Paxlovid and Tikosyn: A Potentially Life-Threatening Drug Interaction
Concomitant use of Paxlovid (nirmatrelvir/ritonavir) and Tikosyn (dofetilide) is absolutely contraindicated due to the high risk of life-threatening cardiac arrhythmias.
Mechanism of Interaction
Paxlovid contains ritonavir, which is a potent inhibitor of CYP3A4 enzymes. This creates a significant drug interaction concern with medications metabolized by this pathway, including Tikosyn (dofetilide).
- Ritonavir strongly inhibits CYP3A4, which is responsible for the metabolism of approximately 60% of available medications 1
- When CYP3A4 is inhibited, plasma concentrations of dofetilide can increase dramatically
- Elevated dofetilide levels significantly increase the risk of QT prolongation and potentially fatal cardiac arrhythmias, including Torsades de Pointes
Clinical Implications
The FDA drug label for Paxlovid explicitly addresses this interaction:
- Antiarrhythmics (including dofetilide) are listed among medications contraindicated with Paxlovid 2
- The label specifically warns that co-administration is contraindicated due to the potential for cardiac arrhythmias 2
Alternative Approaches
For patients requiring COVID-19 treatment who are on Tikosyn:
Consider alternative COVID-19 treatments:
- Remdesivir (intravenous) may be an option as it has fewer drug interactions
- Molnupiravir might be considered, though it has lower efficacy than Paxlovid 3
Temporary medication management options:
- Temporarily discontinuing Tikosyn may be considered in some cases, but only under close cardiac monitoring and with specialist consultation
- This approach carries significant risks and should only be undertaken with cardiology guidance
Risk Assessment and Monitoring
If a patient has inadvertently taken both medications together:
- Immediate ECG monitoring for QT prolongation
- Electrolyte monitoring and correction (particularly potassium and magnesium)
- Cardiac monitoring in a hospital setting may be necessary
- Consider measuring dofetilide plasma levels if available
Similar High-Risk Interactions with Paxlovid
Other medications that are similarly contraindicated with Paxlovid include:
- Other antiarrhythmics: amiodarone, dronedarone, flecainide, propafenone, quinidine 2
- Antianginals: ranolazine 2
- Alpha-1 adrenoreceptor antagonists: alfuzosin 2
Conclusion
The interaction between Paxlovid and Tikosyn represents a serious, potentially fatal drug interaction that must be avoided. The decision to use Paxlovid must always include a thorough medication review, with particular attention to medications with narrow therapeutic indices that are metabolized by CYP3A4, such as Tikosyn.
When treating COVID-19 in patients on Tikosyn, alternative therapies should be strongly considered, and any medication changes should be made only under specialist guidance with appropriate monitoring.