From the Guidelines
The major drug interaction with lithium is with nonsteroidal anti-inflammatory drugs (NSAIDs), which can increase lithium levels in the blood by reducing its kidney clearance, potentially leading to lithium toxicity. This interaction is significant because lithium is eliminated almost entirely through renal excretion, and any medication that affects kidney function or sodium balance can potentially alter lithium levels 1.
Key Interactions
- Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, naproxen, and diclofenac can increase lithium levels by reducing its kidney clearance
- Thiazide diuretics, ACE inhibitors, and angiotensin receptor blockers can also raise lithium levels by affecting kidney function and sodium balance
- Some antipsychotics and anticonvulsants may enhance lithium's neurological side effects
Clinical Implications
Patients taking lithium should avoid regular NSAID use or have their lithium levels monitored closely if NSAIDs are necessary, as recommended by guidelines such as those from the Kidney Disease: Improving Global Outcomes (KDIGO) 1. It is essential for patients on lithium therapy to inform all healthcare providers about their medication and maintain regular blood level monitoring, especially when starting or stopping any other medications. By being aware of these potential interactions and taking steps to mitigate them, healthcare providers can help minimize the risk of lithium toxicity and ensure the safe and effective use of this medication.
From the FDA Drug Label
Drug interactions: Combined use of haloperidol and lithium. An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leucocytosis, elevated serum enzymes, BUN and FBS) followed by irreversible brain damage has occurred in a few patients treated with lithium plus haloperidol 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.
The major drug interactions with lithium include:
- Combined use with haloperidol, which may cause an encephalopathic syndrome
- Concomitant use with diuretics or ACE inhibitors, which may increase the risk of lithium toxicity due to reduced renal clearance
- Interactions with NSAIDs, which may increase lithium levels and cause toxicity 2
From the Research
Major Drug Interactions with Lithium
The major drug interactions with lithium include:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) which can increase serum lithium levels and diminish renal lithium clearance, potentially inducing lithium toxicity 3
- Diuretics, particularly thiazide diuretics, which can increase lithium concentrations by 25 to 40% after initiation of therapy 4
- Renin-angiotensin inhibitors, which may impair lithium elimination, although further investigations are needed to identify patients at risk 4
- Antibiotics, which have been associated with elevated lithium serum levels 5
Mechanisms of Interaction
The mechanisms of these interactions include:
- Alteration of glomerular filtration rates or electrolyte exchange in the nephron, which can influence the pharmacokinetic disposition of lithium 4
- Inhibition of renal lithium clearance, which can lead to increased serum lithium levels and potentially induce lithium toxicity 3
Clinical Significance
These interactions are clinically significant because lithium has a narrow therapeutic window, and relatively minor increases in serum concentrations can induce serious adverse sequelae 4. Therefore, it is essential to monitor serum lithium levels closely when co-administering lithium with other medications, particularly those known to interact with lithium 3, 4.