PII-065 - DRUG-DRUG INTERACTIONS BETWEEN LETERMOVIR AND TARGETED THERAPIES FOR GRAFT VERSUS HOST DISEASE IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS: HOW DO DRUG-DRUG INTERACTION CHECKERS COMPARE?

D. Burger^1,2, L. Nijboer³, J. Maertens⁴, N. Blijlevens³, P. Ljungman⁵, R. Bruggemann³; ¹Radboud University Medical Center, Nijmegen, The Netherlands, ²Global DDI Solutions, Utrecht, The Netherlands, ³RadboudUMC, Nijmegen, The Netherlands, ⁴Univ Hosp Leuven, Leuven, Belgium, ⁵Karolinska Institute, Stockholm, Sweden.

Background: Graft versus host disease (GVHD) may occur in 30-50% of allogeneic hematopoietic stem cell transplant recipients. Approx. half of them develops steroid-refractory GVHD and have an indication for targeted therapy with one of the three FDA-approved treatments for GVHD: ruxolitinib, ibrutinib and belumosudil. CMV seropositive patients are also at risk for developing cytomegalovirus (CMV) infection/disease and may have an indication for letermovir prophylaxis. Although the FDA-approved Product Information of letermovir (Prevymis®; last updated August 2, 2023) contains DDI recommendations for as many as 38 different medications, no specific reference is made to combined use with these agents for GVHD treatment. Clinicians therefore have to rely on on-line DDI information sources (aka “Interaction Checkers”). To explore similarities and discrepancies, we compared the DDI recommendations using four freely available Interaction Checkers.

Methods: On August 5, 2024, we compared the recommendations of the following Interaction Checkers: Lexicomp/UpToDate, Drugs.com, Medscape, and DDIManager.co for combined use of letermovir and either ruxolitinib, ibrutinib and belumosudil. We standardized the DDI recommendations from the Interaction Checkers into the following three categories: “no or minimal interaction expected; no action” (green); “clinically relevant interaction expected; action needed” (orange); or “severe interaction expected, do not co-administer” (red).

Results: Table 1 displays the outcome of the analysis by the four different Interaction Checkers. Belumosudil inhibits OATP1B1/3 and UGT1A1 which may lead to higher plasma levels of letermovir. In contrast, letermovir may inhibit CYP3A-medicated metabolism of ibrutinib and ruxolitinib, possibly causing more toxicity. 75% Agreement was observed for belumosudil and ibrutinib; for ruxolutinib, two Interaction Checkers claimed no/minimal interaction (green) while two others predict a clinically relevant interaction for which action is needed.

Conclusion: The lack of agreement among freely available on-line interaction checkers when investigating DDIs in this vulnerable patient population is worrisome. It would be helpful if Product Information would be more informative regarding clinically relevant DDIs.