ModifiedPremera BluecrossPolicy N/A

Pharmacotherapy of Thrombocytopenia

Clinical pharmacy policy governing medical necessity and prior authorization criteria for pharmacologic treatments of thrombocytopenia (including chronic immune thrombocytopenia, hepatitis C-associated thrombocytopenia, severe aplastic anemia, procedure-related thrombocytopenia in chronic liver disease, and others) for Premera Bluecross members.

Policy Summary

PayerPremera Bluecross

PolicyPharmacotherapy of Thrombocytopenia

Policy CodePolicy N/A

Change TypeCoverage expanded and multiple agent criteria added/updated (material)

Effective DateN/A

Next Review DateN/A

Key ActionSubmit prior authorization with office visit notes documenting diagnosis, relevant history, exam, and medication history to support medical necessity.

SourceLink

POLICY UPDATE CHANGES

Tavalisse (fostamatinib) criteria, dosage, and quantity limits were added and a length of approval table was added covering all drugs listed in the medical policy.

Doptelet (avatrombopag) criteria updated to include coverage for chronic immune thrombocytopenia (ITP) indication and descriptive terminology standardized to 'chronic immune thrombocytopenia (ITP)'.

Second-line therapy guidance updated to add rituximab as a treatment option and to require that insufficient response to corticosteroids includes failure of IVIg, rituximab, or splenectomy.

New indication for Nplate (romiplostim) for treatment of adults and pediatric individuals acutely exposed to myelosuppressive doses of radiation was added.

Added coverage criteria for Alvaiz (eltrombopag choline).

Added coverage criteria for Adzynma (ADAMTS13, recombinant-krhn) for treatment of certain individuals with congenital thrombotic thrombocytopenic purpura (cTTP).

Updated Nplate (romiplostim) to include coverage criteria for chemotherapy-induced thrombocytopenia.

Added coverage criteria for generic eltrombopag and required trial with generic eltrombopag before branded Alvaiz/Promacta in updated criteria.

Removed the step therapy requirement from Doptelet (avatrombopag) criteria that the individual has had an insufficient response to Promacta or Nplate.

Terminated HCPCS code C9167 and added HCPCS J7171; later HCPCS J2796 termed and replaced with J2802.

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Coverage Criteria and Medical Necessity

Chronic Immune Thrombocytopenia (ITP) — Doptelet (avatrombopag)

Covered when ALL of the following are met

Age: The individual is aged 18 years or older

Platelet criteria: Meets one of: platelet count <30,000/µL OR platelet count <50,000/µL with increased bleeding risk

Prior therapy: Has had an insufficient response to corticosteroids, immunoglobulins, rituximab, or splenectomy

Dose limit: The daily dose for Doptelet (avatrombopag) does not exceed the product-specific maximum per the prescribing information<= stated maximum

See full policy for exact mg/day limit

Hepatitis C-associated Thrombocytopenia — Eltrombopag variants and others

Covered when ALL of the following are met

Diagnosis: The individual has been diagnosed with hepatitis C-associated thrombocytopenia

Therapy requirement: Requires initiation and maintenance of interferon-based therapy when specified by the agent's criteria

Prior therapy: Has had an inadequate response or intolerance to generic eltrombopag (required prior trial before branded eltrombopag formulations such as Alvaiz or Promacta)

Generic eltrombopag trial required for branded agents per policy updates

Dose limit: Daily dose does not exceed product-specific limits (examples in policy: generic eltrombopag up to 100 mg/day; Alvaiz up to 72 mg/day; Promacta dose limits vary by indication)

Chronic Liver Disease (scheduled to undergo a procedure) — Doptelet or Mulpleta

Covered when ALL of the following are met

Platelet count: The individual has a platelet count of less than 50,000/µL<50,000/µL

Procedure timing: The individual is scheduled to undergo an invasive procedure within the next 14 days<=14 days

Quantity dispensed does not exceed fifteen 20 mg tablets of Doptelet (avatrombopag) OR seven 3 mg tablets of Mulpleta (lusutrombopag)<=15 Doptelet 20 mg tablets OR <=7 Mulpleta 3 mg tablets

One course of therapy approved per procedure

Severe Aplastic Anemia / Hematopoietic Syndrome / ADAMTS13 for cTTP

Covered when ALL of the following are met

Severe Aplastic Anemia: Used for individuals with severe aplastic anemia who have had an insufficient response to standard immunosuppressive therapy (examples: horse or rabbit ATG, cyclosporine, prednisone)

