Letermovir Dosing for CMV Prophylaxis in Allogeneic HSCT Recipients
The recommended dose of letermovir for CMV prophylaxis in adult CMV-seropositive allogeneic HSCT recipients is 480 mg once daily, reduced to 240 mg once daily when co-administered with cyclosporine, initiated between day 0 through day 28 post-transplant and continued through day 100-200 post-transplant. 1, 2
Standard Dosing Algorithm
Dose Selection Based on Cyclosporine Use
Without cyclosporine co-administration: Administer letermovir 480 mg once daily (oral or IV) 1, 2
With cyclosporine co-administration: Reduce dose to 240 mg once daily due to drug-drug interactions that significantly increase letermovir exposure 1, 3, 2
Timing and Duration
Initiation window: Start letermovir any time between day 0 through day 28 post-transplant 1, 2
Standard duration: Continue through week 14 (approximately day 100) post-transplant 1, 2
Extended duration consideration: May extend prophylaxis through week 28 (approximately day 200) in high-risk patients, particularly those with ongoing immunosuppression or GVHD 3
Route of Administration
Both oral and intravenous formulations use the same dose (480 mg or 240 mg with cyclosporine) 1, 2
Switch between oral and IV routes based on patient's ability to tolerate oral intake without dose adjustment 2
Renal and Hepatic Considerations
No renal dose adjustment required: Letermovir does not require modification for renal impairment, and no nephrotoxicity has been observed 3, 4
Hepatic impairment: Not recommended in severe hepatic impairment (Child-Pugh class C) 4
Monitor serum creatinine when administered to patients with creatinine clearance less than 50 mL/min 4
Critical Clinical Caveats
Concurrent HSV/VZV Prophylaxis Required
- Letermovir lacks activity against HSV and VZV, so concurrent acyclovir or valacyclovir prophylaxis must be continued throughout the letermovir treatment period 3, 5
Resistance Risk with Underdosing
Rapid emergence of resistant mutants can occur if letermovir is interrupted, underdosed, or in patients with other risk factors 1, 3
This makes strict adherence to the cyclosporine dose reduction (240 mg) essential—never underdose, but also never fail to reduce when cyclosporine is present 3
Efficacy Data Supporting This Regimen
The phase III trial demonstrated that letermovir 480 mg daily (240 mg with cyclosporine) through week 14 reduced clinically significant CMV infection from 60.6% with placebo to 37.5% with letermovir (P<0.001) 1, 6
The regimen was well tolerated with no hematologic toxicity or nephrotoxicity, distinguishing it from ganciclovir/valganciclovir 1
Adolescent Dosing
- For adolescents aged 12-18 years, use the same adult dosing: 480 mg once daily (240 mg with cyclosporine) 7