CurrentCentenePolicy CP.PHAR.180

Eltrombopag (Promacta, Alvaiz)

Defines medical necessity, initial and continuation criteria, dosing limits, FDA and NCCN-supported indications, exclusions, prior authorization and approval durations for eltrombopag formulations Promacta and Alvaiz across Commercial, HIM Medicaid lines of business.

Policy Summary

PayerCentene

PolicyEltrombopag (Promacta, Alvaiz)

Policy CodePolicy CP.PHAR.180

Change TypeAdded formulation; criteria updates; NCCN indications; exclusions

Effective DateMar 1, 2016

Next Review Date

Key ActionProvider must submit documentation (office notes, labs, other clinical info) supporting that member meets all approval criteria; prior authorization may be required for referenced therapies.

POLICY UPDATE CHANGES

Added Alvaiz (eltrombopag choline formulation) as a new eltrombopag formulation

Updated criteria to include persistent or chronic ITP consistent with FDA label revision

Added NCCN Compendium indications including post-HCT prolonged thrombocytopenia and clarified MDS criteria

Added exclusion of concurrent spleen tyrosine kinase inhibitor (e.g., Tavalisse) across FDA-labeled indications

For HIM line of business, Alvaiz is non-formulary and should not be approved through these criteria when requested via pharmacy benefit

4Primary Covered Indications (FDA/NCCN)

6Key Approval Criteria Items

Specialist Prescribers Required

Coverage Summary

coverage_stance: covered_with_criteria per policy CP.PHAR.180; scope_summary: defines medical necessity, initial and continuation criteria, dosing limits, FDA and NCCN-supported indications, exclusions, prior authorization and approval durations for eltrombopag formulations Promacta and Alvaiz across Commercial and HIM Medicaid lines of business; subject: Eltrombopag (Promacta, Alvaiz).

supported_formulations: Promacta (oral suspension and tablets) and Alvaiz (eltrombopag choline tablets: 9 mg, 18 mg, 36 mg, 54 mg) with formulation-specific age and dose limits.

high-level exclusions: not covered when prescribed concurrently with another TPO-RA (e.g., avatrombopag/Doptelet, lusutrombopag/Mulpleta, romiplostim/Nplate) or a spleen tyrosine kinase (SYK) inhibitor (e.g., fostamatinib/Tavalisse); additional concurrent exclusion versus rituximab for persistent/chronic ITP. Lines of business applicability: Commercial and HIM (Health Insurance Marketplace) Medicaid; for HIM pharmacy-benefit requests Alvaiz is non-formulary per formulary handling guidance.

Thresholds

ITP initiation platelet count≤ 30,000/µL

Hepatitis C initiation platelet count≤ 75,000/µL

Severe aplastic anemia initiation platelet count≤ 50,000/µL

Continuation monitoring platelet threshold≥ 40,000/µL (within last 90 days)

ITP/Hepatitis C response target> 50,000/µL

Initial Therapy Criteria

Initial Approval Criteria - Persistent or Chronic Immune Thrombocytopenia (ITP)

Eltrombopag (Promacta or Alvaiz) is medically necessary when ALL of the following are met:

ALL of the following

Diagnosis of persistent or chronic ITP (see Appendix D definition)
Prescribed by or in consultation with a hematologist
Age requirement (ONE of)
- For Promacta: age ≥ 1 year
- For Alvaiz: age ≥ 6 years

Continuation Therapy Criteria

Continuation/Repeated Therapy Criteria

Continued therapy is authorized when ALL of the following are met (specifics differ by indication):

ALL of the following

Eligibility for continuation (ONE of)
- Member is currently receiving medication via Centene benefit
- Member has previously met initial approval criteria and documentation supports prior eligibility
- Member is enrolled in state/product with continuity of care regulations and receiving medication
Member is responding positively to therapy (see Appendix D examples: platelet count improvements; platelet >50,000/µL for ITP or hepatitis C; for aplastic anemia hematologic responses including platelet >50,000/µL or other listed responses)

Unproven / Exclusions & Safety

Explicit concurrent-use exclusions: eltrombopag (Promacta or Alvaiz) must not be prescribed concurrently with rituximab for persistent/chronic ITP and must not be prescribed concurrently with another thrombopoietin receptor agonist (e.g., avatrombopag [Doptelet], lusutrombopag [Mulpleta], romiplostim [Nplate]) or with a spleen tyrosine kinase inhibitor (e.g., fostamatinib [Tavalisse]) across labeled indications.

