RXMP-19 Complement C5 Inhibitors Form

Effective Date

Last Reviewed

Original Document

Complement C5 Inhibitors

Updated on: 11/14/2025

Policy Number RXMP-19 Line of Business Medicaid & Medicare Effective Date 10/1/2023 (Medicaid), 1/1/2024 (Medicare) Revision Date 11/14/2025

Products: Soliris (eculizumab), Epysqli (eculizumab-aagh), Bkemv (eculizumab-aeeb), Ultomiris (ravulizumab), and Piasky (crovalimab)

Override(s)
Approval Duration
Prior Authorization
Initial Request: Paroxysmal Noctural Hemoglubinura (PNH) or Neuromyelitis Optica Spectrum Disorder: 6 months Atypical Hemolytic Uremic Syndrome: 12 weeks Generalized Myasthenia Gravis: up to 26 weeks Renewal: 12 months for all indications

HCPCS Description Quantity Limit Medical Benefit: Authorization Required; Pharmacy Benefit: Not Covered J1299 Injection, eculizumab, 2 mg (Soliris 300mg/mL) vial 8 vials per 28 days
Q5151 Injection, eculizumab-aagh (Epysqli), biosimilar, 2 mg (preferred for Medicaid only)
8 vials per 28 days
Q5152 Injection, eculizumab-aeeb (Bkemv), biosimilar, 2 mg
8 vials per 28 days
Initiation of therapy for Atypical Hemolytic Uremic Syndrome (aHUS), generalized Myasthenia Gravis (MG), or neuromyelitis optica spectrum disorder (NMOSD): May approve 4 (four) additional vials (300 mg/mL) in the first 28 days (4 weeks) of treatment.
If individual receives plasma exchange [PE], plasmapheresis [PP], or fresh frozen plasma infusion during therapy, supplemental doses of eculizumab (up to 600 mg following each PE or PP intervention or up to 300 mg following fresh frozen plasma) may be approved.
If individual receives concomitant maintenance intravenous immunoglobulin (IVIg) for gMG, supplemental doses of eculizumab (up to 600 mg per IVIg cycle) may be approved.
J1303 Injection ravulizumab-cwvz 10 mg (Ultomiris) 300mg/3mL; 1100mg/11mL SDV 300mg/3mL vial: 12 vials per 56 days
1100 mg/11 mL vial^: 3 vials per 56 days Initiation of therapy:
May approve 10 (ten) additional vials (300 mg/30mL or 300mg/3mL) in the first 28 days (4 weeks) of treatment.
^May approve 3 (three) additional 1100 mg vials (1100 mg/11 mL) in the first 28 days (4 weeks) of treatment.
^If individual receives plasma exchange [PE], plasmapheresis [PP], or intravenous immunoglobulin [IVIg] interventions during therapy, supplemental intravenous doses of Ultomiris (up to 1800 mg following each PE or PP intervention or up to 600 mg following completion of an IVIg cycle) may be approved
J1307
Injection, crovalimab-akkz, 10 mg (Piasky) 340 mg/ 2mL (170 mg/ mL) single-dose vial
3 vials per 28 days

May approve 9 (nine) additional 340 mg vials in the first 29 days of treatment for a total of 12 (twelve) vials in the first 29 days of treatment; to be given as one IV loading dose [up to 1500 mg or 5 vials] on day 1 followed by SUBQ loading doses of 340 mg [1 vial] each on days 2, 8, 15, and 22. Maintenance dosing begins on day 29 and continues every 4 weeks thereafter. Medicaid preferred agent: Epysqli; Medicare (new starts) preferred agent: N/A

Complement C5 Inhibitors

Updated on: 11/14/2025

Medicare Criteria
Medicare Part B Coverage Criteria
Review using the most current Local Coverage Determination (LCD), National Coverage Determination (NCD), or Local Coverage Article (LCA) that applies to the Hawaii region. The LCD, NCD, or LCA can be found at: https://www.cms.gov/medicare-coverage-database/search.aspx. • No LCD/NCD/LCA found as of 11/4/2025. Review the criteria below Medicare Part B 90-Day Transition Period For new Medicare members, a 90-day transition period applies. During this time, if a member is currently on an active course of the requested treatment, including when furnished by an out-of-network provider, Coverage and Step Therapy do not apply. After the first 90 days of enrollment, Coverage and Step Therapy Criteria must be met for continued coverage. Medicare Part B Step Therapy Criteria • For new starts, Medicare Part B Step Therapy Criteria must be met in addition to Coverage Criteria before a request may be approved.
• Effective 1/1/2026: ▪ Soliris: trial and failure of 2 preferred agent, injection, eculizumab-aeeb (Bkemv) and injection, eculizumab- aagh (Epysqli), biosimilar, 2 mg (preferred) prior to Soliris. ▪ Piasky (crovalimab-akkz): trial and failure of 2 preferred eculizumab (Bkemv/Epysqli) and ravulizumab (Ultomiris) prior to Piasky. ▪ ravulizumab (Ultomiris): trial and failure of 2 preferred agent, injection, eculizumab-aeeb (Bkemv) (preferred) and injection, eculizumab-aagh (Epysqli), biosimilar, 2 mg (preferred) prior to Ultomiris.

