From the Guidelines
Lithium has several important drug interactions that can affect its safety and effectiveness, and it is crucial to avoid combining it with certain medications to prevent toxicity. When taking lithium, it is essential to be aware of potential interactions with other drugs, such as NSAIDs like ibuprofen, diuretics (especially thiazides like hydrochlorothiazide), ACE inhibitors, and certain antibiotics (tetracyclines, metronidazole) as these can increase lithium levels and potentially cause toxicity 1.
Key Interactions to Consider
- NSAIDs: increase lithium levels by decreasing renal clearance
- Diuretics: especially thiazides, can increase lithium levels by decreasing renal clearance
- ACE inhibitors: can increase lithium levels by decreasing renal clearance
- Certain antibiotics: such as tetracyclines and metronidazole, can increase lithium levels by decreasing renal clearance
- Caffeine and sodium changes in diet: can affect lithium levels, and consistent salt intake and hydration are recommended
Monitoring and Precautions
Regular blood monitoring of lithium levels is essential, typically aiming for 0.6-1.2 mEq/L for maintenance therapy 1. It is also crucial to inform healthcare providers about all medications being taken and to be aware of signs of lithium toxicity, which include tremor, confusion, vomiting, diarrhea, and coordination problems - seeking immediate medical attention if these develop while taking lithium. Additionally, caution should be taken when lithium is used concomitantly with anti-arrhythmic drugs, as it may have a QT prolonging effect, and bradycardia, T wave changes, and AV-block have been described 1.
Clinical Considerations
In clinical practice, it is essential to consider the potential for drug-drug interactions when prescribing lithium, and to take a cautious approach to minimize the risk of adverse effects. This includes careful monitoring of lithium levels, renal function, and electrolytes, as well as regular assessment of treatment response and potential side effects. By taking a proactive and informed approach to lithium therapy, healthcare providers can help to minimize the risks associated with this medication and optimize its benefits for patients.
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 A causal relationship between these events and the concomitant administration of lithium and haloperidol has not been established; however, patients receiving such combined therapy should be monitored closely for early evidence of neurological toxicity and treatment discontinued promptly if such signs appear The possibility of similar adverse interactions with other antipsychotic medication exists. Lithium may prolong the effects of neuromuscular blocking agents. 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. When such combinations are used, the lithium dosage may need to be decreased, and more frequent monitoring of lithium plasma levels is recommended 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.
The potential drug interactions with Lithium (lithium carbonate) include:
- Combined use with haloperidol: may cause an encephalopathic syndrome
- Other antipsychotic medication: possibility of similar adverse interactions
- Neuromuscular blocking agents: lithium may prolong their effects
- Diuretics or ACE inhibitors: may increase serum lithium levels with risk of lithium toxicity
- Non-steroidal anti-inflammatory drugs (NSAIDS): may increase steady-state plasma lithium concentrations, including indomethacin, piroxicam, and selective cyclooxygenase-2 (COX-2) inhibitors 2
From the Research
Potential Drug Interactions with Lithium
The following drugs have been reported to interact with lithium, potentially leading to increased serum lithium levels or lithium toxicity:
- Nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, ibuprofen, and naproxen, which can increase serum lithium levels and diminish renal lithium clearance 3, 4
- Diuretics, particularly thiazide diuretics, which can increase lithium concentrations by 25 to 40% 4
- ACE 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 in some cases 5
- Antipsychotics, anticonvulsants, and calcium antagonists, which have been implicated in case reports of neurotoxicity without an apparent effect on lithium pharmacokinetics 4
Mechanisms of Interaction
The mechanisms of these interactions vary, but many involve alterations in renal function or electrolyte exchange in the nephron, which can affect lithium clearance and increase the risk of toxicity 4. Additionally, some drugs may displace lithium from plasma proteins or inhibit its metabolism, leading to increased serum levels 6.
Clinical Implications
Patients receiving lithium should be closely monitored for signs of toxicity, particularly when concomitantly using other medications that may interact with lithium 3, 4, 5. Serum lithium levels should be checked regularly, and dosage adjustments may be necessary to prevent toxicity 3.