Targeting High Calcineurin Inhibitor Levels After Acute Rejection With Less Tremor: A New Strategy
Tacrolimus-LCP (Tac-LCP) (Envarsus XR) is an extended-release once-daily tacrolimus preparation that has lower peak concentration, less fluctuation, similar trough levels, and similar exposure measured by area under the curve as twice daily immediate release tacrolimus (Tac-IR).3 Langone et al4 reported a statistical and clinical improvement in tremor as measured by the Fahan-Tolosa-Marin scale by independent blinded neurologists and tremor amplitude measured by Tremor-Meter in 40 kidney transplant recipients converted from Tac-IR to Tac-LCP. However, this study excluded patients who had a rejection episode within 3 months of screening. The use of Tac-LCP after rejection has not been examined, where higher drug exposure is needed and more tremors are expected.
We report a 38-year-old, white man with end stage kidney disease secondary to Henoch-Schonlein purpura who received a deceased donor kidney transplant with a 1A, 2B, 1DR mismatch, panel-reactive antibody of 0% for class 1 and 2, cytomegalovirus donor negative into recipient negative (D-/R-), and induction with thymoglobulin 5 mg/kg. Maintenance immunosuppression was Tac-IR, mycophenolic acid, and prednisone. During the first month, the patient developed tremor with a tacrolimus trough levels ranging from 8 to 10 ng/mL. Tac-IR dose was reduced to a tough level of 5 to 7 ng/mL in the second month (per our protocol). At 3 months posttransplant, the serum creatinine level increased from 1.7 to 3.3 mg/dL (Figure 1). The tacrolimus trough level on admission was 5.8 ng/mL. A kidney allograft biopsy showed a mixed acute cellular rejection (Banff 2A) and antibody mediated rejection. After treatment with plasmapheresis, intravenous immunoglobulin, thymoglobulin 6 mg/kg, and rituximab 200 mg once, Tac-IR was increased to achieve a higher trough of 10 to 12 ng/mL. Upon this increase, the patient developed a severe tremor that was like the immediate time after transplant. Tac-IR was converted to Tac-LCP at 80% of his total daily Tac-IR dose. Follow-up in a week after conversion showed that despite a tacrolimus trough level of 11 ng/mL, his tremor had almost completely resolved. Tacrolimus trough levels were maintained at 10 to 12 ng/mL for 3 months postrejection and then at 5 to 7 ng/mL. 1-year postrejection, the patient continues to have stable kidney function with a creatinine level of 1.4 ng/mL.
Tac-LCP may be a good alternative for patients requiring high levels of tacrolimus in the setting of recent rejection and suffering from severe tremor as in this patient.