Eltrombopag daily dose limits referenced in policy

ADAMTS13 for cTTP: Adzynma (ADAMTS13, recombinant-krhn) is covered when: diagnosis of congenital TTP (cTTP) is confirmed by molecular genetic testing AND ADAMTS13 activity is <10% measured by the FRETS‑VWF73 assay AND the individual does not have immune‑mediated TTP AND there is an inadequate response or contraindication to plasma transfusion or a documented allergy to plasma productsADAMTS13 activity <10%

For prophylactic therapy the dose is limited to 40 IU/kg once weekly

Chemotherapy-Induced Thrombocytopenia — Nplate (romiplostim)

Covered when ALL of the following are met

Duration: The individual has experienced chemotherapy-induced thrombocytopenia for greater than or equal to 4 weeks>=4 weeks

Response to chemotherapy modification: The thrombocytopenia has not responded to a reduction in the chemotherapy dose or frequency

Dose limit: Nplate (romiplostim) dosing does not exceed product-specific maximum daily dose per prescribing information<= stated maximum

See product label and policy for exact dosing limits

Clinical coverage considerations

Coverage-relevant clinical positions and conditions described in the evidence review and safety sections

Efficacy summary: TPO-receptor agonists (eltrombopag, romiplostim, avatrombopag, lusutrombopag) have demonstrated efficacy in randomized trials for increasing platelet counts and reducing need for transfusions or rescue therapies; evidence strength and trial data vary by agent.

ADAPT trials support avatrombopag; eltrombopag and romiplostim have substantial RCT evidence

Role in treatment sequence: Rituximab may be considered as a second-line option after failure of initial corticosteroid therapy; TPO‑receptor agonists and fostamatinib are options for individuals unresponsive to or relapsing after initial therapy.

Guidelines lack consensus; individualize selection

Baseline and monitoring labs: Obtain a peripheral blood smear and baseline CBC prior to initiation of eltrombopag or romiplostim; monitor CBCs monthly after initiation and weekly for at least two weeks after discontinuation; monitor liver tests with eltrombopag per label and perform ocular exams for cataract monitoring as indicated.

Repeat abnormal liver tests within 3–5 days and manage per label; stop eltrombopag for significant ALT elevation per prescribing information

Coverage updates and additions

Policy was expanded/updated; coverage for specific agents and indications added or revised as noted below.

Alvaiz / generic eltrombopag additions: Added coverage criteria for Alvaiz (eltrombopag choline) and for generic eltrombopag; policy requires trial of generic eltrombopag before branded eltrombopag formulations (Alvaiz, Promacta) per 2024–2025 updates.

See per‑agent criteria

Adzynma (ADAMTS13) addition: Added coverage criteria for Adzynma (ADAMTS13, recombinant‑krhn) for treatment of certain individuals with congenital TTP (cTTP).

Refer to cTTP criteria for diagnostic and activity thresholds

Nplate expansion: Updated Nplate (romiplostim) criteria to include chemotherapy‑induced thrombocytopenia and to reflect previously added radiation‑exposure indication; also updated HCPCS coding for romiplostim.

Step therapy removed for Doptelet in prior updates

The medications listed in this policy (including Adzynma, Alvaiz, Doptelet, generic eltrombopag, Mulpleta, Promacta, and Tavalisse) are considered investigational for indications not specified in the coverage sections. Examples of investigational uses include, but are not limited to, uses outside the policy's enumerated indications (for instance, many off‑label applications of Nplate). Non‑formulary exception requests for these investigational uses may be considered but are subject to the policy's documentation and approval processes.

These thrombopoietic agents (eltrombopag, avatrombopag, lusutrombopag, romiplostim and similar products) should not be used to treat thrombocytopenia etiologies other than immune thrombocytopenia (ITP). The policy explicitly states these agents are not indicated for non‑ITP causes of low platelet counts.

Disclaimer: This medical policy is a guide to evaluating medical necessity and does not apply to Medicare Advantage. Member benefits vary; providers and members should consult the member benefit booklet or customer service to determine coverage for a specific plan.

All other uses of Nplate (romiplostim) that are not specifically listed as covered in this policy are considered investigational (not medically necessary). Approval for uses of romiplostim is limited to the explicit indications and criteria described in the policy.

