What are the potential interactions between piperacillin-tazobactam and oral azithromycin?

No Significant Drug Interaction Between Piperacillin-Tazobactam and Oral Azithromycin

There is no significant pharmacokinetic or pharmacodynamic interaction between piperacillin-tazobactam and oral azithromycin that would require dose adjustment or contraindicate their concurrent use. 1

Pharmacokinetic Considerations

• Azithromycin has no significant interaction with beta-lactam antibiotics such as piperacillin-tazobactam, unlike other macrolides that may interact with various medications 1
• Unlike clarithromycin and erythromycin, azithromycin is not a significant inhibitor of cytochrome P450 enzymes, particularly CYP3A4, resulting in fewer drug interactions 1
• Piperacillin-tazobactam is primarily eliminated by renal excretion and is not significantly metabolized by the cytochrome P450 system, further reducing the potential for interaction 2, 3

Clinical Implications

• The combination of piperacillin-tazobactam and azithromycin can be safely used in various clinical scenarios, including:

  • Treatment of polymicrobial infections where coverage for both typical and atypical pathogens is needed 1
  • Management of severe community-acquired pneumonia requiring both beta-lactam and macrolide therapy 1
  • Empiric therapy for sepsis where broad-spectrum coverage is indicated 1

• When using these antibiotics together, standard dosing regimens can be maintained:

  • Piperacillin-tazobactam: typically 3.375g or 4.5g IV every 6-8 hours 2
  • Azithromycin: 500mg orally on day 1, followed by 250mg daily for 4 days, or alternative regimens based on indication 1

Contrast with Other Macrolides

• Unlike azithromycin, other macrolides such as clarithromycin and erythromycin have significant drug interactions due to their inhibition of CYP450 enzymes 1
• If azithromycin is unavailable, and clarithromycin must be used instead, closer monitoring for potential drug interactions would be necessary 1

Special Considerations

• Both medications can independently cause QT prolongation in certain patients, so electrocardiographic monitoring may be considered in high-risk patients (e.g., elderly, those with cardiac disease, or patients on other QT-prolonging medications) 1
• In patients with severe renal impairment, dose adjustment of piperacillin-tazobactam may be necessary, but this is not due to an interaction with azithromycin 1, 3
• Therapeutic drug monitoring of piperacillin-tazobactam may be considered in critically ill patients with altered pharmacokinetics, but this is not specifically related to azithromycin co-administration 1

Conclusion

The concurrent use of piperacillin-tazobactam and oral azithromycin is safe without the need for dose adjustments or special monitoring due to drug interactions. This combination may be particularly useful in polymicrobial infections requiring coverage for both typical and atypical pathogens.