Approval Criteria Products injection, eculizumab, 2 mg (Soliris); injection, eculizumab-aagh (Epysqli) (preferred), biosimilar, 2 mg; injection, eculizumab-aeeb (Bkemv) biosimilar, 2 mg; and Injection ravulizumab-cwvz 10 mg (Ultomiris), crovalimab-akkz (Piasky) Diagnosis Paroxysmal Noctural Hemoglubinura (PNH) Line of Business Medicare and Medicaid Approval Length Initial Request: 6 months; Renewal: 12 months Override Type PA, QL Initial Criteria Note: Pharmacy staff: For QUEST non-ABD members with cancer, send ADRC (Aid to Disability Referral Committee) referral with chart notes through G8 CM module.
High Cost All approvals must be reviewed with the Pharmacy Director.

Criteria:

Diagnosis of Paroxysmal Noctural Hemoglubinura (PNH) (ICD-10-59.5); AND
Prescribed by or in consultation with a hematologist or oncologist; AND
Member is 18 years of age or older; AND
Paroxysmal Noctural Hemoglubinura (PNH) as verified by flow cytometry, including the presence of: a. PNH type III red cell clone or a measurable granulocyte or monocyte clone; OR

Complement C5 Inhibitors

Updated on: 11/14/2025

b. Glycosylphosphatidylinositol-anchored proteins (GPI-AP)-deficient polymorphonuclear cells (PMNs) AND

One of the following is meet (a or b):
a. History of ≥ 1 red blood cell transfusion in the past 24 months and (1 or 2): 1) Documentation of hemoglobin < 7 g/dL in members without anemia symptoms; OR 2) Documentation of hemoglobin < 9 g/dL in members with anemia symptoms;
OR b. History of thrombosis;
AND
The member has completed or updated meningococcal vaccination (for serogroups A, C, W, and Y, and serogroup B) at least 2 weeks prior to administration of the first dose of eculizumab, unless the risks of delaying eculizumab outweigh the risk of meningococcal infection; AND
The requested medication is not prescribed concurrently with pegcetacoplan (Empaveli), iptacopan (Fabhalta), (crovalimab-akkz) Piasky, or ravulizumab (Ultomiris), unless the member is in a 4-week period of cross-titration between Soliris/Bkemv/Epysqli and Empaveli*;
AND
For Soliris/Bkemv/Epysqli products, one of the following (a or b) and c: a. For Medicaid: For Bkemv, documentation is provided that the member is switching from treatment with Epysqli (preferred) b. For Medicaid/Medicare: For Soliris, documentation is provided that the member is switching from treatment with Epysqli and Bkemv;
AND c. Dose does not exceed 600 mg per week for the first 4 weeks, followed by 900 mg for the fifth dose 1 week later, then 900 mg every 2 weeks thereafter;
OR
For Ultomiris, the following are met (a or b and c): a. Documentation is provided that the member is complement inhibitor treatment naïve (not switching from eculizumab (Soliris/Bkemv/Epysqli) products; AND all of the below: 1) Documentation showing that lactate dehydrogenase is greater than 1.5 times the upper limit of normal; AND 2) One or more PNH-related sign or symptoms (such as but is not limited to anemia or history of major adverse vascular event from thromboembolism); AND 3) Medical justification was provided as to why eculizumab (Bkemv) and eculizumab (Epysqli) (preferred) cannot be used. OR b. Documentation is provided that the member is switching from treatment with eculizumab (Soliris/Bkemv/Epysqli) products; AND treatment with eculizumab (Soliris/Bkemv/Epysqli) products will be discontinued prior to ravulizumab (Ultomiris) initiation AND c. The following weight base dosing are met: 1) Weight ≥ 5 kg to < 20 kg: ≤ 600 mg for one dose, followed by maintenance doses (which start 2 weeks after the loading dose) of ≤ 600 mg every 4 weeks; OR 2) Weight ≥ 20 kg: ≤ 3,000 mg for one dose, followed by maintenance doses (which start 2 weeks after the loading dose) of ≤ 3,600 every 8 weeks
For Piasky (crovalimab-akkz):
a. Documentation is provided showing that the member is switching from treatment with Soliris/Bkemv/Epysqli