Safety warnings: boxed warning/advisory includes risk of hepatotoxicity and hepatic decompensation in patients with chronic hepatitis C; safety and efficacy have not been established in combination with direct-acting antiviral agents used without interferon.

Formulary handling advisory: for the HIM line of business, if the request is through the pharmacy benefit Alvaiz is non-formulary and should not be approved using these criteria; refer to formulary exception policy HIMPA.103.

Applicable Codes

Drug formulations / product availabilitymixed

Promacta oral suspension	12.5 mg/25 mg oral suspension (Promacta availability listed)
Alvaiz oral tablets	9 mg, 18 mg, 36 mg, 54 mg tablets

Provider Actions / Prior Authorization

Prior Authorization

Prior Authorization and Documentation

Provider must submit documentation such as office chart notes, laboratory results, and other clinical information demonstrating the member meets all approval criteria. Prior authorization may be required for related therapies referenced in the policy (for example, immune globulins, Atgam, cyclophosphamide).

Documentation Required

Specialist Prescription Requirement

For most indications the medication must be prescribed by or in consultation with a specialist. Required specialists by indication include: hematologist for ITP and severe aplastic anemia; and hematologist, hepatologist, gastroenterologist, or infectious disease specialist for chronic hepatitis C-associated thrombocytopenia.

Clinical Evidence & References

Key evidence and references cited in the policy: Promacta Prescribing Information (Mar 2023) and Alvaiz Prescribing Information (Jul 2024) are listed as primary product references.

Relevant clinical literature highlighted: Townsley et al., NEJM 2017 (eltrombopag added to standard immunosuppression for aplastic anemia) and additional guideline/compendium sources including NCCN compendia and ASH guidelines (2019 ASH ITP guideline and related reviews) are referenced for indications and off-label support.

Policy history notes that NCCN-supported off-label uses were added/updated (e.g., post-HCT prolonged thrombocytopenia, MDS-related criteria) and that FDA label revisions prompted updates to include persistent/chronic ITP language.

Background

Background: Eltrombopag is a thrombopoietin receptor agonist indicated for immune thrombocytopenia (ITP), thrombocytopenia in chronic hepatitis C to permit interferon-based therapy, and severe aplastic anemia; it increases platelet production and is used where thrombocytopenia increases bleeding risk.

Alvaiz: the policy adds Alvaiz as a newer eltrombopag choline formulation with tablet strengths (9, 18, 36, 54 mg) and formulation-specific age indications (Alvaiz indicated in patients ≥ 6 years for ITP and adults for hepatitis C-associated thrombocytopenia; severe aplastic anemia in adults).

Safety concerns: the policy documents a boxed warning and advisories for risk of hepatotoxicity and hepatic decompensation in patients with chronic hepatitis C, and notes that combination with direct-acting antivirals without interferon has not been established as safe/effective.

Definitions

Persistent ITPITP duration of 3-12 months (per 2019 ASH guideline, Appendix D)

Chronic ITP> 12 months duration (per 2019 ASH guideline, Appendix D)

Revision History

01.08.24added

Added Alvaiz (eltrombopag choline formulation) as a new eltrombopag formulation; referenced in dosing, age-specific criteria, and product availability (Alvaiz oral tablets 9 mg, 18 mg, 36 mg, 54 mg).

02.23.21revised

Updated criteria to include persistent or chronic ITP consistent with FDA label revision (definitions of persistent and chronic ITP reflected in Appendix D per 2019 ASH guideline).

1Q2023revised

NCCN-supported off-label uses added/updated across policy, including additions and clarifications for MDS (symptomatic anemia qualifiers) and later addition of post-hematopoietic cell transplant prolonged thrombocytopenia per NCCN Compendium.

