Lithium Interaction With the Cyclooxygenase 2 Inhibitors Rofecoxib and Celecoxib and Other Nonsteroidal Anti-Inflammatory Drugs

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to increase serum lithium concentrations. We sought to determine whether NSAIDs that selectively inhibit cyclooxygenase (COX) 2 also elevate serum lithium concentrations.

Method: The U.S. Food and Drug Administration’s Adverse Event Reporting System (AERS) database was searched in January 2003 for reports of interactions between lithium and rofecoxib or celecoxib, the selective COX-2 inhibitors marketed in the United States. Additionally, a literature search was performed using PubMed with the MeSH terms anti-inflammatory agents, nonsteroidal and lithium. Reports of interactions between NSAIDs and lithium were selected for review based on titles of retrieved citations.

Results: Eighteen cases of increased serum lithium concentrations after the addition of one of the COX-2 inhibitors to stable lithium therapy were retrieved from AERS, 13 with rofecoxib and 5 with celecoxib. Serum lithium concentration increases of up to 99% and 448% with concomitant celecoxib and rofecoxib use, respectively, were reported. Thirty-six English-language literature articles report interactions between lithium and various NSAIDs. Although some articles report no effect or decreased serum lithium concentrations with concomitant aspirin or sulindac, increased serum lithium concentration reports exist for aspirin, sulindac, and 14 other NSAIDs, including celecoxib and rofecoxib.

Conclusion: Clinicians should consider NSAID use in the differential diagnosis of lithium toxicity, monitor patients’ serum lithium concentrations during the initiation or discontinuation of NSAID therapy, and be aware that the selective COX-2 inhibitors can increase serum lithium concentrations leading to toxicity.