ModifiedmhnPolicy CP.PHAR.367

Clinical Policy: Letermovir (Prevymis)

Defines medical necessity criteria, dosing limits, age/weight requirements, treatment durations, contraindications, and billing codes for Prevymis (letermovir) prophylaxis in CMV-seropositive allogeneic HSCT recipients (including pediatric extension) and CMV D+/R- high-risk kidney transplant recipients.

Policy Summary

Payermhn

PolicyClinical Policy: Letermovir (Prevymis)

Policy CodePolicy CP.PHAR.367

Change TypeMaterial modifications (age expansions, new kidney indication, duration and initiation-window updates, formulation added)

Effective Date03.01.18

Next Review Date

Key ActionProvider must submit documentation demonstrating member meets all approval criteria (e.g., CMV serostatus, transplant date, specialist consultation).

SourceLink

POLICY UPDATE CHANGES

Added pediatric extension to include age ≥ 6 months and weight ≥ 6 kg for prophylaxis in CMV R+ allogeneic HSCT recipients and age ≥ 12 years and weight ≥ 40 kg for kidney transplant recipients; added oral pellets formulation.

Allowed use through Day 200 post-HSCT for patients at risk for late CMV infection and disease; added examples of risk factors to Appendix D.

Added new indication for prophylaxis of CMV disease in adult kidney transplant recipients at high risk (D+/R-).

Added requirement that Prevymis must be initiated within 7 days post-kidney transplant and within 28 days post-HSCT per prescribing information.

Added requirement for initial approval that member is CMV-seropositive for HSCT indication and limited continued therapy to not beyond 100 days (or 200 days if at risk).

Added HCPCS code J8499 to coding implications.

1Q 2025 annual review: no significant clinical changes; references reviewed and updated.

For prophylaxis of CMV in kidney transplant recipients, added criterion limiting usage of Prevymis up to day 200 post-transplantation.

2FDA-approved indications

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6 monthsMin pediatric age (HSCT)

100/200 daysHSCT prophylaxis duration

200 daysKidney prophylaxis duration

multiplePolicy changes (material)

Coverage Summary

This policy defines medical necessity and coverage criteria for Prevymis (letermovir) as CMV prophylaxis in two FDA‑approved populations: CMV‑seropositive (R+) recipients of an allogeneic HSCT (including pediatric extension: age ≥ 6 months and weight ≥ 6 kg) and high‑risk kidney transplant recipients (D+/R-) (age ≥ 12 years and weight ≥ 40 kg). Initiation windows are required: within 28 days post‑HSCT and within 7 days post‑kidney transplant. Standard treatment duration for HSCT prophylaxis is through Day 100 post‑transplant (may be extended through Day 200 if the patient is at risk for late CMV infection/disease); kidney transplant prophylaxis is up to Day 200. Dosing limits depend on age, weight, and concomitant cyclosporine (adult/weight ≥ 30 kg: 480 mg/day; if co‑administered with cyclosporine: 240 mg/day; pediatric weight‑based maxima per FDA labeling). Contraindications include concurrent pimozide, ergot alkaloids, and when cyclosporine is co‑administered with pitavastatin or simvastatin. Product formulations include tablets, oral pellets, and IV vials; clinical and coding context (HCPCS) and prior authorization requirements (specialist prescribing, documentation of CMV serostatus, transplant date, and oral vs IV justification) are specified in the policy.

Thresholds

Initiation window post-HSCT≤ 28 days post-transplant

Initiation window post-kidney transplant≤ 7 days post-transplant

HSCT standard durationThrough Day 100 post-transplant (or through Day 200 if at risk for late CMV infection and disease)

Kidney transplant durationThrough Day 200 post-transplant

Age threshold for HSCT≥ 6 months

Weight threshold for HSCT≥ 6 kg

Initial Approval Criteria — Allogeneic HSCT (CMV R+)

I. Initial Approval Criteria - A. Prophylaxis of CMV Infection in CMV-Seropositive Recipients of an Allogeneic HSCT

Covered when ALL of the following are met:

ALL of the following

Member has received or is scheduled to receive allogeneic HSCT
Member is CMV-seropositive
Prescribed by or in consultation with an oncology, hematology, infectious disease, or transplant specialist
Age ≥ 6 months≥ 6 months
pediatric extension

Initial Approval Criteria — High-Risk Kidney Transplant (D+/R-)