Complement C5 Inhibitors

Updated on: 11/14/2025

or ravulizumab (Ultomiris); AND
b. Treatment with eculizumab (Soliris/Bkemv/Epysqli) or ravulizumab (Ultomiris) will be discontinued prior to initiation with (crovalimab-akkz) Piasky. Renewal Criteria Diagnosis Paroxysmal Noctural Hemoglubinura (PNH) Approval Length Renewal: 12 months Note: Pharmacy staff: For QUEST non-ABD members with cancer, send ADRC (Aid to Disability Referral Committee) referral with chart notes through G8 CM module.
High Cost All approvals must be reviewed with the Pharmacy Director.

Criteria:

Diagnosis of Paroxysmal Noctural Hemoglubinura (PNH) (ICD-10-59.5); AND
Prescribed by or in consultation with a hematologist; AND
Member is 18 years of age or older; AND
Documentation is showing that the member experienced a clinical response as shown by one of the following: a. Stabilization of hemoglobin levels;
b. Reduction in number of transfusions; c. Improvement in hemolysis; d. Normalization or decrease of LDH levels; OR e. increased reticulocyte count
AND
The member has completed or updated meningococcal vaccination (for serogroups A, C, W, and Y, and serogroup B); AND
The requested medication is not prescribed concurrently with Epysqli, Bkemv, and Soliris, iptacopan (Fabhalta), pegcetacoplan (Empaveli), Piasky (crovalimab-akkz), or ravulizumab (Ultomiris), unless the member is in a 4- week period of cross-titration between Soliris/Bkemv/Epysqli and Empaveli*; AND
Soliris (Medicaid): Medical justification was provided as to why eculizumab (Bkemv) and eculizumab (Epysqli) (preferred) cannot be used.
Products injection, eculizumab, 2 mg (Soliris); injection, eculizumab-aagh (Epysqli) (preferred), biosimilar, 2 mg; injection, eculizumab-aeeb (Bkemv) biosimilar, 2 mg; and Injection ravulizumab-cwvz 10 mg (Ultomiris) Diagnosis Neuromyelitis Optica Spectrum Disorder (NMOSD) Line of Business Medicare and Medicaid Approval Length Initial & Renewal: 12 months Override Type PA, QL Initial Criteria Note: Pharmacy staff: For QUEST non-ABD members with cancer, send ADRC (Aid to Disability Referral Committee) referral with chart notes through G8 CM module.
High Cost All approvals must be reviewed with the Pharmacy Director.
Criteria:
Diagnosis of Neuromyelitis Optica Spectrum Disorder (NMOSD) (ICD-10 G36.0 Neuromyelitis optica); AND
Prescribed by or in consultation with a hematologist; AND
Member is 18 years of age or older; AND
Diagnosis of NMOSD is verified by the presence of anti-aquaporin-4 (AQP4) antibodies; AND

