Pharmacy Prior Authorization Criteria

Mitoxantrone

Indications for Prior Authorization

Mitoxantrone

• For diagnosis of Multiple Sclerosis
  Indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic status is significantly abnormal between relapses). It is not indicated in the treatment of patients with primary progressive multiple sclerosis.

• For diagnosis of Prostate Cancer
  Indicated, in combination with corticosteroids, as initial chemotherapy for the treatment of patients with pain related to advanced hormone-refractory prostate cancer.

• For diagnosis of Acute Non-Lymphocytic Leukemia (ANLL)
  Indicated, in combination with other approved drug(s), in the initial therapy of ANLL in adults. This category includes myelogenous, promyelocytic, monocytic, and erythroid acute leukemias.

Criteria

Generic mitoxantrone

Prior Authorization (Initial Authorization)

Length of Approval: 6 Months [5-6, A]
For diagnosis of Multiple Sclerosis

• Diagnosis of one of the following:
• Secondary progressive multiple sclerosis: gradually worsening disability with or without superimposed relapses [2]
OR
• Progressive relapsing multiple sclerosis: progression of disability from the onset with superimposed relapses [2]
OR
• Worsening relapsing-remitting multiple sclerosis: neurological status remains significantly abnormal in between multiple sclerosis relapses [3]
AND
• Trial and failure (of a minimum 4-week supply), contraindication, or intolerance to two disease-modifying therapies for MS (e.g., Kesimpta [Ofatumumab], Avonex [Interferon beta-1a], Betaseron [Interferon beta-1b], Mayzent [Siponimod], Zeposia [ozanimod]): [B, 3, 11]
AND
• Left ventricular ejection fraction (LVEF) greater than or equal to 50% [2, 4-6]
AND
• Neutrophil count greater than or equal to 1,500 cell/mm^3
AND
• Prescribed by or in consultation with a neurologist

Generic mitoxantrone

Prior Authorization (Reauthorization)

Length of Approval: 6 Months [5-6, A]
For diagnosis of Multiple Sclerosis

• Patient demonstrates positive clinical response to therapy.
AND
• Left ventricular ejection fraction (LVEF) greater than or equal to 50% [2, 4-6]
AND
• A lifetime cumulative dose less than 140 mg/m^2 [1]
AND
• Prescribed by or in consultation with a neurologist

Generic mitoxantrone

Prior Authorization (Initial Authorization)

Length of Approval: 6 Months [5-6, A]
For diagnosis of Prostate Cancer

• Diagnosis of advanced hormone-refractory (castration-resistant) prostate cancer
AND
• Used in combination with corticosteroids (e.g., prednisone, methylprednisolone) [7, 8, 10]
AND
• Left ventricular ejection fraction (LVEF) greater than or equal to 50% [2, 4-6]
AND
• Neutrophil count greater than or equal to 1,500 cell/mm^3

Generic mitoxantrone

Prior Authorization (Reauthorization)

Length of Approval: 6 Months [5-6, A]
For diagnosis of Prostate Cancer

• Patient does not show evidence of progressive disease while on therapy
AND
• Left ventricular ejection fraction (LVEF) greater than or equal to 50% [2, 4-6]
AND
• A lifetime cumulative dose less than 140mg/m^2 [1]

Generic mitoxantrone

Prior Authorization (Initial Authorization)

Length of Approval: 6 Months [5-6, A]
For diagnosis of Acute Non-Lymphocytic Leukemia (ANLL)

• Diagnosis of acute non-lymphocytic leukemia (ANLL) (e.g., myelogenous, promyelocytic, monocytic, and erythroid)
AND
• Used in combination with other medications used for the treatment of ANLL [9, 10]
AND
• Left ventricular ejection fraction (LVEF) greater than or equal to 50% [2, 4-6]

Generic mitoxantrone

Prior Authorization (Reauthorization)

Length of Approval: 6 Months [5-6, A]
For diagnosis of Acute Non-Lymphocytic Leukemia (ANLL)

