What Non-Steroidal Anti-Inflammatory Drug (NSAID) can be taken with lithium?

NSAIDs to Avoid with Lithium and Safer Alternatives

Sulindac is the only NSAID that can be safely taken with lithium, as it does not significantly affect lithium levels and is the preferred choice when an NSAID is required in patients on lithium therapy. 1, 2

Interaction Between Lithium and NSAIDs

Lithium has a well-documented interaction with most NSAIDs that can lead to potentially dangerous outcomes:

• Most NSAIDs reduce renal lithium clearance, increasing serum lithium levels and risking lithium toxicity 3
• This interaction occurs even in patients with normal renal function 4
• The FDA drug label for lithium specifically warns that lithium levels should be closely monitored when patients initiate or discontinue NSAID use 3

NSAIDs to Avoid with Lithium

The following NSAIDs have been documented to significantly increase lithium levels and should be avoided:

• Indomethacin - most potent in increasing lithium levels 4, 5
• Piroxicam - significantly increases steady-state plasma lithium concentrations 3
• Diclofenac - reported to interfere with lithium pharmacokinetics 5
• Ketoprofen - can raise plasma lithium levels 5
• COX-2 inhibitors (e.g., celecoxib) - can increase lithium levels by approximately 17% 3
• Naproxen - can significantly increase serum lithium levels with marked interindividual variation (up to 41.9% increase) 2
• Ibuprofen - can significantly increase serum lithium levels with marked interindividual variation 4

Safer NSAID Options with Lithium

1. Sulindac is the safest NSAID to use with lithium:

   • Multiple studies have demonstrated that sulindac does not affect serum lithium levels or lithium clearance 1, 2
   • In controlled studies, sulindac 300 mg/day failed to affect lithium serum levels and renal lithium clearance 1

2. Aspirin appears to be safe:

   • There is no convincing evidence that aspirin affects serum lithium levels to a clinically significant degree 4, 5
   • The exception of aspirin from this interaction suggests that the inhibition of prostaglandin synthesis is not the mechanism responsible for the decrease in lithium elimination 5

Monitoring Recommendations

If an NSAID other than sulindac must be used:

• Check serum lithium levels every 4-5 days until the extent of drug interaction is assessed 4
• A reduction in lithium dosage may be needed in some cases 4
• Monitor for signs of lithium toxicity including diarrhea, vomiting, tremor, mild ataxia, drowsiness, or muscular weakness 3

Clinical Implications and Precautions

• The KDIGO guidelines specifically state to "avoid using concomitant NSAIDs" with lithium 6
• Lithium toxicity can result from interactions between NSAIDs and lithium 3
• Patients should be informed of the risk of interaction resulting from NSAID use 5
• Maintain adequate hydration and normal salt intake while on lithium therapy to prevent sodium depletion, which could further affect lithium levels 3

In conclusion, when an NSAID is required for a patient on lithium therapy, sulindac is the safest choice. If sulindac cannot be used, aspirin may be considered as an alternative, though with more careful monitoring. All other NSAIDs should be avoided when possible, or used with extreme caution and close monitoring of lithium levels.