use of tibolone post-operatively for patients who have undergone gynaecological surgery affecting the uterus and/or ovaries, as it may need to be stopped or switched to a more appropriate HRT preparation.
Interactions with common anaesthetic agents
Midazolam
Tibolone inhibited CYP3A4 in vivo leading to reduced midazolam metabolism; however, this is unlikely to be clinically significant.
The manufacturers suggest drug interactions with other CYP3A4 substrates might be expected, although no case reports have been noted.
Interactions with other common medicines used in the perioperative period
None.
Further information
Risk of VTE
Data from an epidemiological study concluded that the risk of VTE in users of tibolone was lower than the risk with conventional hormone replacement therapy (HRT). However, due to limited data a small increase in risk compared with non-users of HRT could not be excluded therefore the manufacturers advise consideration should be given to stopping tibolone prior to major elective surgery.
A Cochrane review did not find any difference in VTE when tibolone was compared with placebo although they noted the quality of evidence for this outcome was very low. A recent observational study of the UK population included 368 women with VTE and 1859 controls who took tibolone. This study found tibolone was not associated with risk of VTE (p=0.8).
References
Summary of Product Characteristics – Livial® (tibolone). Merck Sharp and Dohme Limited. Accessed via www.medicines.org.uk 24/1/2024 [date of revision of the text August 2023].
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 24th January 2024]
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 24th January 2024]
Formoso G, Perrone E, Maltoni S et. al. (2016) Cochrane Systematic Review – Short-term and long-term effects of tibolone in postmenopausal women. https://www.cochranelibrary.com DOI: 10.1002/14651858.CD008536.pub3
Vinogradova, Y. Coupland, C & Hippisley-Cox, J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019; 364:k4810. DOI: 10.1136/bmj.k4810.