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. 2020 Jun 24;11:2040620720937150. doi: 10.1177/2040620720937150

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.