What are the considerations for administering Journavax (COVID-19 vaccine) to a patient taking Tacrolimus (immunosuppressant) due to an organ transplant?

COVID-19 Vaccination in Patients Taking Tacrolimus

Patients taking tacrolimus for organ transplantation should receive COVID-19 vaccination (Journavax) without discontinuing their immunosuppressive therapy, with timing optimized based on transplant status and vaccination administered 3-6 months post-transplantation when possible. 1

Vaccination Timing Based on Transplant Status

Post-Transplant Recipients (Already on Tacrolimus)

• Postpone vaccination for 3-6 months after transplantation to allow graft stabilization and reduction of high-dose immunosuppression 1
• If the first vaccine dose was received before transplantation, administer the second dose at least 4 weeks (or 6 weeks to 3 months for liver transplant) after the procedure 1
• A third dose may be warranted for optimal immunity given the blunted immune response in immunosuppressed patients 1

Pre-Transplant Patients

• Vaccination is recommended early in the course of the underlying disease, ideally completing the full vaccine series before transplantation 1
• Patients on the transplant list should receive two doses of the vaccine before the transplant whenever possible 1

Critical Management of Tacrolimus During Vaccination

Do NOT Discontinue Tacrolimus

• Continue tacrolimus without interruption during COVID-19 vaccination 1
• Unlike other immunosuppressants (methotrexate, JAK inhibitors, anti-CD20 medications), tacrolimus does not require withholding before or after vaccination 1
• Acute withdrawal of immunosuppressive therapy risks graft rejection, which carries higher morbidity and mortality than reduced vaccine response 1

When to Defer Vaccination

• Withhold vaccination in transplant recipients with active acute cellular rejection (ACR) until the condition is resolved 1
• Defer if receiving high-dose corticosteroids (>20 mg prednisone equivalent daily) until steroid doses are tapered 1
• If active underlying disease requires intensification of immunosuppression, prioritize disease control over vaccination 1

Monitoring Considerations During COVID-19 Infection

Tacrolimus Exposure Increases with COVID-19

• COVID-19 infection causes inflammation-driven downregulation of CYP3A4 metabolism, leading to significantly elevated tacrolimus levels 2
• Multiple case reports document tacrolimus toxicity in kidney transplant recipients with COVID-19 despite unchanged dosing 2
• Implement frequent therapeutic drug monitoring (tacrolimus trough levels) in transplant patients who develop COVID-19 2

Drug-Drug Interactions with COVID-19 Therapies

• If lopinavir-ritonavir is used for COVID-19 treatment, reduce tacrolimus dosage to 2-5% of baseline due to potent CYP3A4 inhibition 1
• Tacrolimus is metabolized via CYP3A4, and strong inhibitors can cause rapid, sharp rises in drug levels 3
• Monitor tacrolimus whole blood trough concentrations frequently when any CYP3A4 inhibitor or inducer is added 1, 3

Expected Vaccine Response

Reduced Immunogenicity

• Immunosuppression with tacrolimus will blunt the antibody response to COVID-19 vaccination 1
• Inactivated vaccines (including mRNA vaccines like Journavax) may not be sufficiently immunogenic during tacrolimus treatment 3
• This reduced response justifies the recommendation for additional booster doses in transplant recipients 1

Theoretical Benefits of Immunosuppression

• Immunosuppression may theoretically prevent progression to severe COVID-19 through cytokine downregulation, though this has not been definitively proven 1
• Immunosuppression per se does not appear to significantly affect the natural history of SARS-CoV-2 infection 1

Common Pitfalls to Avoid

Medication Errors

• Never discontinue tacrolimus for vaccination - this is only recommended for specific agents like methotrexate, JAK inhibitors, and anti-CD20 medications 1
• Ensure medication refills are provided to avoid acute withdrawal if clinic visits are deferred 1

Timing Errors

• Do not vaccinate too early post-transplant (before 3-6 months) as high-dose immunosuppression will render vaccination ineffective 1
• Avoid vaccinating during active rejection episodes or while on high-dose corticosteroids 1

Monitoring Failures

• Failure to increase tacrolimus monitoring during COVID-19 infection can lead to toxicity (nephrotoxicity, neurotoxicity, QT prolongation) 3, 2
• Target tacrolimus trough levels are typically 5-15 ng/mL, but inflammation can elevate levels significantly 1, 2

Additional Safety Considerations

Live Vaccines Are Contraindicated

• Avoid all live vaccines during tacrolimus therapy, including intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and typhoid vaccines 3
• Journavax (COVID-19 mRNA vaccine) is not a live vaccine and is safe to administer 4

Prolonged Viral Shedding

• Immunosuppression may prolong viral shedding in patients who develop COVID-19 after transplantation 1
• Patients with COVID-19 symptoms should not be evaluated in the transplantation clinic; defer visits for at least 14 days 1