What is Prevymis (Letermovir) Used For?
Prevymis (letermovir) is used for prophylaxis of cytomegalovirus (CMV) infection and disease in adult and pediatric CMV-seropositive patients who receive an allogeneic hematopoietic stem cell transplant (HSCT), and for CMV prophylaxis in high-risk kidney transplant recipients. 1
Primary Indication: CMV Prophylaxis in HSCT Recipients
Letermovir is FDA-approved for preventing CMV infection and disease in CMV-seropositive recipients (R+) of allogeneic HSCT, starting from age 6 months and weighing at least 6 kg. 1
Mechanism and Efficacy
- Letermovir works by inhibiting the CMV terminase complex, representing a novel mechanism distinct from traditional polymerase inhibitors like ganciclovir. 2, 3
- In the pivotal phase III trial, letermovir reduced clinically significant CMV infection from 61% with placebo to 38% (P<0.001), demonstrating substantial protective efficacy. 2, 4
- Among CMV-seropositive HSCT recipients, 50-60% experience CMV reactivation even with routine surveillance, making prophylaxis critical. 2
Standard Dosing Protocol
For adult and pediatric patients ≥12 years old weighing ≥30 kg:
- 480 mg once daily orally or intravenously when NOT taking cyclosporine 4, 1
- 240 mg once daily when co-administered with cyclosporine due to significant drug-drug interactions that increase letermovir exposure 4, 1
Timing:
- Start between Day 0 through Day 28 post-transplant 4, 1
- Continue through Day 100 (week 14) post-transplant 4, 1
- Consider extending through Day 200 (week 28) in high-risk patients with ongoing immunosuppression or graft-versus-host disease (GVHD) 4
Secondary Indication: Kidney Transplant Recipients
Letermovir is also FDA-approved for CMV prophylaxis in adult and pediatric patients ≥12 years old weighing ≥40 kg who are kidney transplant recipients at high risk (D+/R- status). 1
- The same dosing principles apply: 480 mg daily, reduced to 240 mg daily with cyclosporine 5
- Initiate between Day 0-28 post-transplant and continue through Day 100-200 5
Critical Safety Advantages Over Traditional Agents
Letermovir has a superior toxicity profile compared to ganciclovir/valganciclovir and foscarnet:
- No nephrotoxicity or myelosuppression observed 5, 3
- No dose adjustment needed for renal impairment 5
- This contrasts sharply with ganciclovir (causes neutropenia/thrombocytopenia) and foscarnet (causes nephrotoxicity), making letermovir particularly valuable in transplant recipients already at risk for these complications. 2
Essential Clinical Caveats
Letermovir lacks activity against herpes simplex virus (HSV) and varicella-zoster virus (VZV), so concurrent acyclovir or valacyclovir prophylaxis MUST be continued throughout letermovir treatment. 4, 5
Resistance can emerge rapidly if letermovir is interrupted, underdosed, or in patients with other risk factors. 2, 4 This makes adherence and appropriate dosing (especially the cyclosporine dose reduction) absolutely critical.
Post-Prophylaxis Monitoring
After completing letermovir prophylaxis, CMV surveillance monitoring is recommended because reactivation can occur after discontinuation. 1 In real-world studies, CMV reactivation and disease have been documented after letermovir cessation, particularly in high-risk patients. 6, 7
Off-Label Use: Secondary Prophylaxis
While not FDA-approved for this indication, letermovir is increasingly used as secondary prophylaxis after at least one treated CMV episode in high-risk HSCT recipients. 8, 7 In the French compassionate program, only 5.5% of patients experienced breakthrough CMV infection/disease during secondary prophylaxis, though resistance mutations (UL56 C325Y or W) were identified in some breakthrough cases. 8