• Patient does not show evidence of progressive disease while on therapy
AND
• Left ventricular ejection fraction (LVEF) greater than or equal to 50% [2, 4-6]
AND
• A lifetime cumulative dose less than 140mg/m^2 [1]

P & T Revisions

2024-05-03, 2023-11-02, 2023-05-03, 2022-05-04, 2021-09-27, 2021-05-10, 2020-03-30

References

1. Mitoxantrone Prescribing Information. Fresenius Kabi USA, LLC. Lake Zurich, IL. December 2019.
2. Hartung HP, Gonsette R, Konig N, et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomized, mulitcentre trial. Lancet 2002;360:2018-25.
3. Marriott JJ, Miyasaki JM, Gronseth G, O’Connor PW. Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2010;74:1463-70.
4. Avasarala JR, Cross AH, Clifford DB, Singer BA, Siegal BA, Abbey EE. Rapid onset mitoxantrone-induced cardiotoxicity in secondary progressive multiple sclerosis. Mult Scler. 2003;9:59-62.
5. Ghalie RG, Edan G, Laurent M, et al. Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS. Neurology. 2002;59:909-13.
6. Bastianello S, Pozzilli C, D’Andrea F, et al. A controlled trial of mitoxantrone in multiple sclerosis: serial MRI evaluation at one year. Can J Neurol Sci. 1994;21:266-70.
7. Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351:1513-20.
8. Tannock IF, de Wit R, Berry WR, et al. Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502-12.
9. Anderson JE, Kopecky KJ, Willman CL, et al. Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study. Blood. 2002;100:3869-76. Epub 2002 Aug 1.
10. The NCCN Drugs and Biologics Compendium (NCCN Compendium). Available at www.nccn.org. Accessed May 2, 2024.
11. Rae-Grant, A., Day, G., Marrie, R., Rabinstein, A., Cree, B., Gronseth, G., Haboubi, M., Halper, J., Hosey, J., Jones, D., Lisak, R., Pelletier, D., Potrebic, S., Sitcov, C., Sommers, R., Stachowiak, J., Getchius, T., Merillat, S. and Pringsheim, T., 2018. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis. Neurology, 90(17), pp.777-788.

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End Notes

1. All patients should be carefully assessed for cardiac signs and symptoms by history and physical examination prior to start of Novantrone therapy. Left ventricular ejection fraction (LVEF) should be evaluated prior to administration of the initial dose of mitoxantrone and all subsequent doses. Mitoxantrone is recommended to be dosed once every three months. Additional doses of mitoxantrone should not be administered to multiple sclerosis patients who have experienced either a drop in LVEF to below 50% or a clinically significant reduction in LVEF during mitoxantrone therapy. [1]
2. Per 2018 American Academy of Neurology (AAN) Multiple Sclerosis (MS) guideline, mitoxantrone should not be prescribed to people with MS due to the high frequency of severe adverse effects unless the potential benefit greatly outweighs the risk. Another MS agent that has relatively more side effects include Lemtrada and its prescribing information recommends reserving use after two prior lines of therapies have been tried. Due to this, a requirement of two prior agents for Mitoxantrone would be more appropriate to align with other MS agents that have more risks than benefit. [11]

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Revision History

• 2024-05-03: 2024 Annual Review. Criteria formatting changes to consolidate clinically driven t/f step within MS criteria to list drugs as examples only instead of requiring trial of specific drugs. Removed specialist requirement for oncology indications. Background updates.
• 2023-11-02: Program update to standard reauthorization language. No changes to clinical intent.
• 2023-05-03: Annual Review, no changes.
• 2022-05-04: Annual Review, no changes.
• 2021-09-27: 2021 UM Annual Review
• 2021-05-10: 2021 UM Annual Review
• 2020-03-30: 2020 UM Annual Review. Removed Zinbryta as a T/F option from Multiple Sclerosis criteria as drug obsolete. For operational clean up, also removed drug name from all reauthorization criteria.

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