I. Initial Approval Criteria - B. Prophylaxis of CMV in Kidney Recipients at High Risk (D+/R-)

Covered when ALL of the following are met:

ALL of the following

Member has received or is scheduled to receive an allograft kidney transplant from a CMV-seropositive donor
D+ donor
Member is CMV-seronegative
R- recipient
Prescribed by or in consultation with a nephrologist or transplant specialist
Age ≥ 12 years≥ 12 years

Continuation (Renewal) Criteria

II. Continued (Renewal) Therapy - All Indications in Section I

Covered when ALL of the following are met:

ALL of the following

Member is currently receiving medication via Centene benefit, or documentation supports member has received Prevymis for a covered indication for at least 30 days≥ 30 days
prior therapy requirement
Member is responding positively to therapy (positive response may be demonstrated if there is no evidence of CMV viremia)
response demonstrated by absence of CMV viremia
Duration constraints depending on transplant type
- HSCT

Unproven / Not Authorized Indications

III. Diagnoses/Indications NOT authorized

Coverage is NOT authorized for:

ALL of the following

Non-FDA approved indications not addressed in this policy, unless sufficient documentation per off-label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) or evidence of coverage documents
off-label uses require supporting policy documentation

Provider Actions & Authorization Requirements

Prior Authorization

Prior authorization and specialist prescribing

Prevymis must be prescribed by or in consultation with an appropriate specialist (oncology/hematology/infectious disease/transplant for HSCT; nephrology/transplant for kidney) and the authorization must reflect initiation within the required post-transplant window (within 28 days for HSCT; within 7 days for kidney transplant).

Documentation Required

Support approval criteria

Provider must submit documentation (office chart notes, laboratory results, or other clinical information) demonstrating that the member meets all approval criteria — for example, CMV serostatus (R+ or D+/R- as applicable), transplant date, and evidence of specialist consultation.

Applicable Codes

HCPCS codes referenced for billing (informational)HCPCS

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

Clinical Evidence & References

Key evidence sources: Prescribing information — Prevymis PI, Merck; August 2024 (updated labeling and dosing/age/weight expansions); the 2021 ASTCT guideline for prevention of CMV infection after HCT; and the randomized trial of letermovir versus valganciclovir for prophylaxis in high‑risk kidney transplant recipients (JAMA 2023).

Background

Background: Letermovir is a CMV DNA terminase complex inhibitor indicated for prophylaxis of CMV infection/disease in CMV‑seropositive allogeneic HSCT recipients (adult and pediatric ≥ 6 months, ≥ 6 kg) and for prevention of CMV disease in high‑risk kidney transplant recipients (D+/R‑) age ≥ 12 years, ≥ 40 kg. Dosing is age‑ and weight‑based with specific maximums and IV/oral equivalence; adult dosing is 480 mg once daily (reduced to 240 mg if co‑administered with cyclosporine). The policy incorporates FDA labeling updates (including oral pellets and pediatric extension), relevant guideline recommendations (e.g., ASTCT 2021), and uses Appendix D for definitions/examples of risk factors for late CMV disease.

Policy-level key facts

FDA‑approved indications count2

Minimum pediatric age (HSCT)6 months

HSCT prophylaxis duration (standard/at‑risk)100 / 200 days

Kidney transplant prophylaxis duration200 days

Definitions

D+: Donor CMV seropositive — donor is CMV seropositive.

R+: Recipient CMV seropositive — recipient is CMV seropositive.

R-: Recipient CMV seronegative — recipient is CMV seronegative.

HSCT: Hematopoietic stem cell transplant — allogeneic stem cell transplant procedure.

Revision History

10.24.22revised

1Q 2023 annual review: added requirement for initial approval that member is CMV-seropositive for HSCT indication; limited continued therapy to not beyond 100 days (or 200 days if at risk); added HCPCS code J8499.

06.21.23added

RT4: Added new indication for prophylaxis of CMV disease in adult kidney transplant recipients at high risk (D+/R-) and added HCPCS code C9399.

10.06.23revised

Policy Summary

Payermhn

PolicyClinical Policy: Letermovir (Prevymis)

Policy CodePolicy CP.PHAR.367

Change TypeMaterial modifications (age expansions, new kidney indication, duration and initiation-window updates, formulation added)

Effective Date03.01.18

Next Review Date

Key ActionProvider must submit documentation demonstrating member meets all approval criteria (e.g., CMV serostatus, transplant date, specialist consultation).

