Acute kidney injury during concomitant use of valacyclovir and loxoprofen: detecting drug-drug interactions in a spontaneous reporting system.
OBJECTIVE
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.
School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
Zhihua
Z
Yue
Jinhai
J
Shi
Pengli
P
Jiang
He
H
Sun
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000212:Acyclovir / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D016017:Odds Ratio; D010666:Phenylpropionates / Q000009:adverse effects* / Q000627:therapeutic use; D000077483:Valacyclovir; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000998:Antiviral Agents; D010666:Phenylpropionates; C040656:loxoprofen; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir
NSAID; acute kidney injury; drug interactions; loxoprofen; pharmacoepidemiology; pharmacovigilance; signal detection; valacyclovir