What are the risks of taking ibuprofen (Nonsteroidal Anti-Inflammatory Drug (NSAID)) with lithium (mood stabilizer)?

Risks of Taking Ibuprofen with Lithium

Concomitant use of ibuprofen with lithium should be avoided due to the significant risk of lithium toxicity caused by increased serum lithium levels and decreased renal lithium clearance. 1, 2

Mechanism of Interaction

The interaction between lithium and ibuprofen is well-documented and clinically significant:

• Ibuprofen decreases renal lithium clearance by approximately 19% 3
• This leads to an average 15% increase in minimum lithium concentration 3
• The effect is attributed to ibuprofen's inhibition of renal prostaglandin synthesis 1

Clinical Consequences

This pharmacokinetic interaction can result in:

• Elevated serum lithium levels reaching toxic range
• Signs of lithium toxicity including:
  • Tremor, confusion, drowsiness
  • Nausea, vomiting, diarrhea
  • Muscle weakness
  • In severe cases: seizures, coma, and death

Risk Factors

The risk of lithium toxicity is higher in:

• Elderly patients
• Patients with renal impairment
• Dehydrated patients
• Patients on higher lithium doses
• Concurrent use of other medications that affect renal function

Management Options

If pain management is needed for a patient on lithium therapy:

1. First-line alternative: Use acetaminophen instead of NSAIDs 2
2. If NSAID is absolutely necessary:
   • Consider sulindac, which appears to have less effect on lithium levels 2, 4
   • Avoid indomethacin, which has the strongest interaction 2
   • Monitor lithium levels frequently (every 4-5 days) until the extent of interaction is established 2
   • Reduce lithium dosage as needed based on serum levels

Monitoring Recommendations

If ibuprofen must be used with lithium:

• Check serum lithium levels before starting ibuprofen
• Recheck lithium levels every 4-5 days for the first two weeks 2
• Continue monitoring until stable levels are confirmed
• Watch for clinical signs of lithium toxicity
• Ensure adequate hydration

Common Pitfalls

1. Failure to recognize the interaction: Many clinicians may not be aware of this significant drug interaction.
2. Over-the-counter availability: Patients may self-medicate with ibuprofen without realizing the risk.
3. Variable response: The magnitude of interaction shows marked interindividual variation 4, making it difficult to predict.
4. Delayed onset: Lithium toxicity may develop gradually over several days after starting ibuprofen.

This interaction represents a significant clinical concern that requires careful consideration when managing patients on lithium therapy who require pain relief. The safest approach is to avoid the combination entirely and use alternative analgesics when possible.