Fluorouracil and fluorouracil related substances (capecitabine, tegafur and flucytosine) containing medicinal products

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CHMP opinion
  • European Commission final decision
Current status:
Procedure started

Overview

EMA starts review on screening patients before treatment with fluorouracil, capecitabine, tegafur and flucytosine

EMA has started a review of medicines containing fluorouracil (also known as 5-fluorouracil or 5-FU) and the related medicines capecitabine, tegafur and flucytosine, which are converted to fluorouracil in the body. The review will examine existing screening methods and their value in identifying patients at increased risk of severe side effects.

Fluorouracil (given by injection), capecitabine and tegafur are cancer medicines, whereas topical (applied to the skin) fluorouracil is used for various skin conditions and flucytosine is a medicine used in severe fungal infections.

It is known that some patients lack a working enzyme called dihydropyrimidine dehydrogenase (DPD) which is needed to break down fluorouracil1. Prescribers may be unaware that their patients lack working DPD, and if these patients are given fluorouracil or related substances, their bodies cannot break fluorouracil down, resulting in its build-up in the blood.

Build-up of high levels of fluorouracil seen with some of these medicines can lead to severe and life-threatening side effects such as neutropenia (low levels of neutrophils, a type of white blood cells needed to fight infection), neurotoxicity (damage to the body’s nervous system), severe diarrhoea and stomatitis (inflammation of the lining of the mouth). Patients with a complete deficiency of DPD should therefore not be given fluorouracil, or medicines that can form it in the body.

The product information for most of these medicines states that they should not be used in patients with complete DPD deficiency. Genetic testing for DPD deficiency is recommended for most medicines used in the treatment of cancer, but systematic screening for DPD deficiency before starting treatment is not mandatory. In addition, new data on genetic testing and other DPD screening methods were recently published which may impact current recommendations.

EMA will now assess the available data in relation to existing screening methods to detect DPD deficiency and recommend whether any changes are needed to the way these medicines are used in order to ensure their safe use.

Patients who have concerns about their medicines should consult their doctor and should not stop taking their medicines without seeking medical advice.


1 Up to 8% of the population have low levels of a working DPD enzyme, and up to 0.5% of the population completely lack the enzyme. 

 

Key facts

About this medicine
Approved name
Fluorouracil and fluorouracil related substances (capecitabine, tegafur and flucytosine) containing medicinal products
International non-proprietary name (INN) or common name

capecitabine, fluorouracil, tegafur, flucytosine

Associated names
  • Xeloda
  • Teysuno
  • Capecitabine Accord
  • Capecitabine Medac
  • Capecitabine Teva
  • Ecansya (previously Capecitabine Krka)
About this procedure
Current status
Procedure started
Reference number
EMEA/H/A-31/1481
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.

Decision making model
PRAC-CHMP-EC
Authorisation model
Centrally and nationally authorised products (mixed)
Key dates and outcomes
Procedure start date
15/03/2019

All documents

Procedure started

Document description

  • Annex I - List of the medicines affected by the referral
  • Annex II - Scientific conclusions of the CHMP or CMDh
  • Annex III - Changes to the summary of product characteristics, labelling or package leaflet - available when the CHMP or CMDh recommends changes to the product information. Also includes conditions for lifting of suspensions, if applicable
  • Annex IV - Conditions of the marketing authorisation - available when the CHMP or CMDh recommends other measures to be taken for the marketing authorisation such as safety measures or additional studies
  • Notification - A letter from a Member State, the European Commission or a marketing-authorisation holder requesting the initiation of a referral procedure
  • Rationale for triggering - Background provided by the party triggering the referral explaining the issues leading to the initiation of the procedure
  • PRAC list of questions - Questions agreed by the PRAC requesting further information to evaluate the issues identified
  • PRAC timetable - Timeframe agreed by the PRAC to receive information, assess the issues and adopt a recommendation
  • PRAC / CHMP or CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

News

How useful was this page?

Add your rating