SourceLink

On This Page

Weight ≥ 6 kg≥ 6 kg

pediatric extension

Prevymis must be initiated within 28 days post-transplant≤ 28 days post-transplant

per prescribing information

If request is for IV Prevymis, documentation supports inability to use oral therapy

IV formulation allowed only with documented inability to use oral

Contraindications (member must NOT be receiving any)

Pimozide or ergot alkaloids
contraindicated
Cyclosporine co-administered with pitavastatin or simvastatin
contraindicated

Duration beyond Day 100 (both required if requesting beyond Day 100)

Member is at risk for late CMV infection and disease (see Appendix D for examples)
Prevymis is prescribed up to day 200 post-HSCTthrough Day 200
only if at risk

Dose limits (must not exceed any of the following)

For age ≥ 12 years
- Weight ≥ 30 kg
  - 480 mg per day480 mg/day
    PO or IV
  - If co-administered with cyclosporine: 240 mg per day240 mg/day when with cyclosporine
    dose reduction required
- Weight < 30 kg: Dose does not exceed the FDA approved maximum recommended dose based on weight (see Section V)per Section V
  weight-based pediatric dosing
For age 6 months to < 12 years: Dose does not exceed the FDA approved maximum recommended dose based on weight (see Section V)per Section V
pediatric weight-based dosing

Weight ≥ 40 kg≥ 40 kg

per PI

Prevymis must be initiated within 7 days post-transplant≤ 7 days post-transplant

per prescribing information

If request is for IV Prevymis, documentation supports inability to use oral therapy

IV only if oral not possible

Contraindications (member must NOT be receiving any)

Pimozide or ergot alkaloids
contraindicated
Cyclosporine co-administered with pitavastatin or simvastatin
contraindicated

Prevymis is prescribed up to day 200 post-transplantationthrough Day 200

maximum duration

Dose limits (must not exceed any)

480 mg per day480 mg/day
standard adult dose
If co-administered with cyclosporine: 240 mg per day240 mg/day when with cyclosporine
dose reduction required

Member has not received Prevymis therapy beyond 100 days post-transplantation≤ 100 days

Member is at risk for late CMV infection and disease and has not received Prevymis therapy beyond 200 days post-transplantation≤ 200 days

HSCT at-risk extension

Kidney transplant: Member has not received Prevymis therapy beyond 200 days post-transplantation≤ 200 days

kidney transplant limit

Dose increase requests

If age ≥ 12 years and weight ≥ threshold
- New dose does not exceed 480 mg per day≤ 480 mg/day
  standard max
- If co-administered with cyclosporine: new dose does not exceed 240 mg per day≤ 240 mg/day
  reduced max with cyclosporine
New dose does not exceed the FDA approved maximum recommended dose based on weight (see Section V)per Section V
weight-based pediatric maxima

Billing Rule

Dose limits and cyclosporine co-administration

Ensure dosing does not exceed specified maximums by age and weight, and reduce the Prevymis dose when co-administered with cyclosporine (e.g., adult 480 mg once daily reduced to 240 mg once daily with cyclosporine).

Denial Risk

Contraindicated concomitant medications

Claims may be denied if the member is receiving contraindicated concomitant medications such as pimozide or ergot alkaloids, or if cyclosporine is co-administered with pitavastatin or simvastatin.

Documentation Required

Oral vs IV formulation justification

If IV Prevymis is requested, the provider must document the inability to use oral therapy to support the IV formulation request.

Documentation Required

Continued therapy evidence

For renewal requests, document that the member has received at least 30 days of Prevymis therapy via the benefit (or equivalent) and is responding positively to therapy (positive response may be demonstrated by absence of CMV viremia).

1Q 2024 annual review: Allowed use through Day 200 post-HSCT for patients at risk for late CMV infection and disease; added examples of risk factors to Appendix D.

09.05.24added

RT4: Added pediatric extension — age ≥ 6 months and weight ≥ 6 kg for prophylaxis in CMV R+ allogeneic HSCT recipients; age ≥ 12 years and weight ≥ 40 kg for kidney transplant recipients — and added oral pellets formulation.

10.31.24revised

1Q 2025 annual review: no significant clinical changes; references reviewed and updated.

05.16.25added

For prophylaxis of CMV in kidney transplant recipients, added criterion limiting usage of Prevymis up to Day 200 post-transplantation.

09.25.25revisedLatest

Added requirement that Prevymis must be initiated within 7 days post-kidney transplant and within 28 days post-HSCT per prescribing information.