ModifiedmhnPolicy CP.PHAR.367

Letermovir (Prevymis) prophylaxis for cytomegalovirus

This policy governs medical necessity criteria, dosing, and authorization requirements for letermovir (Prevymis) used for prophylaxis of CMV infection/disease in HSCT recipients and high-risk kidney transplant recipients; it applies to commercial, HIM, and Medicaid lines of business under the payer.

Policy Summary

Payermhn

PolicyLetermovir (Prevymis) prophylaxis for cytomegalovirus

Policy CodePolicy CP.PHAR.367

Change TypeMaterial updates to indications, age/weight limits, initiation windows, and duration (Day 100 → allowance to Day 200 in select patients)

Effective DateMar 1, 2018

Next Review DateN/A

Key ActionSubmit documentation demonstrating CMV serostatus, transplant type/date, prescriber specialty, age/weight, and initiation timing to support prior authorization.

SourceLink

POLICY UPDATE CHANGES

Added allowance for use through Day 200 post-transplantation for allogeneic HSCT patients at risk for late CMV infection and disease.

Added pediatric extension: age ≥ 6 months and weight ≥ 6 kg for prophylaxis in CMV-seropositive allogeneic HSCT patients; age ≥ 12 years and weight ≥ 40 kg for high-risk kidney transplant recipients.

For prophylaxis in kidney transplant recipients, usage limited up to Day 200 post-transplantation and must be initiated within 7 days post kidney transplant; for HSCT initiation must be within 28 days post HSCT.

Added requirement for initial approval that member is CMV-seropositive and limited continued therapy: member has not received Prevymis beyond 100 days post-transplantation (later updated allowance to Day 200 in some cases).

Added HCPCS codes J8499 and C9399 and mentioned J3490 and C9399 in coding implications.

2Approved indications

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Coverage Criteria

Initial Approval — Prophylaxis in CMV‑Seropositive Allogeneic HSCT Recipients

Covered when ALL of the following are met:

HSCT prophylaxis criteria: 1. Member has received or is scheduled to receive an allogeneic HSCT; 2. Member is CMV‑seropositive; 3. Prescribed by or in consultation with an oncology, hematology, infectious disease, or transplant specialist; 4. Age ≥ 6 months; 5. Weight ≥ 6 kg; 6. Initiation within 28 days post‑transplant; 7. If IV formulation requested, documentation supports inability to use oral therapy; 8. Member is not receiving contraindicated agents (pimozide or ergot alkaloids; cyclosporine co‑administered with pitavastatin or simvastatin); 9. For prophylaxis beyond Day 100 post‑transplantation, both: (a) member is at risk for late CMV infection and disease (see Appendix D) and (b) Prevymis is prescribed up to Day 200 post‑HSCT; 10. Dose does not exceed labeled weight/age maximums or dosing limits specified in Section V (e.g., 480 mg/day for age ≥ 12 years and weight ≥ 30 kg; 240 mg/day if co‑administered with cyclosporine, or FDA weight‑based maximums for younger/smaller patients).

Initial Approval — Prophylaxis in High‑Risk Kidney Transplant Recipients (D+/R-)

Covered when ALL of the following are met:

Kidney transplant prophylaxis criteria: 1. Member has received or is scheduled to receive an allograft kidney from a CMV‑seropositive donor (D+/R‑); 2. Member is CMV‑seronegative; 3. Prescribed by or in consultation with a nephrologist or transplant specialist; 4. Age ≥ 12 years; 5. Weight ≥ 40 kg; 6. Initiation within 7 days post‑transplant; 7. If IV formulation requested, documentation supports inability to use oral therapy; 8. Member is not receiving contraindicated agents (pimozide or ergot alkaloids; cyclosporine co‑administered with pitavastatin or simvastatin); 9. Prevymis is prescribed up to Day 200 post‑transplantation; 10. Dose does not exceed 480 mg/day or 240 mg/day if co‑administered with cyclosporine.

