What is the standard immunosuppressive regimen (induction and maintenance) to prevent graft rejection in adult solid‑organ transplant recipients without contraindications?

Standard Immunosuppressive Regimen for Adult Solid Organ Transplant Recipients

The standard regimen consists of induction therapy with an IL-2 receptor antagonist (basiliximab), followed immediately by triple maintenance therapy with tacrolimus, mycophenolate, and corticosteroids. 1, 2

Induction Phase (At Time of Transplantation)

First-Line Induction Agent

• Use an IL-2 receptor antagonist (basiliximab) as the standard induction agent for patients at low-to-standard immunologic risk 1, 2
• Basiliximab is FDA-approved specifically for prophylaxis of acute organ rejection in renal transplantation when combined with cyclosporine and corticosteroids 3

High-Risk Patients Requiring Alternative Induction

• Switch to a lymphocyte-depleting agent (rabbit antithymocyte globulin or alemtuzumab) instead of IL-2 receptor antagonist for patients with: 1, 2
  • High panel reactive antibodies
  • Repeat transplants
  • African-American recipients in certain high-risk scenarios
• Depleting agents combined with steroids demonstrate the lowest risk of graft failure compared to non-depleting agents 4

Initial Maintenance Immunosuppression (Starting Before or At Transplantation)

Triple-Drug Regimen Components

Calcineurin Inhibitor: Tacrolimus (First-Line)

• Start tacrolimus at 0.1 mg/kg/day divided every 12 hours when combined with IL-2 receptor antagonist and mycophenolate 2
• Begin tacrolimus before or at the time of transplantation rather than delaying until graft function onset 1
• Tacrolimus demonstrates superior efficacy compared to cyclosporine 1, 2
• Target trough levels of 5-10 ng/mL rather than the historically recommended 10-15 ng/mL, as higher levels increase nephrotoxicity without improving rejection rates 2

Antiproliferative Agent: Mycophenolate (First-Line)

• Use mycophenolate mofetil as the first-line antiproliferative agent 1, 2
• Mycophenolate demonstrates superior outcomes compared to azathioprine 1
• Monitor CBC counts every 1-3 months as standard for mycophenolate therapy 5

Corticosteroids

• Include corticosteroids in the initial regimen 1, 2
• In low immunologic risk patients receiving induction therapy, corticosteroids may be discontinued during the first week after transplantation 1
• Otherwise, continue corticosteroids as part of maintenance therapy 1

Long-Term Maintenance Strategy (2-4 Months Post-Transplant Onward)

Dose Optimization Timeline

• Reduce to the lowest planned doses of all maintenance immunosuppression by 2-4 months post-transplant if no acute rejection has occurred 1, 5, 2
• This minimizes cumulative immunosuppressive burden and associated infection/malignancy risks 6

Agent Continuation Decisions

• Continue calcineurin inhibitors (tacrolimus) indefinitely rather than withdrawing them, as withdrawal increases rejection risk 1, 2
• Continue prednisone rather than withdrawing it if being used beyond the first week post-transplant 1

Critical Monitoring Parameters

Tacrolimus Level Monitoring

• Measure tacrolimus trough levels every other day immediately post-operative until target levels are reached 2
• Subsequently monitor with any medication changes or clinical status changes 2

Infection Surveillance

• Screen for BK polyomavirus monthly for the first 3-6 months, then every 3 months through the first year 5
• Maintain CMV prophylaxis for at least 3 months post-transplant, extended to 6 weeks after any T-cell depleting antibody therapy 5
• Monitor for signs of infection including fever, cough, respiratory changes, and neurologic symptoms 5

Important Contraindications and Timing Restrictions

mTOR Inhibitors (If Considered)

• Do not start mTOR inhibitors until graft function is established and surgical wounds are healed, as early initiation increases wound complications and delayed graft function 1, 2

Live Vaccines

• Avoid live vaccines while on this immunosuppressive regimen, as patients will have inadequate immunologic response 5

Common Pitfalls to Avoid

• Do not target tacrolimus trough levels of 10-15 ng/mL in the maintenance phase—this increases nephrotoxicity without improving outcomes 2
• Do not delay starting tacrolimus until graft function begins—early initiation is recommended 1
• Do not use lymphocyte-depleting agents for standard-risk patients—reserve these for high immunologic risk only 1, 2
• Do not maintain high-dose immunosuppression beyond 2-4 months without acute rejection—this significantly increases infection risk (88% vs 38% documented infections with excessive vs. reduced regimens) 6