Table 1.

Letermovir overview.¹⁵

Dose/frequency	Route	Dose adjustment	Pharmacokinetics	Drug interactions	Clinical pearls
480 mg once daily 240 mg once daily with cyclosporine Start between days 0 and 28, continue through day 100	PO (tablet), with or without food IV containing hydroxylpropyl beta-cyclodextrin	Renal impairment: no dose adjustment† Hepatic impairment: no dose adjustment‡	F = 35–94%* Vd = 45.5 l, 99% protein bound Hepatic metabolism through UGT1A1/1A3 (minor) t 1/2 = 12 h Excretion: feces, 93% (70% as unchanged drug)	Substrate: CYP3A, CYP2D6, UGT1A1, UGT1A3; transporters P-gp, OATP1B1/3 Inhibitor: CYP3A (moderate) CYP2C8, P-gp, OAT3, OATP1B1/3 Inducer: CYP2C9, CYP2C19, CYP2B6, CYP3A	28-day blister pack Letermovir decreases voriconazole concentration; recommend monitoring voriconazole levels Only active against CMV; recommend antiviral prophylaxis to prevent herpes simplex virus and varicella zoster virus Consider ordering CMV genotype to assess for resistance if patient develops clinically significant CMV infection on letermovir (>1000 IU/ml)

CMV, cytomegalovirus; CrCL, creatinine clearance; F, bioavailability; IU, international units; t ½, half life; Vd, volume of distribution.

^*Bioavailability in healthy subjects = 94% without cyclosporine (240–480 mg once daily), hematopoietic cell transplant recipients without cyclosporine (480 mg once daily) = 35%, hematopoietic cell transplant recipients with cyclosporine (240 mg once daily) = 85%.

^†Patients with CrCL < 10 ml/min or patients on hemodialysis were excluded from the phase III trial. Caution should be used in patients with CrCL ⩽50 ml/min receiving IV letermovir.

^‡Patients with moderate (Child Pugh Class B) or severe (Child Pugh Class C) liver dysfunction were excluded from the phase III trial.