On September 5, 2007 we published safety information on the drug tibolone (Livial) used for hormone replacement therapy. The basis for this report was the Medicines and Healthcare products Regulatory Agency (MHRA) Drug Safety Update Newsletter. The British authorities were concerned over an increased risk of stroke in older postmenopausal women, those women more than 60 years of age, using tibolone.

The initial safety concerns regard were the result of the Long Term Intervention on Fractures with tibolone (LIFT) study. This large randomized controlled study was discontinued prematurely due to a 2.2-fold increased risk of stroke in tibolone users compared to placebo. The LIFT study also reported one case of endometrial hyperplasia (pre-cancerous changes) as well as four cases of endometrial cancer in tibolone users. Furthermore, The Million Women Study identified a 1.5 fold increase in the risk of developing breast cancer in association with the use of tibolone.

Additional safety concerns with tibolone were raised in a letter to the editor published in the January 4, 2008 British Medical Journal (BMJ).

This letter raised the question of the yet to be published Livial Intervention following Breast cancer; Efficacy, Recurrence And Tolerability Endpoints or LIBERATE trial. The start of both the LIFT and LIBERATE trials received significant positive media attention. There was minimal media reporting when LIBERATE was stopped prematurely in May 2007. Fragmentary media reports suggest that the reason for the premature termination of this trial was because of an excess rate of recurrent breast cancer in those taking tibolone compared to placebo.

The authors of the BMJ letter, a pharmacist and physicians from Italy, note that “Many years after tibolone marketing, data from long term clinical trials on the incidence of relevant outcome – such as deep venous thrombosis, myocardial infarction, or the risk of breast cancer – are still lacking.”

The continued marketing of tibolone in Saudi Arabia raises serious public safety questions. The manufacturer of tibolone should immediately make the results of the LIBERATE study available to drug regulatory authorities around the world. Until these results are released and that drug regulatory authorities can be sure that tibolone is safe in comparison to other drugs approved for the same uses, Tibolone should be prescribed or used with extreme caution.

Actions that Public and Healthcare Professionals Should Follow:

• Patients should and their families should be aware of possible risks associated with the use Tibolone (Livial).
• Healthcare professionals are advised to assist overall risks associated with the use of Tibolone prior to prescribing it.