From the Guidelines
Several factors, including dehydration, decreased salt intake, certain medications like NSAIDs, ACE inhibitors, and diuretics, kidney dysfunction, older age, and acute illness, can increase blood levels of lithium. These factors can lead to elevated lithium levels by either reducing its excretion or increasing its concentration in the bloodstream. According to the study 1, it is recommended to monitor GFR, electrolytes, and lithium levels 6 monthly or more frequently if the dose changes or the patient is acutely unwell, and to avoid using concomitant NSAIDs. Some key points to consider include:
- Dehydration, which can be caused by reduced fluid intake or increased fluid loss due to vomiting, diarrhea, or fever, can concentrate lithium in the bloodstream and increase its levels.
- Decreased salt intake can raise lithium levels because sodium and lithium compete for reabsorption in the kidneys.
- Certain medications, such as NSAIDs like ibuprofen, ACE inhibitors, diuretics (especially thiazides), and some antibiotics like metronidazole, can significantly increase lithium levels by reducing its excretion or increasing its reabsorption.
- Kidney dysfunction, which can be caused by various factors including older age, can slow lithium excretion and cause levels to rise.
- Regular blood monitoring is essential to prevent lithium toxicity, which can cause serious side effects including tremor, confusion, seizures, and kidney damage. It is crucial for patients taking lithium to maintain consistent hydration and salt intake, avoid medication interactions when possible, and undergo regular blood monitoring to prevent toxicity, as lithium has a narrow therapeutic window.
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 The following may increase the blood level of lithium:
- 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
Factors Increasing Blood Level of Lithium
- Nonsteroidal anti-inflammatory drugs (NSAIDs) can increase serum lithium levels, diminish renal lithium clearance, and possibly induce lithium toxicity 3
- The effect of NSAIDs on serum lithium levels varies greatly among different drugs, with indomethacin seeming most potent, and ibuprofen and naproxen can significantly increase serum lithium levels, but with marked interindividual variation 3
- Diuretics, particularly thiazide diuretics, can increase lithium concentrations by 25 to 40% 4
- Angiotensin-converting enzyme (ACE) inhibitors may impair lithium elimination, although further investigations are needed to identify patients at risk 4
- Dehydration can also contribute to increased lithium levels, especially when combined with certain medications such as hydrochlorothiazide 5
- Certain medications such as loop diuretics and potassium-sparing agents have minor variable effects on lithium clearance 4