Letermovir is being developed for human cytomegalovirus infection treatment and 
prophylaxis. In patients receiving transplants, antivirals are coadministered 
with cyclosporine A (CsA) or tacrolimus (TAC) immunosuppressants. Therefore, we 
investigated the potential for letermovir-immunosuppressant interactions. In 2 
phase 1 clinical trials either CsA 50 mg or TAC 5 mg was administered to healthy 
males. Following washout, letermovir 80 mg was dosed twice daily for 7 and 11 
days in the CsA and TAC trials, respectively, with a second dose of 
immunosuppressant coadministered with letermovir at steady state. In addition, 
letermovir 40 mg twice daily was administered for 14 days, and either CsA 50 or 
200 mg administered on days 7 and 14. Pharmacokinetics and tolerability were 
assessed. Letermovir increased CsA and TAC Cmax by 37% and 70%, respectively, 
and exposure by 70% and 78%, respectively, compared with immunosuppressant 
alone; t½ was also increased from 10.7 to 17.9 hours for CsA. CsA (50/200 mg) 
increased letermovir Cmax,ss (109%/167%) and AUCss,τ (126%/237%) and decreased 
t½ (4.33 to 3.68/3.04 hours) versus letermovir alone. TAC did not significantly 
affect letermovir pharmacokinetics. All treatments were well tolerated. 
Concomitant letermovir increased TAC and CsA exposure. CsA altered letermovir 
pharmacokinetics, whereas TAC did not.