Tacrolimus levels monitoring needed when initiating letermovir, says study

Patients receiving the combination of letermovir and tacrolimus with concomitant moderate cytochrome P450 (CYP) 3A4 inhibitors show a decline in tacrolimus dosing requirements, a study has shown.

“The results of this interaction suggest that frequent monitoring of tacrolimus trough levels is warranted when starting letermovir and that empiric reduction of tacrolimus dosing upon letermovir initiation should be considered,” the investigators said.

The charts of 92 consecutive adult recipients of allogeneic haematopoeitic cell transplantation receiving letermovir, tacrolimus, and moderate CYP 3A4 inhibitors for antifungal prophylaxis were included in this retrospective single-centre analysis.

The investigators evaluated the tacrolimus concentration/dose (C/D) ratios for the first 7 days prior to letermovir initiation and for the first and second 7-day periods after letermovir.

The addition of letermovir led to a significant increase in the tacrolimus mean C/D ratios (ng/mL)/(mg/kg/day): 172.99 (95 percent confidence interval [CI], 158.2‒187.78 preletermovir, 268.66 (95 percent CI, 244.34‒292.98) first-week letermovir, and 312.19 (95 percent CI, 279.39‒344.99) second-week letermovir (p<0.001).

Moreover, a significant decrease in the average doses (mg/kg) of tacrolimus was observed across the three-time intervals (p<0.001). Only four patients had clinically significant cytomegalovirus reactivation requiring systemic treatment.

“Letermovir inhibits cytomegalovirus replication and is approved for the prevention of cytomegalovirus infection in cytomegalovirus seropositive haematopoietic cell transplantation recipients,” said the investigators. “Studies have found that letermovir coadministration has minimal effect on tacrolimus levels prior to the start of voriconazole, a strong CYP 3A4 inhibitor.”