Acute kidney injury during concomitant use of valacyclovir and loxoprofen: detecting drug-drug interactions in a spontaneous reporting system

Pharmacoepidemiol Drug Saf. 2014 Nov;23(11):1154-9. doi: 10.1002/pds.3626. Epub 2014 Apr 30.


Purpose: Little is known about the effects of drug-drug interactions between valacyclovir and non-steroidal anti-inflammatory drugs (NSAIDs). In this study, we analysed the adverse event 'acute kidney injury (AKI)' resulting from a possible interaction between loxoprofen (a non-selective NSAID) and valacyclovir in reports received by FDA Adverse Event Reporting System (AERS) database between January 2004 and June 2012.

Methods: Adverse event reports of elderly patients aged ≥65 years old were included in the study. Exposure categories were divided into three index groups (only valacyclovir or loxoprofen was used, and both drugs were concomitantly used) and a reference group (neither valacyclovir nor loxoprofen were used). Case/non-case AKI reports associated with these drugs were recorded and analysed by the reporting odds ratio (ROR).

Results: In total, 447 002 reports were included in the study. The ROR, adjusted for year of reporting, age and sex, for an AKI in elderly patients who used only valacyclovir or loxoprofen compared with elderly patients who used neither valacyclovir nor loxoprofen was 4.6 (95%CI: 4.1-5.2) and 1.4 (95%CI: 1.2-1.6), respectively, while the adjusted ROR was 26.0 (95%CI: 19.2-35.3) when both drugs were concomitantly used.

Conclusions: Case reports in AERS are suggestive that interactions between valacyclovir and loxoprofen resulting in AKI may occur, while this association needs to be analysed by other methods in more detail in order to determine the real strength of the relationship.

Keywords: NSAID; acute kidney injury; drug interactions; loxoprofen; pharmacoepidemiology; pharmacovigilance; signal detection; valacyclovir.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acyclovir / adverse effects
  • Acyclovir / analogs & derivatives*
  • Acyclovir / therapeutic use
  • Adverse Drug Reaction Reporting Systems / statistics & numerical data*
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antiviral Agents / adverse effects*
  • Antiviral Agents / therapeutic use
  • Drug Interactions
  • Female
  • Humans
  • Male
  • Odds Ratio
  • Phenylpropionates / adverse effects*
  • Phenylpropionates / therapeutic use
  • Valacyclovir
  • Valine / adverse effects
  • Valine / analogs & derivatives*
  • Valine / therapeutic use


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antiviral Agents
  • Phenylpropionates
  • loxoprofen
  • Valine
  • Valacyclovir
  • Acyclovir