Complement C5 Inhibitors

Updated on: 11/14/2025

For eculizumab (Soliris/Bkemv/Epysqli) products: a. Documentation is provided that the member has a history of at least 2 acute attacks or relapses in the last 12 months prior to initiation of therapy; OR b. Documentation is provided that the member has a history of at least 3 acute attacks or relapses in the last 24 months prior to initiation of therapy and at least one relapse in the 12 months prior to initiation of therapy;
OR
For ravulizumab (Ultomiris):
a. Documentation is provided that the member has a history of at least 1 acute attacks or relapses in the last 12 months prior to initiation of therapy; AND
The member has completed or updated meningococcal vaccination (for serogroups A, C, W, and Y, and serogroup B) at least 2 weeks prior to administration of the first dose of eculizumab, unless the risks of delaying eculizumab outweigh the risk of meningococcal infection; AND
For Soliris/Bkemv/Epysqli products, one of the following (a or b): a. For Medicaid: For Bkemv, documentation is provided that the member is switching from treatment with Epysqli (preferred); OR b. For Medicaid/Medicare: For Soliris, documentation is provided that the member is switching from treatment with Epysqli and Bkemv. AND
The requested medication is not prescribed concurrently with pegcetacoplan (Empaveli), iptacopan (Fabhalta), (crovalimab-akkz) Piasky, or ravulizumab (Ultomiris), unless the member is in a 4-week period of cross-titration between Soliris/Bkemv/Epysqli and Empaveli. Renewal Criteria Diagnosis Neuromyelitis Optica Spectrum Disorder (NMOSD) Approval Length Renewal: 12 months Note: Pharmacy staff: For QUEST non-ABD members with cancer, send ADRC (Aid to Disability Referral Committee) referral with chart notes through G8 CM module.
*High Cost** All approvals must be reviewed with the Pharmacy Director.
Criteria:
Diagnosis of Neuromyelitis Optica Spectrum Disorder (NMOSD) (ICD-10 G36.0 Neuromyelitis optica; AND
Prescribed by or in consultation with a hematologist; AND
Member is 18 years of age or older; AND
Diagnosis of NMOSD is verified by the presence of anti-aquaporin-4 (AQP4) antibodies; AND
Documentation is provided that the member has experienced a clinical response such as reduction in the frequency of relapse AND
The member has completed or updated meningococcal vaccination (for serogroups A, C, W, and Y, and serogroup B); AND
For Soliris/Bkemv/Epysqli products, one of the following (a or b): a. For Medicaid: For Bkemv, documentation is provided that the member is switching from treatment with Epysqli (preferred); OR b. For Medicaid/Medicare: For Soliris, documentation is provided that the member is switching from treatment with Epysqli and Bkemv. AND
The requested medication is not prescribed concurrently with pegcetacoplan (Empaveli), iptacopan (Fabhalta), (crovalimab-akkz) Piasky, or ravulizumab (Ultomiris), unless the member is in a 4-week period of cross-titration between Soliris/Bkemv/Epysqli and Empaveli*.

Complement C5 Inhibitors

Updated on: 11/14/2025

Products injection, eculizumab, 2 mg (Soliris); injection, eculizumab-aagh (Epysqli) (preferred), biosimilar, 2 mg; injection, eculizumab-aeeb (Bkemv) biosimilar, 2 mg; and Injection ravulizumab-cwvz 10 mg (Ultomiris) Diagnosis Myasthenia Gravis (ICD-10: G70.00-G70.01) Line of Business Medicare and Medicaid Approval Length Initial: 6 months, Renewal: 12 months Override Type PA, QL Initial Criteria Note: Pharmacy staff: For QUEST non-ABD members with cancer, send ADRC (Aid to Disability Referral Committee) referral with chart notes through G8 CM module.
High Cost All approvals must be reviewed with the Pharmacy Director

Criteria:

Diagnosis of Myasthenia Gravis (ICD-10: G70.00-G70.01) AND
Prescribed by or in consultation with a nephrologist; AND
Member is 18 years of age or older; AND
Documentation showing positive serologic test for binding anti-acetylcholine receptor antibodies (AChR-ab) AND
The member has Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II to IV disease; AND
Documentation is provided that the member has a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 6 or higher; AND
One of the following are met: a. History of failure of at least two immunosuppressive agents for at least 12 months (e.g., azathioprine, corticosteroids, cyclosporine, methotrexate, mycophenolate, etc.); OR b. Member has a history of failure of both of the following:
1) At least one immunosuppressive therapy; AND 2) Four or more courses of plasmapheresis/plasma exchanges and/or intravenous immune globulin over the course of at least 12 months without symptom control
The member has completed or updated meningococcal vaccination (for serogroups A, C, W, and Y, and serogroup B) at least 2 weeks prior to administration of the first dose of eculizumab, unless the risks of delaying eculizumab outweigh the risk of meningococcal infection; AND
The requested medication is not prescribed concurrently with pegcetacoplan (Empaveli), iptacopan (Fabhalta), (crovalimab-akkz) Piasky, or ravulizumab (Ultomiris),;
AND
For Soliris/Epysqli products, one of the following (a or b): a. For Medicaid: For Bkemv, documentation is provided that the member is switching from treatment with Epysqli (preferred); OR b. For Medicaid/Medicare: For Soliris, documentation is provided that the member is switching from treatment with Epysqli and Bkemv. OR
For ravulizumab (Ultomiris): documentation is provided that the member is switching from treatment with Epysqli, Bkemv, or Soliris. Renewal Criteria Diagnosis Myasthenia Gravis (ICD-10: G70.00-G70.01) Approval Length Renewal: 12 months

