What is the dosing of letermovir (antiviral medication) for patients under 12 years old with Cytomegalovirus (CMV) infection?

Letermovir Dosing for CMV Infection in Children Under 12 Years Old

Letermovir is not FDA-approved for children under 12 years of age, but based on recent clinical evidence, weight-based dosing of 10 mg/kg/day (with a maximum of 480 mg daily, or 240 mg daily when co-administered with cyclosporine) can be used for CMV prophylaxis in pediatric transplant recipients.

Current Approval Status and Evidence

Letermovir is a CMV terminase complex inhibitor that has been primarily studied and approved for adult populations. The available evidence shows:

• Letermovir is currently only FDA-approved for CMV prophylaxis in adult CMV-seropositive recipients of allogeneic hematopoietic stem cell transplants (HSCT) 1
• Recent clinical studies have begun evaluating letermovir in pediatric populations:
  • A phase 2b study has evaluated letermovir in adolescents (12-18 years) and found that adult dosing (480 mg daily, or 240 mg with cyclosporine) achieved comparable exposure to adults 2
  • Another phase 2b study has investigated letermovir across three pediatric age groups (birth to <2 years, 2 to <12 years, and 12 to <18 years) 3

Dosing Recommendations Based on Available Evidence

For children under 12 years old with CMV infection requiring letermovir:

Weight-Based Approach

• General dosing: 10 mg/kg/day (mean and median dose used in retrospective studies) 4
• Maximum dose: 480 mg daily (or 240 mg daily when co-administered with cyclosporine A) 2, 3

Age-Group Specific Considerations

• Children 2 to <12 years: Adult letermovir dosing (480 mg daily, or 240 mg with cyclosporine) has been shown to achieve exposures generally within the adult reference range 3
• Infants (birth to <2 years): Limited data suggests initial dosing with cyclosporine may require dose increases to achieve target exposure 3

Administration Considerations

• Letermovir can be administered orally or intravenously 1
• For children who cannot swallow tablets, crushing and administration via nasogastric tube has been reported 4
• Treatment should be initiated between day 0 through day 28 post-allogeneic HSCT and continued through day 100 post-transplantation 1

Special Considerations

Hepatic Impairment

• Letermovir is primarily metabolized by hepatic OATP1B1/3 1
• Not recommended for patients with severe hepatic impairment (Child-Pugh class C) 1

Renal Impairment

• No dosage adjustments needed until creatinine clearance (CrCl) falls below 10 mL/min 1
• Monitor serum creatinine when administered to patients with CrCl <50 mL/min 1

Drug Interactions

• Dose should be reduced to 240 mg daily when co-administered with cyclosporine 1, 2
• Potential for drug-drug interactions should be evaluated, as letermovir can interact with CYP enzymes 5

Clinical Efficacy and Safety in Pediatrics

Limited but promising data from retrospective studies show:

• In a study of 17 pediatric patients (median age 12.2 years, range 3.5-19 years), letermovir was effective for both prophylaxis and pre-emptive therapy 6
• In another cohort of 9 pediatric patients (age 4-19 years), only 1 patient experienced low-level CMV viremia while on letermovir prophylaxis 4
• Safety profile appears similar to adults, with only transient mild transaminitis noted in some pediatric patients 4

Important Caveats

• Letermovir lacks coverage against HSV and VZV, so additional prophylaxis for these viruses should be continued 5
• Formal pediatric investigation plans and FDA approval for pediatric use are still pending 6
• Monitoring of CMV viral load should continue during therapy

While awaiting formal approval for pediatric use, these dosing recommendations represent the best available evidence for managing CMV infection in children under 12 years old requiring letermovir.