Can Paxlovid (nirmatrelvir/ritonavir) be taken with methimazole, acetaminophen (APAP), Wellbutrin (bupropion), and testosterone?

Paxlovid Interactions with Methimazole, Acetaminophen, Wellbutrin, and Testosterone

Paxlovid can be safely taken with methimazole and acetaminophen, but Wellbutrin (bupropion) requires dose reduction and monitoring, while testosterone therapy should be temporarily adjusted during the 5-day Paxlovid course due to potential drug interactions.

Drug Interaction Analysis

Methimazole

• No clinically significant interaction expected with Paxlovid
• Methimazole is not primarily metabolized by CYP3A4 enzymes that are inhibited by ritonavir (component of Paxlovid)
• Can be continued at the same dose during Paxlovid treatment

Acetaminophen (APAP)

• No clinically significant interaction expected with Paxlovid
• Acetaminophen is primarily metabolized through glucuronidation and sulfation pathways, not significantly affected by CYP3A4 inhibition
• Can be continued at regular dosing during Paxlovid treatment

Wellbutrin (Bupropion)

• Potential interaction requiring dose adjustment
• Bupropion is partially metabolized by CYP2B6, and ritonavir can inhibit this pathway
• Ritonavir's inhibition of metabolism may increase bupropion levels, potentially increasing risk of adverse effects including seizures
• Recommendations:
  • Reduce bupropion dose by 50% during Paxlovid treatment
  • Monitor for signs of bupropion toxicity (agitation, insomnia, seizures)
  • Return to regular dosing 3-5 days after completing Paxlovid

Testosterone

• Potential interaction requiring monitoring
• Testosterone is partially metabolized by CYP3A4
• Ritonavir inhibition may increase testosterone levels
• Recommendations:
  • Consider reducing testosterone dose by 30-50% during the 5-day Paxlovid course
  • Monitor for signs of testosterone excess (acne, edema, mood changes)
  • Resume normal dosing after completing Paxlovid

Important Considerations

1. Duration of Interaction: Paxlovid is typically prescribed for 5 days, so drug interactions are time-limited

2. Monitoring Requirements:

   • For Wellbutrin: Watch for increased side effects like anxiety, insomnia, tremor
   • For testosterone: Monitor for fluid retention, increased blood pressure

3. Timing of Medication Administration:

   • Paxlovid should be taken at the same time each day for 5 days 1
   • No special timing separation is needed between Paxlovid and these medications

4. Renal Function Considerations:

   • If the patient has moderate renal impairment (eGFR 30-59 mL/min), Paxlovid dosing should be adjusted to nirmatrelvir 150 mg/ritonavir 100 mg twice daily 1
   • If severe renal impairment is present, different dosing is required

Common Pitfalls to Avoid

1. Abrupt Discontinuation: Do not abruptly stop Wellbutrin or testosterone as this may cause withdrawal symptoms or hormonal fluctuations

2. Ignoring New Symptoms: Any new symptoms during co-administration should be evaluated promptly as they may indicate drug interaction effects

3. Overlooking Renal Function: Failure to adjust Paxlovid dosing based on renal function can lead to toxicity

4. Assuming All Psychiatric Medications Interact Similarly: Unlike some other antidepressants that have severe interactions with Paxlovid, Wellbutrin can be continued with dose adjustment

Conclusion

The 5-day course of Paxlovid can be safely administered with appropriate adjustments to the medication regimen. The primary concerns are with Wellbutrin and testosterone, which require dose adjustments and monitoring, while methimazole and acetaminophen can be continued without changes.