Initial prophylaxis coverage criteria

Covered when ALL of the following are met

Prevymis prophylaxis criteria: Member is CMV‑seropositive (CMV‑R+); member is an allogeneic HSCT recipient or a high‑risk kidney transplant recipient; therapy is initiated within required post‑transplant window (≤28 days for HSCT; ≤7 days for kidney transplant); duration does not exceed Day 100 post‑transplant except when patient has documented risk factors for late CMV infection/disease allowing use through Day 200; pediatric age/weight limits apply (HSCT: ≥6 months and ≥6 kg; kidney transplant: ≥12 years and ≥40 kg).see initiation window and maximum prophylaxis duration

Dose must adhere to age/weight and cyclosporine coadministration limits (e.g., 480 mg/day or 240 mg/day with cyclosporine; FDA weight‑based max for pediatric patients).

Other/Off‑Label Uses

Coverage for uses not specified in Sections I–III:

Off‑label or new label changes: 1. If letermovir has undergone a recent label change (within the last 6 months) not yet reflected in this policy, the request should follow the applicable formulary/no‑coverage or non‑formulary policy for the member's line of business; 2. If the requested use is not listed under 'Diagnoses/Indications for which coverage is NOT authorized' and criterion 1 does not apply, refer to the off‑label use policy for the relevant line of business (see CP.CPA.09 for commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid).

Continued Therapy — All Indications

Continued coverage when ALL of the following are met:

Continued therapy criteria: 1. Member is currently receiving Prevymis via the benefit or documentation supports current receipt for a covered indication and at least 30 days of therapy; 2. Member is responding positively to therapy (e.g., no evidence of CMV viremia); 3. For HSCT: either member has not received Prevymis beyond 100 days post‑transplantation, or member is at risk for late CMV infection/disease and has not received Prevymis beyond 200 days post‑transplantation; for kidney transplant: member has not received Prevymis beyond 200 days post‑transplantation; 4. If request is for a dose increase, the new dose does not exceed FDA weight/age maximums or 480 mg/day (240 mg/day with cyclosporine) as applicable.

Non‑FDA approved indications that are not addressed in this policy are not authorized unless the provider submits sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies (CP.CPA.09 for commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or other evidence of coverage documents.

The policy no longer redirects requests to alternative antivirals (for example, valacyclovir or ganciclovir). Per the updated guidance and policy edits, Prevymis (letermovir) is the indicated prophylactic option for the specified CMV‑seropositive transplant prophylaxis populations and initial approval requires documentation that the member is CMV‑seropositive.

Use of letermovir is contraindicated in patients receiving pimozide, ergot alkaloids, or pitavastatin or simvastatin when co‑administered with cyclosporine. Requests for therapy that involve these concomitant medications are not medically necessary and may be denied without documentation that the contraindicated agents have been stopped or appropriately managed.

Continued coverage beyond the routine prophylaxis period is limited. Typically, prophylaxis is not supported beyond Day 100 post‑transplant unless the member has documented risk factors for late CMV infection or disease; in such cases use may be extended through Day 200 post‑transplant when supported by the updated prescribing information and policy documentation. Requests that exceed these durations without documented risk factors are not supported.

Initial Therapy Criteria

Initial therapy — Initial therapy coverage rules by indication

Initial therapy coverage rules by indication

HSCT initial therapy: See 'Initial Approval — Prophylaxis in CMV‑Seropositive Allogeneic HSCT Recipients' criteria: age ≥ 6 months and weight ≥ 6 kg; initiation within 28 days post‑HSCT; specialist prescriber; contraindication checks; dosing limits and duration through Day 100 (extendable to Day 200 if at risk).

Kidney transplant initial therapy: See 'Initial Approval — Prophylaxis in High‑Risk Kidney Transplant Recipients' criteria: D+/R‑ serostatus; initiation within 7 days post‑transplant; nephrologist/transplant prescriber; age ≥ 12 years and weight ≥ 40 kg; contraindication checks; dosing limits and duration through Day 200.

Initial therapy — Initial therapy criteria (additional/alternate wording)

Initial therapy criteria

Initial therapy requirements:

Continuation Criteria

Continuation — Criteria for continued therapy for all indications

Criteria for continued therapy for all indications

Continued therapy: Member has used Prevymis for ≥30 days via benefit or documentation supports current use; member is responding to therapy; member remains within allowed treatment duration (through Day 100 for HSCT or up to Day 200 if at risk for late CMV disease for HSCT; through Day 200 for kidney transplant). Dose changes must adhere to specified maximums.

