Why can't ibuprofen (Nonsteroidal Anti-Inflammatory Drug (NSAID)) be given with lithium (lithium carbonate)?

Why Ibuprofen Should Not Be Given With Lithium

Ibuprofen should not be given with lithium because it can significantly increase serum lithium levels by decreasing renal lithium clearance, potentially leading to lithium toxicity even in patients with normal renal function. 1, 2

Mechanism of Interaction

The interaction between NSAIDs like ibuprofen and lithium occurs primarily through renal mechanisms:

• NSAIDs inhibit prostaglandin synthesis in the kidneys
• This reduces sodium excretion and decreases lithium clearance
• The result is increased lithium reabsorption in the renal tubules
• Consequently, serum lithium concentrations rise, potentially reaching toxic levels 2, 3

Evidence of Risk

The FDA drug label for lithium explicitly warns about this interaction:

• "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." 2

Clinical studies have demonstrated:

• Ibuprofen can increase serum lithium levels with marked interindividual variation 4
• The effect can occur rapidly, within days of starting the NSAID 3
• The interaction has been observed even in patients with normal renal function 3

Clinical Significance

The consequences of this interaction can be severe:

• Lithium has an extremely narrow therapeutic index
• Even small increases in lithium levels can lead to toxicity
• Symptoms of lithium toxicity include tremor, ataxia, drowsiness, muscle weakness, vomiting, diarrhea, and in severe cases, seizures, coma, and death 2

Management Recommendations

1. Avoid combination when possible:

   • The KDOQI guidelines specifically advise: "Avoid using concomitant NSAIDs" with lithium 1

2. If combination cannot be avoided:

   • Monitor lithium levels every 4-5 days until the extent of interaction is assessed 3
   • Consider reducing lithium dosage 3, 4
   • Monitor for signs of lithium toxicity (tremor, ataxia, drowsiness, muscle weakness) 2

3. Alternative options:

   • Consider acetaminophen as an alternative analgesic (does not have this interaction)
   • If anti-inflammatory effect is needed, consider consulting with psychiatrist for medication adjustment

Special Considerations

• The elderly are particularly vulnerable to this interaction 5
• Patients with renal impairment are at even higher risk 1
• The risk may be compounded when other medications affecting lithium clearance (like ACE inhibitors or diuretics) are used concurrently 5, 6

Clinical Pitfalls to Avoid

• Don't assume all NSAIDs have the same effect - while ibuprofen, indomethacin, and naproxen significantly increase lithium levels, aspirin and sulindac appear to have minimal effect 3, 7
• Don't rely on normal baseline renal function as protection - this interaction occurs even in patients with normal renal function 3
• Don't forget to educate patients about avoiding over-the-counter NSAIDs - many patients may not realize ibuprofen (Advil, Motrin) is an NSAID

The evidence clearly demonstrates that the combination of ibuprofen and lithium poses a significant risk of lithium toxicity and should be avoided whenever possible.