Letermovir (AIC246, MK-8228) is a novel anti-cytomegalovirus (CMV) agent that inhibits CMV replication by targeting the viral terminase complex. In December 2017, letermovir was approved by the Food and Drug Administration (FDA) for the prophylaxis of CMV infection and disease in adult CMV-seropositive recipients of an allogenic haematological stem cell transplantation. Letermovir shows a favourable pharmacokinetic profile in haematological stem cell transplantation recipients after oral administration. The recommended dose for CMV-prophylaxis is once daily 480 mg (oral or intravenous). Letermovir demonstrated superiority in a placebo (plus polymerase chain reaction-monitoring and pre-emptive therapy)-controlled phase III randomised clinical trial. Letermovir is an inhibitor of the cytochrome P450 (CYP)3A family, CYP2B8 and an inducer of the CYP2C9/19. Dose-adjustments (240 mg/day) are necessary when letermovir is combined with cyclosporine. Combinations of letermovir with either voriconazole, midazolam and rosiglitazone require close monitoring of the plasma levels of the latter agents. Letermovir-resistant CMV mutants share mutations that are mostly located between the codon range 230–370 of the UL56 gene. Letermovir is not nephrotoxic nor myelotoxic, but slightly higher rates of atrial fibrillation and tachycardia have been described. In conclusion, letermovir is the first FDA approved anti-CMV agent for prophylaxis in haematological stem cell transplantation patients.
(BELG J HEMATOL 2019;10(4):136–45)