Complement C5 Inhibitors

Updated on: 11/14/2025

Note: Pharmacy staff: For QUEST non-ABD members with cancer, send ADRC (Aid to Disability Referral Committee) referral with chart notes through G8 CM module.
High Cost All approvals must be reviewed with the Pharmacy Director

Criteria:

Diagnosis of Atypical Hemolytic Uremic Syndrome (aHUS) (ICD-10: D59.32 Hereditary hemolytic uremic syndrome [when specified as atypical hemolytic uremic syndrome]; or D59.39 Other hemolytic uremic syndrome [when specified as atypical hemolytic uremic syndrome]; AND
Prescribed by or in consultation with a hematologist; AND
The diagnosis of Atypical Hemolytic Uremic Syndrome (aHUS) is supported by the absence of Shiga toxin-producing E. coli infection; AND
The member has completed or updated meningococcal vaccination (for serogroups A, C, W, and Y, and serogroup B); AND
There is clinical improvement after the initial trial (for example, increased platelet count or laboratory evidence of reduced hemolysis) until an individual becomes a candidate for physician-directed cessation as evidenced by the following:
a. Complete clinical remission has been achieved (that is, resolution of thrombocytopenia and mechanical hemolysis, and normalization or new baseline plateau of renal function) and improvement of precipitating illness is clinically apparent; AND
b. Duration of clinical remission has been stable for 2 months.
The requested medication is not prescribed concurrently with pegcetacoplan (Empaveli), iptacopan (Fabhalta), (crovalimab-akkz) Piasky, or ravulizumab (Ultomiris); AND
For Soliris/Epysqli products, one of the following (a or b): a. For Medicaid: For Bkemv, documentation is provided that the member is switching from treatment with Epysqli (preferred); OR b. For Medicaid/Medicare: For Soliris, documentation is provided that the member is switching from treatment with Epysqli and Bkemv.
Products injection, eculizumab, 2 mg (Soliris); injection, eculizumab-aagh (Epysqli) (preferred), biosimilar, 2 mg; injection, eculizumab-aeeb (Bkemv) biosimilar, 2 mg; and Injection ravulizumab-cwvz 10 mg (Ultomiris) Diagnosis Atypical Hemolytic Uremic Syndrome (aHUS) (ICD-10 D59.32) Line of Business Medicare and Medicaid Approval Length Initial: 12 weeks, Renewal: 12 months Override Type PA, QL Initial Criteria Note: Pharmacy staff: For QUEST non-ABD members with cancer, send ADRC (Aid to Disability Referral Committee) referral with chart notes through G8 CM module.
High Cost All approvals must be reviewed with the Pharmacy Director Criteria:
Diagnosis of Atypical Hemolytic Uremic Syndrome (aHUS) (ICD-10: D59.32; or D59.39 Other hemolytic uremic; AND
Prescribed by or in consultation with a hematologist or nephrologist; AND
Member is 1 month of age or older; AND
The diagnosis of Atypical Hemolytic Uremic Syndrome (aHUS) is supported by: a. The absence of Shiga toxin-producing E. coli infection; AND

Complement C5 Inhibitors

Updated on: 11/14/2025

b. Thrombotic thrombocytopenic purpura has been ruled out [for example, normal ADAMTS 13 activity and no evidence of an ADAMTS 13 inhibitor], or if thrombotic thrombocytopenic purpura cannot be ruled out by laboratory and clinical evaluation, a trial of plasma exchange did not result in clinical improvement;
AND

