What are the potential interactions between Relafen (nabumetone) and Skelaxin (metaxalone)?

Potential Interactions Between Nabumetone (Relafen) and Metaxalone (Skelaxin)

There are no significant direct pharmacokinetic interactions documented between nabumetone (Relafen) and metaxalone (Skelaxin), but caution is warranted due to potential additive central nervous system depressant effects.

Pharmacological Properties and Mechanisms

• Nabumetone (Relafen) is a non-acidic NSAID prodrug that is converted to its active metabolite 6-methoxy-2-naphthylacetic acid (6-MNA), which preferentially inhibits COX-2 1, 2
• Metaxalone (Skelaxin) is a skeletal muscle relaxant that may cause central nervous system depression 3
• Both medications are metabolized by the liver, which creates a theoretical potential for interaction, though no specific documented interactions exist between these two medications 3, 4

Potential Additive Effects

• The primary concern when combining these medications is the potential for additive sedative effects:
  • Metaxalone can cause drowsiness and dizziness 3
  • When combined with other CNS depressants, including NSAIDs like nabumetone, there may be enhanced sedation 3
• The Mayo Clinic recommends that metaxalone should be held on the day of surgical procedures to avoid potentiating anesthetic agents, suggesting its potential to enhance the effects of other medications 3

Special Considerations

Hepatic Function

• Both medications have considerations regarding hepatic function:
  • Metaxalone is contraindicated in patients with significant hepatic dysfunction 3
  • Nabumetone undergoes extensive first-pass metabolism in the liver, and patients with severe hepatic impairment may have reduced bioavailability of 6-MNA 4
  • Dosage adjustments may be required in patients with hepatic impairment when using nabumetone 4

Renal Function

• Metaxalone is contraindicated in patients with significant renal dysfunction 3
• Renal failure significantly reduces 6-MNA (nabumetone's active metabolite) elimination, though steady-state concentrations may not increase due to nonlinear protein binding 4
• Dosage adjustment for nabumetone is generally not required in patients with mild-to-moderate renal failure 4

Recommendations for Clinical Practice

• Monitor patients for excessive sedation, especially when initiating therapy or changing dosages 3
• Consider reduced dosing in elderly patients, who may be more sensitive to CNS effects 5
• Use caution in patients with hepatic or renal impairment 3, 4
• Be aware that nabumetone has been shown to have a more favorable gastrointestinal safety profile compared to many other NSAIDs, which may be beneficial when combination therapy is necessary 1, 6
• Avoid alcohol and other CNS depressants when possible, as they may enhance the sedative effects of this combination 3

Monitoring Parameters

• Assess for signs of excessive sedation or dizziness, particularly when initiating therapy 3
• Monitor hepatic function periodically, especially in patients with pre-existing liver conditions 3, 4
• Evaluate renal function in patients with known renal impairment 3, 4
• Watch for gastrointestinal symptoms, though nabumetone has shown lower rates of GI complications compared to many other NSAIDs 6

While no direct pharmacokinetic interactions have been documented between these specific medications, clinicians should remain vigilant for potential additive CNS depressant effects and adjust treatment accordingly.