Continuation therapy — Conditions for continued therapy (extensions to Day 200 in select cases)

Conditions for continued therapy

Continued therapy conditions: Member has not exceeded the allowed prophylaxis duration (typically Day 100; Day 200 allowed for patients at risk for late CMV infection/disease documented per Appendix D); for initial approvals the member must have been CMV‑seropositive and treatment initiated within specified post‑transplant windows (≤28 days for HSCT; ≤7 days for kidney transplant).Day 100 / Day 200 as applicable

Provider Actions and Authorization

Prior Authorization

Prior Authorization Required

Prevymis (letermovir) is subject to prior authorization. Requests must include documentation supporting that the member meets all approval criteria (e.g., office chart notes, transplant records, laboratory results). Prior authorization will require evidence of CMV serostatus, transplant type, timing of initiation relative to transplant, prescribing specialist consultation when specified, and any other criteria listed in the policy.

Required documentation: office/chart notes, lab results showing CMV serostatus, transplant operative report or scheduling, weight and age, reason for IV vs oral formulation if applicable, medication list to identify contraindicated co‑medications.
Step therapy changes: policy removed redirection to valacyclovir or ganciclovir per 2021 ASTCT guidelines; Prevymis is the indicated prophylactic agent for CMV‑seropositive allogeneic HSCT recipients and for specified high‑risk kidney transplant recipients.
Denial triggers: requests lacking required documentation, requests for non‑FDA indications without sufficient evidence per off‑label policies, or requests not meeting timing/serostatus/transplant criteria may be denied.
Coding/billing note: ensure claims use established HCPCS codes (e.g., J8499, C9399 when applicable) or appropriate unspecified drug codes to avoid coding‑related denials.

Coding and Dosing Thresholds

Referenced HCPCS/J-codes for Prevymis/unclassified drugsHCPCS

C9399	Unclassified drugs or biologicals
J3490	Unclassified drugs
J8499	Prescription drug, oral, non chemotherapeutic, nos

Weight and age dosing thresholds

HSCT age/weight cutoffAge ≥ 6 months and weight ≥ 6 kg required for prophylaxis in CMV‑seropositive allogeneic HSCT recipients.

Kidney transplant age/weight cutoffAge ≥ 12 years and weight ≥ 40 kg required for prophylaxis in high‑risk (D+/R−) kidney transplant recipients.

Adult dosing band (≥30 kg)For age ≥ 12 years and weight ≥ 30 kg: 480 mg once daily (or 240 mg once daily if co‑administered with cyclosporine).

Pediatric weight bandsWeight-based maximums for pediatric patients per Section V: ≥30 kg = 480 mg; ≥15 to <30 kg = 240 mg PO (120 mg IV); ≥7.5 to <15 kg = 120 mg PO (60 mg IV); ≥6 to <7.5 kg = 80 mg PO (40 mg IV).

Initiation window

Kidney transplant initiation window

Step Therapy

Step therapy summary	Details / policy language
No explicit step therapy required	The policy references that alternative agents (e.g., ganciclovir, valganciclovir, foscarnet, acyclovir, valacyclovir) have been studied and that primary prophylaxis with alternative agents is generally not recommended per the 2021 ASTCT guideline; however, the document does not mandate a trial of alternative antivirals prior to letermovir (Prevymis).

Step therapy summary	Details / policy language
Prior redirection removed — Prevymis is the indicated prophylactic agent	Policy history documents removal of prior redirection to valacyclovir or ganciclovir per 2021 ASTCT guidelines and clarifies that Prevymis is the indicated prophylactic option for CMV‑seropositive recipients; the policy therefore does not require switching or trial of those alternative antivirals before approval of Prevymis for its labeled populations.

Quantity Limits

letermovir (Prevymis) — Maximum daily dose

Maximum adult dose (no cyclosporine)480 mg once daily for patients ≥12 years and ≥30 kg.

Maximum adult dose (with cyclosporine)240 mg once daily when co‑administered with cyclosporine for patients ≥30 kg.