The member has completed or updated meningococcal vaccination (for serogroups A, C, W, and Y, and serogroup B) at least 2 weeks prior to administration of the first dose of eculizumab, unless the risks of delaying eculizumab outweigh the risk of meningococcal infection; AND
The requested medication is not prescribed concurrently with pegcetacoplan (Empaveli), iptacopan (Fabhalta), (crovalimab-akkz) Piasky, or ravulizumab (Ultomiris); AND
For Soliris/Epysqli products, one of the following (a or b): a. For Medicaid: For Bkemv, documentation is provided that the member is switching from treatment with Epysqli (preferred); OR b. For Medicaid/Medicare: For Soliris, documentation is provided that the member is switching from treatment with Epysqli and Bkemv. OR
For ravulizumab (Ultomiris): documentation is provided that the member is switching from treatment with Epysqli, Bkemv, or Soliris. Renewal Criteria Diagnosis Atypical Hemolytic Uremic Syndrome (aHUS) Approval Length Renewal: 12 months Note: Pharmacy staff: For QUEST non-ABD members with cancer, send ADRC (Aid to Disability Referral Committee) referral with chart notes through G8 CM module.
High Cost All approvals must be reviewed with the Pharmacy Director
Criteria:
Diagnosis of Atypical Hemolytic Uremic Syndrome (aHUS) (ICD-10: D59.32; or D59.39 Other hemolytic uremic syndrome; AND
Prescribed by or in consultation with a hematologist or nephrologist; AND
There is clinical improvement after the initial trial (such as reduction of plasma exchanges, reduction of dialysis, increased platelet count, reduction of hemolysis) or complete clinical remission for 2 months (such as resolution of thrombocytopenia and mechanical hemolysis, and normalization or new baseline plateau of renal function) and improvement of precipitating illness is clinically apparent; AND
The requested medication is not prescribed concurrently with pegcetacoplan (Empaveli), iptacopan (Fabhalta), (crovalimab-akkz) Piasky, or ravulizumab (Ultomiris); AND
For Soliris/Epysqli products, one of the following (a or b): a. For Medicaid: For Bkemv, documentation is provided that the member is switching from treatment with Epysqli (preferred); OR b. For Medicaid/Medicare: For Soliris, documentation is provided that the member is switching from treatment with Epysqli and Bkemv. Resumption Criteria Diagnosis Atypical Hemolytic Uremic Syndrome (aHUS) Approval Length 12 months Note: Pharmacy staff: For QUEST non-ABD members with cancer, send ADRC (Aid to Disability Referral Committee) referral with chart notes through G8 CM module.
High Cost All approvals must come from the Pharmacy Director.

Complement C5 Inhibitors

Updated on: 11/14/2025

Criteria:

Diagnosis of Atypical Hemolytic Uremic Syndrome (aHUS) (ICD-10: D59.32 Hereditary hemolytic uremic syndrome [when specified as atypical hemolytic uremic syndrome]; or D59.39 Other hemolytic uremic syndrome [when specified as atypical hemolytic uremic syndrome]; AND
Prescribed by or in consultation with a hematologist or nephrologist; AND
Documentation is provided that member experienced a relapse after discontinuation of therapy as defined by:
Reduction in platelet count to less than 150,000/mm3 or greater than 25% from baseline; OR
Mechanical hemolysis (having 2 or more features of hemoglobin less than 10 g/dL, lactate dehydrogenase greater than 2 times upper limit of normal, undetectable haptoglobin, or presence of schistocytes on smear); OR
Acute kidney injury with serum creatinine increase greater than 15% from baseline levels. AND
The requested medication is not prescribed concurrently with pegcetacoplan (Empaveli), iptacopan (Fabhalta), (crovalimab-akkz) Piasky, or ravulizumab (Ultomiris); AND
For Soliris/Epysqli products, one of the following (a or b): a. For Medicaid: For Bkemv, documentation is provided that the member is switching from treatment with Epysqli (preferred); OR b. For Medicaid/Medicare: For Soliris, documentation is provided that the member is switching from treatment with Epysqli and Bkemv.

Exclusion Conditions Not Covered
Concomitant Use with Empaveli > 4 Weeks. Concomitant use of eculizumab with Empaveli is not recommended. However, to reduce the risk of hemolysis from abrupt treatment discontinuation in a patient switching from eculizumab to Empaveli, member should use both therapies for 4 weeks; after which, eculizumab is discontinued and member is continued on Empaveli monotherapy.
Concomitant Use with Another Complement Inhibitor Except Voydeya (danicopan tablets). There is no evidence to support concomitant use of eculizumab with another complement inhibitor, except Voydeya. Note: Examples of complement inhibitors are Fabhalta (iptacopan capsules), PiaSky (crovalimab-akkz intravenous infusion or subcutaneous injection), Ultomiris (ravulizumab-cwvz intravenous infusion), and eculizumab intravenous infusion (Soliris, biosimilars).
Concomitant Use with a Rituximab Product, a Neonatal Fc Receptor Blocker, or Zilbrysq (zilucoplan subcutaneous injection). There is no evidence to support concomitant use of eculizumab with a rituximab product, a neonatal Fc receptor blocker, or Zilbrysq. Note: Examples of Neonatal Fc receptor blockers are Imaavy (nipocalimab-aahu intravenous infusion), Rystiggo (rozanolixizumab-noli subcutaneous infusion), Vyvgart (efgartigimod alfa-fcab intravenous infusion), and Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc subcutaneous injection).
Concomitant Use with Enspryng (satralizumab-mwge subcutaneous injection) or Uplizna (inebilizumab-cdon intravenous infusion). There is no evidence to support concomitant use of eculizumab or ravulizumab-cwvz with Enspryng or Uplizna.