Clinical safety guidance warns against administering TPO‑receptor agonists with the goal of normalizing platelet counts. Excessive increases in platelet counts have been associated with thrombotic and thromboembolic events, so these agents should be dosed to achieve a safe platelet level rather than normalization. In addition, baseline and ongoing monitoring are required (peripheral blood smear and CBC prior to initiation, monthly CBCs after initiation, and weekly CBCs for at least two weeks after discontinuation) and clinicians should exercise caution in patients with known thromboembolic risk factors.

Coding and Billing Codes

HCPCSHCPCS

J2796	Injection, romiplostim (Nplate); 10 mcg (code terminated 01/01/25).
J2802	Injection, romiplostim (Nplate); 1 microgram (new code effective 01/01/25).
J7171	Injection, adamts13, recombinant-krhn; (Adzynma) 10 iu

HCPCS coding updatesHCPCS

C9167	HCPCS code (terminated)
J7171	HCPCS code (added to replace C9167)
J2796	HCPCS code (termed)
J2802	HCPCS code (replacement for J2796)

What Providers Must Do / Authorization and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for the thrombocytopenia pharmacotherapies listed in this policy. Requirements vary by agent and indication; approvals are contingent on meeting the specific medical necessity criteria (including required prior trials, dose limits, and course length) outlined in the policy.

PA required for Alvaiz (eltrombopag choline), generic eltrombopag, Promacta (eltrombopag olamine), Doptelet (avatrombopag), Mulpleta (lusutrombopag), Tavalisse (fostamatinib), Nplate (romiplostim), Adzynma (ADAMTS13 recombinant)
Dose limits and course lengths follow the drug-specific criteria (e.g., Alvaiz ≤72 mg/day for Hep C-associated thrombocytopenia; generic eltrombopag and Promacta daily limits as specified)
Authorizations are subject to FDA dosing and administration prescribing information

Background and Rationale

Thrombocytopenia is a condition of abnormally low platelet counts that increases bleeding risk. Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by antibody‑mediated platelet destruction and often reduced platelet production; consensus definitions commonly use a platelet threshold of 100,000/µL to define ITP, and adult incidence is on the order of approximately 2 per 100,000 per year. Clinical management of ITP balances bleeding risk, platelet counts, prior therapy responses, and treatment safety profiles when selecting second‑line agents.

Definitions and Key Terms

Chronic immune thrombocytopenia (ITP) — definition and key threshold/diagnostic points

DefinitionChronic immune thrombocytopenia (ITP) is an autoimmune disorder characterized by destruction of normal platelets and often decreased platelet production.

IWG platelet thresholdInternational Working Group (IWG) consensus defines platelet count threshold as less than 100,000 per µL.

EpidemiologyAdult ITP annual incidence approximately 2 cases per 100,000; estimated ~30,000 individuals with ITP in the U.S. and ~15,000 with chronic ITP.

Clinical significanceITP leads to increased risk of bleeding due to immune-mediated platelet destruction; treatment selection depends on age, symptoms, and platelet count.

Chronic immune thrombocytopenia (ITP) — additional definition entry

Alternate definition phrasing

Step Therapy

Step Therapy / Prerequisite Failure

Step therapy and prerequisite-failure requirements are enforced where specified in the clinical criteria; document prior inadequate responses or intolerance to required therapies.

Examples: Many ITP indications require prior insufficient response to corticosteroids and IVIg; some criteria require failure/intolerance to eltrombopag or romiplostim before Tavalisse
Where policy specifies trial of generic eltrombopag, that trial must be documented before approving branded eltrombopag agents (Alvaiz, Promacta)
2023 update: step therapy requirement removed for Doptelet (no longer requires prior failure of Promacta or Nplate)

Documentation Required

Documentation Required — Provide Complete Medical Record

If required medical record documentation is not provided, the request may be denied or delayed. Ensure submitted records demonstrate the clinical history, prior therapies, and lab/monitoring data required by the criteria.

Required documentation includes office visit notes with diagnosis, relevant history, physical exam, and medication history
Document prior trials/failures or intolerances to specified agents (e.g., corticosteroids, IVIg, rituximab, splenectomy, eltrombopag, romiplostim) when those are prerequisites
Provide baseline and monitoring labs (peripheral smear and CBC prior to initiation and ongoing monitoring as required)
Non-formulary exception authorizations may be approved up to 12 months — include rationale and supporting documentation for exceptions