Bicalutamide 150 mg - referral

Current status

European Commission final decision

Overview

Following a request from Belgium, the European Medicines Agency's (EMEA's) Committee for Medicinal Products for Human Use (CHMP) has reviewed the available information on the effectiveness and safety of medicines containing 150 mg bicalutamide, used orally (by mouth) for the treatment of locally advanced prostate cancer.

The Committee has concluded that the benefits of these products still outweigh their risks, but has recommended some changes to their prescribing information to ensure that they are prescribed only to patients who are at a high risk of disease progression.

Which medicines have been reviewed?

The CHMP has reviewed the data for all medicines containing bicalutamide 150 mg, both those that are authorised in the European Union, as well as those for which applications for authorisation are under review, for the treatment of locally advanced prostate cancer. These medicines are available as 150 mg tablets and can be marketed by AstraZeneca under the trade name Casodex or by other companies as generics (medicines that are similar to Casodex and can be marketed because the 'market exclusivity' [patent] for this medicine has expired). This review does not include other doses of bicalutamide, which may be used in other stages of prostate cancer.

Bicalutamide 150 mg is used to treat patients with locally advanced prostate cancer. This is cancer that affects the prostate gland, the gland below the bladder in men that produces the liquid in the semen. 'Locally advanced' means that the tumour in the gland is large or the cancer has spread beyond the gland to some lymph nodes, but not to other organs. Bicalutamide can be used on its own, or after surgery or radiation treatment. It is designed for long-term use.

Bicalutamide is an anti-androgen. It acts by blocking the receptors in the body for androgens (the male hormones such as testosterone). Since the growth of prostate cancer is stimulated by testosterone, bicalutamide can help to slow down the growth of the cancer.

Why did the CHMP review these medicines?

The original approval of bicalutamide 150 mg for locally advanced prostate cancer was based on the results of three main studies, which compared it with placebo (a dummy treatment). These studies are continuing, and are regularly analysed. Following the publication of the second analysis in 2004, when the patients had been followed for over 5 years, the Belgian medicines regulatory authority became concerned that the benefits of the medicine do not outweigh their risks, as the analysis showed that slightly more patients taking bicalutamide had heart side effects than those taking placebo.

Consequently, Belgium requested a review by the CHMP of all available data on medicines containing 150 mg bicalutamide. The aims of the review were to find out whether there is any change to the benefit-risk balance of these medicines, and for the CHMP to give an opinion on whether any action was necessary.

Which data has the CHMP reviewed?

The companies that market bicalutamide 150 mg tablets gave the CHMP the scientific data relevant to the safety and effectiveness of the product in locally advanced prostate cancer. This included data from clinical trials (third analysis of the main studies, after patients had been followed for over 7 years), reports of side effects and information published in scientific journals.

What are the conclusions of the CHMP?

The CHMP has concluded that the benefits of the use of bicalutamide 150 mg tablets in locally advanced prostate cancer still outweigh their risks in patients who are at high risk of their disease getting worse. The CHMP has requested more data to be collected by the companies on the heart-related side effects of bicalutamide. It also recommended some changes to the product information for bicalutamide-containing medicines (the information that is made available to doctors and to patients) in all countries where it is authorised, to reflect that their use should be restricted to high-risk patients.

What are the recommendations for patients?

Patients who are using bicalutamide 150 mg tablets should not stop or modify their treatment without first speaking with the doctor who prescribed it to them. No action is needed for patients who are taking bicalutamide 50 mg tablets (used in advanced prostate cancer, often with other medicines).

What are the recommendations for prescribers?

When prescribing bicalutamide 150 mg tablets, doctors should be aware that:

• These medicines should not be used in patients with localised disease (when the tumour is small and the cancer affects the prostate only),
• These medicines should only be used in locally advanced disease in patients at high risk of disease progression. How such patients are identified may vary from country to country, according to treatment guidelines, and could be based on criteria such as PSA levels (prostate-specific antigen, a marker of prostate disease), Gleason score (based on how the cancer cells look under a microscope, and used to assess how aggressive the cancer cells are), and stage of disease.

The safety of bicalutamide 150 mg tablets will be closely monitored. As with all medicines, doctors should actively report any side effects thought to be related to bicalutamide.

Questions and answers on Bicalutamide 150 mg tablets

Adopted Reference Number: EMEA/218760/2007

Key facts

About this medicine

• Approved name:
  Bicalutamide 150 mg
• International non-proprietary name (INN) or common name:
  bicalutamide

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  CHMP/378451/07
• Type:
  Article 31 referrals

  This type of referral is triggered when the interest of the Union is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

Key dates and outcomes

• CHMP opinion date:
  24/05/2007
• EC decision date:
  03/09/2007

All documents

Bicalutamide - Article 31 referral - Annex I, II, III, IV

Adopted

Summary information on referral opinion pursuant to Article 31 of Council Directive 2001/83/EC, as amended for Bicalutamide 150 mg-containing medicinal products (see Annex 1) International Non-Proprietary Name (INN): bic...

Adopted Reference Number: EMEA/378451/2007

Questions and answers on Bicalutamide 150 mg tablets

Adopted Reference Number: EMEA/218760/2007

Description of documents published

Please note that some of the listed documents apply only to certain procedures.

• Overview - lay-language summary of the stage of the procedure
• Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
• Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
• List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
• Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
• List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
• List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
• Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
• Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
• Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
• Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
• Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
• Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
• Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
• Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

Note that older documents may have different titles.