Complement C5 Inhibitors

Updated on: 11/14/2025

FDA Indications & Dosing

Indication Dosing/Administration Piasky (crovalimab) Paroxysmal nocturnal hemoglobinuria Note: Dosing consists of an initial IV loading dose, followed by 4 weekly SUBQ loading doses, and then SUBQ maintenance dosing every 4 weeks. Dosing is based on actual body weight; modify the maintenance dose if the patient’s weight changes to become consistently above or below 100 kg during the course of maintenance therapy. • ≥40 kg to <100 kg: 1,000 mg IV on day 1, then 340 mg SUBQ on days 2, 8, 15, and 22. Then 680 mg SUBQ on day 29 and then every 4 weeks thereafter. • ≥100 kg: 1,500 mg IV on day 1, then 340 mg SUBQ on days 2, 8, 15, and 22; then 1,020 mg SUBQ on day 29 and then every 4 weeks thereafter. Soliris and eculizumab biosimilars Atypical hemolytic uremic syndrome
900 mg IV weekly for the first 4 weeks, followed by 1.2 g IV for the fifth dose 1 week later, then 1.2 g IV every 2 weeks thereafter. Soliris and eculizumab biosimilars Myasthenia gravis, generalized refractory
900 mg IV once weekly for 4 doses, followed by 1.2 g IV at week 5, then 1.2 g IV every 2 weeks thereafter Soliris and eculizumab biosimilars Paroxysmal nocturnal hemoglobinuria Note: Monitor for recurrence for at least 8 weeks after discontinuation. 600 mg IV weekly for the first 4 weeks, followed by 900 mg IV for the fifth dose 1 week later, then 900 mg IV every 2 weeks thereafter. Soliris and eculizumab biosimilars Neuromyelitis optica spectrum disorder
900 mg IV weekly for the first 4 weeks, followed by 1.2 g IV for the fifth dose 1 week later, then 1.2 g IV every 2 weeks thereafter. Ultomiris (ravulizumab-cwvz) Atypical hemolytic uremic syndrome Note: A minimum treatment duration of 6 months is recommended. Dose is based on weight at time of treatment. • Weight 20 kg to <30 kg: 900 mg IV as a single dose, then 2,100 mg IV once every 8 weeks starting 2 weeks after the loading dose. • Weight 30 kg to <40 kg: 1,200 mg IV as a single dose, then 2,700 mg IV once every 8 weeks starting 2 weeks after the loading dose. • Weight 40 kg to <60 kg: 2,400 mg IV as a single dose, then 3,000 mg IV once every 8 weeks starting 2 weeks after the loading dose. • Weight 60 kg to <100 kg: 2,700 mg IV as a single dose, then 3,300 mg IV once every 8 weeks starting 2 weeks after the loading dose. • Weight ≥100 kg: 3,000 mg IV as a single dose, then 3,600 mg IV once every 8 weeks starting 2 weeks after the loading dose. Ultomiris (ravulizumab-cwvz) Myasthenia gravis, generalized Note: Dose is based on weight at time of treatment. For use as chronic immunosuppressive therapy in patients with anti-acetylcholine receptor antibody-positive (AChR+) myasthenia gravis as monotherapy (eg, in patients who cannot tolerate glucocorticoids), as bridge therapy with slower acting immunosuppressive agents, or in combination with glucocorticoids in patients with glucocorticoid-resistant or glucocorticoid-dependent disease. • Weight 40 kg to <60 kg: 2,400 mg IV as a single dose, then 3,000 mg IV once every 8 weeks starting 2 weeks after the loading dose.