Policy Summary

PayerCentene

PolicyEltrombopag (Promacta, Alvaiz)

Policy CodePolicy CP.PHAR.180

Change TypeAdded formulation; criteria updates; NCCN indications; exclusions

Effective DateMar 1, 2016

Next Review Date

On This Page

Current (within 30 days) platelet count is ≤ 30,000/µL≤ 30,000/µL

Bleeding or risk (ONE of)

Member has an active bleed
Degree of thrombocytopenia and clinical condition increase risk for bleeding

Failure of a systemic corticosteroid

If corticosteroid intolerance or contraindication (ONE of)

Member has intolerance or contraindication to systemic corticosteroids, and failure of an immune globulin; unless contraindicated or clinically significant adverse effects are experienced
Prior authorization for immune globulins may be required

Eltrombopag is not prescribed concurrently with rituximab, another thrombopoietin receptor agonist (e.g., avatrombopag [Doptelet], lusutrombopag [Mulpleta], romiplostim [Nplate]) or spleen tyrosine kinase inhibitor (e.g., fostamatinib [Tavalisse])

Dose does not exceed (ONE of)

For Promacta: 75 mg per day≤ 75 mg/day
For Alvaiz: 54 mg per day≤ 54 mg/day

Initial Approval Criteria - Chronic Hepatitis C-Associated Thrombocytopenia

Eltrombopag (Promacta or Alvaiz) is medically necessary when ALL of the following are met:

ALL of the following

Diagnosis of chronic hepatitis C-associated thrombocytopenia
Prescribed by or in consultation with a hematologist, hepatologist, gastroenterologist, or infectious disease specialist
Age > 18 years> 18 years
Degree of thrombocytopenia has prevented initiation of interferon-based therapy or limited ability to maintain interferon-based therapy
Eltrombopag will be used concomitantly with interferon-based therapy
Current (within 30 days) platelet count is ≤ 75,000/µL≤ 75,000/µL
Eltrombopag is not prescribed concurrently with another thrombopoietin receptor agonist or spleen tyrosine kinase inhibitor (e.g., Tavalisse)
Dose does not exceed (ONE of)
- For Promacta: 100 mg per day (2 tablets per day)≤ 100 mg/day
- For Alvaiz: 72 mg per day (2 tablets per day)≤ 72 mg/day

Initial Approval Criteria - Severe Aplastic Anemia

Eltrombopag (Promacta or Alvaiz) is medically necessary when ALL of the following are met:

ALL of the following

Diagnosis of severe aplastic anemia
Prescribed by or in consultation with a hematologist
Age requirement (ONE of)
- For Promacta: ≥ 2 years≥ 2 years
- For Alvaiz: ≥ 18 years≥ 18 years
Line of therapy (ONE of)
- For Promacta only: first-line therapy in combination with immunosuppressive therapy
- Refractory or second-line treatment as single agent following insufficient response to immunosuppressive therapy (e.g., Atgam, cyclosporine, cyclophosphamide)
  Prior authorization for some immunosuppressive agents may be required
Eltrombopag is not prescribed concurrently with another thrombopoietin receptor agonist or spleen tyrosine kinase inhibitor
Current (within 30 days) platelet count is ≤ 50,000/µL≤ 50,000/µL
Dose does not exceed (ONE of)
- For Promacta: 150 mg per day (2 tablets per day for some regimens)≤ 150 mg/day
- For Alvaiz: 108 mg per day (2 tablets per day)≤ 108 mg/day

Initial Approval Criteria - NCCN Compendium Indications (off-label)

Eltrombopag is medically necessary for NCCN Compendium-supported indications when ALL of the following are met:

ALL of the following

Supported off-label diagnoses (ONE of)
- Myelodysplastic syndromes (MDS)
- Post-hematopoietic cell transplant with prolonged thrombocytopenia
Prescribed by or in consultation with an oncologist or hematologist
For MDS: member must have ONE of
- Refractory thrombocytopenia following disease progression or no response to hypomethylating agents (e.g., azacitidine, decitabine), immunosuppressive therapy (e.g., Atgam, cyclosporine), or clinical trial
- Severe thrombocytopenia
- Thrombocytopenia or neutropenia with hypocellular marrows or other qualifiers (e.g., <60 years with <5% marrow blasts; PNH clone positivity; STAT-3 mutant cytotoxic T-cell clones)
- Symptomatic anemia with probability to respond to immunosuppressive therapy
Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)
Eltrombopag is not prescribed concurrently with another thrombopoietin receptor agonist
Prescribed regimen must be FDA-approved or recommended by NCCN

Other Diagnoses/Indications (Initial)