Pediatric IV/PO dose adjustmentsWeight‑based PO and IV daily doses provided: ≥15 to <30 kg = 240 mg PO (120 mg IV); ≥7.5 to <15 kg = 120 mg PO (60 mg IV); ≥6 to <7.5 kg = 80 mg PO (40 mg IV).

Site of Care

Note

Hospital outpatient: document inability to use oral therapy for IV Prevymis

When IV Prevymis is requested for hospital outpatient administration, include documentation that the member cannot tolerate or use the oral formulation; the IV formulation requires justification.

If IV requested, submit clinical rationale or documentation demonstrating inability to use oral therapy.
Dosing tables include IV dose equivalents by weight where applicable.

Definitions

D+ / R- definition

Definition D+ / R-D+ / R- = donor CMV seropositive / recipient CMV seronegative.

Context of useUsed to identify high‑risk kidney transplant recipients for CMV prophylaxis.

Abbreviation sourceListed in Appendix A: Abbreviation/Acronym Key.

HSCT definition

TermHematopoietic stem cell transplant (HSCT).

UsageHSCT refers to recipients of allogeneic hematopoietic stem cell transplantation covered under HSCT prophylaxis criteria.

Source

Background

Letermovir (Prevymis) is a CMV DNA terminase complex inhibitor indicated for prophylaxis of CMV infection and disease in CMV‑seropositive allogeneic hematopoietic stem cell transplant (HSCT) recipients. Updated prescribing information allows extension of prophylaxis through Day 200 post‑transplant for patients who are at risk for late CMV infection or disease; examples of such risk factors are provided in the policy Appendix D.

Policy Summary

Payermhn

PolicyLetermovir (Prevymis) prophylaxis for cytomegalovirus

Policy CodePolicy CP.PHAR.367

Change TypeMaterial updates to indications, age/weight limits, initiation windows, and duration (Day 100 → allowance to Day 200 in select patients)

Effective DateMar 1, 2018

Next Review DateN/A

Key ActionSubmit documentation demonstrating CMV serostatus, transplant type/date, prescriber specialty, age/weight, and initiation timing to support prior authorization.

SourceLink

On This Page

Documentation Required

Submit clinical documentation demonstrating that member meets all applicable policy criteria. For initial approvals this must include evidence of CMV serostatus (positive for HSCT recipients or donor/recipient serostatus for kidney recipients), documentation of transplant type and date, and that Prevymis will be initiated within the required post‑transplant window (within 28 days for HSCT; within 7 days for kidney transplant). For IV requests, include rationale demonstrating inability to use oral therapy. For extensions beyond standard durations, include documentation that the member is at risk for late CMV infection and disease (see Appendix D) if seeking HSCT prophylaxis through Day 200.

Acceptable documentation: clinic notes, transplant discharge summary, lab confirmation of CMV IgG serostatus, medication administration records, and specialist consultation notes.
Timing documentation: transplant date and proposed or actual date of Prevymis initiation to confirm initiation within required window.

Step Therapy

Step Therapy Update

Step therapy requirements were updated to reflect guideline changes: redirection to alternative antivirals (valacyclovir or ganciclovir) has been removed. Prevymis is the preferred prophylactic agent for CMV‑seropositive allogeneic HSCT recipients and for specified high‑risk kidney transplant recipients per updated clinical guidelines and FDA‑labeled indications.

Do not require trial or failure of valacyclovir or ganciclovir prior to Prevymis for the covered prophylactic indications.
Ensure serostatus and transplant criteria are documented rather than documenting trials of alternative antivirals.

Denial Risk

Denial and Coding Risk

Requests lacking sufficient clinical documentation to demonstrate the member meets policy criteria, or requests for non‑FDA indications without adequate supporting evidence, are at high risk for denial. Additionally, claims submitted without the appropriate HCPCS or unspecified drug codes may result in coding‑related denials.

Denial triggers: missing CMV serostatus, missing transplant date/type, initiation outside required post‑transplant windows, absence of specialist involvement when required, or contraindicated co‑medications present.
Billing risk: use established HCPCS codes (e.g., J8499, C9399) or appropriate unspecified/compounded drug codes to reduce coding denials.