Tibolone


  Issues for Surgery


Potential for menopausal symptoms if discontinued.

Risk of venous thromboembolism (VTE) if continued (see Further Information).


  Advice in the Perioperative period


Elective surgery

Consider stopping 4-6 weeks before surgery where prolonged immobilisation is likely (e.g. abdominal surgery or orthopaedic lower limb surgery)1.

If continuing, ensure adequate thromboprophylaxis1.

Emergency surgery

Consider stopping on admission if prolonged immobilisation is likely. 

Ensure adequate thromboprophylaxis1.

Post-operative advice

If discontinued pre-operatively, restart when fully mobile.


  Interaction(s) with Common Anaesthetic Agents


Midazolam

Tibolone inhibited CYP3A4 in vivo leading to reduced midazolam metabolism1, 2; however, this is unlikely to be clinically significant2.

The manufacturers suggest drug interactions with other CYP3A4 substrates might be expected, although no case reports have been noted1, 2.


  Interaction(s) with other Common Medicines used in the Perioperative Period


None1, 2, 3.


  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 surgery1.

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 low4.   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)5.


  References


  1. Summary of Product Characteristics – Livial® (tibolone). Merck Sharp and Dohme Limited. Accessed via www.medicines.org.uk 01/06/2019 [date of revision of the text March 2016.
  2. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 1st June 2019]
  3. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 1st June 2019]
  4. 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 [Accessed on 27th May 2019].
  5. 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.