Is Paxlovid (nirmatrelvir/ritonavir) safe to use in a patient with COVID-19 who is currently taking Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) and acyclovir?

Paxlovid Should Not Be Administered with Biktarvy Due to Significant Drug-Drug Interactions

Paxlovid (nirmatrelvir/ritonavir) should not be administered to patients taking Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) due to significant drug-drug interactions that could lead to increased tenofovir concentrations and potential toxicity. 1

Drug Interaction Analysis

• Paxlovid contains ritonavir, a strong CYP3A inhibitor that can significantly interact with many medications, as highlighted in the FDA boxed warning 1
• Coadministration of ritonavir (a component of Paxlovid) with tenofovir alafenamide (a component of Biktarvy) can increase tenofovir concentrations by 275-316%, potentially leading to increased risk of renal impairment 2
• The FDA label for Paxlovid specifically warns about significant drug interactions that may lead to potentially severe, life-threatening, or fatal events 1
• Prior to prescribing Paxlovid, all medications must be reviewed to assess potential drug-drug interactions with ritonavir 1

Specific Concerns with Biktarvy

• Biktarvy contains tenofovir alafenamide, which when combined with ritonavir-containing regimens like Paxlovid, can lead to dramatically increased tenofovir concentrations 2
• While no dose adjustment of tenofovir alafenamide is specifically recommended in guidelines, close monitoring of renal function would be required if coadministration occurred 2
• Biktarvy also contains bictegravir, which is primarily metabolized by CYP3A4, making it susceptible to interaction with the ritonavir component of Paxlovid 2

Alternative Approaches

• For patients on Biktarvy requiring COVID-19 treatment, alternative COVID-19 therapies that don't contain ritonavir should be considered 1
• If Paxlovid is deemed necessary due to high risk of COVID-19 progression, temporarily switching from tenofovir alafenamide to entecavir during Paxlovid treatment could be considered, though this would require consultation with an infectious disease specialist 2
• Acyclovir does not have significant interactions with Paxlovid and can be continued during Paxlovid treatment 3

Monitoring Requirements if Coadministration Cannot Be Avoided

• If coadministration cannot be avoided due to clinical necessity:
  • Close monitoring of renal function is essential 2
  • Watch for adverse reactions associated with tenofovir toxicity (renal impairment, bone density loss) 2
  • Monitor for signs of hepatotoxicity, as ritonavir can cause hepatic transaminase elevations 1

Important Considerations

• The 5-day course of Paxlovid treatment presents a significant risk period for drug interactions 4
• Paxlovid has been shown to reduce the risk of COVID-19 progression and has been associated with reduced incidence of long COVID 2
• The decision to use Paxlovid must balance the benefit of preventing severe COVID-19 against the risk of drug interactions 5
• Drug interactions with Paxlovid are not limited to prescription medications; herbal medicines and supplements should also be evaluated 6

Conclusion for Clinical Practice

• The safest approach is to avoid coadministration of Paxlovid with Biktarvy 1, 2
• If COVID-19 treatment is necessary, consult with infectious disease and HIV specialists to determine the safest approach to temporary HIV medication management 2
• Consider alternative COVID-19 treatments that don't contain ritonavir for patients on Biktarvy 4