Azithromycin-containing medicinal products for systemic use - referral

Current status

Under evaluation

Overview

EMA starts review of azithromycin-containing medicines

EMA’s human medicines committee (CHMP) has started a review of systemic medicines (given by mouth or by injection) that contain the antibiotic azithromycin. Antimicrobial resistance (AMR) against azithromycin is increasing in the European Union (EU). Therefore, and in view of the broad use of these medicines, a re-evaluation of the benefits and risks of azithromycin in its many authorised uses is considered warranted to optimise its use and minimise the risk of AMR development. 

Many azithromycin-containing medicines have been in use for decades and were authorised by national procedures in the EU. This has led to large differences in the product information regarding the indications, treatment dose and duration, and relevant safety information. These differences may conflict with rational use of antibiotics and antibiotic stewardship and may result in further development of antimicrobial resistance to azithromycin. 

EMA will now review all available information on the benefits and risks of azithromycin and will consider whether any changes are required to its approved uses across EU Member States.

 

Use of azithromycin

Azithromycin has been classified by the World Health Organization (WHO) as an antibiotic that carries a higher risk of antimicrobial resistance and is included in WHO’s Watch list (AWaRe classification)¹. It is also included in WHO’s list of essential medicines^2,3.

As part of its actions to fight antimicrobial resistance, EMA commissioned a study in 2022 to investigate prescription of antibiotics that are included in WHO’s Watch list. This study, performed by DARWIN EU®⁴, showed that azithromycin is frequently prescribed in the EU in adults and children. Antibiotic surveillance data⁵ from Germany has also shown that azithromycin was increasingly used during the COVID-19 pandemic in the hospital setting.
 

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^{1 2021 AWaRe classification. WHO access, watch, reserve, classification of antibiotics for evaluation and monitoring of use: https://www.who.int/publications/i/item/2021-aware-classification}

^{2 WHO Model List of Essential Medicines - 23rd list, 2023: https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2023.02}

^{3 WHO Model List of Essential Medicines for Children - 9th list, 2023: https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2023.03}

^{4 https://www.encepp.eu/encepp/viewResource.htm?id=104143}

^{5 https://avs.rki.de/Content/ReferenceData/HospitalComparisonTime.aspx}

More about the medicines

Azithromycin is one of a group of antibiotics known as macrolides. It can be given by mouth or by injection to treat infections caused by Gram-positive and Gram-negative bacteria, such as, but not limited to, upper and lower respiratory tract infections and community-acquired pneumonia. 

Azithromycin-containing systemic medicines have been authorised nationally in the EU for many years and are marketed under a variety of brand names. 

A few azithromycin-containing medicines are approved in the EU for topical use (as eye drops). These medicines are out of scope for this review procedure.
 

More about the procedure

The review has been initiated at the request of the German Federal Institute for Drugs and Medical Devices under Article 31 of Directive 2001/83/EC.

The review is being carried out by the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which will adopt the Agency’s opinion. The CHMP opinion will then be forwarded to the European Commission, which will issue a final legally binding decision applicable in all EU Member States.

Key facts

About this medicine

• Approved name:
  Azithromycin-containing medicinal products for systemic use
• International non-proprietary name (INN) or common name:
  azithromycin
• Class:
  Macrolides

About this procedure

• Current status:
  Under evaluation
• Reference number:
  EMEA/H/A-31/1532
• 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.

• Authorisation model:
  Nationally authorised product(s)

All documents

Procedure started

Azithromycin Article-31 referral - Annex I

Draft

Azithromycin Article-31 referral - Start of referral

Azithromycin Article-31 referral - CHMP list of questions

Azithromycin Article-31 referral - Notification

Under evaluation

Azithromycin Article-31 referral - Timetable for the procedure

Reference Number: EMA/CHMP/488796/2023 - Rev. 3

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.