Safety and Tolerability of Nebulized Amoxicillin-Clavulanic Acid in Patients with COPD (STONAC 1 and STONAC 2)

Abstract

The safety and tolerability of nebulized amoxicillin clavulanic acid were determined in patients with stable COPD and during severe exacerbations of COPD. Nine stable COPD patients received doses ranging from 50:10 mg up to 300:60 mg amoxicillin clavulanic acid and eight patients hospitalised for a COPD exacerbation received fixed doses 200/40 mg twice daily. Safety was evaluated by spirometry before and after inhalation. Tolerability was evaluated by questionnaire. Plasma and expectorated sputum samples were assayed for amoxicillin content.

Seventeen patients underwent in total 100 nebulizations with amoxicillin clavulanic acid. In this safety and tolerability study no clinically relevant deteriorations in FEV₁ were observed. Nebulized amoxicillin clavulanic acid produces sputum concentrations well above the Minimal Inhibiting Concentration of 90% for potential pathogenic micro-organisms, with low concentrations in the central compartment (low systemic exposure).

Based on spirometry and reported side effects, inhalation of nebulized amoxicillin clavulanic acid seems to be safe and well tolerated, both in stable patients with COPD as in those experiencing a severe exacerbation. Levels of amoxicillin were adequate.

Keywords:

• COPD
• inhalation
• antibiotics
• nebulization
• amoxicillin clavulanic acid

Acknowledgments

Authors Nijdam and Assink contributed equally to this work. The authors wish to thank Mr. P. Robberts (Mediq Romedic Netherlands) for providing the nebulizers and the particle size measurements of the nebulized amoxicillin clavulanic acid.

Declaration of interest statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.