Is there a contraindication between bupropion (Wellbutrin) and metoprolol?

Contraindication Between Bupropion (Wellbutrin) and Metoprolol

Yes, there is a significant drug interaction between bupropion (Wellbutrin) and metoprolol that should be considered a relative contraindication due to the risk of increased metoprolol levels and potential adverse effects.

Mechanism of Interaction

• Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors 1
• Metoprolol is primarily metabolized by the CYP2D6 enzyme, making it vulnerable to this interaction 2
• When used concomitantly, bupropion can significantly increase metoprolol blood levels by inhibiting its metabolism 1, 2

Clinical Significance

• Bupropion can increase the biologically available dose of metoprolol approximately 4-6 fold, similar to other potent CYP2D6 inhibitors like paroxetine and fluoxetine 2
• This interaction can lead to serious adverse effects including:
  • Severe bradycardia 3, 2
  • Atrioventricular block 2
  • Hypotension 3
  • Enhanced beta-blocker side effects 3

Expert Recommendations

• According to research, metoprolol should not be used concomitantly with bupropion due to extensive interactions and the risk of serious adverse effects 2
• The FDA label for bupropion specifically warns that when used concomitantly with CYP2D6 substrates like metoprolol, it may be necessary to decrease the dose of these medications, particularly for drugs with a narrow therapeutic index 1
• If both medications are deemed necessary, consider:
  • Significant dose reduction of metoprolol 2
  • Close monitoring for bradycardia and hypotension 3
  • Alternative beta-blockers that are less dependent on CYP2D6 metabolism 2

Alternative Options

• Consider using beta-blockers that are less dependent on CYP2D6 metabolism, such as atenolol or bisoprolol 2
• Alternative antidepressants with minimal CYP2D6 inhibition that may be safer with metoprolol include:
  • Sertraline 2
  • Venlafaxine 2
  • Mirtazapine 2
  • Mianserin 2

Clinical Monitoring

• If concurrent use cannot be avoided, monitor closely for:
  • Bradycardia 3, 2
  • Hypotension 3
  • Heart block 2
  • Other signs of beta-blocker toxicity 3

Common Pitfalls

• Failing to recognize this interaction when patients are on stable doses of metoprolol and then adding bupropion 3
• Not adjusting metoprolol dosage when bupropion is initiated 1, 2
• Overlooking the interaction because bupropion is generally considered to have a favorable cardiovascular profile when used alone 4, 5

This drug interaction represents a significant clinical concern that requires careful consideration of alternative medications or close monitoring if concurrent use is unavoidable.