Management of Rinvoq (Upadacitinib) in RA Patients Requiring Paxlovid for COVID-19
Continue Rinvoq during Paxlovid treatment for COVID-19 in patients with rheumatoid arthritis, but carefully manage the significant drug-drug interaction by monitoring for increased upadacitinib-related adverse effects, as ritonavir will substantially increase upadacitinib exposure through CYP3A4 inhibition. 1, 2
Drug Interaction Management
Understanding the Interaction Mechanism
Ritonavir is a potent CYP3A4 inhibitor that will significantly increase plasma concentrations of upadacitinib (a JAK1/JAK2 inhibitor metabolized primarily through CYP3A4), creating risk for dose-dependent adverse effects during the 5-day Paxlovid course 3, 2
The interaction occurs rapidly with ritonavir's potent inhibition of CYP3A4 in both the gut and liver, affecting first-pass metabolism 3
Specific Dosing Recommendations
No dose adjustment of upadacitinib is recommended when co-administered with Paxlovid - maintain the standard RA dosing (15 mg once daily) throughout the 5-day COVID-19 treatment course 2
The short duration of ritonavir exposure (5 days) limits the cumulative risk compared to chronic CYP3A4 inhibitor use 2
Pragmatic options for DDI management with short-course ritonavir are largely confined to counseling and monitoring rather than dose adjustment, given the brief treatment window 2
Continuation of Immunosuppressive Therapy
General Principle for JAK Inhibitors
The American College of Rheumatology recommends temporarily withholding JAK inhibitors (including upadacitinib) in patients with symptomatic COVID-19 infection due to concerns about dampening innate antiviral interferon responses 4, 1
However, this recommendation must be balanced against the risk of RA disease flare and the anti-inflammatory benefits that may mitigate COVID-19 cytokine storm 1
Clinical Decision Algorithm
For mild COVID-19 symptoms (sore throat, rhinorrhea, low-grade fever <38°C, mild myalgia):
- Continue upadacitinib while treating with Paxlovid 4, 1
- The anti-inflammatory effects may provide benefit in preventing progression to severe disease 1
For significant COVID-19 symptoms (fever ≥38°C, shortness of breath, tachypnea >20/min, hypoxia):
- Consider temporarily withholding upadacitinib during the acute infection period 4
- Resume once symptoms improve and patient is afebrile for 24-48 hours 4
For patients with well-controlled RA on stable therapy:
- Prioritize maintaining disease control to prevent flare, which itself can increase morbidity 4, 5, 6
- The immunosuppressive effect of upadacitinib has not been definitively shown to worsen COVID-19 outcomes in RA patients 5, 6
Monitoring During Co-Administration
Adverse Effects to Monitor
Increased infection risk: Monitor for secondary bacterial infections, herpes zoster reactivation, or opportunistic infections during and after treatment 1
Hematologic toxicity: Watch for worsening cytopenias (lymphopenia, neutropenia, anemia) as upadacitinib levels will be elevated 1
Hepatotoxicity: Monitor for elevated transaminases, particularly if baseline liver function is abnormal 1
Thrombotic events: Counsel patients on signs of deep vein thrombosis or pulmonary embolism, as JAK inhibitors carry this risk 1
Practical Monitoring Schedule
Baseline assessment before starting Paxlovid: Complete blood count, liver function tests if clinically indicated 1
Daily symptom monitoring via telehealth or patient self-reporting during the 5-day Paxlovid course 7
Follow-up assessment 7-10 days after completing Paxlovid to evaluate for delayed adverse effects or disease flare 7
Common Pitfalls to Avoid
Do not empirically reduce upadacitinib dose - there is no established reduced dosing regimen for short-term CYP3A4 inhibition, and subtherapeutic dosing may precipitate RA flare 2
Do not discontinue upadacitinib abruptly without considering flare risk - patients with highly active RA or recent disease control may experience rapid symptom recurrence 4, 6
Do not delay Paxlovid initiation due to concerns about the drug interaction - Paxlovid must be started within 5 days of symptom onset for maximal efficacy in preventing severe COVID-19, and the interaction can be managed through monitoring 7, 2
Do not assume all immunosuppressed RA patients have worse COVID-19 outcomes - emerging data suggests RA patients on DMARDs do not have significantly worse outcomes than the general population, and may benefit from baseline anti-inflammatory therapy 5, 6
Post-Treatment Considerations
Resume normal upadacitinib dosing schedule if it was held, once patient is clinically improved and afebrile 4
CYP3A4 activity returns to baseline within 2-3 days after stopping ritonavir, so drug interaction effects resolve quickly 3, 2
Reassess RA disease activity 2-4 weeks after COVID-19 resolution to ensure adequate disease control 4, 6