From the Guidelines
Drugs that can increase lithium blood levels include NSAIDs, which should be avoided in patients taking lithium due to the potential for renal tubular dysfunction and increased lithium toxicity, as noted in the 2014 commentary on the KDIGO clinical practice guideline 1. When considering medications that can affect lithium levels, it's crucial to prioritize those that have the most significant impact on renal function and lithium excretion.
- NSAIDs are highlighted as a particular concern due to their potential to cause renal tubular dysfunction, even at therapeutic levels of lithium, emphasizing the need to monitor GFR, electrolytes, and lithium levels closely, especially if the dose changes or the patient is acutely unwell 1.
- The risk-benefit of using such drugs in specific situations must be carefully weighed, considering the potential for increased lithium toxicity.
- Other medications like ACE inhibitors, angiotensin receptor blockers, certain antibiotics, calcium channel blockers, and some antipsychotics may also elevate lithium levels by altering renal handling, but the most recent and highest quality evidence emphasizes the caution with NSAIDs in the context of lithium therapy 1.
- Given the potential for severe consequences, including lithium toxicity characterized by tremor, nausea, diarrhea, and confusion, it is essential to monitor lithium levels frequently when these medications are necessary and consider dose adjustments as needed.
From the FDA Drug Label
Caution should be used when lithium and diuretics or angiotensin converting enzyme (ACE) inhibitors are used concomitantly because sodium loss may reduce the renal clearance of lithium and increase serum lithium levels with risk of lithium toxicity. Non-steroidal anti-inflammatory drugs (NSAIDS): Lithium levels should be closely monitored when patients initiate or discontinue NSAID use. In some cases, lithium toxicity has resulted from interactions between an NSAID and lithium. Indomethacin and piroxicam have been reported to increase significantly steady-state plasma lithium concentrations There is also evidence that other nonsteroidal anti-inflammatory agents, including the selective cyclooxygenase-2 (COX-2) inhibitors, have the same effect. In a study conducted in healthy subjects, mean steady-state lithium plasma levels increased approximately 17% in subjects receiving lithium 450 mg BID with celecoxib 200 mg BID as compared to subjects receiving lithium alone
The following drugs may increase lithium blood levels:
- Diuretics
- Angiotensin converting enzyme (ACE) inhibitors
- Non-steroidal anti-inflammatory drugs (NSAIDS), including:
- Indomethacin
- Piroxicam
- Selective cyclooxygenase-2 (COX-2) inhibitors, such as celecoxib 2
From the Research
Drugs that Increase Lithium Blood Level
- Loop diuretics may interact pharmacodynamically with lithium, potentially increasing lithium blood levels 3
- Thiazide diuretics have been shown to increase lithium concentrations by 25 to 40% 4
- Nonsteroidal anti-inflammatory drugs (NSAIDs) have also been associated with lithium toxicity, although the relative interactive potential of specific NSAIDs is difficult to determine 4
- ACE inhibitors may impair lithium elimination, but further investigations are needed to identify patients at risk 4
- Other medications that may increase lithium blood levels include:
- Amphotericin B
- Digoxin
- Antidiabetic drugs
- Antifungal agents
- Dobutamine
- Gossypol
- Sotalol due to diuretic-associated hypokalemia 3
- Cisplatin, aminoglycoside antibiotics, or phosphodiesterase 5 (PDE 5) inhibitors may enhance the risk of ototoxicity when used concomitantly with loop diuretics 3