Polymyxin-containing medicines

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

Overview

Recommendations issued for safe use in patients with serious infections resistant to standard antibiotics

On 23 October 2014 the European Medicines Agency (EMA) completed a review of the safety and effectiveness of products containing the antibiotics colistin or colistimethate sodium (known as polymyxins) and recommended changes to their product information to ensure safe use in the treatment of serious infections that are resistant to standard antibiotics.

Polymyxin-based products have been available since the 1960s, but their use quickly decreased due to the availability of antibiotics with fewer potential side effects. Due in part to this limited use, colistimethate sodium has retained activity against a number of bacteria which have become resistant to commonly used antibiotics. This has led to a resurgence in recent years in the use of polymyxins in patients with few other options. However, current experience has raised concerns that the existing product information, in particular relating to dosing and the way the medicine is handled in the body (pharmacokinetics), might need updating. The European Commission therefore requested the EMA to review the available data and make recommendations on whether the marketing authorisations for these medicines should be changed and the product information amended appropriately.

The Agency's Committee for Medicinal Products for Human Use (CHMP) reviewed the available data about the pharmacokinetics, effectiveness and safety of these medicines. The review considered products given by injection or inhaled as a liquid into the lungs (systemic use) containing colistimethate sodium, which is converted to the active substance colistin in the body. Products taken by mouth (which mainly contain colistin and are not absorbed into the body in significant amounts but act locally on the gut) and those applied externally were not covered in this review.

The CHMP concluded that injection or infusion (drip) of colistimethate sodium should be reserved for the treatment of serious infections due to susceptible bacteria, in patients whose other treatment options are limited. The medicine should be given with another suitable antibiotic where possible. The Committee recommended that doses should always be expressed in international units (IU) but because doses of colistimethate sodium can be expressed in different ways a conversion table should be included in the product information. Critically ill patients should be given a higher starting dose (loading dose) to provide an effective level of the antibiotic in the body more quickly. Although data were very limited, the Committee recommended doses for use in patients with kidney problems and in children, and provided guidance on dosage in adults when given directly into fluid surrounding the brain or spinal cord (intrathecal or intraventricular injection).

CHMP concluded that colistimethate sodium may also be given by inhalation or in a nebuliser to treat ongoing (chronic) infections with the bacterium Pseudomonas aeruginosa in patients with cystic fibrosis. (Products for inhalation as a dry powder have a different dosage and distribution in the body, and were not affected by the conclusions of the review.)

The CHMP opinion was forwarded to the European Commission, which issued a final decision valid throughout the EU on 15 December 2014.

Key facts

Approved name
Polymyxin-containing medicines
International non-proprietary name (INN) or common name
colistimethate sodium
Associated names
Colobreathe
Class
antibiotics
Reference number
EMEA/H/A-31/1383
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.

Status
European Commission final decision
Opinion date
23/10/2014
EC decision date
16/12/2014

All documents

Document description

  • Questions and answers (Q&A) - easy-to-understand summary of key issues and Committee conclusions
  • Summary of Opinion - contains the CHMP opinion of the referred medicine(s)
  • List of the medicines affected by the referral (Annex I)
  • Scientific conclusions of the Committee (Annex II)

The following two documents are sometimes available:

How useful was this page?

Add your rating