Complement C5 Inhibitors

Updated on: 11/14/2025

• Weight 60 kg to <100 kg: 2,700 mg IV as a single dose, then 3,300 mg IV once every 8 weeks starting 2 weeks after the loading dose. • Weight ≥100 kg: 3,000 mg IV as a single dose, then 3,600 mg IV once every 8 weeks starting 2 weeks after the loading dose. Ultomiris (ravulizumab-cwvz) Paroxysmal nocturnal hemoglobinuria Note: Dose is based on weight at time of treatment. • Weight 20 kg to <30 kg: 900 mg IV as a single dose, then 2,100 mg IV once every 8 weeks starting 2 weeks after the loading dose. • Weight 30 kg to <40 kg: 1,200 mg IV as a single dose, then
• 2,700 mg IV once every 8 weeks starting 2 weeks after the loading dose. • Weight 40 kg to <60 kg: 2,400 mg IV as a single dose, then 3,000 mg IV once every 8 weeks starting 2 weeks after the loading dose. • Weight 60 kg to <100 kg: 2,700 mg IV as a single dose, then 3,300 mg IV once every 8 weeks starting 2 weeks after the loading dose. • Weight ≥100 kg: 3,000 mg IV as a single dose, then 3,600 mg IV once every 8 weeks starting 2 weeks after the loading dose. Ultomiris (ravulizumab-cwvz) Neuromyelitis optica spectrum disorder
Note: Dose is based on weight at time of treatment. Use in patients with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder. • Weight 40 kg to <60 kg: 2,400 mg IV as a single dose, then 3,000 mg IV once every 8 weeks starting 2 weeks after the loading dose. • Weight 60 kg to <100 kg: 2,700 mg IV as a single dose, then 3,300 mg IV once every 8 weeks starting 2 weeks after the loading dose. • Weight ≥100 kg: 3,000 mg IV as a single dose, then 3,600 mg IV once every 8 weeks starting 2 weeks after the loading dose.

References

DailyMed. Package inserts. U.S. National Library of Medicine, National Institutes of Health website. http://dailymed.nlm.nih.gov/dailymed/about.cfm. Accessed: September 16, 2024.
DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated periodically.
Lexi-Comp ONLINE™ with AHFS™, Hudson, Ohio: Lexi-Comp, Inc.; 2024; Updated periodically.
Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006; 355(12):1233-1243.
Parker CJ, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005; 106(12):3699-3709.
Loirat C, Fremeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011; 6:60.
Loirat C, Fakhouri F, Ariceta G, et al; HUS International. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2016; 31(1):15-39.
Fakhouri F, Fila M, Provot F, et al. Pathogenic variants in complement genes and risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation. Clin J Am Soc Nephrol. 2017; 12:50-59.
Merrill SA, Brittingham ZD, Yuan X, et al. Eculizumab cessation in atypical hemolytic uremic syndrome. Blood. 2017; 130(3):368-372.
Sanders DB, Wolfe GI, Benatar M, et al for the Task Force of the Myasthenia Gravis Foundation of America (MGFA). International consensus guidance for management of myasthenia gravis. Neurology 2016; 87:419.

Complement C5 Inhibitors

Updated on: 11/14/2025

Narayanaswami P, Sanders DB, Wolfe G, et al for the Task Force of the Myasthenia Gravis Foundation of America (MGFA). International consensus guidance for management of myasthenia gravis 2020 update. Neurology 2021; 96:114-122.
Lee JW, Fontbrune FS, et al. Ravulizumab vs Eculizumab in Adult Patients with PNH Naïve to Complement Inhibitors: The 301 Study. Blood 2018; prepublished online December 3, 2018; DOI 10.1182/blood-2018-09-876136.
Kulasekararaj AG, Hill A, Rottinghaus ST, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2018; Pre-published online December 3, 2018; doi: 10.1182/blood- 2018-09-876805.
Pittock SJ, Barnett M, Bennett JL, Berthele A, de Sèze J, Levy M, Nakashima I, Oreja-Guevara C, Palace J, Paul F, Pozzilli C, Yountz M, Allen K, Mashhoon Y, Kim HJ. Ravulizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. Ann Neurol. 2023 Jun;93(6):1053-1068. doi: 10.1002/ana.26626. Epub 2023 Apr 5. PMID:
Scheinberg P, Clé DV, Kim JS, et al. Phase 3 randomized COMMODORE 1 trial: Crovalimab versus eculizumab in complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2024;99(9):1757-1767. doi:10.1002/ajh.27413.
Röth A, He G, Tong H, et al. Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients
with paroxysmal nocturnal hemoglobinuria naive to complement inhibition. Am J Hematol. Published online June 17,
1. doi:10.1002/ajh.27412.
Review History 11/4/2025: Updated to include Piasky. 11/14/2025: Add Q5152 Injection, eculizumab-aeeb (Bkemv), biosimilar, 2 mg as preferred for Medicaid.

Book a walkthrough

Walk through this policy with us

Review how this policy can be converted into cited criteria, prior authorization checks, and operational automation.

GenHealth is the best way to run RCM including eligibility, prior auth, billing, and denials with AI that works like a teammate in your EMR and billing systems.

RXMP-19 Complement C5 Inhibitors Form

Previewing the first 5 questions