If the requested use is not listed in approved or NCCN indications, follow formulary/non-formulary/off-label policies:

ANY of the following

If drug is on formulary/PDL: follow no coverage criteria policy for relevant line of business (CP.CPA.190 commercial; HIM.PA.33 HIM; CP_PMN.255 Medicaid)
If drug NOT on formulary/PDL: follow non-formulary policy for relevant line of business (CP.CPA.190 commercial; HIM.PA.103 HIM; CP_PMN.16 Medicaid)
HIM: Alvaiz non-formulary via pharmacy benefit per HIM.PA.103
If use not listed and criterion 1 above does not apply: refer to off-label use policy for relevant line of business (CP.CPA.09 commercial; HIM.PA.154 HIM; CP_PMN.53 Medicaid)

target platelet >50,000/µL for ITP/hepatitis C

For chronic hepatitis C-associated thrombocytopenia: member continues interferon-based therapy

Current (within last 90 days) platelet count is ≥ 40,000/µL≥ 40,000/µL

Eltrombopag is not prescribed concurrently with another thrombopoietin receptor agonist or spleen tyrosine kinase inhibitor

For persistent/chronic ITP: not prescribed concurrently with rituximab

If request is for a dose increase, new dose must not exceed (ONE of)

Persistent/chronic ITP: For Promacta: 1 tablet per day (max 75 mg/day); For Alvaiz: 1 tablet per day (max 54 mg/day)Promacta ≤75 mg/day; Alvaiz ≤54 mg/day
Chronic hepatitis C-associated thrombocytopenia: For Promacta: 2 tablets per day (max 100 mg/day); For Alvaiz: 2 tablets per day (max 72 mg/day)Promacta ≤100 mg/day; Alvaiz ≤72 mg/day
Severe aplastic anemia: For Promacta: 2 tablets per day (max 150 mg/day); For Alvaiz: 2 tablets per day (max 108 mg/day)Promacta ≤150 mg/day; Alvaiz ≤108 mg/day

Continuation - NCCN Compendium Indications

Continuation for NCCN indications (off-label) requires:

ALL of the following

Eligibility (ONE of)
- Currently receiving medication via Centene benefit
- Documentation supports that member is currently receiving eltrombopag for a covered indication and has received it for at least 30 days≥ 30 days
Member is responding positively to therapy
See Appendix D for response examples
Eltrombopag not prescribed concurrently with another thrombopoietin receptor agonist
Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence)
Prescribed regimen must be FDA-approved or recommended by NCCN

Billing Rule

Dose limits enforced

Requests for doses above the policy-specified maximums for Promacta and Alvaiz will not meet criteria. Dose increase requests must not exceed the listed per-indication maximums.

Persistent/chronic ITP: Promacta max 75 mg/day; Alvaiz max 54 mg/day
Chronic hepatitis C-associated thrombocytopenia: Promacta max 100 mg/day; Alvaiz max 72 mg/day
Severe aplastic anemia: Promacta max 150 mg/day; Alvaiz max 108 mg/day

Denial Risk

Concurrent therapy exclusions

Claims may be denied if eltrombopag is prescribed concurrently with excluded therapies. The policy excludes concurrent use with rituximab (for persistent/chronic ITP), another thrombopoietin receptor agonist (for example, avatrombopag [Doptelet], lusutrombopag [Mulpleta], romiplostim [Nplate]), or a spleen tyrosine kinase (SYK) inhibitor (for example, fostamatinib [Tavalisse]).

Documentation Required

Off-label evidence submission

For NCCN Compendium-supported off-label indications or when the requested dose exceeds FDA maximum limits, the prescriber must submit supporting evidence such as practice guideline recommendations or peer-reviewed literature to justify the use.

1Q2024added

Concurrent use exclusion added: for all FDA-labeled indications added exclusion of concurrent spleen tyrosine kinase inhibitor (e.g., fostamatinib [Tavalisse]); exclusions for concurrent thrombopoietin receptor agonists were clarified/expanded across indications.

11.20.24 - 02.25clarifiedLatest

Advisory referencing HIMPA.103: for Health Insurance Marketplace (HIM), if request for Alvaiz is through the pharmacy benefit, Alvaiz is non-formulary and should not be approved using these criteria; refer to formulary exception policy HIMPA.103. (Non-material guidance regarding formulary/benefit processing.)