The European Medicines Agency's human medicines committee (CHMP) has announced significant restrictions on the use of azithromycin across the European Union, following a comprehensive review of the antibiotic's benefits and risks. The decision comes amid growing concerns about antimicrobial resistance (AMR) against this widely prescribed medication.
Azithromycin, a macrolide antibiotic that has been used for decades to treat various infectious diseases in both children and adults, is included in the World Health Organization's (WHO) list of essential medicines. However, it is also classified in WHO's "Watch" category under the AWaRe classification system, indicating a higher risk of developing antimicrobial resistance.
Rising Resistance Prompts Regulatory Action
Data analysis has revealed an alarming trend: antimicrobial resistance against azithromycin has increased significantly in recent years. Simultaneously, consumption data indicates growing use of the antibiotic across EU member states, contradicting recommendations for prudent use of medicines in the Watch category.
A recent study commissioned by EMA and conducted by DARWIN EU analyzed the prescription patterns of 141 antibiotics in WHO's Watch category between 2012 and 2021 across five European countries (France, Germany, Spain, the Netherlands, and United Kingdom). The findings were concerning: azithromycin ranked among the top five most prescribed antibiotics in most databases assessed and appeared in the top ten across all databases included.
"To promote a more rational use of this antibiotic based on current evidence and preserve its effectiveness, the CHMP re-evaluated the benefits and risks of azithromycin medicines given by mouth or infusion for the various authorised uses," the EMA stated in its announcement.
Key Changes to Azithromycin Usage
The CHMP's recommendations include several significant modifications to how azithromycin should be prescribed and used:
Refined and Harmonized Indications
Most authorized uses of oral and intravenous azithromycin have been amended to align with the latest clinical data and to make them more precise. The revisions primarily affect:
- Upper and lower respiratory tract infections, including acute bacterial sinusitis, acute streptococcal tonsillitis and pharyngitis, acute exacerbations of chronic bronchitis, and community-acquired pneumonia
- Sexually transmitted diseases, such as urethritis and cervicitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae
- Infections of the female reproductive system, including pelvic inflammatory disease
- Dental infections, such as periodontal abscesses and periodontitis
- Treatment and prevention of Mycobacterium avium complex infections in people living with HIV-1
Discontinued Uses
The committee recommended discontinuing oral azithromycin for several indications where evidence of effectiveness was deemed insufficient:
- Moderate acne vulgaris
- Eradication of Helicobacter pylori
- Prevention of exacerbations of eosinophilic and non-eosinophilic asthma
For these conditions, the CHMP concluded that the benefits do not outweigh the risks, particularly considering the threat of antimicrobial resistance.
New Warning on Resistance Risk
A new warning will be included in the product information highlighting the risk of antimicrobial resistance. This warning explains that azithromycin could favor resistance development due to its long-lasting, decreasing levels in plasma and tissues after treatment ends.
The warning emphasizes that azithromycin should only be initiated after careful assessment of benefits and risks, taking into account local resistance prevalence, and when preferred treatment regimens are not indicated.
Implications for Healthcare Providers and Patients
Healthcare professionals are advised to familiarize themselves with the updated product information and prescribing guidelines. The CHMP has harmonized dosing recommendations, including those for different age groups, to ensure consistent usage across all EU member states.
For patients currently prescribed azithromycin, the EMA recommends consulting with their doctor or pharmacist if they have questions about their treatment. The agency emphasizes that these changes aim to preserve the effectiveness of this important antibiotic for future use.
Next Steps
The CHMP opinion will now be forwarded to the European Commission, which will issue a final legally binding decision applicable in all EU member states. The review was initiated on October 30, 2023, at the request of the German Federal Institute for Drugs and Medical Devices, under Article 31 of Directive 2001/83/EC.
It's worth noting that azithromycin medicines approved for topical use, such as eye drops, were outside the scope of this review procedure and remain unaffected by these changes.
This regulatory action represents a significant step in the global fight against antimicrobial resistance, addressing one of the most pressing public health challenges of our time.
